WO 2005/061477 PCT/US2003/040835 BIARYL SULFONAMIDES AS MMP INHIBITORS FIELD OF THE INVENTION The present invention relates to biaryl sulfonamides and their use as for example, metalloprotcinasc inhibitors. BACKGROUND OF THE INVENTION Mctalloproteinases, including matrix metalloproteinases and aggrecanases, are known to have a roJe in the breakdown of connective tissue. Matrix mctalloproteinases ("MMPs") constitute a superfamily of proteolytic enzymes that are genetically related and capable of degrading almost all the constituents of,extracellular matrix and basement membrane that restrict cell movement. Aggrecanases, members of the ADAMTS (A disintegrin and metalloprotcinase with thrombospondin motifs) family of proteins, cleave aggrecan, a cartilage component also known as the large aggregating chondroitin sulphate proteoglycan. MMPs and aggrecanases can degrade various components of connective tissue, including collagen and proteoglycan. In the absence of natural checks on this activity, a variety of pathologies and undesirable effects can occur. In fact, MMPs and aggrecanases are known to play a role in many disorders in which extracellular protein degradation/destruction occurs, such as cancer, osteoarthritis, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease ("COPD"), atherosclerosis, age-related macular degeneration, myocardia] infarction, cornea] ulceration and other ocular surface diseases, hepatitis, aortic aneurysms, tendonitis, central nervous system diseases, abnormal wound healing, angiogenesis, restenosis, cirrhosis, multiple sclerosis, glomerulonephritis, graft versus host disease, diabetes, inflammatory bowel disease, shock, invertebral disc degeneration, stroke, osteopenia, and periodontal diseases. 1 WO 2005/061477 PCT/US2003/040835 Therefore, metalloproteinase inhibitors are needed, including inhibitors of MMPs and aggrecenases. Additionally, selective inhibitors directed to specific MMPs and aggrecanases are valuable to avoid potential side effects. SUMMARY OF THE INVENTION In one embodiment, the present invention provides novel biaryl sulfonamide compounds. Preferred compounds of the invention are thoseof the formula 1: wherein: R1 and R2 are, independently, H, CH(OH)R4, phenyl, heteroaryl, or CI-C6 alky], with the proviso that when Rl or R2 is CH(OH)R4, then Z is substituted with NR4SO2R5, SO2NR4R5, heterocycloalkyl, heteroaryl, orC3-C6cycloalkyl; R3 is H or Cl-C6alkyl; R4 and R5 are, independently With respect to each occurrence, a bond to the other, H, Cl-C6 alkyl, or phenyl; G and E are, independently, S, O, N(R4), C(R6)=C(R6), or N=C(R6); R6 is, independently with respect to each occurrence, H, halogen, NR4RS, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2RS, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyl, heteroaryl, CI-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; X is N(R3)C(=O), OC(=O), OS(O)2, NHSO2, OCH2, CH2S(O), or CH2S(O)2; and Z is at least one heteroaryl moiety. In another aspect, the present invention provides methods for using biaryl sulfonamide compounds to modulate and, preferably, inhibit metalloproteinases. Preferred methods involve in vitro and in vivo contacting of the metalloprotcinase with a biaryl sulfonamide. Preferred methods of this type are ones in which the activity of the metalloproteinase is determined before or after such contacting and, optionally, the determination is used to assess the extent to which the compound modulates the activity of the enzyme. 2 WO 2005/061477 PCT/US2003/040835 DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention it has been discovered that biaryl sulfonamide compounds of the present invention are useful in inhibiting metalloproteinases. Moreover, some compounds so great specifity for certain metalloproteinases. Such compounds can be useful in the treatment of cancer, osteoarthritis, rheumatoid arthritis, asthma, COPD, atherosclerosis, age-related macular degeneration, myocardial infarction, comcal ulceration and other ocular surface diseases, hepatitis, aortic ancurysms, tendonitis, central nervous system diseases, abnormal wound healing, angiogenesis, restenosis, cirrhosis, multiple sclerosis, glomerulonephritjs, graft versus host disease, diabetes, inflammatory bowel disease, shock, invcrtebral disc degeneration, stroke, osteopenia, and periodontal diseases. The metalloproteinase is preferably, Gelatinase A (MMP-2), Macrophage metalloclastase (MMP-12), ColIagenasc-3 (MMP-13), or Aggrecanase-1 (ADAMTS4). More preferably, the metalloproteinase is MMP-13. Preferred compounds of the invention are those of the formula 1: wherein: R1 and R2 are, independently, H, CH(OH)R4, phenyl, hcteroaryl,orCl-C6 alkyl, with the proviso that when R1 or R2 is CH(OH)R4, then Z is substituted with NR4SO2R5, SO2NR4RS, heterocycloalkyl, heteroaryl, or C3-C6 cycloalkyl; R3 is H or Cl-C6 alkyl; R4 and R5 are, independently with respect to each occurrence, a bond to the other, H, C]-C6 alkyl, or phenyl; G and E are, independently, S, O, N(R4), C(R6)=C(R6), or N=C(R6); R6 is, independently with respect to each occurrence, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=O)RS, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4RS, CN, phenyl. heteroaryl, C1-C6 alkyl, C2-C6 alkenyl, orC2-C6 alkynyl; X is N(R3)C(=O), OC(=O), OS(O)2, NHSO2, OCH2, CH2S(O), or CH2S(O)2; and Z is at least one heteroaryl moiety. 3 WO 2005/061477 PCT/US200J/040835 When other than H, R1 may be optionally substituted with halogen, CO2R4, C(=O)NR4R5, phenyi, or heteroaryl. When other than H, R3 may be optionally substituted with NR4R5, N^CH^O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=##)R5, NHC(=O)OR4, NO2. SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, pheny], or heteroaryl. In one embodiment, R6 is each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=O)R3, NR4C(=O)OR4, NO2) SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONRV, CN, phenyi, or heteroaryl. In one embodiment, Z is a 5 membered ring. In another embodiment, Z is bicyclic. In yet another embodiment, Z is furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, isoxazole, isothiazole, thiazole, 1,2,5-thiadiazole, 1,2,3-triazole, 1,3,4-thiadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,4-triazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, and furazan, or wherein: U is selected from S, O, and N(R4); W is selected from C(R6), and N; M is selected from C(R6), and N; L is selected from C(R6)=C(R^), CCR^N, and N(R4); R7 is selected from a bond to R6, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyi, heteroaryl, and C1-C6 alky), C2-C6 alkenyl, and C2-C6 alkynyl, each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=0)OR<, NO2, SO2NR4R5, SO2R4, OR8, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyi, or heteroaryl; and R8 is selected from H, phenyi, heteroaryl, and C1-C6 alky], optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)7)2NR4, NR4SO2R5, NR4C(=O)R5, NHC(=O)OR4. NO2, SO2NR4R5, SO2R4, C(=O)R4, COOR4, CONR4Rs CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl. Preferably, Z is: 4 WO 2005/061477 PCT/US2003/040835 wherein: U is selected from S, O, and N(R4); W is selected from C(R6), and N; M is selected from C(R6), and N; L is selected from C(R6)=C(R6), C(R6)=N, and N(R4); R7 is selected from a bond to R6, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2:)2NR4, NHSO2R4, NR4C(=O)RS, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4. CONR4R5, CN, phenyl, hetcroaryl, and C1-C6 alky], C2-C6 alkenyl, and C2-C6 alkynyl, each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)RS, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR8, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl; and R8 is selected from H, phenyl, heteroaryl, and C1-C6 alky], optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4RS, SO2R4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or hetcroaryl. In another embodiment: R3 is H; G is CCH)=C(If); E is C(H)=C(H) or N=C(H); X is NHC(=O), or OCH2; and wherein: U is selected from S, O, and N(R4); W is selected from C(R6). and N: 5 WO 2005/061477 PCT/US2003/040835 M is selected from C(R6), and N; L is selected from C(R6)=C(R6), C(R6)=N, and N(R4); R7 is selected from a bond to R6, H, halogen, NR4R5, N[(CH2)2J2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyl, beteroaryl, and C1-C6 alky], C2-C6 alkenyl, and C2-C6 alkynyl, each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2) SO2NR4R5, SO2;R4, OR8, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl; and R8 is selected from H, phenyl, heteroaryl, and C1-C6 alky], optionally substituted with NR4RS, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=O)R5, NHC(=O)0R4, NO2, SO2NR4RS, SO2R4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl. Preferably: E is C(H)=C(H); U is O; W is C(H), or C(CH3); M is C(R9), wherein R9 is H, halogen, C1-C6 alky], or CN; and L is C(H)=C(H). The term "alkyl", as used herein, whether used alone or as part of another group, refers to a substituted or unsubstituted aliphatic hydrocarbon chain and includes, but is not limited to, straight and branched chains containing from 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms, unless explicitly specified otherwise. For example, methyl, ethyl, propyl, isopropyl, butyl, i-buty] and t-buty] are encompassed by the term "alkyl." C1-C6 alkyl includes straight and branched chain aliphatic groups having from 1 to 6 carbons. Specifically included within the definition of "alkyl" are those aliphatic hydrocarbon chains that are optionally substituted. The carbon number as used in the definitions herein refers to carbon backbone and carbon branching, but does not include carbon atoms of the substituents, such as alkoxy substitutions and the like. The term "alkenyl", as used herein, whether used alone or as part of anoiher group, refers to a substituted or unsubstituted hydrocarbon chain and includes, but is not limited to, straight and branched chains having 2 to 8 carbon atoms and containing at least one double bond. Preferably, the alkenyl moiety has 1 or 2 double bonds. Such alkenyl moieties may exist in the E or Z conformations and the compounds of this invention include both conformations. C2-C6 alkenyl includes a 1 to 6 carbon straight or branched chain having at least one carbon-carbon double bond. Specifically included within the definition of "alkenyl" are those aliphatic 6 WO 2005/061477 PCT/US2003/040835 hydrocarbon chains that are optionally substituted. Heteroatoms, such as O, S or NR4R5, attached to an alkenyl should not be attached to a carbon atom that is bonded to a double bond. The term "alkynyl" refers to a hydrocarbon moiety containing at least one carbon-carbon triple bond. C2-C6 alkynyl includes a 2 to 6 carbon straight or branched chain having at least one carbon-carbon triple bond. The term "cycloalkyl" refers to a monocyclic, bicyclic, tricyclic, fused, bridged, or spiro monovalent saturated hydrocarbon moiety, wherein the carbon atoms are located inside or outside of the ring system. Any suitable ring position of the cycloalkyl moiety may be covalently linked to the defined chemical structure. Examples of cycloalkyl moieties include, but are not limited to, chemical groups such as cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohcptyl, norbornyl, adamantyl, spiro[4.5]decanyl, and homologs, isomers, and the like. C3-C6 cycloalkyl includes monocyclic, saturated rings of 3 to 6 carbons, optionally substituted with R6. "Heteroaryl" refers to a 5 to 6 membered aromatic heterocyclic ring which contains from 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur atoms in the ring and may be fused with a carbocyclic or heterocyclic ring at any possible position. "Hetcrocycloalkyl" refers to a 5 to 7-membered saturated ring containing carbon atoms and from 1 to 2 heteroatoms selected from N, O, and S. The term "phenyl", as used herein, whether used alone or as part of another group, refers to a substituted or unsubstitutcd phenyl group. An optionally substituted moiety may be substituted with one or more substituents. Suitable substituents for a phenyl or heteroary! moiety may be selected independently from H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSOjR4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4RS, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, and CN. When such moieties are substituted, for example, they may typically be mono-, di-, tri- or persubstituted. Examples for a halogen substituent include 1-bromo vinyl, 1-fluoro vinyl, 1,2-difluoro vinyl, 2,2-difluorovinyl, 1,2,2-trifluorovinyl, 1,2-dibromo ethane, 1,2 difluoro ethane, 1-fluoro-2-bromo ethane, CF2CF3, CF2CF2CF3, and the like. The term halogen includes bromine, chlorine, fluorine, and iodine. For the sake of simplicity, connection points ("-") are not depicted. When an atom or compound is described to define a variable, it is understood that it is intended to replace the variable in a manner to satisfy the valency of the atom or compound. For example, when L is C(R6)=C(R6), both carbon atoms form a part of the ring in order to satisfy their respective valences. Likewise, when divalent substituents are presented, it is understood that they are not 7 WO 2005/061477 PCT/US2003/040835 limited to the order listed, for example, as used in this specification "OCH2" encompasses CH2O and OCH2. The term "pharmaceutically acceptable salt", as used herein, refers to salts derived form organic and inorganic acids such as, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids when a compound of this invention contains a basic moiety. Salts may also be formed from organic and inorganic bases, preferably alkali metal salts, for example, sodium, lithium, or potassium, when a compound of this invention contains acarboxylate or phenolic moiety, or similar moiety capable of forming base addition salts. The term "patient", as used herein, refers to a mammal, preferably a human. The terms "administer", "administering", or "administration", as used herein, refer to either directly administering a compound or composition to a patient, or administering a prodrug derivative or analog of the compound to the patient, which will form an equivalent amount of the active compound or substance within the patient's body. The term "carrier", as used herein, shall encompass carriers, excipients, and diluents. The compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centers and may thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry in formula I, the present invention includes such optical isomers and diastereomers; as well as the racemic and resolved, enantiomerically pure R and S stereoisomers; as well as other mixtures of the R and S stereoisomers and pharmaceutically acceptable salts thereof. Where a stereoisomer is preferred, it may in some embodiments be provided substantially free of the corresponding enantiomer. Thus, an enantiomer substantially free of the corresponding cnantiomer refers to a compound that is isolated or separated via separation techniques or prepared free of the corresponding cnantiomer. "Substantially free", as used herein, means that the compound is made up of a significantly greater proportion of one steriosomer, preferably less than about 50% of the other, more preferably less than about 75%, and even more preferably less than about 90%. Preferred among the above noted R1 and R2 groups are C1-C6 alkyl. Preferred among the above noted R3 groups is H. Preferred among the above noted R4 and R5 groups are C1-C6 alkyl. Preferred among the above noted G and E groups are C(H)=C(H). Preferred among the above noted U groups are O and S. 8 WO 2005/061477 PCT/US2003/040835 Preferred among the above noted W groups arc C(H) and C(CH3). Preferred among the above noted M groups are CR6. Preferred among the above noted L groups are CH=CH. Preferred among the above noted R7 groups are those other than H. The following compounds are preferred: N-({4-[(I-bcnzofuran-2-yJcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)glycine; L-2-14'-[(Benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; N-({4'-[(lH-indol-2-y]carbonyl)amino]-],r-biphenyI-4-yl)sulfonyl)glycine; (4'-{[(5-chJoro-l-benzofuran-2-yl)carbonyl]amino}-l,l -biphenyl-4-yl)sulfonyl]-L-valine; N-[(4-{[(7-methoxy-l-benzofuran-2-yl)carbony]]amino}-l,r-biphenyl-4-yl)sulfonyl]-L-valine; N-[(4'-{[(5-nitro-l-benzofuran-2-yl)carbony]]amino}-l,r-biphenyl-4-yl)sulfonyl)-L-valine; N-[(4'-{[(5-amino-l-benzofuran-2-yl)carbonyl]amino}-l,l -biphenyl-4-yl)sulfonyl]-L-valine; N-({4'-[({5-[(methylsulfonyl)amino]-l-benzofuran-2-yI}carbonyl)amino]-l,l -biphenyl-4-yl }sulfony])-L-valine; N-{[4'-({[5-(acety]amino)-l-bcnzofuran-2-yl]carbonyl)amino)-l,l -biphenyl-4-yl]sulfonyl)-L-valine; 4-l(5-BenzcnesulfonyIamino-benzofuran-2-carbonyl)-amino]-biphcnyl-4-suIfonyl-L-valine; N-[(4'-{[(4-methoxy-l-benzofuran-2-yl)carbonyl]amino)-l,1-biphenyl-4-yl)sulfonyl]-L-valine; 4'-[(Benzo[P]thiophene-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valinc; 4'-[(4-Benzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine; 4'-{[4-(l-Carboxy-ethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonyl-L-valine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-L-Asparagine; L-2-{4'-[(Benzofuran-2-carbonyl)-amino]biphenyl-4-suIfonylamino]-3-methyl-butyric acid; N-(|4'-[(l-Benzofuran-2-ylcarbonyl)amino)-l,1-biphenyl-4-yl}sulfonyl)-L-Histidine; N-({4'-[(l-Benzofuran-2-ylcarbonyI)amino]-l,1-biphenyl-4-yI}suIfonyl)-L-lcucinc; 9 WO 2005/061477 PCT/US2003/040835 L-2-{4'-[(Benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-2-{4'-[(4-Cyano-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonylamino)-3-methyl-butyric acid ; L-3-Methy]-2-{4'-[(3-methy]-4-prop-l-)ynyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfony}amino)-butyric acid; L-2-{4'-{[4-(3-Methoxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbony])-amino}-biphenyl-4-sulfony)amino)-3-methy];butyric acid; 2-{4'-[(4-Cyc)opropy]ethyny]-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-mcthy]-butyric acid; L-2-(4-{[4-(2-Cyc]opropyl-ethyI)-3-methyl-b€nzofuran-2-carbony]]-amino}-bjphenyl-4-sulfonylamino)-3-methy]-butyric acid; L-2-(4'-{(4-(3-Mcthoxy-Z-propcnyl)-3-methyl-benzofuran-2-carbonyI]-amino}-biphenyl-4-su!fonylamino)-3-methyl-butyric acid; L-2-(4-{[4-(3-Hydroxy-prop-i-ynyI)-3-methyl-benzofuran-2-carbony]]-amino}-biphenyI-4-sulfonylamino)-3-methyl-butyric acid; L-2-(4-{[4-(3-Hydroxy-propyl)-3-rnethy]-benzofuran-2-carbony]]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-3-Methyl-2-(4'-{[3-methyl-4-(4-methy]-pent-l-ynyJ)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; L-3-Methy]-2-(4'-{[3-methyl-4-(4-methyl-pentyl)-benzofuran-2-carbonyl-amino}-biphcnyl-4-sulfonylamino)-butyric acid; L-2-(4'-{[4-(3-Methoxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acjd; L-2- (4-{[4-(3-Dimcthylamino-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-2- {4-{[4-(3-Dimethylamino-propyl)-3-mefhyJ-benzofuran-2-carbonyI]-amino}-bipbenyl-4-sulfonylamino)-3-methyl-butyric acid; L- 2-(4'-[(4-Ethynyl-3-melhyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino)-3-methyl-butyric acid;. L-2-(4'-{[4-(3,3-Dimethyl-but-1-ynyl)-3-methyl-benzofuran-2-carbony]]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L- 3-Methy]-2- (4'-{[3-methyl-4- (3-methyl-isoxazol-5-y])-benzofuran-2-carbonyl]-amino} -biphenyl-4-sulfony)amino)-butyric acid; 10 WO 2005/061477 PCT/US2003/040835 L-2- {4'-{(4-Methanesulfony]amino-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonylamino} -3-mcthyl-butyric acid; L-2-(4'-{[4-(Methancsu]fonyl-methy]-amino)-3-methyl-benzofuran-2-carbony)]-amino} bjphenyl-4-sulfonylamino)-3-methy]-butyric acid; L-3-Hydroxy-2-(4-{5-[(4-methanesulfonyIamino-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesu]fonylamino)-butyric acid; L-2-(4-{5-[(4-Me(hanesulfony)amino-3-melhy]-benzofuran-2-carbonyl)-amino]-pyridin 2-y)}-bcnzenesu]fony]amino)-3-methyl-butyric acid; L-2-(4-{5-[(4-Cyano-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-yl]-benzenesulfonyJamino)-3-methyl-butyric acid; D-2-{4'-[(4-Methancsulfonylamino-3-methy]-benzofuran-2-carbonyl)-amino]-bipheny}-4-sulfonylamino}-3-methyl-butyric acid; L-2-(|4'-[(4-Cyano-3-methyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-su]fonyl}-methyl-amino)-3-methyl-butyric acid; (L-3-Melhyl-2-{4-[(3-methyl-4-methylcarbamoyl-benzofuran-2-carbony))-amino]-biphcny)-4-sulfony]amino]-butyric acid triethylamine salt; 2-{4'-[(4-Dimcthylcarbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fony]amino}-3-methyl-butyric acid triethylamine salt L-2-{4'-[(4,6-Dimethoxy-3,7-dimethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-3-mclhyl-butyric acid; 2-{4'-[(5-Bromo-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid ; L-2-{4'-[(4-Carbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-2-(4-{[4-(Cyclopropanccarbonyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-2- {4'-[(4-Acety]amino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-3-Methyl-2- {4'-[(3-methyl-4-propionylainino-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyIamino}-butync acid; L-2- {4-[(4-Isobutyrylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid;, L- 2-{4'-[(4-Cyclopropylmethoxy-3-methy]-benzofuran-2-carbonyl)-amino]-bipheny]-4 sulfonylamino)-3-methyl-butyric acid; 11 WO 2005/061477 PCT/US2003/040835 L- 2-{4-[(lH-Benzoimidazo]e-2-carbony))-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L- 2-{4'-[(4-scc-Butoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L- 3-Methyl-2- {4'-[(3-phenyl-benzofuran-2-carbony])-amino]-bipheny]-4-sulfonylamino}-butyric acid; L- 2-(4-{[4-(Acetyl-mcthyI-amino)-3-methyl-benzofuran-2-carbony]]-amino)-biphenyl-4-su]fonylamino)-3-methy]-butyric acid; L-3-MethyI-2- (4'-{[3-methyl-4- (2H-tetrazol-5-yl)-benzofuran-2-carbonyl]-amino)-biphenyl-4-su]fony]amino)-butyric acid; L-2-(4'-{[4-(3,3-Dimethyl-buty])-3-methyl-benzofuran-2-carbony])-amino}-bipheny]-4-su]fony]amino)-3-methyl-butyric acid; L- 2-{4'-[(3-EthyI-bcnzofuran-2-carbonyl)-amino]-bipheny]-4-su]fony)amino}-3-methyl-butyric acid; L- 2-{4-((4-tert-Butoxycarbonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyJ-4-sulfony]amino}-3-methy]-butyric acid; L-3-Methyl-2- {4'-[(3-inethy]-4-methy]amino-benzofuran-2-carbonyl)-amino)-bipheny)-4-sulfonylamino}-butyric acid; L-2- {4 -[(4-Amino-3-methyI-bcnzofuran-2-carbony])-amino]-bipheny)-4-sulfonylamino}-3-methyl-butyric acid; L-2- {4'-[(4-Dimethylamino-3-methyl-benzofuran-2-carbonyJ)-amino]-bipheny)-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2- {4'-[(3-methyl-4-pyrro!idin-l-y]-benzofuran-2-carbonyJ)-amino)-biphenyl-4-sulfonylamino}-butyric acid; L-2-({4 '-[(4-Methanesulfonylamino-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-sulfonyl} -methy]-amino)-3-methyl-butyric acid; L-3-Hydroxy-2- {4-[(4-methanesulfonylamino-3-methy]-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfony]amino}-butyric acid; (S)-3-MethyI-2-(4-{[4-methy]-2-(4-(rifluoromethyl-pheny])-thiazole-5-carbonyl]-amino) -biphenyl-4-su]fonylamino)-butyric acid; L-3-Mcthyl-2- (4'-{[3-methyl-4- (2,2,2-trinuoro-acc(ylamino)-bcnzofuran-2-carbony]]-amino)-bipheny]-4-sulfonylamino)-butyric acid; L-2- {4'-[(4-Ethancsu]fony)amino-3-methy]-benzofuran-2-carbony])-amino]-bipheny]-4-su)fony]amino}-3-methyl-butyric acid; 12 WO 2005/061477 PCT/US2003/040835 L-3-Methyl-2-(4-{[3-methyl-4-(propanc-2-sulfonylamino)-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-butyric acid; L-2-(4'-{[4-(Ethanesulfonyl-methyl-amino)-3-methy]-benzofuran-2-carbonyl]-amino]-bipheny]-4-sulfonylamino)-3-methyl-butyric acid; L- 2-{4-[(4-Benzencsulfonylamino-3-methy]-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino)-3-methyl-butyric acid; L-3-Methyl-2-(4-{(3-methyl-4- (thiophene-2-sulfonylamino)-bcnzofuran-2-carbonyl]-amino}-bipbenyl-4-sulfony]arnino)-butyric acid; L-2- (4'-{ [4-(l ,1-Dioxo-l D6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-su]fonylamino)-3-methyl-butyric acid; D-3-Me(hyl-2-{4-[(3-methy]-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; D-2-{4'-[(Benzofuran-2-carbonyJ)-methyl-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; 4-{5-[(Benzofuran-2-carbony])-amino]-pyridin-2-y]}-benzencsi)Ifony]-L-valine; N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfony])-N-methyl-D-valine; N-({4'-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl}sulfony])-N-methyl-I.,-valinc; N-({4-[(l-Benzofuran-2-y)carbony))amino]-1,1-biphenyl-4-yl}sulfony])-N-methylglycine; (S)-2-{4'-[(l,3-Dimethyl-lH-thieno[2,3-c]pyra2ole-5-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}suIfony])-N-(pyridin-3-ylmethyl)-L-valine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,r-biphcnyl-4-yl}sulfonyl)-N-(2-morpholin-4-ylethyl)-L-valine; N-[(4'-[(3-Methyl-l-benzofuran-2-yl)carbonyl]amino)-l,1-bipheny]-4-yl)sulfonyl]-L-valine; N-I(4'-f[(5-Bromo-l-benzofuran-2-y])carbony]]amino}-l,l -biphenyl-4-yl)sulfonyl]-L-valine; N.[(4'.{[(4.Methyl-3,4,5,6-teirahydrofuro[4,3,2-ef][3]benzazepin-2-yl)carbonyl]amino)-1,1 -biphenyl-4-yl)sulfonyl]-L-valine; N-[(4'-{((5-Ethyl-4-methoxy-3-methyl-l-benzofuran-2-yl)carbony]]amino)-l,1-biphenyl-4-yl)sulfonyl]-L-valine; 13 WO 2005/061477 PCT/US2003/040835 N-[(4-{[(4-Ethyl-3-methyl-l-benzofuran-2-yl)carbony]]amino}-l,r-biphcnyl-4-y))sulfenyl]-L-va]inc; N-[(4-{[(5-Ethy]-4-jsopropoxy-3-methyl-l-benzofuran-2-yl)carbonyI]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-{[4'-({{4-(Benzy]oxy)-5-ethyl-3-methyl-l-benzofuran-2-y)]carbonyJ}amino)-l,l -biphenyl-4-y]]sulfonyl} -L-valine; N-[(4-{[(5-Ethyl-4-hydroxy-3-mcthyl-l-bcnzofuran-2-y])carbonyl]amino}-l,l-bipheny]-4-yJ)sulfony]]-L-valinc; N-{[4'-({[4-(2,2-Dimethy)-],3-dioxolan-4-)'l)-3-methyl-l-benzofuran-2-yljcarbonyl }amino)-l,1'-biphenyl-4-yl]sulfonyl)-L-valine; N-{[4-({[4-(Hydroxymethy])-3-methyl-I-benzofuran-2-yl]carbonyl}amino)-l,l -biphenyl-4-y)]sulfony]}-L-valinc; N-[(4-{[(3,4-Dimethy]-]-benzofuran-2-yl)carbony]]amino}-ltl-biphenyl-4-yl)sulfonyl]-L-valine; N-[(4 - {[(4- Acety]-3-methyl-1 -bcnzofuran-2-yl)carbonyi]amino}-1,1 -bipbeny]-4-yl)sulfonyl]-L-valine; N-{[4'-({4-(l-Hydroxyethyl)-3-methy1-l-benzofuran-2-y)]carbony]}amino)-l,1-biphenyl-4-y]]sulfonyl}-L-valine; N-[(4-{[(3-methy]-4-viny]-l-benzofuran-2-yl)carbonyl]amino)-l,r-bipheny]-4-yl)su]fonyl]-L-valine; N-{[4'-({[4-(],2-dihydroxyethyI)-3-methyl-l-bcnzofuran-2-y]]carbonyl}amino)-l,1-biphenyl-4-yl]sulfonyl) -L-valine; N-melhyI-N-[(4'-{[(3-methyl-4-vinyl-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-{[4'-({[4-(l,2-dibydroxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,1-biphenyl-4-yl]sulfonyl}-N-methyl-L-vaIine; N-{[4'-({[4-(methoxymethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,1-biphcnyl-4-y))sulfonyl} -L-valine; N-{[4-({[4-(l-methoxyethyl)-3-methyl-I-benzofuran-2-yl]carbony]}amino)-l,l -biphenyl-4-yl]sulfonyl)-L-valinc; N-{[4'-({(4-(2-methoxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino-l,1-biphenyl-4-yl]sulfonyl} -L-valinate; N-[(4'-{[(4-Isopropoxy-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-y])sulfony])-L-valine; 14 WO 2005/061-177 PCT/US2003/040835 N-[(4'-{[(5-methoxy-1-benzofuran-2-yl)carbonyl]amino}-l,r-biphenyl-4-yl)sulfonyl]-L-valine;' (S)-2-{4'-[(4-Me(hoxy-3-methyl-benzofuran-2-carbonyJ)-amino]-biphenyl-sulfonylamino}-3-methy]-butyric acid; (S)-2-{4-[(4-cthoxy-3-methy]-benzofuran-2-carbony])-amino)-biphenyl-4-sulfonylamino}-3-rnethy]-butyric acid; (S)-3-Methyl-2-{4'-[(3-methyl-4-propoxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid; (S)-2-{4'-[(4-Isopropoxy-3-methyl-benzofuran-2-carbony))-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-3-Methyl-2-{4'-f(3-methyl-4-phenyi-benzofuran-2-carbonyJ)-amino)-biphenyl-4-sulfonylamino}-butyric acid; (S)-3-Mcthyl-2-(4-{[3-melhyl-4-(3-nitro-phenyl)-benzofuran-2-carbonyl]-amino}-bipheny]-4-sulfonylamino)-butyric acid; (S)-3-methyl-2-{4'-[(3-methy]-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-bipheny)-4-sulfonylamino}-butyric acid; (S)-3-Methyl-2-{4-[(3-methyl-4-pyridin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; (S)-2-{4'-[(4-Furan-3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamjno}-3-methyl-butyric acid; (S)-3-methy]-2-{4'-((3-methyl-4-morpholin-4-yl-benzofuran-2-carbonyl)-amino]- •t bipheny]-4-sulfonylamino}-butyric acid; (S)-2-{4-((5-Chloro-4-isopropoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-{4-[(5-ChIoro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-suJfony]amino}-3-methyl-butyric acid; (S)-2-{4-[(5,7-Dichloro-4-methoxy-3-methyl-benzofuran-2-carbony1)-amino]-biphenyl-4-su]fony)amino}-3-mcthy]-butyric acid; (S)-2-{4-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-su]fony]amino}-3-methyl-butyric acid; (R)-2-{4-[(5-Bromo-4-methoxy-3-methyl-benzofuran-2-carbony])-amino3-biphenyl-4-sulfonylamino}-3-methy]-butyric acid; (S)-2-{4-[(S-Iodo-4-methoxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; 15 WO 2005/061477 PCT/US2003/040835 (S)-2-{4'-[(5-Accty]-4-incthoxy-3-mcthl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfoftylamino}-3-methyl-butyric acid; S)-2-(4-{[5-(l-Chloro-vinyJ)-4-methoxy-3-methyl-benzofuran-2-carbony]]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; (S)-2-{4'-((5-Acetyl-4-hydroxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-{4-[(5-Cyano-4-methoxy-3-methyl-benzofuran-2-carbony])-amino]-bipheny]-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-{4'-[(5-Methyl-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-meihyl-butyric acid; (S)-2-{4-[(5-Hydroxymethyl-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino)-biphenyl-4-sulfonylamir)o)-3-methyl-butyric acid; (S)-3-Methyl-2-{4'-[(benzooxazole-2-carbony])-amino]-biphenyl-4-sulfony]amino}-butyric acid; (S)-3-Methyl-2-{4'-[(4-methyl-benzooxazole-2-carbonyl)-arruno]-biphenyl-4-sulfonylamino}-butyric acid; (S)-3-Mcthy]-2-i4'-[(5-methyl-benzooxazo]c-2-carbonyl)-ajnino]-bipheny]-4-sulfonylamino)-butyric acid; (S)-3-Melhyl-2-{4-[(5-chloro-benzothiazo]e-2-carbony])-amino]-bipheny]-4-sulfonylaminoj-butyric acid; (S)-3-Methyl-2-{4-[(5-trifIuorometthyl)-bcnzothiazole-2-carbonyl)-amiino]-biphenyl-4-sulfonylamino}-butyric acid; D-3-Methyl-benzofuran-2-carboxylic acid 4'-(l -carboxy-2-methyl-propylsulfamoy])-3,5-dimethyl-biphcnyl-4-yl ester; D-Benzofuran-2-carboxylic acid 4'-(l-carboxy-2-methyl-propy]sulfamoyl)-3,5-dimethyl-biphcnyl-4-yl ester; D-3-Methyl-benzofuran-2-carboxylic acid 4-(l-carboxy-2-methyl-propylsulfamoy])-biphenyl-4-yl ester; Benzofuran-2-carboxylic acid 4-(l-carboxy-2-methyl-propylsulfamoyl)-biphenyl-4-yl ester, D-2-[4'-(5-Bromo-4-methoxy-3-methyl-benzofuran-2-y]methoxy)-biphenyl-4-sulfonylamino]-3-methyl-butyricacid; D-2-[4'-(BenzothiazoI-2-y]methoxy)-bipheny]-4-su]fony]amino]-3-methyl-butyric acid; D-3-Methyl-2-[4'-(l-methyl-lH-benzoimidazol-2-ylmethoxy)-biphenyl-4-sulfonylamino]-butyric acid; 16 WO 2005/061477 PCT/US2003/040835 D-3-Methyl-2-[4'-(3-methyl-benzofuran-2-y]me(hoxy)-biphenyl-4-sulfony]amino]-butyric acid; D-2-[4'-(Benzofuran-2-y]methoxy)-3'-methoxy-bipheny]-4-suIfony]ainino]-3-methyl-butyric acid; D-2-[4'-(Bcnzofuran-2-y]methoxy)-biphenyl-4-sulfonylamino]-3-methyl-butyricacid; L-2-[4'-(5-Ch)oro-4-methoxy-3-jnethyl benzofuran-2-ylmethoxy)-bipheny]-4-sulfonylamino]-3-methyl butyric acid; L-2-[4'-(5-Cyano-4-methoxy-3-methylbenzofuran-2-ylmethoxy)-biphenyl-4-sulfonylamino]-3-niethyl butyric acid; N-{[4'-(2-Furoyloxy)-l,r-biphenyl-4-y)]sulfonyl)-D-va]ine; N-{[4'-(3-Furoyloxy)-l,r-biphenyl-4-yl]sulfonyl}-D-valinc; L-2-[4'-(4-Ethy]-3-methyl benzofuran-2-ylmethoxy)-bipheny]-4-sulfony]amino]-3-melhyl butyric acid; N-[(4'-{[4-(3-methoxypropy])-3-methyl-I-benzofuran-2-yl]methoxy}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-({4'-[(5-Bromo-4-methoxy-3-methyl-l-benzofuran-2-yl)methoxy]-l,1-biphnyl-4-yl}sulfonyl)-L-valine; N-({4'-[(5-Bromo-4-isopropoxy-3-methyl-l-bcnzofiiran-2-yl)methoxy]-l,1-bipheny]-4-yl }sulfonyl)-D-valine; N-{(4'-{[(5-bromo-4-methoxy-3-methyl-l-benzofuran-2-yl)methyl]amino}-l,1'-biphenyl-4-yl)sulfonyl]-L-valinc; L-2-{4'-[(Bcnzothazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; D-2-{4'-[(Benzothiazo]e-2-carbony])-amino]-bipfienyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2-{4'-((naphtho[2,l-b]furan-2-carbony!)-amino]-bipheny]-4-su]fony]amino}-butyric acid; L-3-Methyl-2-(4'-[(l-methyl-naphtho[2,l-b]furan-2-carbonyl)-amino]-bipheny]-4-sulfonylamino)-butyric acid; L-3-Mcthyl-2-{4'-[(3-methyl-4-phenoxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-suifonylamino)-butyric acid; L-2-(4'-{[4-(J-Methoxycarbonyl-]-niethy!-ethoxy)-3-methyl-benzofuran-2-carbonyl]-amino}-biphcnyl-4-su]fonyJamino)-3-methyl-butyric acid; L-2-{4'-[(4-Ethoxycarbony]methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino}-3-methyl-butyric acid; 17 WO 2005/061477 PCT/US2003/040835 L-2-{4'-[(4-Methoxycarbony)methoxy-3-methyl-benzofuran-2-carbony))-amino]-biphenyl-4-sulfonylamino}-3-rnethy]-butyric acid; L-2-{4-[(4-Carboxymethoxy-3-methy]-benzofuran-2-carbonyl)-ainino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Mcthy]-2-(4-{[3-methyl-4-(pyridin-3-y]methoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; L-2-{4-[(4-Hydroxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-2-(4-{5-[(l-Ethy]-lH-benzimidazole-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonylamino)-3-methyl-butyric acid; N-({4'-[(l,2,3-thiadiazol-4-ylcarbonyJ)amino]-l,1-biphenyl-4-y]}su]fony])-L-valine; D-2-[4'-(Benzofuran-2-sulfony]methyl)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid; D-2-[4'-(Benzofuran-2-sulfinylmethyl)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid; (S)-2-4'-{[3-(4-Chloro-phenyl)-isoxazolc-5-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; (S)-3-Methyl-2-{4'-[(l-methyl-3-phenyl-lH-thieno[2,3-c]pyrazo]e-5-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid; (S)-3-Methyl-2-{4-[(5-methyl-l-phenyl-lH-pyrazo)e-3-carbonyl)-amino]-biphenyl-4-sulfonylamino} -butyric acid; (S)-3-Methyl-2-{4-[(2-pyridin-4-y]-thiazo]e-4-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid; (S>3-Methyl-2-[4'-(thiophene-2-sulfonylamino)-biphenyl-4-su]fony]amino]-butyric acid; (R)-3-Methyl-2-[4-(thiophenc-2-sulfonylamino)-biphenyl-4-sulfonylamino]-butyric acid; (R)-2-{4-[(Furan-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (R)-3-Methyl-2-{ 4'-[(thiophene-2-carbonyl)-amino]-biphenyl-4-suIfonylamino}-butyric acid; (S)-3-Methyl-2-{4'-[(thiophene-2-carbonyl)-amino]-biphenyl-4-sulfonylamino]-butyric acid; (S)-2-{4'-[(Furan-2-carbonyl)-amino]-biphenyl-4-suJfonylamino}-3-methyl-butyic acid; (S)-2-{4-[(4-Dimethylcarbamoylmethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-(4'-{[4-(2-tert-Butoxycarbonylamino-ethoxy)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; 18 WO 2005/061477 PCT/US2003/0-I0835 (S)-3-Methyl-2-(4-{[3-methyl-4-(pyridin-2-ylmethoxy)-ben2ofuran-2-carbonyl]-amino}-biphcnyl-4-sulfonylamino)-butyricacid; (S)3-Methy)-2-(4'-{[3-methyl-4-(pyridin-4-ylmethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; (S)-2-{4-[(4-Carbamoy]methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-(4'-{[4-(2-Amino-ethoxy)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-rnethy]-butyric acid; (S)-2-(4-{[4-(2-Dimethylamino-ethoxy)-3-mcthy]-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; N-((4-{[(5-Chloro-l-benzofuran-2-y])carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-({4'-[(5-Bromo-2-furoyl)amino]-l 1'-biphenyl-4-y]}sulfonyl)-L-valine; N-[(4'-{[(7-Nitro-1 H-indol-2-yl)carbonyl]amino}-1,1 -biphenyl-4-yl)sulfonyl]-L-valine; N-[(4-|[(2-Pyridin-4-y]-l,3-thiazo]-5-y])carbonyl]amino)-l,1-biphcnyl-4-yl)sulfonyl]-L-valine; N-[(4-{[5-(2-Nitrophenyl)-2-furoyJ]amino}-l,l-biphenyl-4-yl)sulfonyl]-L-valine; N-{[4'-({[2-(2,3-Dihydro-l,4-benzodioxin-2-yl)-l,3-thiazol-4-yl]carbonyl}amino)-l,1-biphenyJ-4-y]]sulfonyl}-L-valinc; N-[(4'-{[(5-Melhyl-3-phenylisoxazol-4-yl)carbonyl]amino}-l,1-biphenyl-4-yl)suJfony]]-L-valine; N-[(4-{t(4-Mcthyl-l,2,3-thiadiazol-5-yl)carbonyl]amino}-I,1 -biphenyl-4-yl)sulfonyl]-L-valine; N-[(4-{[(l-tert-Butyl-3-methyl-lH-pyrazoI-5-yl)carbonyl]aminoJ-l,l-biphenyl-4-yl)sulfonyl]-L-valinc; N-[(4-{[(3-Chloro-l-benzothicn-2-yl)carbonyl]amino1-l,1-biphenyl-4-yl)sulfonylJ-L-valinc; N- {[4'-({[3-(2-Chlorophenyl)-5-methylisoxazol-4-yl]carbonyl) amino)-1 ,1 '-biphenyl-4-yl]sulfonyl)-L-valine; N-((4-[(l-Bcnzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl)sulfonyl)-D-alaninc; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-L-valine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}suIfonyl)-D-valine; N-({4'-[(i-Bcnzofuran-2-ylcarbonyl)amino]-],1,1'-biphenyl-4-yl}sulfonyl)-L-norvaline; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-D-norvaIine; N-({4-((l-Benzofuran-2-yJcarbonyl)amino]-1,1-biphenyl-4-yl}sulfonyl)-L-aspartic acid; 19 WO 2005/061477 PCT/US2003/040835 N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-y]}sulfonyl)-D-aspanic acid; N-2-({4-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-bipheny)-4-y))sulfonyl)-L-g]utamine; N~2—({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-D-glutamine; N-({4'-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl)sulfonyl)-L-histidine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl]sulfonyl)-D-histidine; N-({4'-[(l-Benzofuran-2-yJcarbony))aminoJ-l,l -biphenyl-4-yl]sulfonyl)-L-isoIcucinc; N-({4'-[(l-Benzofuran-2-ylcarbony!)amino]-l,l-biphenyl-4-yl}sulfonyl)-D-isoleucine; N-({4-[(l-Benzofuran-2-y)carbonyl)amino]-l,1-biphenyl-4-y]}su]fonyl)-L-leucine; N-({4'-I(l-Ben7.ofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-y])su]fony])-D-]cucinc; N-({4'-[(l-Benzofuran-2-yJcarbonyJ)amino]-l,l'-biphenyl-4-y]}sulfonyl)-L-norleucine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyJ-4-yJ)sulfonyl)-D-nor]eucinc; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphcnyl-4-yl)sulfonyl)-L-phenylalanine; N-({4'-[(l-Benzofuran-2-y)carbony))amino]-l,1-biphenyl-4-y]}su]fonyl)-D-phenylalaninc; l-({4-[(l-Benzofuran-2-ylcarbonyl)ainino]-l,l'-biphenyl-4-yl}sulfonyl)-L-proline; l-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l-biphenyl-4-yl)sulfonyl)-D-proline; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphcnyl-4-y]}sulfonyl)-L-tryptophan; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l-biphcnyl-4-y]}sulfonyl)-D-tryptophan; N-({4'-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl}su]fony])-N-methylglycine; N-({4-[(l-Benzofuran-2-y]carbonyl)amino]-I,1 -biphenyl-4-y]}su]fonyl)-2-methylalanine; N-( {4 -[(1 -Bcnzofuran-2-ylcarbonyl)amino]-1,1 -biphenyl-4-y]} sulfonyl)-N-methyl-L-alanine; 1-[({4'-[(l-Bcnzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-y] }sulfonyl)amjno]cyc]opentanccarboxylic acid; N-(4'-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-y]}su]fony])-N- methylvaline; N-({4'[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-y]}su]fony])-3-methyl-L-valine; N.({4'.[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-2-methylleucine; 20 WO 2005/061477 PCT/US2003/040835 N-({4'-[(l-Benzofuran-2-y]carbonyJ)amino]-l,1-biphenyl-4-yl)sulfonyl)-D-g]utamic acid (2R)[({4'-[(]-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl}su]fonyl)ainino](pheny})acetic acid; [({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)amino](thien-2-yl)acetic acid; (2S)-2-[({4'-[(l-Bcnzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)amino]-5-methoxy-5-oxopentanoic acid; 3-[(14-[(l-Benzofuran-2-y]carbonyl)amino]-)-1,1-biphenyl-4-yl)sulfonyl)amino]-3-phenylpropanoic acid; 2-[({4-[(l-Benzofnran-2-ylcarbonyl)amino]-1,1-bjphenyJ-4-yl}sulfonyl)amino]-4-phenylbutanoic acid; N-({4'-[(l-Benzofuran-2-y)carbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-L-tyrosine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-D-tyrosine; (2S)-2-[({4>-[()-Bcnzofuran-2-y]carbony))amino]-l,1-biphenyl-4-y]}sulfonyl)amino]-4-tert-butoxy-4-oxobutanoic add; (2R)-2-[({4-[(l-Benzofuran-2-ylcarbonyl)amino]-],1,1-biphenyl-4-yl}sulfony])amino]-4-tcrt-butoxy-4-oxobutanoic acid; (2S) [({4-{(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphcny]-4-y])sulfonyl)amino](2,3-dihydro-lH-inden-2-yl)acetic acid; N-({4-[(l-Benzofuran-2-ylcarbony))amino]-l,1 -biphenyl-4-yl}sulfony])-O-methyl-L-tyrosine; [({4-[(l-Benzofuran-2-ylcarbonyl)amino1-l,l-bipheny]-4-yl}sulfonyl)amino](l-methyl-lH-indol-5-yl)acetic acid; [({4 -[(l-Benzofuran-2-y]carbonyl)amino]-l,1 -biphcny]-4-yl}sulfonyl)amino](l-benzothien-5-yl)acetic acid; N-({4-[(l-Bcnzofuran-2-y]carbonyl)amino]-l,1'-biphenyl-4-yl}sulfony))-4-nitro-L-phenylalanine; N-({4'.[(2-Benzofuran-2-y]carbonyl)amino]-1,1'-biphenyl-4-yl}sulfonyJ)-3-(2-naphthyl)alanine; N-({4-[(J-Benzofuran-2-y]carbonyJ)amino]-],l,1 -bipbenyJ-4-yl}sulfony])-beta-methylphenylalanine; N.({4'.[(1-Benzofuran.2-ylcarbonyl)amino]-],1,1'-biphenyl-4-yl}sulfony])-N-methyl-L-tryptophan; 21 WO 2005/061477 PCT/US2003/040835 N-2-({4'-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-y]}sulfonyl)-N-5— phen-ylglutamine; N-({4-[(l-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-4,4,4,4',4',4-hexafluorovaline; 4-Amino-N-({4-[(l-benzofuran-2-y)carbony))amino]-l,l -biphenyl-4-yl}su]fonyl)-L-phenylalanine; (2R)-2-[({4'-[(l-Bcnzofuran-2-y]carbonyJ)amino]-l,1-bjphenyl-4-y]}sulfony])amino]-5-(benzyloxy)-5-oxopentanoic acid; N-({4 -[(l-Benzofuran-2-y]carbonyl)amino]-],l'-bjphenyl^}-yl)su]fonyl)-l-bcnzy]-L-histidine; and N-({4 -[(l-Benzofuran-2-y)carbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-O-benzyl-L-tyrosine. Particularly preferred compounds are: L-2-(4'-{[4-(3-Methoxy-propyl)-3-methyl-benzofuran-2-caxbonyl]-amino)-biphcny]-4-su]fonylarnino)-3-methyl-butyric acid; L- 3-Methyl-2- (4'-{[3-methyl-4- (3-mcthy)-isoxazol-5-yl)-benzofuran-2-carbonyl]-amino} -biphenyl-4-sulfonylamino)-butyric acid; D-2-{4'-[(4-Methancsulfony)amino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-btiiyric acid; L- 2-(4-[(4-Cyclopropylmethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony)amino)-3-mcthy]-butyric acid; L-3-Methyl-2- (4'-{ [3-methyl-4- (2H-tctrazol-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-suJfonylamino)-butyric acid; L-2- (4'-[(4-Dimethylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyricacid; L- 2-{4'-[(4-Benzenesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-3-Methyl-2-(4-{[3-methyl-4- (thiophene-2-sulfonylamino)-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-butyric acid; N- [(4'- {[(5-Ethyl-4-methoxy-3-methyl-1 -benzofuran-2-yl)carbonyl]amino) -1,1 -biphenyl-4-yl)sulfonyl]-L-valine; N-[(4'-{[(4-Ethyl-3-methyl-l-benzofuran-2-yl)carbonyl]amino1-l,l'-biphenyl-4-yl)sulfonyl]-L-valine; N-[(4'-{[(5-Ethyl-4-hydroxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino}-1,1 -biphenyl-4-yl)sulfonyl)-L-valine; 22 WO 2005/061477 PCT/US2003/040835 N.{[4'-({[4.(2,2-Dimethyl-],3-dioxolan-4-y])-3-mcthy]-l-benzofuran-2-yl]carbonyl} amino)-1 ,l'-biphenyl-4-yl]su]fonyl }-L-valinc; N-[(4'-|[(3,4-Dimethyl-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-[(4-{[(4-Acetyl-3-methyl-]-benzofuran-2-y])carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-{[4-({[4-(l-Hydroxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,l-biphcnyl-4-y)]sulfonyl) -L-valine; N-[(4-{[(3-methyl-4-vinyl-l-benzofuran-2-y])carbonyl]ainino}-l,1-biphcny]-4-y])sulfonyl]-L-va]ine; N-([4-({[4-(methoxymethyl)-3-methyl-]-benzofuran-2-yJ]carbonyl}amino)-l,l-biphenyl-4-yl]sulfonyl} -L-valinc; N-{[4-({[4-(l-methoxyethy])-3-methyl-l-benzofuran-2-y)]carbonyl}amino)-l,1-biphenyl-4-y]]sulfonyl)-L-valine; N-{[4'-({[4-(2-methoxycthyl)-3-methyl-l-benzofuran-2-y]]carbonyl}amino)-l,1-biphenyl-4-yl]suIfony)}-L-valinate; (S)-2-{4'-[(4-ethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-bipheny)-4-sulfonylamino}-3-methyl-butyric acid; (S)-3-methyl-2-{4'-[(3-methyl-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; (S)-3-McthyJ-2-{4'-[(3-methyl-4-pyridin-4-y]-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid; (S)-2-{4'-[(4-Furan-3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino} -3-methyl-butyric acid; (S)-2-{4'-l(5-Chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphcny]-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-{4 -[(5-bromo)-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; (R)-2-{4-[(5-Bromo-4-metho'xy-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamjno)-3-methyl-butyric acid; (S)-2-{4-[(5-Iodo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-{4'-[(5-Cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; 23 WO 2005/061477 PCT/US2003/040835 (S)-2-{4'-[(5-Methyl-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-suJfonylamino}-3-methyl-butyricacid; (5)-3-Methyl-2-{4'-[(5-methyl-benzooxazo]e-2-carbony))-amino]-biphenyl-4-sulfonylamino)-butyric acid; D-2-[4-(5-Bromo-4-methoxy-3-methyl-benzofuran-2-y]methoxy)-biphenyl-4-su)fonylamino]-3-methyl-butyric acid; L-2-{4'-[(4-Ethoxycarbonylmethoxy-3-mcthyJ-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-2-{4'-[(4-Carboxymethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2-(4'-{[3-methyl-4-(pyridin-3-ylmethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; (S)-3-Mcthyl-2-{4'-[(l-methyl-3-phenyl-lH-thicno(2,3-c]pyrazo)e-5-carbonyl)-amino]-biphenyl-4-su]fonylamino}-butyric acid; and (S)-3-Mcthyl-2-(4'-{[3-methyl-4-(pyridin-4-yJmethoxy)-benzofuran)-2-carbonyl]-amino}-biphenyl-4-sulfony)amino)-butyric acid. The terms "effective amount", "therapeutically effective amount" and "effective dosage" as used herein, refer to the amount of a compound, that, when administered to a patient, is effective to at least partially ameliorate (and, in preferred embodiments, cure) a condition form which the patient is suspected to suffer. Biary] sulfonamide compounds have been found to act as mctalloprotcinasc inhibitors. They are therefore useful in the treatment of cancer, osteoarthritis, rheumatoid arthritis, asthma, COPD, atherosclerosis, age-related macular degeneration, myocardial infarction, comeal ulceration and other ocular surface diseases, hepatitis, aortic aneurysms, tendonitis, central nervous system diseases, abnormal wound healing, angiogenesis, restenosis, cirrhosis, multiple sclerosis, glomerulonephritis, graft versus host disease, diabetes, inflammatory bowel disease, shock, invertebral disc degeneration, stroke, osteopenia, and/or periodontal diseases. The present invention thus provides pharmaceutical compositions comprising at least one biaryl sulfonamide compound and one or more pharmaceutically acceptable carriers, excipients, or diluents. Examples of such carriers are well known to those skilled in the art and are prepared in accordance with acceptable pharmaceutical procedures, such as, for example, those described in Remington's Pharmaceutical Sciences, 17th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton, PA (1985), which is incorporated herein by reference in its entirety. 24 WO 2005/061477 PCT/US2003/040835 Pharmaceutically acceptable carriers are those that are compatible with the other ingredients in the formulation and biologically acceptable. The compounds of this invention may be administered orally or parenterally, neat or in combination with conventional pharmaceutical carriers. Applicable solid carriers can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents or encapsulating materials. They are formulated in conventional manner, for example, in a manner similar to that used for known antihypertensive agents, diuretics and P-blocking agents. Oral formulations containing the active compounds of this invention may comprise any conventionally used oral forms, including tablets, capsules, buccal forms, troches, lozenges and oral liquids, suspensions or solutions. In powders, the carrier is a finely divided solid, which is an admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the active ingredient. Capsules may contain mixtures of the active compound(s) with inert fillers and/or diluents such as the pharmaceutically acceptable starches (e.g. corn, potato or tapioca starch), sugars, artificial sweetening agents, powdered celluloses, such as crystalline and microcrystalline celluloses, flours, gelatins, gums, etc. Useful tablet formulations may be made by conventional compression, wet granulation or dry granulation methods and utilize pharmaceutically acceptable diluents, binding agents, lubricants, disintegrants, surface modifying agents (including surfactants), suspending or stabilizing agents, including, but not limited to, magnesium stearate, stearic acid, sodium lauryl sulfate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, polyvinylpyrrolidine, alginic acid, acacia gum, xanthan gum, sodium citrate, complex silicates, calcium carbonate, glycine, sucrose, sorbitol, dicalcium phosphate, calcium sulfate, lactose, kaoolin, mannitol, sodium chloride, low melting waxes and ion exchange resins. Preferred surface modifying agents include nonionic and anionic surface modifying agents. Representative examples of surface modifying agents include, but are not limited to, poloxamer 188, benzalkonium chloride, calcium stearate, cetostearl alcohol, cetomacrogol emulsifying wax, sorbitan esters, colliodol silicon dioxide, phosphates, sodium dodecylsulfate, magnesium aluminum silicate, and triethanolamine. Oral formulations herein may utilize standard delay or time release formulations to alter the absorption of the active compound(s). The oral formulation 25 WO 2005/061477 PCT/US2003/040835 may also consist of administering the active ingredient in water or fruit juice, containing appropriate solubilizers or emulisifiers as needed. Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs. The active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat. The liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water {particularly containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, and oils {e.g. fractionated coconut oil and arachis oil). For parenteral administration the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. The liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propellant. Liquid pharmaceutical compositions, which are sterile solutions or suspensions, can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. Compositions for oral administration may be in either liquid or solid form. Preferably the pharmaceutical composition is in unit dosage form, e.g. as tablets, capsules, powders, solutions,.suspensions, emulsions, granules, or suppositories. In such form, the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient; the unit dosage forms can be packaged compositions, for example, paclceted powders, vials, ampoules, prefilled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. Such unit dosage form may contain from about 1 mg/kg to about . 250 mg/kg, and may given in a single dose or in two or more divided doses. Such doses may be administered in any manner useful in directing the active compounds herein to the recipient's bloodstream, including orally, via implants, parenterally (including intravenous, intraperitoneal and subcutaneous injections), rectally, vaginally, and transdermally. Such administrations may be carried out using the present compounds, or phaxmaceutically acceptable salts thereof, in lotions, creams, foams, patches, suspensions, solutions, and suppositories (rectal and vaginal). When administered for the treatment or inhibition of a particular disease state or disorder, it is understood that the effective dosage may vary depending upon the particular compound 26 WO 2005/061477 PCT/US2003/040835 utilized, the mode of administration, the condition, and severity thereof, of the condition being treated, as well as the various physical factors related to the individual being treated. In therapeutic application, compounds of the present invention are provided to a patient already suffering from a disease in an amount sufficient to cure or at least partially ameliorate the symptoms of the disease and its complications. An amount adequate to accomplish this is defined as a "therapeutically effective amount". The dosage to be used in the treatment of a specific case must be subjectively determined by the attending physician. The variables involved include the specific condition and the size, age and response pattern of the patient. In some cases it may be desirable to administer the compounds directly to the airways in the form of an aerosol. For administration by intranasal or intrabrochial inhalation, the compounds of this invention may be formulated into an aqueous or partially aqueous solution. The compounds of this invention may be administered parchterally or intraperitoneally. Solutions or suspensions of these active compounds as a free base or pharmaceutically acceptable salt may be prepared in water suitably mixed with a surfactant such as hydroxyl-propylcellulose. Dispersions may also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to inhibit the growth of microorganisms. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylcne glycol and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils. The compounds of this invention can be administered transdermally through the use of a transdermal patch. For the purposes of this disclosure, thransdermal administrations are understood to include all administrations across the surface of the body and the inner linings of bodily passages including epithelial and mucosal tissues. Such administrations may be carried out using the present compounds, or pharmaceutically acceptable salts thereof, in lotions, creams, foams, patches, suspensions, solutions, and suppositories (rectal and vaginal). Transdermal administration may be accomplished through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is non toxic to the skin, and allows delivery of the agent for systemic absorption into the blood stream via the skin. The carrier may take any number of forms such as creams and ointments, pastes, gels and 27 WO 2005/061477 PCT/US2003/040835 occlusivc devices. The creams and ointments may be viscous liquid or semisolid emulsions of either the oil-in-water or water-in-oil type. Pastes comprised of absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable. A variety of occlusive devices may be used to release the active ingredient into the blood stream, such as a semi-permeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient. Other occlusive devices are known in the literature. The compounds of this invention may be administered rectally or vaginally in the form of a conventional suppository. Suppository formulations may be made from traditional materials, including cocoa butter, with or without the addition of waxes to alter the suppository's melting point, and glycerin. Water soluble suppository bases, such as polyethylene glycols of various molecular weights, may also be used. In certain embodiments, the present invention is directed to prodrugs of biaryl sulfonamide compounds. Various forms of prodrugs are known in the art, for example, as discussed in, for example, Bundgaard, (ed.), Design of Prodrugs, Elsevier (1985); Widder, et al. (ed.), Methods in Enzymology, vol. 4, Academic Press (1985); Krogsgaard-Larscn, et al. (ed.), "Design and Application of Prodrugs", Textbook of Drug Design and Development, Chapter 5, 113-191 (1991), Bundgaard,'et al, Journal of Drug Deliver reviews, 8:1-38 (1992), Bundgaard, J. of Pharmaceutical Sciences, 77:285 et scq. (1988); and Higuchi and Stella (eds.) Prodrugs as Novel Drug Delivery Systems, American Chemical Society (1975), each of which is incorporated by reference in its entirety. It is understood that the dosage, regimen and mode of administration of these compounds will vary according to the malady and the individual being treated and will be subject to the judgment of the medical practitioner involved. It is preferred that the administration of one or more of the compounds herein begin at a low dose and be increased until the desired effects are achieved. The compounds of the invention can be prepared using a variety of methods starting from commercially available compounds, known compounds, or compounds prepared by known methods. General synthetic routes to many of the compounds of the invention are included in the following schemes. It is understood by those skilled in the art that protection and deprotection steps not shown in the Schemes may be required for these syntheses, and that the order of steps may be changed to accommodate functionality in the target molecules. In Scheme 1 the compounds of the invention, 1, are prepared by hydrolysis of the corresponding esters, 2, where R10 is an alkyl ester such as methyl, ethyl or t-butyl, or a linker to a Wang resin for solid phase synthesis. Methyl and ethyl esters can be cleaved with aqueous 28 WO 2005/061477 PCT/US2003/040835 base, including sodium or lithium hydroxide. t-Butyl esters and esters linked to resin can be cleaved using trifluoroacetic acid or hydrochloric acid. In addition, lithium iodide in ethyl acetate can be used to cleave methyl esters of general structure 2. Routes to compounds of structure 2 are shown in Scheme 2. 4-Nitrobiphenyl, 3, is converted into sulfonyl chloride 4 in two steps with chlorosulfonic acid, followed by thionyl chloride or oxalyl chloride with catalytic DMF. Sulfonylation of an a-amino acid derivative, 5, with sulfonyl chloride 4 provides sulfonamide 6. Sulfonamide 6 may optionally be alkylated with an alky] halide, tosylate, mesylate or triflatc (R11 = I, Br, C), Ots, Oms, OTf) to give the corresponding N-R3 alkyl sulfonamide. The R3 side chain can be further functionalized at any point in the synthesis. The NH or N-R3 sulfonamide is reduced with tin (II) chloride, or hydrogenated over palladium on carbon, or via transfer hydrogenation, to give aniline 7. Aniline 7 is then derivatized to provide 2 by acylation with an acid chloride, or with a carboxylic acid using a peptide coupling reagent such as EDCI, or BOP in the presence of a tertiary amine in a polar aprotic solvent. Sulfonamides 2 are provided by the reaction of aniline 7 with heteroarylsulfonyl chlorides and a tertiary amine base. Secondary anilines 2 are formed by reductive amination of 7 with a heteroaryl aldehyde in the presence of a reducing agent such as sodium cyanoborohydride or preferably sodium triacetoxyborohydridc. 29 WO 2005/061477 PCT/US2003/040835 An alternative route to amides 2 is shown in Scheme 3. Commercially available sulfonyl fluoride 8 is acylated with acid chlorides to give amide derivatives 9. The analogous sulfonyl chlorides are available from via nitrobiphenyl 10 through reduction to aniline 11, acylation to give 12 and conversion of the sulfonic acid to the sulfonyl chloride 13. Reaction of amino acids or animo esters, 5, with 9 or 12 in the presence of a tertiary amine base provides compounds 2. WO 2005/061477 PCT/US2003/040835 In Scheme 4 amino acid 5 is reacted with 4-bromobcnzcnesulfony] chloride to give sulfonamide 14. Palladium catalyzed coupling of 14 with commercially available boronate esters 15 or 16 provides biphenyl sulfonamides 17, where R12 is -OH or -NH2. Functionalization of the phenol or aniline affords 2. Pyridyl analogs of the biphcnyls are prepared by palladium catalyzed conversion of bromophenylsulfonamide 14 to the corresponding boronate ester, 18, followed by palladium coupling with 2-bromo-5-nitropyridine to afford 19. Hydrogenation of 19 gives aniline 20 which can be functionalized to give 2. Similar routes are available to additional hcteroaryl analogs of the biphenyl sulfonamides claimed in the invention. 31 WO 2005/061477 PCT/US2003/040835 Thioethers of the invention are prepared according to Scheme 5 starting from the commercially available benzylic bromide 21. Displacement of the bromide with hcteroaryl thiols in the presence of an acid scavenger provides thioethers 22 which are coupled to bromoaryl 14 using palladium (0) and a base such as potassium carbonate or sodium carbonate to give 23. Ester cleavage of 23 provides thioether compounds of the invention. WO 2005/061477 PCT/US2003/040835 The biphcnylsulfonamidcs of the invention can also be prepared by the route shown in Scheme 6. Boronate esters 15 and 16 can be functionalizcd to the corresponding amides, sulfonamjdes, amines, esters, or ethers prior to palladium catalyzed coupling with bromosulfonamide 14 to give analogs 2. Ester hydrolysis of 2 provides the compounds of the invention. Furthermore, it is understood that the methods shown in Schemes 1-6 for the construction of biphenylsulfonamides are applicable to heteroaryl analogs of biphenyl claimed in the invention. WO 2005/061477 PCT/US2003/040835 New and known benzofurans of the invention are prepared as shown in Schemes 7-12. Each of the benzofuran esters in Schemes 7-12 can be converted into the corresponding acid, acid chloride, alcohol or aldehyde and coupled as shown in schemes 2-6. It is understood that some of the methodology used for the construction and derivatization of the benzofurans shown is applicable to other heteroaryl ring systems of the invention. In Scheme 7 salicyladehydes and ketones 25, bearing a variety of substituents R7, are alkylated with a-bromoacetic acid esters to give 26 which is next cyclized in the presence of an alkoxide base in alcohol or potassium carbonate in DMF to afford the substituted benzofurans 27. Esters 27 arc hydrolyzed with aqueous hydroxide, or TFA (for R10 = t-butyl) to give the carboxylic acids 28, which can in turn be converted into the acid chlorides, 29, with oxalyl or thionyl chloride and catalytic DMF. Reduction of esters 28 with diisobutylaluminum hydride or lithium aluminum hydride gives alcohols 30. The alcohols can be oxidized, preferably with Dess-Martin reagent to give the corresponding aldehydes 31. Alternatively, alcohols 30 can be converted into the corresponding chloride or bromide, 32, with thionyl chloride, phosphorus tribromide, carbon tetrabromide-triphenylphosphine or other known method. Functionalization of the benzofuran core is shown in Scheme 8. Although only 2-, 3-, and 4-substituents are shown on the benzofuran, the nethodology shown in the scheme can accommodate additional substituents and the hydroxy group of 33 can be placed at other WO 2005/061477 PCT/US2003/040835 positions on the benzofuran. The 4-hydroxybenzofurans, 33, prepared according to Scheme 7, are converted into the corresponding inflates, 34, with trifluormethanesulfonic anhydride an a tertiary amine, pyridine or lutidine. Palladium catalyzed reaction of 34 with zinc cyanide gives nitriles 35. The nitriles can be hydrolyzed in the presence of H peroxide to give amide 36, which can optionally be alkylated with alkyl halides in the presence of sodium hydride or other strong base. Triflates 34 can also undergo stille coupling with tributylvinyltin, or other alkenyl tin reagent, to provide the styrenes 37. Similarly, triflates 34 can be coupled with alkyne derivatives to provide benzofurans 38-40 where R14 is an alkyl or aryl group. Although not shown in the Scheme, the alkyncs can be partially hydrogenated to provide olefins, or saturated to give the corresponding alkanes. The alkynes can also be substrates in [3+2] or [4+2] cycloadditions to afford, for example, isoxazoles such as 41. Olefin 37 can be derivatized according to the methods shown in Scheme 9. Dihydroxylation with osmium tetroxide and N-methylmorpholine N-oxide affords diols 42 which can in turn be converted into dioxolanes 43 through the acid catalyzed reaction with acetone or other ketone or aldehyde. Oxidative cleavage of the olefin of 37 with osmium 35 WO 2005/061477 PCT/US2003/040835 tetroxide and sodium periodate gives aldehydes 44. The aldehydes can be reduced with sodium borohydride in methanol or ethanol to give alcohols 45, which may in turn be alkylated with an alkyl halide in the presence of silver oxide, sodium hydride or other base. Conversion of 45 to the corresponding bromide with carbon tetrabromide and triphenylphosphine, followed by reduction with sodium borohydride in DMSO, or other known method for the reduction of benzylic alcohols, provides the methyl-substituted benzofurans 46. Hydrogenation of olefins 37 on palladium on carbon gives the ethyl-substituted-benzofurans 47. Additional transformations of inflates such as 34 are show in Scheme 10. Palladium catalyzed reactions with amines, amides, sulfonamides or carbamates provide derivatives 48-50, each of which can then be further functionalized by alkylation of the newly installed nitrogen with an alkyl halide and base such as sodium hydride. Carbamate 50 can be deprotected by exposure to TPA or HC1 to give primary aniline 51. This aniline may be mono- or di-alkylated with an alkyl halide in the presence of potassium carbonate in a polar aprotic solvent to give 48, or acylated or sulfonylated to give 49. Palladium catalyzed Suzuki coupling of triflates 34 with aryl or heteroaryl boronic acids or boronate esters provides 52. 36 WO 2005/061477 PCT/US2003/040835 The synthesis of acetyl-benzofurans is shown in Scheme 11. Palladium catalyzed coupling of inflate 34 with butyl vinyl ether followed by hydrolysis in aqueous acid gives methyl ketone 53. Reduction of the methyl Ketone provides the secondary alcohols, 54, which may in turn be alkylated with an alkyl halide in the presence of silver oxide, sodium hydride or other base. The synthesis of selected 2,4,5-trisubstituted benzofurans (R6 = H) and 2,3,4,5-tetrasubstituted benzofurans is shown in Scheme 12. Hydroxybenzofuran 33 can be converted into aryl or heteroaryl ethers, 55, by the reaction with aryl/heteroaryl boronic acids in the 37 WO 2005/061477 PCT/US2003/040835 presenece of copper acetate. Alkyl ether derivatives, 56, are synthesized by alkylation of 33 with alky] halides in the presence of sodium hydride or potassium carbonate in a polar aprotic solvent such as DMF or THF. Compounds of structure 33 are readily halogenated with N-halogen succinimides to provide compounds 61, which may in turn be alkylated to give ethers 62. Phenols 33, and their O-alkylated derivatives undergo ortho-acylation with acetyl chloride and titanium tetrachloride to give acetophenones 59, which may in turn be converted into the vinyl chlorides, 60, in the presence of oxalyl chloride and catalytic DMF. Reaction of 33 with magnesium methoxide followed by paraformaldehyde produces the ortho-formyl phenol 57, which can be reduced to the 5-methyl benzofuran 58. The phenol of 58 can subsequently be etherified by raction with an alkyl halide in the presence of sodiumhydride or potassium carbonate. Certain N-alkyl benzimidazoles of the invention are available as shown in Scheme 13. Thus, 2-methylbenzimidazole, 63, is N-alkylated with an alkyl halide and sodium hydride to give 64, followed by selenium dioxide oxidation to provide the aldehyde, 65. Oxidation of the aldehyde to the carboxylic acid, 66, may be accomplished with silver nitrate. The aldehyde and carboxylate may be coupled with the compounds of Schemes 2-6. 38 WO 2005/061477 PCT/US2003/040835 The present invention is further described in ihe following examples. EXAMPLES The following abbreviations are used throughout the experimental section: DMSO = dimethyl sulfoxide TFA = trifluoroacetic acid DMF = N,N-dimethylformamide McOH = methanol THF = tetrahydrofuran The term "work-up" denotes dilution of the reaction mixture with ethyl acetate, washing the combined organics over water and brine, drying over magnesium sulfate or sodium sulfate, filtration and concentration of the filtrate in vacuo. 39 WO 2005/061477 PCT/US2003/040835 Example l:N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,l'-biphenyl-4-yl}sulfonyl)glycine Step 1: To a flame-dried flask was added 4-aminobiphenylsulfony] fluoride (0.75 g, 3 ramol) and methylcne chloride (20 mL). The solution was cooled with an ice bath. Benzofuran-2-carbonyl chloride (0.54 g, 3 mmol) was added after the addition of N,N- N,N-diisopropylethylamine (1.50 equiv.). The ice bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction proceeded at room temperature for 5 h. The reaction mixture was diluted with aqueous ammonium chloride solution (15 mL) and the precipitate was filtered and washed with aqueous ammonium chloride solution twice and water twice. The resulting solid was dried over vacuum and 1.05 g of N-{4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,l -bjphcnyl-4-yl)sulfonyl fluoride was obtained (Yield 89%). Step 2: To a 10 mL round-bottom flask was added N-{4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl fluoride (0.1 118 g, 0.3 mmol) and DMSO (2 mL), followed by the addition of glycinc r-butyl ester hydrochloride (5.0 equiv.), N,N- NN-diisopropylethylamine (10 equiv.), 4-(dimethylamino)pyridine (0.3 mmol) and sodium iodide (cat.). The mixture was heated to 120°C for 5h, cooled to room temperature and diluted with aqueous ammonium chloride solution (5 mL) and ethyl acetate (15 mL). The aqueous layer was extracted with ethyl acetate (10 mLx 2). The combined organic layers were washed with brine twice, dried with anhydrous sodium sulfate and filtered. After concentration, the crude product (110 mg) was purified by flash chromatography to give N-({4'-[(l-benzofuran-2-y!carbonyl)amino]-l,l-biphcnyl-4-yl}sulfonyl)glycinc /-butyl ester (75 mg). Step 3: N-(|4'-[(l-benzofuran-2-ykarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)glycine t-butyl ester (75 mg) was dissolved in a 95% solution of TFA in methylene chloride (5 mL). The solution was stirred at room temperature for 4h and the solvent was removed under vacuum. The crude product was triturated with hexane/ethyl acetate (95:5) three times. The product was lyophilized with benzene to give 56 mg of N-({4'-l(l-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl)sulfonyl)glycine. LCMS MH+ (m/z) 451. 'H NMR (300 MHz, DMSO-d6): 5 10.54 ppm (s, 1H), 7.95-7.54 ppm (m, 11H), 7.34 ppm (dd, 1H, J,=7.5 Hz, J2=7.5 Hz), 7.20 ppm (dd, 1H, J,=7.5 Hz, J2=7.5 Hz), 3.42 ppm (d. 2H 3=63 Hz). Example 2: L-2-{4'-[(Benzofuran-2-carbonyl)-amino]-bipIienyJ-4-sulfonylamino}-3-mefhyl-butyric acid 40 WO 2005/061477 PCT/US2003/040835 Step 1: To a 10 mL round-bottom flask was added N-{4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl fluoride (0.118 g, 0.3 mmol) and DMSO (2 mL), followed by the addition of L-Valine /-butyl ester hydrochloride (5.0 equiv.), N,N-diisopropylethylamine (20 equiv.), 4-(dimetnyJamino)pyridinc (0.3 mmol) and sodium iodide (cat.). The mixture was heated to 120 °C for 6 h and was diluted with aqueous ammonium chloride solution (5 mL) and ethyl acetate (15 mL). The aqueous layer was extracted with ethyl acetate (10 mL x 2). The combined organic layers were washed with brine twice, dried with anhydrous sodium sulfate. After concentralion, the crude product (110 mg) was purified with flash chromatography to give N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl }sulfonyl)glycine /-butyl ester (65 mg). Step 2: N-({4'-[(]-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}suJfonyl)-L-vaIine /-butyl ester (60 mg) was dissolved in a 95% solution of TFA in methylene chloride (5 mL). The solution was stirred at room temperature for 4 h and the solvent was removed under vacuum. The crude product was triturated with bexane/ethyl acetate (95:5) three times. The product was lyophilized with benzene to give 36 mg of N-({4'-((l-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl]sulfonyl)glycine. LCMS MH+ (m/z) 493. 'H NMR (300 MHz, DMSO-d6): 5 10.53 ppm (s, 1H), 7.81-7.54 ppm (m, 11H), 7.34 ppm (dd, 1H, J,=8.4 Hz, J2=8.4 Hz), 7.20 ppm (dd, 1H, J,=8.4 Hz, J2=8.4 Hz), 3.35 ppm (d, 1H J=6.0 Hz), 1.79 ppm (m, 1H). 0.63 ppm (dd, 6H, J,=13.8 Hz, J2=6.6 Hz). Example 3: N-({4'-[(lH-indol-2-ylcarbonyl)amino]-l,l'-l>ipbenyl-4-yl}sulfonyl)glycine N-({4'-[(lH-indol-2-ylcarbonyl)arnino]-l,1-biphenyl-4-yl)sulfonyl)glycinc was prepared according to the procedure of Example 1, using indolc-2-carbonyl chloride and 4-aminobipheriylsulfonyl fluoride in Step 1, and L-valine-t-butyl ester hydrochloride in Step 2. LCMS MH+m/z) 492. 'H NMR (300 MHz, DMSO-d6): d 11.62 ppm (s, 1H), 10.20 ppm (s, 41 WO 2005/061477 PCT/US2003/040835 1H), 7.95-7.22 ppm (m, 11H), 7.04 ppm (dd, 1H, J,=7.2 Hz, J2=7.5 Hz), 6.89 ppm (dd, 1H, J,iv7.-2 Hz, J2=7.5 Hz), 3.43 ppm (d, 2H J=5.8 Hz). Example 4: (4'-{[(5-chIoro-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-yl)sulfonyl]-L-valine Step 1: To a 120 mL shaking vessel was added Fmoc-L-Valine-Wang resin (10 g, 0.9 mmol/g) purchased from Advanced ChemTech. The resin was rinsed with DMF (60 mL x 2). A 20% solution of piperidine in DMF was added and the mixture was shaken for 20 min. The solvent was filtered and the resin washed with DMF (2X), methanol (IX) and methylene chloride (5X). Step 2: To the resin product of Step 1 was then added anhydrous methylene chloride (60 mL), N,N-diisopropylethylamine (40.5 mmol) and 4-nitrobiphenylsulfonyl chloride (27 mmol). The mixture was shaken at room temperature for 4 h before filtration. The resin was washed with methanol followed with methylene chloride (3X). Step 3: The resin product of Step 2 resin was rinsed with DMF (2X) and then treated with a 2 M DMF solution of tin chloride (60 mL). The mixture was shaken at room temperature overnight and the solvent and reagent were removed by filtration. The resin was washed with DMF (2X), methanol followed with methylene chloride (5X). Step 4: The resin product of Step 3 (0.25 g) was treated with anhydrous methylene chloride (5 mL), N,N-diisopropylethylamine (I.0mmol) and 5-chlorobenzofuran-2-carbonyl chloride (0.67 mmol). The mixture was shaken at room temperature for 2h before filtration. The resin was washed with methylene chloride (2X), and methanol, followed by melhylcne chloride (3X). Step 5: The resin product of Step 4 was then treated with a 95% solution of TFA in methylene chloride and agitated at room temperature for 2h. The solution was collected by filtration and the solvent was removed under vacuum. The crude product was then purified by 42 WO 2005/061477 PCT/US2003/040835 flash chromatography to give 4 -{[(5-chIoro-l-benzofuran-2-y])carbonyl]amino}-l,l-biphenyl-4-y])sulfonyl]-L-valine. LCMS MH+ (m/z) 528. 'H NMR (300 MHz, DMSO-d6): d10.58 ppm (s, 1H), 7.80-7.59 ppm (m, 11H), 7.36 ppm (dd, 1H, J,=7.2 Hz, J2=1.8 Hz), 3.35 ppm (d, ]H J=6.0 Hz), 1.75 ppm (m, 1H), 0.63 ppm (dd, 6H, J,=10.2 Hz, J2=6.6 Hz). Example 5: N-[(4'-{[(7-methox7-l-benzofuran-2-yl)carbonyl]aniino)-l,1-biphenyl-4-yl)sulfonyl]-L-valine According to the procedure of Example 4, using 7-methoxybenzofurancarbonyJ chloride, N-[(4'-{[(7-methoxy-l-benzofuran-2-yl)carbonyl]amino)-l,1-biphcnyl-4-yl)sulfonyl]-L-valinc was prepared. LCMS MH+(m/z) 523. 'H NMR (300 MHz, DMSO-d6): d10.45 ppm (s, 1H), 7.79-7.62 ppm (m, 10H), 7.14 ppm (d, 1H, J=21.0 Hz). 6.94 ppm (d, 1H. J=5.0 Hz), 3.81 ppm (s, 1H), 3.36 ppm (d, 1H J=6.0 Hz), 1.75 ppm (m, 1H), 0.63 ppm (m, 6H). Example 6: N-[(4'-{[(5-nitro-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-yl)sulfonyl]-L-valine According to the procedure of Example 4, using 5-nitrobenzofurancarbonyl chloride, N-[(4'-{[(5-nitro-l-benzofuran-2-yl)carbonyl]amino}-l,l-biphenyl-4-yl)sulfonyl]-L-valine was prepared. LCMS MH+ (m/z) 538. 'H NMR (300 MHz, DMSO-d6): d10.71 ppm (s, 1H), 8.69 ppm (s, 1H), 8.21 ppm (d, 1H, J=7.0 Hz), 7.84-7.61 ppm (m, 10H), 3.38 ppm (d, 1H J=6.0 Hz), 1.75 ppm (m, 1H), 0.64 ppm (dd, 6H, J,=8.7 Hz, J2=6.6 Hz). Example 7: N-[(4'-{[(5-amino-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-yl)sulfonyl]-L-valine Step 1: To a 120 mL shaking vessel was added Fmoc-L-Val-Wang resin (10 g, 0.9 mmol/g) purchased from Advanced ChemTech. The resin was rinsed with DMF (60 mL x 2). A 20% piperidine solution in DMF was added and the mixture was shaken for 20 min. The solvent was filtered and the resin washed with DMF (2X), methanol (IX) and methylene chloride (5X). Step 2: To the resin was then added with anhydrous methylene chloride (60 mL), NN-diisopropylethylamine (40.5 mmol) and 4-nitrobiphenylsulfonyl chloride (27 mmol). The mixture was shaken at room temperature for 4 h before filtration. The resin was washed with methanol followed with methylcne chloride (3X). 43 WO 2005/061477 PCT/US2003/040835 Step 3: The obtained resin was rinsed with DMF (2X) and then treated with a 2 M DMF solution of tin chloride (60 mL). The mixture was shaken at room temperature overnight and the solvent and reagent were removed by filtration. The resin was washed with DMF (2X), methanol followed with meihylene chloride (5X). Step 4: The resin (0.6 g) was treated with anhydrous methylene chloride (10 mL), N,N-diisopropylethylamine (2.2.0mmol) and 5-niirobenzofuran-2-carbbnyl chloride (1.50 mmol). The mixture was shaken at room temperature for 2 h before filtration. The resin was washed with methylene chloride (2X), methanol followed by methylene chloride (2X). The resin was added with tin (II) chloride solution in DMF (2 M, 12 mL) and shaken at room temperature overnight. The reagent was removed by filtration and the resin was washed with DMF (2X), methanol, and methylene chloride (5X). Step 5: The above-obtained resin was divided into two portions of 0.3 g of resin. One portion of the resin was treated with a 95% solution of TFA in methylene chloride (5 mL) and agitated at room temperature for 2h. The solution was collected by filtration and the solvent was removed under vacuum. The crude product was then purified by flash chromatogTaphy to give N-[(4-{[(5-amino-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine. LCMS MH+(m/z) 508. 'H NMR (300 MHz, DMSO-d6): d10.56 ppm (s, 1H), 7.80-730 ppm (m, 12H), 3.50 ppm (m, 1H), 1.90 ppm (m, 1H), 0.63 ppm (m, 6H). Example 8: N-({4'-[({5-[(melhylsulfonyl)amino]-l-benzofuran-2-yl}carbonyl)amino]-l,l'-bipheny!-4-yl}sulfonyl)-L-valine N-[(4'-{[(5-amino-l-benzofuran-2-yl)carbonyl]amino}-1,1'-biphenyl-4-yl)sulfonyl)-L-valine-Wang resin (0.3 g), from Example 7, was suspended in methylene chloride ( 6 mL). To the suspension was added with N,N-diisopropylethylamine (6.0 equjv.) and methanesulfonyl chloride (3.0 equiv.). The reaction was allowed to proceed at room temperature for 1 h and the reagent was removed by filtration. The resin was washed with methylene chloride (2X), methanol and methylene chloride (2X) before being treated with a 95% solution of TFA in methylene chloride (5 mL) and agitated at room temperature for 2 h. The solution was collected by filtration and the solvent was removed via vacuum. The crude product was then purified by flash chromatography to give N-({4 -[({5-[(methylsulfony))amino]-l-benzoruran-2-yl}carbonyl)amino]-l,1-biphcnyl-4-yl}sulfonyl)-L-valine LCMS MH+(m/z) 586. 'HNMR (300 MHz, DMS0-d6): d10.53 ppm (s, 1H), 9.59 ppm (s, 1H), 7.78-7.16 ppm (m, 12H), 3.30 ppm (m, 1H), 1.87 ppm (m, 1H), 0.63 ppm (m, 6H). 44 WO 2005/061477 PCT/US2003/040835 Example 9: N-{[4'-({[5-(acetylamino)-l-ben2ofuran-2-yl]carbonyl}amino)-l,1-biphenyl-4- yl]sulbnyl}-L-valine N-[(4 - {[(5- amino-1 -benzofuran-2-yl )carbonyl]amino} -1,1 -biphcnyl-4-yl)sulfonyl]-L-valine-Wang resin (0.3 g). from Example 7, was suspended in methylene chloride ( 6 mL). To the suspension was added N,N-diisopropylethylamine (6.0 equiv.) and acetyl chloride (3.0 equiv.). The reaction was allowed to proceed at room temperature for 0. h and the reagent was removed by filtration. The resin was washed with methylene chloride (2X), methanol and methylene chloride (2X) before being treated with a 95% solution of TFA in methylene chloride (5 mL) and agitated at room temperature for 2 h. The solution was collected by filtration and the solvent was removed via vacuum. The crude product was then purified by flash chromatography to give N-{[4*-({[5-(acetylamino)-l-benzofuran-2-yl]carbonyl)amino)-l,l -biphenyl-4-yl]sulfonyl} -L-valine. LCMS MH+ (m/z) 550. 'H NMR (300 MHz, DMSO-d6): d10.50 ppm (s. 1H), 9.92 ppm (s, 1H), 8.00-7.34 ppm (m, 12H), 3.33 ppm (m, 1H), 1.89 ppm (s, 3H), 1.76 ppm (m, 1H), 0.63 ppm (m. 6H). Example 10: 4'-[(5-Benzenesulfonylamino-benzofuran-2-carbonyl)-amino]-bjphcnyl-4-sulfonyl-L-valine N-[(4-{[(5-amino-l-benzofuran-2-yl)carbonyl]aminoJ-l,1-biphenyl-4-y])sulfonyl]-L-valine-Wang resin (0.3 g), from Example 7, was sulfonylated with benzencsulfonyl chloride according to the procedure of Example 8 followed by cleavage from the resin to provide 4 -[(5-benzenesulfonylamino-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine. LCMS MH+ (m/z) 648. 'H NMR (300MHz, CD3OD): d7.92-7.69 ppm (m, 9H), 7.58-7.43 ppm (m, 6H), 7.22-7.18 ppm (dd, 2H, Ji=9.0 Hz, J2=2.5Hz), 3.64 ppm (d, 1H, J=5.0 Hz), 2.09-2.01 ppm (m, 1H), 0.97 ppm (d, 3H, J=7.0 Hz), 0.90 ppm (d, 3H, J=7.0 Hz). 45 Example 11: N-[(4'-{[(4-m€thoxy-l-benzoruran-2-yl)carbonyl]amino}-l,l'-biphcnyl-4- WO 2005/061477 PCT/US2003/040835 According to the procedure of Example 4, N-[(4'-{ [(4-methoxy-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine was prepared starting from Fmoc-L-Val-Wang resin and using 4-methoxybenzofurancarbonyl chloride. LCMS MH+ (m/z) 523. 'H NMR (300 MHz, DMSO-d6): d10.62 ppm (s, 1H), 8.19-7.79 ppm (m, 9H), 7.47 ppm (dd, 1H, J,=8.1 Hz, J2=8.1 Hz), 7.32 ppm (d, 1H. J=8.4 Hz), 6.90 ppm (d, 1H, J=8.1 Hz), 3.96 ppm (s, 3H), 1.97 ppm (m, 1H), 0.82 ppm (dd, 6H, J,=18.0 Hz, J2=6.9 Hz). Example 12: 4'-[(Benzo[b]thiophene-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine According to the procedure of Example 4, 4'-[(bcnzo[P]thiophenc-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine was prepared starting from Fmoc-L-Val-Wang resin and using benzothiophenecarbonyl chloride. LCMS MI-T(m/z) 509. 'H NMR (300MHz, CD3OD): d10.68 ppm (s, 1H),8.41 ppm (s, III), 8.09-7.80 ppm (m, 12H), 7.54-7.47 ppm (m, 1H). 1.99-1.94 ppm (m, 1H), 0.86-0.80 ppm (m, 6H). Example 13: 4'-[(4-Bcn7.yloxy-benzofuran-2-carbony!)-amino]-biphenyl-4-sulfonyl-L-valinc Step 1: 4-Benzyloxy-benzofuran-2-carbonyl chloride (0.61 mmol) was added to a solution of the product of Example 2A-Step 4, L-2-(4-amino-biphenyl-4-sulfonylamino)-3- 46 WO 2005/061477 PCT/US2003/040835 methyl-butyric acid methyl ester 0.55 mmol), and N,N-diisopropylethylamine (1.4 mmol) in 2 mL of CH2Cl2 maintained at 0 °C. The reaction was allowed to warm to room temperature and stirred for 5h. The mixture was diluted with ethyl acetate and washed with brine (3x). The organic layer was separated and dried over anhydrous sodium sulfatc, filtered and then concentrated to give 350 mg of 2-{4'-[(4-benzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl)-L-valine methyl ester. Step 2: 2-{4'-[(4-Bcnzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl}-L-valine methyl ester (0.24 mmol) was dissolved in THF and MeOH (2:1) (0.6 mL). A 5 M solution of LiOH in water (5.0 equiv.) was then added. The reaction was stirred at room temperature overnight. The reaction was diluted with ethyl acetate and acidified with IN hydrochloric acid. The organic layer was washed with brine (2X), dried (magnesium sulfate), filtered and concentrated to afford 55 mg of the pure 2-{4'-[(4-bcnzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl)-L-valine. LCMS MH4 (rn/z) 599. 'H NMR (300MHZ, DMSO-d6): 5 10.55 ppm (s, 1H), 8.08 ppm (d, 1H, J=9.2 Hz), 7.97-7.76 ppm (m, 8H), 7.58-7.28 ppm (m, 7H), 7.02 ppm (d, 1H, J=8.0 Hz), 5.31 ppm (s. 2H), 3.94 ppm (s, 2H), 3.58-3.52 ppm (m, 1H), 1.96-1.90 ppm (m, 1H), 0.84 ppm (d, 3H, J=7.0 Hz), 0.81 ppm (d, 3H, J=7.0 Hz). Example 14: 4'-{[4-(l-Carboxy-ethoxy)-benzofuran-2-carbony)]-amino}-biphenyl-4-suJfonyl-L-valine The product of Example 13-Step 1, 4'-[(4-benzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester (0.32 mmol), was dissolved in 3 mL of ethyl acetate-MeOH (2:1) and 10% Pd/C (20 mg) was added. The reaction was stirred under a hydrogen atmosphere for 5h. The reaction mixture was filtered through celite and then concentrated to give 4 -[(4-hydroxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester in 80% yield. The product (0.13 mmol) was dissolved in anhydrous DMF(1 mL), and CS2CO3 p:26Tnmo]) was added, followed by 2-bromo-propionic acid ethyl ester (0.13 mmol). After the 47 WO 2005/061477 PCT/US2003/040835 reaction was complete by TLC the reaction was diluted with ethyl acetate and acidified with IN hydrochloric acid. The organic layer was washed with brine (2X), dried (magnesium sulfate), filtered and concentrated to afford 79 mg of 4'-{[4-(l-ethoxycarbonyl-ethoxy)-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonyl-L-vaIine methyl ester. The ester was taken up in THF:MeOH (2:1, 2 mL) and treated with NaOH (5N, 5 eq). The reaction was stirred overnight, diluted with ethyl acetate and acidified with IN HC1. The organic layer was isolated and washed with brine (2X), dried (magnesium sulfate), filtered and concentrated to afford 4'-{[4-(l-carboxy-ethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonyl-L-valine. LCMS MH+ (m/z) 581. 'H NMR (300MHZ, CD3OD): 5 7.91-7.68 ppm (m, 6H), 7.40-7.09 ppm (m, 3H), 6.70 ppm (d, 1H, J=8 Hz), 4.99 ppm (q, 1H, J=13 Hz), 3.69 ppm (d, 1H, J=5.8 Hz), 2.08-2.00 ppm (m, 1H), 1.69 ppm (d, 3H, J=6.9 Hz), 0.97 ppm (d, 3H, J=7.0 Hz), 0.96 ppm (d, 3H, J=7.0 Hz). Example 15: N2-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l'-biphenyl-4-yl}sulfonyl)-L-Asparagine According to the procedure of Example 4, N-2-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-],r-biphenyl-4-yl}sulfonyl)-L-asparagine was prepared from Fmoc-L-asparagine-Wang resin. LCMS MH^m/z) 508. !H NMR (300 MHZ, DMSO-d6): 5 10.71 ppm (s, 1H), 8.16-7.50 ppm (m, 12H), 7.39 ppm (dd, 1H, J,=7.5 Hz, J2=7.5 Hz), 3.95 ppm (m, 1H), 2.34 ppm (d, 2H, J=6.0 Hz). Example 16: L-2-{4'-[(Benzofuran-2-carbonyl)-ainino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid Step 1: To a stirred solution of 4-nitrobiphcnyl (50.00 g, 0.25 mol) in chloroform (750 mL) was added dropwise at room temperature chlorosulfonic acid (17 mL, 0.3 mol). The 48 WO 2005/061477 PCT/US2003/040835 reaction mixture was stirred at 60°C for 6 h. The white-precipitate formed was collected by filtration and washed with cold chloroform. The product was air dried to give 31.00 g of 4-nitrobiphenylsulfonic acid (Yield 61%). Step 2: The crude 4-nitrobiphenylsulfonic acid obtained above (31.00 g, 0.11 mol) was diluted with thionyl chloride (100 mL) and treated with a catalytic amount of DMF (0.1 mL). The reaction mixture was refluxed for 4 h, cooled to room temperature, and concentrated under vacuum. To remove the residual thionyl chloride, toluene was added and was concentrated to give 29.00 g (yield 84%) of the desired product, 4 -nitro-biphenyl-4-suJfonyl chloride. Step 3: To a dry round-bottomed flask was added 4-nitro-biphenyl-4-sulfonyl chloride (5.09 g), anhydrous dichloromethane (50 mL), and L-valine methyl ester hydrochloride (1.10 equiv.). The mixture was cooled with an ice bath before the addition of N,N-diisopropylethylamine (2.50 equiv.). The ice bath was removed and the reaction mixture was warmed up to room temperature and stirred at room temperature for 2 h. The reaction was then diluted with ethyl acetate (100 mL) and saturated ammonium chloride solution (20 mL). The organic layer and aqueous layer were separated and the aqueous layer was extracted with ethyl acetate (30 mL x 2). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate, filtered and evaporated under vacuum to provide 6.31 g of product, L-3-methyl-2-(4'-nitro-biphcnyl-4-sulfonylarnino)-butyric acid methyl ester (yield 95%). Step 4: The product obtained in Step 3 above was dissolved in ethyl acetate (120 mL). To the solution was added SnCl2 dihydrate (4.0 equiv.). The reaction was allowed to proceed at room temperature for 6 h. The reaction mixture was cooled with a water bath, and 2 M sodium carbonate solution (30 mL) and ethyl acetate (100 mL) were added. The mixture was transferred to a centrifuge bottle and centrifuged for 20 min. The supernatant was separated and washed with water and brine and dried over anhydrous sodium sulfate. After filtration and concentration, 5.52 g of product L-2-(4'-amino-biphenyl-sulfonylamino)-3-methyl-butyric acid methyl ester was obtained. Step 5: To an oven-dried flask was added L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (5.52 g), anhydrous methylene chloride (100 mL), and NN-diisopropylcthylamine (2.0 equiv.). The solution was cooled with an ice bath and 2-benzofurancarbonyl chloride (1.0 equiv.) was then added. The reaction proceeded at 0°C for 4 h. Water was added and the precipitate was filtrated and washed with cold ether. After drying in vacuo, the product L-2-{4'-[(benzofuran-2-carbonyl)-arnino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was obtained as a white solid (6.98 g, yield 90%). Step 6: The methyl ester product of Step 5 above was dissolved in THF (150 mL). Methanol (100 mL) and water (100 mL) were added followed by lithium hydroxide monohydrate 49 WO 2005/061477 PCT/US2003/040835 (3.60 g). The reaction mixture was stirred at room temperature until no starting material remained. The reaction mixture was cooled in an ice bath and acidified with concentrated hydrochloric acid to ~pH 3. The resulting precipitate was filtered and washed with cold water and cold ether to provide 5.65g of L-2-{4'-[(benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-rnethyl-butyric acid. Example 17: N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l'-biphenyl-4-yl}sulfonyl)-L-Histidine According to the procedure of Example 4, N-({4'-[(l-benzofuran-2-ylcarbonyl)arnino]-1,1 -biphcnyl-4-yl}sulfonyl)-L-histidine was prepared from Fmoc-N-Boc-L-histidinc-Wang resin. LCMS MH+ (m/z) 531. 'H NMR (300 MHz, DMSO-d6): d10.72 ppm (s, IH), 8.25 (s, 1H), 7.98 ppm (d, IH, J=9.3 Hz), 7.86-7.73 ppm (m, 10H), 7.44 ppm (dd, IH, J,=9.6 Hz, J2=7.8 Hz), 7.38 ppm (dd, IH, J,=7.2 Hz, J2=7.2 Hz), 6.68 ppm (s, IH), 6.54 ppm (s, IH), 2.85 ppm (d, 2H,J=5.1Hz). Example 18: N-({4'-[(l-Benzofuran-2-yJcarbonyl)amino]-l,l'-biphenyl-4-yl}sulfonyl)-L-leucine According to the procedure of Example 4, N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-1,1 -biphenyl-4-y])su]fonyl)-L-]cucine was prepared from Fmoc-L-leucine-Wang resin. LCMS MH+(m/z) 507. 'H NMR (300 MHz, DMSO-d6): 5 10.75 ppm (s, 1H), 8.33 (s, 1H), 7.98 ppm (d, 1H, J=9.3 Hz), 7.84-7.73 ppm (m, 10H), 7.52 ppm (dd, 1H, J1=7.2 Hz, J2=7.2 Hz), 7.38 ppm (dd, 1H, J,=7.5 Hz, J2=7.5 Hz), 3.23 ppm (m, 1H), 1.45 (m, 2H), 0.81 (m, 7H). 50 WO 2005/061477 PCT/US2003/040835 Example 19: L-2-{4'-[(Benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-metyl-butyric acid Step 1: To 0.838g of L-valine methyl ester hydrochloride in 15mL of dichloromethane, cooled in an ice bath, 1.34g of 4-bromobenzenesulfonyl chloride was added followed by 2.79 mL of triethylamine. The mixture was stirred at room temperature overnight and then diluted with dichloromethane. The dichloromethane was washed with water and brine, dried over Na2SO4 filtered, and concentrated in vacuo to provide 1.77g of methyl N-[(4-bromophenyl)sulfonyl]-L-valinate as,a colorless solid. Yield -100%. m.p. 88-90°C; MS: 348.2 (M-H): Step 2: A mixture of 0.175g (0.5mmol) of methyl N-[(4-bromophenyl)sulfonyl]-L-valinate, 0.25g (1.5mmol) of 4-nitrophenylboronic acid, 0.087g of tetrakis(triphenylphosphine)palladium and 8mL of saturated sodium bicarbonate in 8mL of ethylene glycol dimethyl ether were refluxed for 2h, then cooled to room temperature. To the reaction was added 50mL of ethyl acetate and 40mL of water. The water layer was extracted with ethyl acetate. The combined ethyl acetate layers was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexane:ethyl acetate (2:1) to provide 0.159g of methyl N-[(4'-nitro-l,l'-biphenyl-4-yl)sulfonyI]-L-valinate as a yellow solid. Yield 81%. m.p. 144-146°C; MS: 391.0(M-H): Step 3: To 1.72g of 4-bromoaniline was added to 1.89g of benzofuran-2-carboxylic acid chloride in 35mL of dichloromethane cooled in ice bath, followed by the addition of 4.9mL of triethylamine. The reaction was stirred at room temperature overnight and then diluted with dichloromethane. The dichloromethane layer was washed with water, IN HC1, water and brine, dried over Na2SC4 filtered, and concentrated in vacuo to provide 2.61g of N-(4-bromophenyl)-l-benzofuran-2-carboxamide as a yellow solid. Yield 72%. m.p. 178-180°C; MS: 314.1 (M-H)". Step 4: A mixture of 0.74g of N-(4-bromophenyl)-l-benzofuran-2-carboxamide, 0.653g of bis(pinacolato)diboron, 0.689g of potassium acetate and 0.096g of bis(diphenyl phoshino)ferrocene] dichloropalladium (II) dichloromethane complex in 15rnL of DMSO were heated at ~80°C for 2h, then cooled to room temperature. Then 20mL of toluene, 40mL of ethyl acetate and 40mL of water were added to the reaction. The water layer was extracted with 30mL of ethyl acetate. The combined organic layers were filtered and washed 4 times with 40mL of water, dried over Na2SO4, filtered and concentrated in vacuo to obtain 0.34g of the boronate ester as a black oily compound. To the above product, 0.273g of methyl N-[(4-bromophenyl)sulfonyl]-L-valinate, 0.13g of tetrakis(triphenylphosphine)palladium, 7.5mL saturated sodium bicarbonate and 12mL of 51 WO 2005/061477 PCT/US2003/040835 ethylene glycol dimethyl ether were added and the resulting mixture was refluxed for 2h. The reaction was then cooled to room temperature. Ethyl acetate and water were added to the reaction and the mixture was filtered. The organic layer was washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by column chromatography, eluting with hexanc:cthyl acetate (2:1) to provide 0.112g of methyl N-({4-[(l-benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-L-valinate as a white solid. Yield 28.4%. m.p. 195-200°C; MS: 507.1 (M+H)+. Step 5: According to the procedure of Example 2A, Step 6, methyl N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-L-valinate was converted into L-2-j4'-[(benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyI-butyric acid. Example 20: L-2-{4'-[(4-Cyano-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-rnethyl-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (6.336 g, 28.8 mmol, 1 eq) in methylene chloride (120 mL) in a round bottom flask under nitrogen was added N.N'-diisopropylethylamine (12.54 mL, 72.0 mmol, 2.5 eq). The mixture was cooled to 0°C and trifluoromethanesulfonic anhydride (7.27 mL, 43.2 mmol, 1.5 eq) was added dropwise. After stirring for one hour, the mixture was diluted with methylene chloride (350 mL), and washed with water twice. The organic layer was dried and evaporated in vacuo to give 3-methyl-4-trifluorornethancsulfonyloxy-benzofuran-2-carboxylic acid ethyl ester suitable for use without purification. 'H NMR (400 MHz, CDC13) dppm 1.5 (t, 7=7.1 Hz, 3 H) 2.8 (s, 3 H) 4.5 (q, 7=7.2 Hz, 2 H) 7.2 (d, 7=9.6 Hz, 1II) 7.5 (t, 7=8.2 Hz, 1 H) 7.6 (d. 7=8.3 Hz, 1 H). Step 2: To 3-methyl-4-trifluoromethanesulfonyJoxy-benzofuran-2-carboxylic acid ethyl ester (721 mg, 2.0 mmol, 1 eq) in 10 mL of DMF under nitrogen was added 322 mg of Zn(CN)2 (2.74 mmol, 1.37 eq), and 123 mg of Pd(PPh3)4 (0.1 mmol, 0.05 eq). The reaction mixture was heated to 85 °C. The reaction was complete in 2.5 h by TLC. After work up and column chromatography eluting with 5% ethyl acetate/hexane, 4-cyano-3-methyl-benzofuran-2-carboxylic add ethyl ester was obtained in 80% yield (367 mg). 'H NMR (400 MHz, CD3OD) 8 ppm 1.6 (t, 7=7.1 Hz, 3 H) 3.0 (s, 3 H) 4.6 (q, 7=7.2 Hz, 2 H) 7.8 (dd, 7=8.3, 7.6 Hz, 1 H) 7.9 (m, 1 H) 8.1 (dd, 7=8.3, 1.0 Hz, 1 H). 52 WO 2005/061477 PCT/US200J/040835 Step 3: To 550 mg of 4-cyano-3-meihyl-benzofuran-2-carboxylic acid ethyl ester (2.4 mmol) in 15 mL of THF was added 5 mL of McOH and 5 mL of IN LiOH. The reaction was complete in 2h. After quenching with 5 mL of 1 N HC1 and work up, 4-cyano-3-methyl-benzofuran-2-carboxylic acid was obtained in quantitative yield. 'H NMR (400 MHz, DMSO-d6) 5 ppm 2.7 (s, 3 H) 7.7 (m, 1 H) 7.9 (d, 7=7.3 Hz, 1 H) 8.1 (m, 1 H). Step 4: To a mixture of 4-cyano-3-methyl-benzofuran-2-carboxylic acid (525 mg, 2.6 mmol, 1 eq), l-(3-dime(hy]aminopropyl)-3-ethyJcarbodiimide bydrochloride (EDCI, 752 mg, 3.9 mmol, 1.5 eq), and 4-(dimethylamino)pyridine,(335 mg, 2.7 mmol, 1 eq) in 15 mL of DMDF under nitrogen was added L-2-(4'-amino-biphcnyl-4-su]fony)amino)-3-methyl-butyric acid mehyl ester, the product of Example 2A, Step 4. The mixture was stirred at 100 °C for 8h. After work up and column chromatography (20% ethyl acetate/hcxane), L-2-4'-[(4-cyano-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid meihyl ester was obtained (643 mg, 1.18 mmol) in 45% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.7, 6.8 Hz. 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, 7=9.3, 7.1 Hz. 1 H) 7.7 (dd, 7=8.3, 7.6 Hz, 1 H) 7.8 (dd, 7=8.8, 3.3 Hz, 4 H) 7.9 (m, 3 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (m, 1 H) 8.3 (d, 7=9.6 Hz, 1 H) 10.8 (s, 1 H). Step 5: The methyl ester obtained in Step 4 (183 mg) was dissolved in THF (8 mL) and methanol (3 mL) and IN LiOH (1 mL) were added. The reaction mixture was stirred at room temperature until the reaction was complete (-1-2 days). The reaction mixture was then acidified with IN hydrochloric acid to -pH 4. The resulting mixture was extracted with ethyl acetate and the combined organic layers were dried, filtered and concentrated in vacuo to provide 2-{4'-[(4-cyano-3-methyl-benzofuran-2-carbonyl)-amJno]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=29.7, 6.7 Hz, 6 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 1 H) 7.7 (rn, 1 H) 7.8 (m, 6 H) 7.9 (d, J=7.1 Hz, 1 H) 8.0 (d, J=8.8 Hz, 2 H) S.I (d. J=8.6 Hz, 1 H) 10.8 (s, 1 H). 53 Example 21: L-3-MethyI-2-{4'-[(3-methyl-4-prop-l-ynyl-benzofuran-2-carbonyI)-amino]-bipbenyl-4-sulfonylaminol-butyric acid WO 2005/061477 PCT/US2003/040835 Step 1: To 3-metbyl-4-tifluororoethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester(550 mg, 1.6 mmol, 1 eq), the product of Example 20, Step 1, in 5 mL of toluene under nitrogen was added 60 mg of Pd(PPh3)4 (0.05 mmol, 0.03 eq) and tributyl-prop-1-ynyl-stannane (0.55 mL, 1.8 mmol, 1.13 eq). The resulting reaction mixture was heated to reflux for 18h. After work up and column chrornatography (3% ethyl acetate/hexane), 3-methyl-4-prop-l-ynyl-benzofuran-2-carboxylic acid ethyl ester was obtained in 14% yield (56 mg). 'HNMR (400 MHz, CDC13) 5 ppm 1.4 (t, J=zl. 1 Hz, 3 H) 2.1 (s, 3 H) 2.8 (s, 3 H) 4.5 (q, J-l. 1 Hz, 2 H) 7.3 (m, 2 H) 7.5 (dd, J=7.6,1.8 Hz, 1 H). Step 2: According to the procedure of Example 20, Step 3, 3-methyl~4-prop-l-ynyl-benzofuran-2-carboxylic acid ethyl ester was hydrolyzed to give 3-metnyl-4-prop-l-ynyl-benzofuran-2-carboxyhc acid in 99% yield. 'H NMR (400 MHz, CDC13) dppm 2.2 (s, 3 H) 2.9 (s, 3 H) 7.3 (m, 2 H) 7.5 (m, 1 H). Step 3: To a mixture of 3-metbyJ-4-prop-l-ynyl-benzofuran-2-carboxylic acid (46 mg, 0.21 mmol, 1 eq), was added L-2-(4'-amino-biphenyl-4-stJlfonylamino)-3-methyl-butyric acid methyl ester (79 mg, 0.22 mmol, 1 eq), the product of Example 2A, Step 4, and benzotriazol-1-yloxytris(dirnethylamino)phosphonium hexafluorophosphate (BOP, 127 mg, 0.29 mmol, 1.4 eq) in 5 mL DMF under nitrogen was added 0.05 mL of N,N-diisopropylethylamine (0.29 mmol, 1.4 eq). The reaction mixture was stirred at room temperature for 18h. After work up and column chromatography (25% ethyl acetate/hexane), L-3-methyl-2-{4'-I(3-mcthyl-4-prop-l~yny]-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid methyl ester was obtained in 45% yield (55 mg). 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.8, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.2 (dd, 3 H) 2. d (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.4 (d, 7=7.1 Hz, 1 H) 7.5 (m, 1 H) 7.7 (d, 7=7.6 Hz, 1 H) 7.8 (t, J=8.8 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, J=9.6 Hz, 1 H) 10.6 (s, 1 H). Step 4: According to the procedure of Example 20, Step 5, L-3-methyl-2-{4 -[(3-merhyl-4-prop-l -ynyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was hydrolyzed to give L-3-methyl-2-{4'-[(3-methyl-4-prop-l-ynyl-benzofuran-2-carbbnyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid in quantitative yield. !H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12.4,6.8 Hz, 6 H) 1.9 (m, 1 H) 2.2 (s, 3 H) 2.8 (s, 3 H) 3.6 (dd, J=9.3, 6.1 Hz, 1 H) 7.4 (d, J=6.8 Hz. 1 H) 7.5 (m, 1 H) 7.7 (d, J=8.3 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m; 4 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (d, J=9.6 Hz, 1 H) 10.6 (s, 1 H). 54 WO 2005/061477 PCT/US2003/040835 Example 22: L-2-(4'-{[4-(3-Mcthoxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbony)]-amino}-bipheny)-4-sulfonylamino)-3-rnethyl-butyric acid Step 1: To the product of Example 20, Step 1, 3-mcthyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (860 mg, 2.4 mmol, 1 eq), in 7 mL of DMF under nitrogen was added 98 mg of PdC]2(PPh3)2 (0.14 mmol, 0.06 eq), 0.42 mL of 3-methoxy-propyne (5.0 mmol, 2.1 cq) and 1.36 mL of triethylaminc (9.7 mmol, 4.0 cq). The reaction mixture was heated to 90°C for 18 h. After work up and column chromatography (4% ethyl acetate/hexane), 4-(3-methoxy-proprl-ynyI)-3-methyl-benzofuran-2-carboxyIic acid ethyl ester was obtained in 53% yield (343 mg)..'H NMR (400 MHz, CDG3) dppm 1.4 (t, 7=7.2 Hz, 3 H) 2.8 (t, 3 H) 3.5 (s, 3 H) 4.4 (s, 2 H) 4.5 (q, 7=7.2 Hz, 2 H) 7.4 (m, 2 H) 7.5 (dd, J=7.7, 1.6 Hz, 1 H) Step 2: According to the procedure of Example 20, Step 3, 4-(3-methoxy-prop-l-ynyl)-3-mcthyJ-benzofuran-2-carboxylic acid ethyl ester was hydrolyzed to give 4-(3-methoxy-prop-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid in 100% yield. 'H NMR (400 MHz, CD3OD) 5 ppm 2.7 (s, 3 H) 3.4 (s, 3 H) 4.3 (s, 2 H) 7.3 (m, 2 H) 7.4 (dd, 7=7.8, 1.5 Hz, 1 H) Step 3: According to the procedure of Example 21, Step 3, 4-(3-methoxy-prop-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid was coupled with L-2-(4'-amino-biphenyl-4-su]fony)amino)-3-methyl-butyric acid methyl ester to give L-2-(4'-{[4-(3-methoxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 88% yield. 'H NMR (400 MHz, CDC13) 5 ppm 0.9 (dd, 7=32.5, 6.7 Hz, 6 H) 2.1 (m, 1 H) 2.9 (s, 3 H) 3.4 (s, 3 H) 3.5 (s, 3 H) 3.8 (dd, 7=10.1, 5.1 Hz, 1 H) 4.4 (s, 2 H) 5.1 (d, 7=10.1 Hz, 1 H) 7.4 (m, 2 H) 7.5 (m, 1 H) 7.6 (d, 7=8.6 Hz, 2 H) 7.7 (d, 7=8.6 Hz, 2 H) 7.9 (dd, 7=17.8, 8.7 Hz, 4 H) 8.4 (s, 1 H). Step 4: According to the procedure of Example 20, Step 5, L-2-(4'-{[4-(3-methoxy-prop-l-yny])-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was hydrolyzed to give L-2-(4'-{[4-(3-methoxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in 100% 55 WO 2005/061477 PCT/US2003/040835 yield. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.0, 6.4 Hz, 6 H) 2.0 (dd, 7=13.4, 8.1 Hz, 1-H) 2.8 (s, 3 H) 3.4 (s, 3 H) 3.6 (m, 1 H) 4.4 (s, 2 H) 7.5 (m, 2 H) 7.8 (m, 7 H) 8.0 (m, 3 H) 10.6 (s,lH) 12.6 (s.lH). Example 23: 2-{4'-[(4-Cyclopropylethynyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-bulyric acid Step 1: To the product of Example 20, Step 1, 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (1.8 g, 5.1 mmol, 1 eq), in 2 mL of DMF under nitrogen was added 200 mg of PdCl2(PPh3)2 (0.28 mmol, 0.05 eq), Et3N (2.85 mL, 20.4 mmol, 4 eq), cyclopropylethynyl-trimethylsilane (1 g, 7.2 mmo], 1.4 eq), and tetrabutylammonium fluoride (5.1 mL, 1.0 M in THF, 5.1 mmol, 1 eq). The reaction mixture was sealed and heated to 80°C for 12h. After workup and column chromatography (2% ethyl acetate/hexanc), 4-cyclopropylethyl-3-methyl-benzofuran-2-carboxylic acid ethyl ester was obtained in 15% yield (202.6 mg). 'H NMR (400 MHz, CD3OD) dppm 0.7 (m, 2 H) 0.9 (m, 2 H) 1.3 (t, 7=7.1 Hz. 3 H) 1.5 (m, 1 H) 2.7 (s, 3 H) 4.3 (q, 7=7.2 Hz, 2 H) 7.2 (m, 1 H) 7.3 (dd, 7=8.3, 7.3 Hz, 1 H) 7.4 (m, 1 H). Step 2: According to the procedure of Example 20, Step 3, 4-cyclopropylethynyl-3-mcthyl-benzofuran-2-carboxylic acid ethyl ester was hydrolyzed to give 4-cyclopropylethynyl-3-methyl-benzofuran-2-carboxylic acid in quantitative yield. !H NMR (400 MHz, DMSO-d6) dppm 0.8 (m, 2 H) 0.9 (m, 2 H) 1.6 (m, 1 H) 2.7 (s, 3 H) 7.3 (dd, 7=7.6, 1.0 Hz, 1 H) 7.4 (m, 1 H) 7.6 (dd, 7=8.3, 1.0 Hz, 1 H). Step 3: According to the procedure of Example 23, Step 3, coupling of 4-cycIopropylethynyJ-3-methyl-benzofuran-2-carboxy]ic acid with L-2-(4 -amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester gave L-2-{4'-[(4-cyclopropylethynyl-3-methyI-benzofuran-2-carbonyl)-amino]-b]phenyI-4-suJfonylamino}-3-methyl-butyric acid methyl ester in 54% yield. 1H NMR (400 MHz, CDC13) dppm 0.9 (m, 10 H) 1.6 (m, 1 H) 2.1 (m, lH)2.9(s, 3 H) 3.4 (s, 3 H) 3.8 (dd, 7=10.1, 5.1 Hz, 1 H) 5.1 (d, 7=10.1 Hz, 1 H) 7.3 (m, 2 H) 7.4 (m, 1 H) 7.6 (d, 7=8.8 Hz, 2 H) 7.7 (d, 7=8.6 Hz, 2 H) 7.9 (dd, 7=18.8, 8.7 Hz, 4 H) 8.4 (s, 1 H). 56 WO 2005/061477 PCT/US2003/040835 Step 4: According to the procedure of Example 20, Step 5, L-2-{4-[(4-cyclopyethynyl-3-methyl-ben2ofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was hydrolyxcd in quantitative yield to provide L-2-{4'-[(4-cyclopropylethynyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (m, J=12.6, 6.6 Hz, 8 H) 1.0 (m, 2 H) 1.7 (m, 1 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, J=9.1,5.8 Hz, 1 H) 7.3 (dd, J=7.6,0.8 Hz, 1 H) 7.5 (m, 1 H) 7.6 (d, J=7.3 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2II) 8.1 (d, J=9.3 Hz, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 24: L-2-(4'-{[4-(2-CycIopropyl-etbyl)-3-methyl-benzoruran-2-carbonyl]-amino}-biphenyI-4-su]fonylamino)-3-methyl-butyric acid Step 1: To a solution of the product of Example 23, Step 3, L-2-{4'-[(4-cyclopropylcthynyl-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester (132 mg, 0.23 mmol), in 10 mL of THF under nitrogen was added 5% Pd/C (32 mg). A balloon of hydrogen was attached to the reaction mixture. After 36h the reaction was filtered through celite, and the filtrate was concentrated in vacuo. The crude product was purified using preparative HPLC to give L- 2-(4'-{[4-(2-cyc]opropyl-ethy])-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester in 56% yield. 1H NMR (400 MHz, DMSO-d6) dppm 0.1 (d, 7=4.8 Hz, 2 H) 0.4 (dd, 7=8.0,1.6 Hz, 2 H) 0.8 (dd, 7=14.7, 6.8 Hz, 6 H) 1.6 (m, 2 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.1 (m, 2 H) 3.4 (s, 3 H) 3.6 (m, 1 H) 7.1 (d, 7=7.3 Hz. 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (dd, 7=10.2, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=10.1 Hz, 1 H) 10.5 (s, 1 H). Step 2: According to the procedure of Example 20, Step 5, L- 2-(4-{[4-(2-cyclopropyl-ethyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was hydrolyzed to give L- 2-(4-{[4-(2-cyclopropyl-ethyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.1 (d, J=5.6 Hz, 2 H) 0.4 (d, J=8.1 Hz, 2 H) 0.8 (m, 6 H) 1.6 (m, 2 H) 2.0 (dd, J=13.4, 7.8 Hz. 1 H) 2.8 (s, 3 H) 3.1 (m, 1 H) 3.6 (m, 3 H) 7.1 (d, J=7.8 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (d, J=8.6 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.6 Hz, 2 57 WO 2005/061477 PCT/US2003/040835 H) 8.0 (d, J=10.4 Hz, 1 H) 10.5 (s, 1 H). Example 25: L-2-(4'-{[4-(3-Mcthoxy-Z-propenyl)-3-mcthyl-benzoruran-2-carbonyl] amino}-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid Step 1: To a solution of the product of Example 22, L-2-(4'-{ [4-(3-methoxy-prop-l -ynyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonyIamino)-3-methyl-butyric acid methyl ester (132 mg, 0.22 mmol), in 10 mL of toluene under nitrogen was added Pd/CaCO3 (poisoned with lead, 34 mg). A balloon of hydrogen was attached to the reaction mixture. After 24h the reaction was filtered through eclite, and the filtrate was concentrated in vacuo. The crude product was purified using preparative HPLC to give L-2-(4 -{[4-(3-methoxy-Z-propenyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 38% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.7. 6.8 Hz, 6 H) 1.9 (dd, 1 H) 2.7 (s, 3 H) 3.2 (s, 3 H) 3.4 (s, 1 II) 4.1 (m, .7=6.3, 1.5 Hz, 2 H) 6.0 (m 1 H) 7.1 (d, 7=7.3 Hz, 1 H) 7.2 (d, 7=12.4 Hz, 1 II) 7.5 (d, 1 H) 7.6 (d, 7=8.1 Hz, 1 H) 7.8 (t, 7=8.8 Hz, 4 H) 7.9 (d, 7=8.8 Hz, 2 H) 8.0 (d, 7=9.1 Hz, 2 H) 8.3 (s, 1 H) 10.6 (s, 1 H). Step 2: According to the procedure of Example 20, Step 5, L-2-(4'-{[4-(3-methoxy-Z-propenyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was hydrolyzed to provide L-2-(4'-{[4-(3-me.thoxy-Z-propenyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in 100% yield. !H NMR (400 MHz, DMSO-d6) 5 ppm 0.8 (dd, 7=12.8, 6.7 Hz, 6 II) 2.0 (dd. 7=13.3, 6.4 Hz, 1 H) 2.7 (s, 3 H) 3.2 (s, 3 H) 4.1 (d, 7=7.8 Hz, 2 H) 6.0 (m, 1 H) 7.1 (d, 7=7.8 Hz. 1 H) 7.2 (d, 7=10.4 Hz. 1 H) 7.5 (m, 1 H) 7.6 (d, 7=7.6 Hz. 1 H) 7.8 (d. 7=8.8 Hz, 2 H) 1.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). 58 WO 2005/061477 PCT/US2003/040835 Example 26: L-2-(4'-{[4-(3-Hydroxy-prop-l-ynyl)-3-methyl-ben7.ofuran-2-carbonyI]-amino]-biphenyl-4-suIfonyIamino)-3-methyl-butyricacid Sicp 1: According to the procedure of Example 22, Step 1,4-(3-hydroxy-prop-l-ynyl)-3-meihyl-benzofuran-2-carboxylic acid ethyl ester was prepared from propargy] alcohol and 3-methyl-4-trif]uoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester in 38% yield. 'll NMR (400 MHz, DMSO-d6) 8 ppm 1.4 (t, 7=7.1 Hz, 3 H) 2.8 (s, 3 H) 4.4 (m, 4 H) 5.4 (t, 7=6.1 Hz, 1 H) 7.4 (dd, 7=7.6, 0.8 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3, 0.8 Hz, ] H). Step 2: According to the procedure of Example 20, Step 3, hydrolysis of 4-(3-hydroxy-prop-l-yny])-3-methyl-benzofuran-2-carboxylic acid ethyl ester provided 4-(3-hydroxy-prop-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 2.8 (s, 3 H) 4.4 (d. 7=6.1 Hz, 2 H) 5.4 (t. 7=5.9 Hz, 1 H) 7.4 (dd. 7=7.5,0.9 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3, 1.0 Hz, 1 H). Step 3: According to the procedure of Example 21, Step 3, coupling of L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester with 4-(3-hydroxy-prop-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid provided L-2-(4'-{[4-(3-hydroxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl3-amino)-biphcnyl-4-sulfony)amino)-3-methyl-butyric acid methyl ester in 51% yield. 'H NMR (400 MHz, DMSO-d6) 5 ppm 0.8 (dd, 7=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.3, 7.1 Hz, 1 H) 4.4 (d, 7=6.1 Hz, 2 H) 5.4 (m, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3, 0.8 Hz, 1 H) 7.8 (t, 7=8.6 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). Step 4: According to the procedure of Example 20, Step 5, hydrolysis of L-2-(4'-{ [4-(3-hydroxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester provided L-2-(4'-{r4-(3-hydroxy-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyI-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=13.0, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.5 (m. 1 H) 4.4 (d, J=5.8 Hz, 2 H) 5.4 (t. J=6.1 Hz, 1 H) 7.4 (dd, J=7.6,1.0 Hz, I H) 7.5 (m, I H) 7.7 (dd, J=8.3,1.0 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=9.1 Hz, 2 H) 8.0 (d,J=7.8Hz, lH)10.6(s, 1 H). 59 WO 2005/061477 PCI7US2003/040835 Example 27: L-2-(4'-{[4-(3-Hydroxy-propyl)-3-methyl-benzofuran-2-carbony1]-amino}-biphehyl-4-sulfonylamino)-3-melhyl-butyric acid Step 1: The product of Example 26, Step 1,4-(3-hydroxy-prop-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid ethyJ ester, was hydrogenated to give 4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carboxylic acid ethyl ester according to the procedure of Example 24, Step 1, in quantitative yield. 'H NMR (400 MHz, CDC13) dppm 1.3 (t, 7=5.2 Hz, 1 H) 1.4 (t, .7=7.1 Hz, 3 H) 2.0 (m, 2 H) 2.8 (s, 3 H) 3.1 (m, 2 II) 3.8 (m, 2 H) 4.5 (q, .7=7.2 Hz, 2 H) 7.1 (dd, 7=7.2, 0.9 Hz, 1 H) 7.3 (m, 1 H) 7.4 (m, 1 H). Step 2: Hydrolysis of 4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carboxylic acid ethyl ester was carried out according to the procedure of Example 20, Step 3, to provide 4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carboxylic acid in quantitative yield. 'HNMR (400 MHz, DMSO-d6) dppm 1.8 (m, 2 H) 2.7 (s, 3 H) 3.0 (m, 2 H) 3.5 (m, 2 H) 4.6 (t, 7=5.1 Hz, 1 H) 7.1 (dd, 7=7.1, 1.0 Hz l H) 7.4 (m, 1 H) 7.4 (m, 1 H). Step 3: Amide coupling of L-2-(4'-amino-biphenyl-4-su]fonylarnino)-3-methyl-butyric acid methyl ester with 4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carboxylic acid according to the procedure of Example 21, Step 3, provided L-2-(4 -{[4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 100% yield. 'H NMR (400 MHz, CDC13) 5 ppm 0.9 (dd, 7=32.1, 6.8 Hz, 6 H) 2.0 (m, 3 H) 2.9 (s, 3 H) 3.1 (m, 2 H) 3.4 (s, 3 H) 3.8 (m, 3 H) 5.1 (d, 7=10.1 Hz, 1 H) 7.1 (m, 1 H) 7.4 (m, 2 H) 7.6 (d, 7=8.6 Hz, 2 H) 7.7 (d, 7=8.8 Hz, 2 H) 7.9 (dd, 7=16.7, 8.6 Hz, 4 H) 8.5 (s, 1 H). Step 4: Hydrolysis of L-2-(4-{[4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyJ-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 5, provided L-2-(4'-{l4-(3-hydroxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12.55, 6.7 Hz, 6 H) 1.8 (m, 2 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.1 (m, 2 H) 3.5 (m, 2 H) 3.6 (dd, J=9.3, 6.1 Hz, 1 H) 4.6 (s, 1 H) 7.1 (d, J=7.3 Hz, 1 H) 7.4 (m, 1 H) 7.5 (d, J=8.3 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (d, J=9.1 Hz, 1 H) 10.5 (s, 1 H). 60 WO 2005/061477 PCT/US2003/040835 Example 28: L-3-Methyl-2-(4'-{[3-methyl-4-(4-methyl-pent-l-ynyl)-benzoruran-2-carbonyI]-amino}-biphenyl-4-sulfonylamino)-bulyric acid Step 1: According to the procedure of Example 22, Step 1, 3-methyl-4-(4-methyl-pcnt-l-ynyl)-ben2ofuran-2-carboxylic acid ethyl ester was prepared from 4-methyl-pent-l-yne and 3-rnethy]-4-trifluorornethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester in 81% yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.0 (s, 3 H) 1.0 (s, 3 H) 1.3 (t, 7=7.1 Hz, 3 H) 1.9 (m, 1 H) 2.4 (d, 7=6.6 Hz, 2 H) 2.8 (s, 3 H) 4.4 (q, .7=7.1 Hz, 2 H) 7.4 (dd, 7=7.6, 1.0 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3,1.0 Hz, 1H). Step 2: Hydrolysis of 3-methyl-4-(4-methyl-penl-l-ynyl)-benzofuran-2-carboxylic acid ethyl ester was carried out according to the procedure of Example 20, Step 3, to provide 3-rncthyl-4-(4-methyl-pent-l-ynyl)-benzofuran-2-carboxylic acid in quantitative yield. 'HNMR (400 MHz, DMSO-d6) dppm 1.0 (d, 7=6.6 Hz, 6 H) 1.9 (m, J H) 2.4 (d, 7=6.6 Hz, 2 H) 2.8 (s, 3 H) 7.3 (dd, 7=7.5, 0.9 Hz, I H) 7.4 (m, I H) 7.6 (dd, 7=8.3, l.0 Hz, I H) 13.5 (s, I H). Step 3: Amide coupling of L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester with 3-methyl-4-(4-methyl-pent-l-ynyl)-benzofuran-2-carboxylic acid was carried out according to the procedure of Example 21, Step 3, to provide L-3-methyl-2-(4 -{[3-methyl-4-(4-methyl-pcnt-l-ynyl)-bcnzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-butyric acid methyl ester in 42% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.7, 6.8.Hz, 6 H) 1.1 (d, 7=6.6 Hz, 6 H) 1.9 (m, 2 H) 2.5 (d, 7=6.6 Hz, 2 H) 2.8 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, 7=9.0, 6.9 Hz, 1 H) 7.4 (d, 7=7.3 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3,1.0 Hz, 1 H) 7.8 (m, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2H) 8.3 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L-3-methyl-2-(4'-{ [3-methyl-4-(4-methyl-pent-l-ynyl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid methyl ester was carried out according to the procedure of Example 20, Step 5 to provide L-3-methyl-2-(4'-{[3-methyJ-4-(4-methyl-pcnt-l-ynyl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylainino)-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12.9, 6.8 Hz, 6 H) 1.1 (d, J=6.8 Hz, 6 H) 1.9 (m, 2 H) 2.5 (d, J=6.6 Hz, 2 H) 2.8 (s, 3 H) 3.5 (m, 1 H) 7.4 (d, J=7.3 Hz, 1 H) 7.5 (m, 1 H) 7.7 (d, J=8.1 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2 H) 61 WO 2005/061477 PCT/US2003/040835 8.0 (d, J=9.1 Hz, 1 H) 10.6 (s, 1 H). Example 29: L-3-Methyl-2-(4'-{(3-melhy]-4-(4-methyl-pentyl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid Step 1: Hydrogenation of the product of Example 28, Step 1, L-3-methyl-2-(4-{{3-methyl-4-(4-mcthyI-pcnt-l-ynyl)-benzofuran-2-carbonyI]-amino}-biphenyl-4-sulfonylamino)-butyric acid methyl ester, was carried out according to Example 24, Step 1 to provide L-3-methyl-2-(4'-{[3-methyl-4-(4-methyl-pentyl)-bcnzofuran-2-carbonyl]-amino}-biphenyI-4-sulfonylamino)-butyric acid methyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd,7=14.9, 6.8 Hz, 6 H) 0.9 (m, 7=6.6 Hz, 6H)1.3(m,2H) 1.6 (m, 3 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.0 (m, 2 H) 3.3 (s, 3 H) 3.6 (t, .7=6.8 Hz, 1 ID 7.1 (d, 7=7.3 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (dd, J=10.0, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=9.1 Hz, 2 H) 8.3 (d, 7=8.6 Hz, 1 H) 10.5 (s, J H). Step 2: Hydrolysis of L-3-methyl-2-(4'-{ [3-methyl-4-(4-methyl-pentyl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid methyl ester according to the procedure of Example 20, Step 5 provided L-3-mcthyl-2-(4'-{[3-methyl-4-(4-methyl-pentyl)-benzofuran-2-carbonyI]-amino}-biphcnyl-4-sulfonyIamino)-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) 5 ppm 0.8 (dd, J=12.6, 6.8 Hz, 6 H) 0.9 (d, J=6.6 Hz, 6 H) 1.3 (m, 2 H) 1.6 (m, 3 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.0 (d, 2 H) 3.6 (dd, J=9.3, 6.1 Hz, 1 H) 7.1 (d. J=6.8 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2 H) **.1 (d,J=9.6Hz, 1 H) 10.5 (s, 1 H). 62 Example 30: L-2-(4'-{[4-(3-Methoxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid WO 2005/061477 PCT/US2003/040835 Step 1: Hydrogenation of the product of Example 22, Step 3, L-2-(4'-{[4-(3-methoxy-prop-l-yny])-3-mcthy]-bcnzofuran-2-carbony))-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 24, Step 1 provided L-2-(4'-{ [4-(3-methoxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-'1-sulfonylamino)-3-methyl-butyric acid methyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.8, 6.7 Hz, 6 H) 1.9 (m, 3 H) 2.8 (s, 3 H) 3.1 (m, 2 H) 3.3 (s, 3 H) 3.4 (s, 3 H) 3.4 (m, 7=6.2. 6.2 Hz, 2 H) 3.6 (dd, 7=9.3, 7.1 Hz, 1 H) 7.1 (d, 7=6.6 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (dd, 7=10.0, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H). Step 2: Hydrolysis of L-2-(4'-{[4-(3-methoxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 5 provided L-2-(4'-{[4-(3-methoxy-propyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-melhyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12.4, 6.8 Hz, 6 H) dppml.9 (m, 2 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.1 (m, 2 H) 3.3 (s, 3 H) 3.4 (t, J=6.2 Hz, 2 H) 3.6 (dd, J=9.3, 6.1 Hz, 1 ID 7.1 (d, J=7.6 Hz, 1 H) 7.4 (dd, J=8.3,7.3 Hz, 1 H) 7.5 (m, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (d, J=9.3 Hz, 1 H) 10.5 (s, 1 H). Example 31: L-2- (4'-{[4-(3-Dimethylamino-prop-l-ynyI)-3-n)ethyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid Step 1: To the product of Example 20, Step 1, 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (900 mg, 2.56mmoJ, 1 eq), under nitrogen was added 1-dimcthylamino-2-propyne (425mg, 5.11 mmol, 2 cq), PdCl2(PPh3)2 (90 mg, 0.13 mmol, 0.05 cq), and triethylamine (1.4mL, 10.23 mmol, 4 eq), in 25 mL of toluene. The reaction mixture was heated at reflux for I6h until the reaction-was complete by TLC. After work up and column chromatography (0-10% MeOH/dichloromethane), 4-(3-dimcthyJamino-prop-l-ynyl)-3-methyl- 63 WO 2005/061477 PCT/US2003/040835 benzofuran-2-carboxylic acid ethyl ester was obtained in 65% yield (474 mg). 'H NMR (400 MHz,ADMSO-d6) dppm 1.4 (t, J=7.1 Hz, 3 H) 2.3 (s, 6 H) 2.8 (s, 3 H) 3.6 (s, 2 H) 4.4 (q, J=7.1 Hz, 2 H) 7.4 (dd, J=7.3, 1.0 Hz, 1 H) 7.5 (m, l H). 7.7 (dd, 3=8.2,0.9 Hz, 1 H). Step 2: Hydrolysis 4-(3-dimethylamino-prop-l-ynyl)-3-methyl-bcnzofuran-2-carboxylic acid ethyl ester according to the procedure of Example 20, Step 3, provided 4-(3-dimethylamino-prop-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid in 70% yield. 'H NMR (400 MHz, DMSO-d6) dppm 2.8 (s, 3 H) 2.9 (s, 6 H) 4.4 (s, 2 H) 7.5 (m, 2 H) 7.8 (m, 1 H). Step 3: Coupling of 4-(3-dimcthylamino-prop-l-yny])-3-methyl-benzofuran-2-carboxylic acid with L-2-(4-amino-bipheny)-4-sulfony)amino)-3-methyl-butyric acid methyl ester according to the procedure of Example 21, Step 3, provided L-2-(4'-{[4-(3-dimethylamino-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyI]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 60% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.8, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.9 (s, 3 H) 2.9 (s, 6 H) 3.4 (s, 3 H) 3.6 (dd, J=9.3, 7.1 Hz, 1 H) 4.4 (s. 2 H) 7.6 (m, 2 H) 7.8 (t, J=8.3 Hz, 5 H) 7.9 (m, 2 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 1 H). Step 4: Hydrolysis of L-2-(4 -{f4-(3-dimethylamino-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamJn6)-3-"methyl-butyric acid methyl ester according to the procedure of Example 20, Step 5, provided L-2-(4 -{[4-(3-dimethylamino-prop-J-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, .7=12.4, 6.8 Hz, 6 H) 2.0 (m. 1 H) 2.9 (s, 3 H) 2.9 (s, 6 H) 3.6 (dd, .7=9.3, 6.1 Hz, 1 H) 4.4 (s, 2 H) 7.6 (m, 2 H) 7.8 (m, 7 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.6 Hz, 1 H) 10.7 (s, 1 H) 12.6 (s, 1 H). Example 32: L-2- (4'-{[4-(3-DimethyInmino-propyJ)-3-methyI-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid Step 1; To a solution of the product of Example 31, Step 3, L-2- (4-{[4-(3-dimethylamino prop-Lynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-bjphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (200 mg, 0.33 mmol) in 5mL of dichloromethane, was added 5% Pd/C (66 mg) and the reaction was stirred at room temperature 64 WO 2005/061477 PCT/US2003/040835 under 1 atm of hydrogen for 72h. The reaction mixture was filtered through celite, and the filtrate was concentrated in vacuo to provide the crude product which was purified by prep-HPLC to gjve L-2-(4'-{[4-(3-dimethy]amino-propy])-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 50% yield. 'H NMR (400 MHz, DMSO-d6) 5 ppm 0.8 (dd, J=14.9, 6.8 Hz, 6 H) 1.8 (dd, 2 H) 1.9 (m, 1 H) 2.2 (s, 6 H) 2.4 (m, 2 H) 2.8 (s, 3 H) 3.0 (m, 2 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.1 (d, J=7.3 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (dd, 3=9.9, 8.8 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d. J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.5 (s, 1 H). Step 2: Hydrolysis of L-2-(4'-{[4-(3-dimethylamino-propyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 4, provided L-2-(4 -{[4-(3-dimethylamino-propyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, .7=12.4, 6.8 Hz, 6 H) 2.0 (m, J H) 2.1 (m, 2 H) 2.8 (d, 7=4.5 Hz, 6 H) 2.8 (s, 3 H) 3.1 (m, 2 H) 3.2 (m, 2 H) 3.6 (dd, 7=9.3,6.1 Hz, 1 H) 7.2 (d, 7=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.6 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H) 10.6 (s, 1 H). Example 33: L- 2-{4'-[(4-EthynyI-3-mcthyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-mcthyl-butyric acid Step 1: Coupling of the product of Example 20, Step 1,3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester, with (trimethylsilyl)acetylene according to the procedure of Example 31, Step 1, provided 3-methyl-4-trimethylsilany]cthynyl-benzofuran-2-carboxylic acid ethyl ester in 41% yield after purification using flash chromatography (1-5% ethyl acetate/hexane). Step 2: Hydrolysis 3-methyl-4-trimethylsilanylethynyl-benzofuran-2-carboxylic acid ethyl ester according to the procedure of Example 20, Step 3, provided 4-cthynyl-3-methyl-benzofuran-2-carboxylic acid in 73% yield. Step 3: Coupling of 4-ethynyl-3-methyl-benzofuran-2-carboxyIic acid with L-2-(4-amino-bipbenyl-4-sulfonylarnino)-3-methyl-butyric acid methyl ester according to the procedure 65 WO 2005/061477 PCT/US2003/040835 of Example 21, Step 3, provided L- 2-{4'-[(4-ethynyl-3-methyl-benzofuran-2-Carbonyl)-amino)-biphenyl-4-sulfonyIamino}-3-methyl-butyric acid methyl ester in 96% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.9, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, J=9.3, 7.1 Hz, 1 H) 4.6 (s, 1 H) 7.5 (m, 2 H) 7.8 (m, 5 H) 7.9 (m, 2 H) 8.0 (d, J=9.1 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L- 2-{4-[(4-ethynyl-3-mcthyl-benzofuran-2-carbonyl)-amino]-biphenyJ-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 4, provided L- 2-{4'-[(4-ethynyl-3-methyl-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-mcthyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.3,6.1 Hz, 1 H) 4.6 (s, 1 H) 7.5 (m, 2 H) 7.8 (m, 3 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, J=93 Hz, 1 H)10.6(s, 1 H) 12.6 (s, 1 H). Example 34: L- 2-(4'-{[4-(3,3-Dimethyl-but-l-ynyl)-3-methyl-benzofuran-2-carbonyl)-amino}-biphenyI-4-sulfonylamino)-3-methyl-butyric acid Step 1: Coupling of the product of Example 20, Step 1, 3-methyl-4- trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester, with 3,3-dimethyM-butyne according to the procedure of Example 31, Step 1, provided 4-(3,3-dimethyl-but-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid ethyl ester in 58% yield after purification via flash chromatography eluting with 1-5% ethyl acetate/hexanes. 'H NMR (400 MHz.DMSO-d6) dppm 1.3 (s, 12 H) 2.8 (s, 3 H) 4.4 (q, J=7.2 Hz, 2 H) 7.3 (dd, J=7.5,0.9 Hz, 1 H) 7.4 (dd, J=8.3,7.6 Hz, 1 H) 7.6 (m, 1 H). Step 2: Hydrolysis 4-(3,3-dimcthyl-but-l-ynyl)-3-mcthyl-bcnzofuran-2-carboxy]ic acid ethyl ester according to the procedure of Example 20, Step 3, provided 4-(3,3-dimethyJ-but-l-ynyl)-3-methyl-benzofuran-2-carboxy]jc acid in 80% yield. Step 3: Coupling of 4-(3,3-dimethyl-but-l-ynyl)-3-methyl-benzofuran-2-carboxylic acid with L-2-(4'-amino-bipheny)-4-sulfonylamino)-3-methyl~butyric acid methyl ester according to 66 WO 2005/061477 PCT/US2003/040835 the procedure of Example 21, Step 3, provided L- 2-(4'-{[4-(3,3;.dimethyl-but-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 52% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.8,6.7 Hz, 6 H) 1.4 (s, 9 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.3 (d, J=7.3 Hz, 1 H) 7.5 (m, 1 II) 7.7 (d, J=9.1 Hz, I H) 7.8 (t, J=8.8 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1H) 10.6 (s, 1H). Step4: Hydrolysis of L- 2-(4'-{[4-(3,3-dimethyl-but-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 5, provided L- 2-(4'-{[4-(3,3-dimethyl-but-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphcnyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6. 6.8 Hz, 6 H) 1.4 (s. 9 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.3 (dd, 7=7.5,0.9 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3,1.0 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m. 4 II) 8.0 (d, 7=9.1 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 35: L- 3-Methyl-2- (4'-{[3-methyl-4- (3-methyl-isoxazo1-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid Step 1: To the product of Example 33, Step 1, 3-methyl-4-trimethylsilanylethyny]-bcnzofuran-2-carboxylic acid ethyl ester (1.5g, 4.99 mmol, 1 eq), in THF (10 mL) under argon, was added tetrabutylammonium fluoride (1.0 M in THF, 6 mL, 5.99 mmol, 1.2 eq.) and the reaction was stirred at ambient temperature for 45 minutes. After work-up and flash column chromatography, 4-ethynyl-3-methyl-benzofuran-2-carboxylic acid ethyl ester was obtained in 35% yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.4 (t, J=7.1 Hz, 3 H) 2.8 (s, 3 H) 4.4 (m, J=7.1, 7.1.7.1 Hz, 2 H) 4.6 (s, 1 H) 7.5 (m, 2 H) 7.7 (dd, J=7.7, 1.4 Hz, 1 H). Step 2: To a solution of 4-ethynyl-3-mcthyl-benzofuran-2-carboxylic acid ethyl ester (228 mg, 0.99 mmol, 1 eq.) in acetonitrile (5 mL) under argon, was added di-tert-butyl dicarbonate (327 mg, 1.5 mmol, 1.5 eq.), and 4-(dimethylamino)pyridine (12 mg, 0.1 mmol, 0.1 eq.). Nitroethane (79 uL, 1.1 mmol, and 1.1 eq.) in acetonitrile (5 mL) was added drop-wise to 67 WO 2005/061477 PCT/US2003/040835 the reaction mixture, and the reaction was stirred at room temperature for 72 hours. After work-up and a flash column chromatography, 3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofuran-2-carboxylic acid ethy] ester was obtained in 25% yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.4 (t, J=7.1 Hz, 3 H) 2.3 (s, 3 H) 2.4 (s, 3 H) 4.4 (q, J=7.1 Hz, 2 H) 6.8 (s, 1 H) 7.5 (dd, J=7.5, 0.9 Hz, 1 H) 7.6 (m, 1 H) 7.9 (dd, J=8.5,0.9 Hz, 1H). Step 3: Hydrolysis of 3-methyl-4- (3-methyI-isoxazol-5-yl)-benzofuran-2-carboxylic acid ethyl ester according to the procedure of Example 20, Step 3, provided 3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofurarj-2-carboxylic acid in quantitative yield. 1H NMR (400 MHz, DMSO-d6). dppm 2.3 (s, 3 H) 2.4 (s, 3 H) 6.8 (s, 1 H) 7.5 (d, J=8.3 Hz, 1 H) 7.6 (m, 1 H) 7.9 (d, J=9.1 Hz; lH). Step 4: Coupling of 3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofuran-2-carboxylic acid with L-2- (4-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 21, Step 3, provided L- 3-methyl-2- (4'-{[3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid methyl ester in 52% yield. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.4 (s, 3 H) 2.5 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 6.8 (s, 1 H) 7.5 (d, J=7.6 Hz, 1 H) 7.7 (m, 1 H) 7.8 (dd, J=8.5,6.4 Hz, 4 H) 7.9 (m, 3 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.1 Hz, 1 H) 10.7 (s, 1 H). Step 5: Hydrolysis of L-3-methyl-2- (4'-{[3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-su]fonylamino)-butyric acid methyl ester according to the procedure of Example 20, Step 5, provided L-3-methyl-2- (4-{[3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofuran-2-carbonyI3-amino}-biphenyl-4:sulfonylamino)-butyric acid in 38% yield after purification by preparative HPLC. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12.4, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.4 (s, 3 H) 2.5 (s, 3 H) 3.6 (dd, J=9.3, 5.8 Hz, 1 H) 6.8 (s, 1 H) 7.5 (dd, J=7.6,1.0 Hz, 1 H) 7.7 (dd, J=8.3,7.3 Hz, 1 H) 7.8 (rn, 4 H) 7.9 (m, 3 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (d, J=9.3 Hz, 1 H) 10.7 (s, 1 H). 68 WO 2005/061477 PCT/US2003/040835 Example 36: L-2- {4'-[(4-Methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid Step 1: To the product of Example 20, Step 1,3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (800 mg, 2.27mmol), in 25 mL of toluene were added methane sulfonamide (650 mg, 6.82 mmol, 3 eq), Pd2 (dba)3 (208 mg, 0.23 mmol, 0.1 eq), biphenyl-2-yl-di-tert-butyl-phosphane (68 mg, 0.23 mmol, 0.1 eq), and tribasic potassium phosphate (965 mg, 4.55 mmol, 2 eq) under nitrogen and the resulting mixture was heated at reflux for 3h. After work up and trituration, 4-methanesulfonylarnino-3-rnethyl-benzofuran-2-carboxylic acid ethyl ester was obtained in 67% yield (450 mg). !H NMR (400 MHz, DMSO-do) 5 ppm 1.3 (t, J=7.1 Hz, 3 H) 2.7 (s, 3 H) 3.1 (s, 3 H)4.4 (q, J=7.] Hz, 2 H) 7.3 (dd, J=7.7, 0.9 Hz, 1 H) 7.5 (dd, J=8.3,7.6 Hz, 1 H) 7.6 (m, 1 H) 9.5 (s, 1 H). Step 2: According to the procedure of Example 20, Step 3,4-mcthancsulfonylamino-3-methyl-bcn7.ofuran-2-carboxylic acid ethyl ester was hydrolyzcd to provide 4-methanesuJfonylamino-3-methyJ-benzofuran-2-carboxylic add in 92% yield. 1H NMR (400 MHz, DUSO-d6) dppm 2.7 (s, 3 H) 3.1 (s, 3 H) 7.2 (dd, J=7.8,0.8 Hz, 1 H) 7.5 (dd, J=8.3,7.6 Hz, 1 H) 7.6 (m, 1 H) 9.5 (s, 1 H). Step 3: According to the procedure of example 21, Step 3, 4-methanesulfonylamino-3-methyl-benzofuran-2-carboxylic acid was coupled with L-2-(4 -amino-biphenyI-4-sulfonylamino)-3-methyl-butyric acid methyl ester to provide L-2-{4*-l(4-methanesulfonyIamino-3-methyl-benzofuran-2-carbonyl)-arnino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester in 23% yield. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.8,6.7 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3, 7.1 Hz, 1 H) 7.3 (d, J=7.8 Hz, 1 H) 7.5 (m. 1 H) 7.6 (d, J=9.1 Hz, 1 H) 7.8 (t, J=8.6 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 9.5 (s, 1 H) 10.6 (s, 1 H). Step 4: According to the procedure of example 20, Step 5, L-2-{4-{(4- methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was hydrolyzed to L-2-{4'-[(4-methanesulfonylamino-3- 69 WO 2005/061477 PCT/US2003/040835 methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid in qualitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.S (s, 3 H) 3.1 (s, 3 H) 3.6 (dd, 7=9.3,5.8 Hz, 1 H) 7.3 (dd, 7=7.7,0.9 Hz, 1H) 7.5 (m, 1 H) 7.6 (m, 1 H) 7.8 (d. 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d. 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 9.5 (s, lH)10.6(s, 1H)12.6(S,1H). Example 37: L-2-(4'-{[4-(MethanesulfonyJ-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylam)-3-methyl-butyric acid Step 1: To a mixture of the product of Example 36, Step 1,4-methanesulfonylamino-3-methyl benzofuran-2-carboxylic acid ethyl ester (438 mg, 1.47 mmol, 1 eq) and K2CO3 (430 mg, 3.11 mmol, 2.1 eq) in 4 mL of DMF under nitrogen was added 0.18 mL of iodomethane (2.89 mmol, 2 eq). The reaction mixture was scaled and heated to S0cC for 18h. After cooling to room temperature and work up, 4-(methanesulfonyl-mcthyl-amino)-3-methyl-benzofuran-2-carboxylic acid ethyl ester was obtained in pure form without further purification (100% yield). 'H NMR (400 MHz, CDCl3) dppm 1.4 (t, 7=7.1 Hz, 3 H) 2.8 (s, 3 H) 3.0 (s, 3 H) 3.4 (s, 3 H) 4.5 (q, 7=7.1 Hz, 2 H) 7.2 (dd, 7=7.6, 0.8 Hz, 1 H) 7.4 (m, 1 H) 7.6 (m, 1 H). Step 2: According to the procedure of Example 20, Step 3, hydrolysis of 4-(methancsulfonyl-mcthyl-amino)-3-methyl-bcnzofuran-2-carboxylic acid ethyl ester provided 4-(methanesulfonyl-methyl-amino)-3-methyl-benzofuran-2-carboxylic acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 2.7 (s, 3 H) 3.1 (s, 3 H) 3.3 (s, 3 H) 7.5 (m, 2 H) 7.7 (dd, 7=8.2,1.1 Hz, 1 H). Step 3: According to the procedure of Example 21, Step 3, coupling of 4-(methanesulfonyl-mcthyl-amino)-3-methyl-bcnzofuran-2-carboxylic acid with L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-rnethyl-butyric.acid methyl ester provided L-2-(4'-{[4-(mcthancsulfonyl-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 100% yield. 1HNMR (400 MHz, DMSO-d6) 8 ppm 0.8 (dd, 7=14.9, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.7 (d, 7=0.5 Hz, 3 H) 2.8 (s, 3 H) 2.9 (s, 3 H) 3.1 (s, 3 H) 3.6 (dd, 7=9.3, 7.1 Hz, 1 H) 7.6 (m, 2 H) 7.7 (m, 1 H) 7.8 (dd, 7=8.7,7.2 Hz, 4 H) 7.9 (m, 2 H) 8.0 (m73 H) 8.3 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). 70 WO 2005/061477 PCT/US2003/040835 Step 4: According to the procedure of Example 20, Step 5, hydrolysis of L-2-(4' [4-(methanesulfonyl-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acjd methyl ester provided L-2-(4'-{ [4-(methanesulfonyl-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-rnethyl-butyric acid in 100% yield. 1H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.1 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, 7=9.5,6.2 Hz, 1 H) 7.6 (m, 2 H) 7.7 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.6 Hz, 1 H) 10.6 (s, 1 H) Example 38: L-3-Hydroxy-2-(4-{5-[(4-methanesulfonyIamino-3-rnethyI-benzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonylamino)-butyric acid Step 1: To a mixture of L-2-amino-3-tert-butoxy-butyric acid methyl ester hydrochloric salt (4.87 g, 21.6 mmol, 1 eq) and 4-bromo-benzenesulfonyl chloride (5.51 g, 21.6 mmol, 1 eq) in 50 mL of dichloromethanc at 0 °C under nitrogen was added N,N-diisopropylethyfaminc (7.5 mL, 43.1 mmol, 2 eq) dropwise. The ice bath was removed and the reaction was allowed to react at room temperature for lh. After work up and trituration with hexanes, L-2-(4-bromo-benzenesuIfonylamino)-3-tert-butoxy-butyric acid methyl ester was obtained in 88% yield (7.77 g). 'H NMR (400 MHz, DMSO-d«) 6 ppm 1.0 (s, 9 H) 1.0 (s, 3 H) 3.4 (s, 3 H) 3.8 (dd, 7=9.7, 3.4 Hz, 1 H) 4.0 (dd, 7=6.2. 3.7 Hz, 1 H) 7.7 (d, 7=8.8 Hz, 2 H) 7.8 (m, 2 H) 8.2 (d, 7=9.6 Hz, 1 H) Step 2: To a mixture of L-2-(4-bromo-benzenesulfonylamino)-3-tert-butoxy-butyric acid methyl ester (811 mg, 2 mmol, 1 eq), bis(pinacolato)diboron (1.55 g, 6.1 mmol, 2.05 eq), and KOAc (622 mg, 6.34 mmol, 3.17 eq) under nitrogen in 45 mL of DMSO was added PdCl2(dppf)CH2Cl2 (110 mg, 0.13 mmol, 0.065 eq). The reaction mixture was heated to 80°C for 18h. After work up and column chromatography, L-3-tert-butoxy-2-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yJ)-ben7.enesu!fonylamino]-butyric acid methyl ester was obtained in 77% yield (696 mg). 'H NMR (400 MHz, DMSO-d6) dppm 1.0 (s, 9 H) 1.3 (s, 12 H) 3.4 (s, 3 H) 3.8 (dd, 7=9.7,3.7 Hz, I H) 3.9 (dd, 7=6.2, 3.7 Hz, 1 H) 7.8 (m, 4 H) 8.1 (d, 7=9.9 Hz, 1 H). Step3: A mixture of L-3-tert-butoxy-2-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yI)-benzenesulfonylamino]-butyric acid methyl ester (696 mg, 1.53 mmol, 1 eq), 2-bromo-5- 71 WO 2005/061-477 PCT/US2003/040835 nitropyridine (932 mg, 4.59 mmol, 3 eq), Pd(PPh3)4 (88 mg, 0.076 mmo], 0.05 eq), and K2CO3 (423 fing, 3.06 mmol, 2 eq) in 10 mL of 1,2-dimethoxyethane and 5 mL of water was heated to 90°C under nitrogen. After 3h, the reaction was complete and subjected to work up and column chromatography (20% ethyl acetate/hexane) to give L-3-tert-butoxy-2-[4-(5-nitro-pyridin-2-yl)-benzenesulfonylamino]-butyric acid methyl ester in 81% yield (557 mg). 'H NMR (400 MHz, DMSO-d6) dppm 1.0 (s, 12 H) 3.4 (s, 3 H) 3.9 (dd, 7=9.9,3.5 Hz, 1 H) 4.0 (m, 1 H) 8.0 (d, 7=8.6 Hz, 2 H) 8.2 (d, 7=9.9 Hz, 1 H) 8.4 (m, 3 H) 8.7 (dd, 7=8!8, 2.8 Hz, 1 II) 9.5 (d, 7=2.5 Hz, 1H). Step 4: To 550 mg of L-3-tert-butoxy-2-[4-(5-nitro-pyridin-2-yl)-benzenesulfonylamino]-butyric acid methyl ester in 10 mL of THF under a nitrogen atmosphere was added 125 mg of 5% PcVC. A hydrogen balloon was introduced to the reaction mixture. After 24h the mixture was worked up to give L-2-[4-(5-amino-pyridin-2-yl)-benzer)esuJfonylamino]-3-tert-butoxy-butyric acid methyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.0 (s, 9 H) 1.0 (s, 3 H) 3.4 (s, 3 H) 3.8 (dd, 7=9.7,3.7 Hz, 1 H) 3.9 (dd, 7=6.2, 3.7 Hz, 1 H) 5.7 (s, 2 H) 7.8 (t, 7=9.0 Hz, 3 H) 8.0 (d, 7=9.6 Hz, 1 H) 8.1 (m,3H). Step 5: Amide coupling of the product of Example 36, Step 2\ 4-methanesulfonylamino-3-mcthyl-benzofuran-2-carboxylic acid, with L-2-[4-(5-amino-pyridin-2-yl)-benzcnesulfonyIamino]-3-tert-butoxy-butyric acid methyl ester according to the procedure of Example 21, Step 3, provided L-3-tert-butoxy-2-(4-{5-[(4-methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-yl]-benzenesulfonylamino)-butyric acid methyl ester in 42% yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.0 (s, 9 H) 1.0 (s, 3 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.4 (s, 3 H) 3.9 (dd, 7=9.7, 3.7 Hz, 1 H) 4.0 (dd, 7=6.2, 3.7 Hz, 1 H) 7.3 (dd, 7=7.8, 0.8 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, 7=8.3. 0.8 Hz, 1 H) 7.9 (d, 7=8.6 Hz, 2 H) 8.1 (m, 2 H) 8.3 (d, 7=8.8 Hz, 2 H) 8.4 (dd, 7=8.7, 2.7 Hz, 1 H) 9.1 (d, 7=3.0 Hz, 1 H) 9.6 (s, 1 H) 10.8 (s, 1 H). Step 6: To l00 mg of L-3-tert-butoxy-2-(4-{5-[(4-methanesulfonylamino-3-methyl-benzofuran-2-caxbonyl)-amino]-pyridin-2-yl}-benzcncsulfonylamino)-butyric acid methyl ester in 8 mL of dichloroethane was added 0.5 mL of trifluoroacetic acid. After 1.5h the solvent was removed in vacuo. To the crude residue was added THF (8 mL), MeOH (3 mL), and 1 N LiOH (4.5 mL). The reaction mixture was stirred at room temperature until the starting material was consumed (-1-2 days). The reaction mixture was then acidified with IN hydrochloric acid to pH 4. The resulting mixture was extracted with ethyl acetate. The combined organic layers were concentrated in vacuo, and the crude residue was recrystallized to give 3-hydroxy-2-(4-{5-[(4-methanesu]fonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-yl)-benzenesulfonylamino)-butyric acid in 72% yield. ]H NMR (400 MHz, DMSO-d6) dppm 1.0 (s, 9 H) 1.0 (s, 3 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.4 (s, 3 H) 3.9 (dd, 7=9.7, 3.7 Hz, 1 H) 4.0 (dd, 7=6.2, WO 2005/061477 PCT/US2003/040835 3.7 Hz, 1 H) 7.3 (dd, 7=7.8, 0.8 Hz, 1 H) 7.5 (m, 1 H) 7.7 (dd, .7=8.3, 0.8 Hz, 1 H) 7.9 (d, 7=8.6 Hz, 2 H) 8.1 (m, 2 H) 8.3 (d, 7=8,8 Hz, 2 H) 8.4 (dd, 7=8.7,2.7 Hz, 1 H) 9.1 (d, 7=3.0 Hz, 1 H) 9.6 (s, 1 H) 10.8 (s, 1 H) Example 39: L-2-(4-{5-[(4-MethanesuironyJamino-3-methyI-benzofuran-2-carbonyl)-amino]-pyridin-2-yl)-benzenesulfonylamino)-3-mcthyI-butyric acid Step 1: L-3-Methyl-2-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-benzenesulfonylamino]-butyric acid methyl ester was prepared according to the procedure of Example 38, Step 2, from L-2-(4-bromo-benzcnesulfonylamino)-3-mcthyl-butyric acid methyl ester and bis(pinaco]ato)diboron in 90% yield. ]H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=9.0, 6.7 Hz, 6 H) 1.3 (s, 12 H) 1.9 (m, 1 II) 3.4 and (s, 3 H) 3.5 (dd, 7=9.2, 6.9 Hz, 1 II) 7.8 (d, 7=8.6 Hz, 2 H) 7.8 (m, 2 H) 8.3 (d, 7=9.3 Hz, 1 H). Step 2: L-3-Methy]-2-[4-(5-nitro-pyridin-2-y])-benzenesulfonylamino]-butyric acid methyl ester was prepared according to the procedure of Example 36, Step 3, from L-3-mcthy]-2-[4-(4,4,5,5-tetramethyl-[ 1,3,2]dioxaborolan-2-yl)-benzenesulfonylamino)-butyric acid methyl ester and 2-bromo-5-nitropyridine in 78% yield. 'H NMR (400 MHz, CDC13) dppm 0.9 (dd, 7=36.1, 6.8 Hz, 6 H) 2.1 (m, 1 H) 3.5 (s, 3 H) 3.8 (dd, 7=10.0,4.9 Hz, 1 H) 5.2 (d, 7=9.9 Hz, 1 H) 8.0 (dd, .7=8.7, 1.9 Hz, 3 H) 8.2 (d, 7=8.8 Hz, 2 H) 8.6 (dd, 7=8.7, 2.7 Hz, 1 H) 9.5 (d, 7=3.3 Hz, 1 H). Step 3: Hydrogenation of L-3-mcthyl-2-[4-(5-nitro-pyridin-2-yl)-benzenesuIfonylamino]-butyric acid methy] ester according to the procedure of Example 36, Step 4, provided L-2-[4-(5-amino-pyridin-2-yl)-benzenesulfonyIamino]-3-methyl-butyric acid methyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.9, 6.8 Hz, 6 H) 1.9 (m, 1 H) 3.3 (s, 3 H) 3.5 (dd, 7=9.3,7.1 Hz, 1 H) 5.7 (s, 2 H) 7.0 (dd, 7=8.6, 2.8 Hz, 1 H) 7.7 (m, 3 H) 8.1 (m, 3 H) 8.2 (d, 7=9.3 Hz, 1 H). Step 4: Amide coupling of 4-methanesulfonylamino-3-methyI-benzofuran-2-carboxylic acid with L-2-[4-(5-amino-pyridin-2-yl)-benzenesulfonylamino]-3-methyl-butyric acid methyl ester according to the procedure of Example 21, Step 3, provided L-2-(4-{5-[(4-Methanesulfony]amino-3-methy]-benzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonylamino)-3-methyl-butyric acid methyl ester in 22% yield. 'H NMR (400 MHz, 73 WO 2005/061477 PCT/US2003/040835 DMSO-d6) dppm 0.8 (dd, J=\2.5, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, 7=9.3, 7.1 Hz, 1 H) 7.3 (d, 7=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.7 (d, 7=7.6 Hz, 1 H) 7.8 (d, 7=8.6 Hz, 2 H) 8.1 (d, 7=8.8 Hz, 1 H) 8.3 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 8.4 (dd, 7=8.8, 2.5 Hz, 1 H) 9.1 (dd. 7=2.0 Hz, 1 H) 9.6 (s, 1 II) 10.8 (s, 1 H). Step 5: Hydrolysis of L-2-(4-{5-[(4-methancsulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-yl)-benzenesuIfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 5, provided L-2-(4-{5-[(4-methanesulfonylamino-3-methyl-bcnzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonylamino)-3-mcthyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=13.4, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.6 (dd, 7=9.3, 5.8 Hz, 1 H) 7.3 (d, 7=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.7 (d, 7=7.3 Hz, 1 II) 7.9 (d, 7=8.8 Hz. 2H) 8.1 (dd, 7=9.0, 3.2 Hz, 2 H) 8.3 (d, 7=8.6 Hz, 2 H) 8.4 (dd, 7=8.7, 2.4 Hz, 1 H) 9.1 (d, 7=2.5 Hz, 1 H) 9.6 (s, 1 H) 10.8 (s, 1 H). Example 40: L-2-(4-{5-[(4-Cyano-3-melhyl-benzofuran-2-carbonyl)-amino]-pyridin-2-y)}-benzenesulfonylamino)-3-methyl-butyric acid Step 1: Amide coupling of the product of Example 20, Step 3, 4-cyano-3-mcthyl-benzofuran-2-carboxylic acid, with L-2-[4-(5-amino-pyridin-2-yl)-benzenesulfonylamino]-3-methyl-butyric acid methyl ester, the product of Example 39, Step 3, was earned according to the procedure of Example 21, Step 3, to give L-2-(4-{5-[(4-cyano-3-methyl-benzofuran-2-carbony])-amino]-pyrjdin-2-yl]-benzenesulfonylamino)-3-mcthyl-butyric acid methyl ester in 57% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.4, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, 7=9.3,7.1 Hz, 1 H) 7.7 (dd, 7=8.3,7.6 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (dd, 7=7.5, 0.9 Hz, 1 H) 8.1 (m, 2 H) 8.3 (d, 7=8.8 Hz. 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 8.4 (dd, 7=8.8, 2.5 Hz, 1 H) 9.1 (d, 7=1.8 Hz, 1 H) 11.0. (s, 1 H). Step 2: Hydrolysis of L-2-(4-{5-[(4-cyano-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-y))-benzenesulfonylamino)-3-methyl-butyric acid methyl ester according to the procedure of Example 20, Step 5, provided L-2-(4-{5-[(4-cyano-3-methyl-benzofuran-2-carbonyJ)-amino]-pyridin-2-yl}-benzenesulfonylamino)-3-methyl-butyric acid in quantitative yiel'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=13.1, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 WO 2005/061477 PCT/US2003/040835 H) 3.6 (dd, J=9.3, 6.3 Hz 1 H) 7.7 (dd, 7=8.3, 7.6 Hz, 1 H) 7.9 (d, J=8.6 Hz, 2 H) 7.9 (dd, J=7.6, 0.8.Hz, 1 H) 8.1 (m, 3 H) 8.3 (d, 7=8.8 Hz, 2 H) 8.4 (dd, 7=8.8, 2.5 Hz, 1 H) 9.1 (dd, 7=2.5,0.8 Hz, lH)11.0(s, 1H). Example 41: D-2-{4'-[(4-Melhanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylarnino}-3-rnethyl-butyric acid Step 1: Suzuki coupling of D-2-(4-bromo-benzenesulfonylamino)-3-methyl-butyric acid methyl ester with 4-(4,4,5,5-tetramethy]-[1,3.2]dioxaborolan-2-yl)-phenylamine was carried out according to Example 38, Step 3 to give D-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 88% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=15.2, 6.8 Hz, 6 H) 1.9 (m, 1 H) 3.3 (s, 3 H) 3.5 (dd, 7=9.3,7.1 Hz, 1 H) 5.4 (s, 2 H) 6.7 (d, 7=8.6 Hz, 2 H) 7.5 (d, 7=8.6 Hz, 2 H) 7.7 (d, 7=4.5 Hz, 4 H) 8.2 (d, 7=9.3 Hz, 1 H). Step 2: Amide coupling of D-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester with 4-methanesulfonylamino-3-methyl-benzofuran-2-carboxylic acid was carried out according to Example 21, Step 3 to give D-2-(4'-[(4-methanesu]fonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester 58% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.8, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.3 (s, 3H) 3.6 (dd, 7=9.3,7.3 Hz, 1 H) 7.3 (d, 7=7.8 Hz, 1 H) 7.5 (m, 1 H) 7.6 (d, 7=8.8 Hz, 1 H) 7.8 (t, 7=8.3 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 9.5 (s, 1 H) 10.6 (s, 1 H) Step 3: Hydrolysis of D-2-{4'-[(4-methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was carried out according to Example 20, Step 5 in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.9,6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.6 (dd, 7=9.5,5.9 Hz, 1 H) 7.3 (d, 7=7.8 Hz, 1 H) 7.5 (m, 1 H) 7.6 (m, 1 H) 7.8 (d, 7=8.6 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 9.5 (s, 1 H) 10.6 (s, 1 H) 75 WO 2005/061477 PCT/US2003/040835 Example 42: L-2-({4'-[(4-Cyano-3-mcthyl-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfenyl)-methyl-amino)-3-methyl-butyric acid Step 1: L-3-MethyI-2-(4'-nitro-biphenyl-4-su]fonylamino)-butyric acid methyl ester was prepared from 4-nitro-biphenyl-4-sulfony) chloride and 2-amino-3 methyl-butyric acid methyl ester hydrochloride acid salt according to Example 38, Step 1. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=13.4, 6.8 Hz, 6 H) 1.9 (m, 1 H) 3.3 (s, 3 H) 3.6 (dd, 7=9.3, 7.1 Hz, 1 H) 7.9 (d, 7=8.6 Hz, 2 H) 8.0 (dd, 7=15.8, 9.0 Hz, 4 H) 8.3 (d, 7=8.8 Hz, 2 H) 8.4 (d, 7=9.3 Hz, 1 H). Step 2: To a mixture of L-3-methyl-2-(4'-nitro-bipheny-4-sulfonylamino)-butyric acid methyl ester (1.05 g, 2.7 mmol, 1 eq) and K2CO3 (1.1 g, 8 mmol, 3 eq) in 8 mL of DMF was added iodomethane (0.25 mL, 4.0 mmol, 1.5 eq) under nitrogen. After 12 h, the mixture was worked-up to give L-3-methyl-2-[methyl-(4'-nitro-biphenyl-4-sulfonyl)-amino]-butyric acid methyl ester in 94% yield (1.023 g). 'H NMR (400 MHz, DMSO-d6) dppm 0.9 (dd. 7=8.8, 6.6 Hz, 6 H) 2.1 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 4.0 (d, 7=10.6 Hz, 1 H) 7.9 (d, 7=8.8 Hz, 2 H) 8.0 (m, 4 H) 8.4 (d, 7=9.1 Hz, 2 H). Step 3: Hydrogenation of L-3-methyl-2-[methyl-(4 -nitro-biphenyl-4-sulfonyl)-amino]-butyric acid methyl ester was carried out according to Example 38, Step 4 to give L-2-[(4'-amino-biphenyl-4-sulfonyJ)-methyl-amino]-3-methyl-butyric acid methyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.9 (dd, 7=10.4, 6.6 Hz, 6 H) 2.0 (dd, 1 H) 2.8 (s, 3 H) 3.4 (s, 3 H) 4.0 (d, 7=7.1 Hz, 1 H) 5.4 (s, 2 H) 6.7 (d, 7=8.6 Hz, 2 H) 7.5 (d, 7=8.6 Hz, 2 H) 7.7 (d, 7=8.8 Hz, 2 H) 7.8 (m, 2 H). Step 4: Amide coupling of L-2-[(4'-amino-biphenyl-4-sulfonyl)-methyl-amino]-3-methyl-butyric acid methyl ester with 4-cyano-3-methyl-benzofuran-2-carboxylic acid (Example 20, Step 3) in 75% yield. ]H NMR (400 MHz, DMSO-d6) dppm 0.9 (dd, 7=10.6, 6.6 Hz, 6 H) 2.1 (dd, 1 H) 2.8 (s, 3 H) 2.8 (s, 3 H) 3.4 (s, 3 H) 4.0 (d, 7=10.6 Hz, 1 H) 7.7 (dd, 7=8.6, 7.6 Hz, 1 H) 7.8 (dd, 7=8.7, 3.2 Hz, 4 H) 7.9 (m, 3 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (dd, 7=8.5,0.9 Hz, 1 H) 10.8 (s, 1 H). Step 5: Hydrolysis of L-2-({4'-[(4-cyano-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyM-sulfonyl]-methyl-amino)-3-methyl-butyric acid methyl ester was carried out according to Example 20, Step 5 to give-2-({4'-[(4-cyano-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl}-methyl-amino)-3-methyl-butyric acid in quantitative yield. !H 76 WO 2005/061477 PCT/US2003/040835 NMR (400 MHz, DMSO-d6) dppm 0.9 (dd, J=21.3, 6.7 Hz, 6 H) 2.0 (m, 1 H) 2.8 (d, J=I0.1 Hz, 6 H) 4.0 (d, J=10.6 Hz, 1 H) 7.7 (dd, J=8.3, 7.6 Hz, 1 H) 7.8 (t, J=8.8 Hz, 4 H) 7.9 (m, 3 H) S.O (d, J=8.8 Hz, 2 H) 8.1 (dd, J=8.5,0.9 Hz, 1 H) 10.8 (s, 1 H). Examples 43A and B (L-3-Methyl-2-{4'-[(3-methyl-4-methylcarbamoyl-benzofuran-2-carbonyl)-amino]-bipheny)-4-sulfonylamino}-butyric acid triethylamine salt and 2-{4'-[(4-DimethyIcarbamoyl-3-mcthyI-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyJamino}-3-methyl-butyric acid triethylamine salt Step 1: To 213 mg of 4-cyano-3-methyl-benzofuran-2-carboxylic acid ethyl ester (Example 20, Step 2) in 6 mL of cthanol and 6 mL of DMSO was added 3 mL of Na2CO3 (3M), followed by 3 mL of H2O2 (30% in water). After 24h of reaction, the mixture was worked up to give 4-carbamoy]-3-methyl-benzofuran-2-carboxylic acid ethyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.4 (t, 7=7.1 Hz, 3 H) 2.6 (s, 3 H) 4.4 (q, 7=7.1 Hz, 2 H) 7.4 (dd, 7=7.3, 1.0 Hz, 1 H) 7.5 (dd, 7=8.3, 7.3 Hz, 1 H) 7.7 (s, 1 H) 7.8 (m, 1 H) 8.0 (s, 1 II). Step 2: To 200 mg of 4-carbamoy)-3-methyl-bcnzofuran-2-carboxylic acid ethyl ester (0.81 mmol, 1 cq.) in 5 mLof DMF was added 50 mg of NaH (60% in mineral oil, 1.25 mmol, 1.5 eq) under nitrogen. After 30 min of reaction, iodomethane (0.053 mL, 0.85 mmol, 1 eq) was added to the reaction. The mixture was then heated to 50°C for 12h. After work up and column chromatography, a mixture of 3-methyl-4-methyJcarbamoyl-benzofuran-2-carboxylic acid ethyl ester and 4-dimethylcarbamoyl-3-methyl-benzofuran-2-carboxylic acid ethyl ester was obtained (76 mg). 'H NMR (400 MHz, DMSO-d6) dppm 1.3 (t, 7=7.1 Hz, 3 H) 2.8 (d, 7=4.5 Hz, 6 H) 4.4 (q, 7=7.2 Hz, 2 H) 7.3 (dd, 7=7.3, 1.0 Hz, 1 H) 7.5 (dd, 7=8.3,7.3 Hz, 1 H) 7.8 (dd, 7=8.5, 0.9 Hz, IH). Step 3: Hydrolysis of the mixture of 3-methyl-4-methylcarbamoyl-benzofuran-2-carboxylic acid ethyl ester and 4-dimethy]carbamoy]-3-methy]-benzofuran-2-carboxy]ic acid ethyl ester was carried out according to Example 20, Step 3. The mixture of 3-methy]-4-methylcarbamoyl-benzofuran-2-carboxyJic acid and 4-dimethyJcarbamoyl-3-methy]-benzofuran-2-carboxylic acid obtained was used for the next reaction without purification. 'H NMR (400 77 WO 2005/061477 PCT/US2003/040835 MHz, DMSO-d6) dppm 2.8 (d, 7=4.8 Hz, 6 H) 7.3 (d, 7=7.3, 0.8 Hz, 1 H) 7.5 (dd, 7=8.5, 7.5 Hz, 1 H) 2.7 (dd, 7=8.5, 0.9 Hz, 1 H). Step 4: Amide coupling using material from Step 3 and L-2-(4'-amino-biphenyl~4-sulfonylamino)-3-methyl-butyric acid methyl ester was carried out according to Example: 21, Step 3. After column chromatogTaphy, a mixture of two products was obtained. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.6 (s, 3 H) 2.8 (d, 7=4.5 Hz, 3 H) 3.4 (s, 3 H) 3.6 (m, 1 H) 7.4 (dd, 7=7.3, 1.0 Hz, 1 H) 7.5 (dd, 7=8.3,7.6 Hz, 1 H) 7.8 (m, 5 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 1 H) 8.3 (d, 7=9.3 Hz, 1 H) 8:5 (d, 7=4.5 Hz, 1 H) ]0.6 (s, 1 H). Step 5: Hydrolysis of the above mixture was carried out according to the procedure of Example 20, Step 5. Final purification using preparative HPLC (triethylamine as additive to improve compound solubility) provided 40 mg of (L-3-methyl-2-{4'-[(3-methyl-4-mcthyIcarbamoyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid triethylamine salt (43A) and 12 mg of 2-{4'-[(4-dimethylcarbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino]-3-methyl-butyric acid triethylamine salt (43B). 43A 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=33.9, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.6 (s, 3 H) 2.8 (d, J=4.8 Hz, 3 H) 7.4 (d, J=7.3 Hz, 1 H) 7.5 (m, 1 H) 7.8 (m, 7 H) 8.0 (d, J=8.8 Hz, 2 H) 8.5 (d, J=4.5 Hz, 1 H) 10.6 (s, 1 H). 43B 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=28.3, 6.8 Hz, 6 H) 2.0 (dd, J=l 1.9, 7.1 Hz, 1 H) 2.5 (s, 3 H) 2.8 (s, 3 H) 3.1 (s, 3 II) 7.2 (d, J=7.1 Hz, 1 H) 7.6 (m, 1 H) 7.8 (m, 7 H) 8.0 (d, J=8.8 Hz, 2 H) 10.6 (s, 1 H). Example 44: L-2-{4'-[(4,6-Dimethoxy-3,7-dimethyI-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfony)amino}-3-methyI-butyric acid Step 1: Amide coupling of 4,6-dimethoxy-3,7-dimethyl-benzofuran-2-carboxylic acid with L-2-(4'-amino-biphenyl-4-sulfonylarnino)-3-rnethyl-butyric acid methyl ester was carried out according to Example 21, Step 3, to provide 2-{4-[(4,6-dimethoxy-3,7-dimethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester in 74% yield. JH NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.3,6.7 Hz, 6 H) 1.9 (dd, 7=13.8, 6.9 Hz, 1 H) 2.3 (s, 3 H) 2.7 (s, 3 H) 3.4 (s, 3 H) 3.6 (m, 1 H) 3.9 (d, 7=8.1 Hz, 6 H) 6.6 (s, 1 H) 7.8 (m,4 H) 7.9 (m, 2H) 7.9 (d, 7=9.1 Hz, 2 H) 8.3 (d, 7=9.1 Hz, 1 H) 10.1 (s, 1 H). 78 WO 2005/061477 PCT/US2003/040835 .Step 2:-Hydrolysis of 2-{4'-[(4,6-dimethoxy-3,7-dimethyl-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]arnino)-3-methy]-butyric acid methyl ester was carried out according to Example 20, Step 5 to provide.2-{4'-[(4,6-diinethoxy-3,7-dimcthy]-benzofuran-2-carbony])-amino]-bipheny]-4-sulfony]amino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMS0-d6) dppm 0.8 (dd, J=14.1,6.8 Hz, 6 H) 2.0 (dd, J=13.3,6.4 Hz, 1 H) 2.3 (s, 3 H) 2.7 (s. 3 H) 3.4 (s, 1 H) 3.9 (m, J=8.1 Hz, 6 H) 6.6 (s, 1 H) 7.8 (m, J=8.8 Hz, 2 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 2 H) 7.9 (d, J=8.8 Hz. 2 H) 10.1 (s, 1 H). Example 45: 2-{4'-[(5-Bromo-3-methyl-benzofuran-2-carbonyI)-amino]-biphenyl-4-suIfonylamino}-3-methyI-butyric acid Step 1: To a mixture of l-(5-bromo-2-hydroxy-phenyl)-ethanone (2.1 g, 9.8 mmol, 1 eq) and K2CO3(2.4 g, 17.4 mmol, 1.8 eq)in 15 mL of DMFwas added 1.3 mL of bromo-acctic acid ethyl ester (11.7 mmol, 1.2 eq) under nitrogen. After 12h, the mixture was worked up and crude compound recrystallized to give (2-acctyl-4-bromo-phenoxy)-acctic acid ethyl ester in 97% yield (2.87 g). 'HNMR (400 MHz, CDC13) dppm 1.3 (t, 7=7.1 Hz, 3 H) 2.7 (s, 3 H) 4.3 (q, 7=7.1 Hz, 2 H) 4.7 (s, 2 H) 6.7 (d, 7=8.8 Hz, 1 H) 7.5 (dd, 7=8.8, 2.8 Hz, 1 H) 7.9 (d, 7=2.8 Hz, 1 H). Step 2: A mixture of (2-acetyl-4-bromo-phenoxy)-acetic acid ethyl ester (2.87 g, 9.5 mmol, 1 eq) and sodium cthoxidc (0.65 g, 9.5 mmol, 1 eq) in 100 mL of ethanol under nitrogen was heated to 75°C for 3h. After work up followed by column chromatography (20% MeOH/dichloromethane), 5-bromo-3-methyl-benzofuran-2-carboxylic acid was obtained in 72% yield (1.74 g). 'H NMR (400 MHz, CD3OD) dppm 2.5 (s, 3 H) 7.5 (d, 7=8.8 Hz, 1 H) 7.6 (m, 1 H) 7.9 (d, 7=2.0 Hz, 1 H). Step 3: Amide coupling of 5-bromo-3-methyl-benzofuran-2-carboxylic acid with L-2-(4 -amino-biphenyl-4-sulfonylamino)-3-rnelhyl-butyric acid methyl ester was carried out according to Example 21, Step 3 provided L-2-{4-[(5-bromo-3-rnethyl-benzofuran-2-carbonyl)-arnino]-biphenyJ-4-sulfony]amino)-3-methyI-butyric acid methyl ester in 50% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=14.8,6.7 Hz, 6 H) 1.9 (m, 1 H) 2.6 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, 7=9.3,7.1 Hz, 1 H) 7.7 (d, 7=1.3 Hz, 2 H) 7.8 (t, 7=8.6 Hz, 4 H) 7.9 (m,2H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (t, 7=1.4 Hz, 1 H) 8.3 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L-2-{4'-[(5-bromo-3-methyl-benzofuran-2-carbonyl)-amino]- 79 WO 2005/061477 PCT/US2003/040835 biphenyl-4-sulfonylamino}-3-methy)-butyric acid methyl ester according to Example 20, Step 5 provided L-2-{ 4'-[(5-bromo-3-mcthyI-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methy]-butyric acid in quantitative yield. 'H NMR (400 MHz, CD3OD) dppm 1.1 (dd, J=24.0, 6.8 Hz, 6 H) 2.2 (m, 1 H) 2.8 (s, 3 H) 3.9 (d, J=5.8 Hz, 1 H) 7.8 (m. 2 H) 7.9 (d, J=8.8 Hz, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (m, 5 H) 10.4 (s, 1 H). Example 46: L-2-{4'-[(4-Carbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid Step 1: To a solution of the product of Example 20, L-2-{4-[(4-cyano-3-mcthyl-bcnzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester (128 mg), in a mixture of MeOH (6 mL) and DMSO (4 mL) was added 3 mL of Na2CO3 (3M) and 3 mL of hydrogen peroxide (30% in water). The reaction was complete in 12h. After work up, L-2-{4-[(4-carbamoyl-3-mcthyl-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was obtained in quantitative yield. !H NMR (400 MHz, DMSO-oV) 5 ppm 0.8 (dd, .7=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.6 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, .7=9.3, 7.1 Hz, 1 H) 7.4 (dd. J=7.3. 0.8 Hz, 1 H) 7.5 (dd, 7=8.3, 7.3 Hz, 1 H) 7.7 (s, 1 II) 7.8 (m, 5 H) 7.9 (m, 2 H) 8.0 (d, J=9.l Hz, 2 H) 8.0 (s, 1 H) 8.3 (m, J=93 Hz, 1 H) 10.6 (s, 1 H). Step 2: Hydrolysis of L-2-{4'-[(4-carbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyIamino}-3-methyl-butyric acid methyl ester was carried out according to Example 20, Step 5 to provide L-2-{4 -[(4-carbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonyIamino]-3-rnethyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12.6, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.6 (s, 3 H) 3.6 (m, 1 H) 7.4 (d, J=7.3 Hz, 1 H) 7.5 (m, 1 H) 7.7 (s, 1 H) 7.8 (m, 5 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (m, 2H)10.6(s,l H). 80 WO 2005/061477 PCT/US2003/040835 Example 47: L-2-(4'-{[4-(CycIopropanecarbonyl-amino)-3-methyl-benzofuran-2-carbonyl)]-amino}-biphenyl-4-sulfonylamino)-3-methy)-bulyric acid Step 1: To 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (300 mg, 0.85 mmol, 1 eq, prepared according to Example 20, Step 1) in 8 mL of dioxane under nitrogen were added cyclopropy] carboxamide (87 mg, 1.02 mmol, 1.2 cq), Pd2 (dba)3 (16 mg, 0.017 mmol, 0.02 eq), 4,5-bis(diphenylphosphino)-9,9-dirnethylxanthcne (30 mg, 0.051 mmol, 0.06 cq), and cesium carbonate (390 mg, 1.19 mmol, 1.4 eq). The reaction mixture was heated at reflux for 72h. After work up and column chromatography (dichloromethane/hexancs), 4-(cyclopropanecarbonyl-amino)-3-mcthy]-benzofuran-2-carboxylic acid ethyl ester was obtained in 98% yield (238 mg). 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (m, 4 H) 1.3 (t, J=7.1 Hz, 3 H) 1.8 (s, 1 H) 2.6 (s, 3 H) 4.4 (q, 1=1.2 Hz, 2 H) 7.2 (d, J=7.1 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m. 1H) 10.1 (s, 1H). Step 2: Hydrolysis of 4-(cyclopropanecarbony]-amino)-3-mcthyl-benzofuran-2-carboxylic acid ethyl ester was done according to Example 20, Step 3 to provide 4-(cyclopropanecarbony]-amino)-3-mcthy]-benzofuran-2-carboxylic acid in 40% yield. 'HNMR (400 MHz, DMSO-d6) dppm 0.8 (d, J=5.3 Hz, 4 H) 1.9 (s, 1 H) 2.6 (s, 3 H) 7.2 (d, J=7.6 Hz, 1 H) 7.5 (m, 2 H) 10.1 (s, 1 H) 13.4 (s, 1 H). Step 3: To a mixture of 4-(cyclopropanecarbonyl-amino)-3-methyl-benzofuran-2-carboxylic acid (83 mg, 0.32 mmol, 1 eq), L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester (116 mg, 0.32 mmol, 1 eq) and benzotriazol-l- yloxytris(dimethylamino)phosphoniurn hexafluorophosphatc (BOP, 170 mg, 0.38 mmol, 1.2 eq) in 3 mL DMF under nitrogen was added 0.07 mL of N,N-diisopropylethylamine (0.38 mmol, 1.2 eq). The reaction mixture was stirred at room temperature for 18 h. The desired product precipitated out upon the addition of ethyl acetate, and was collected via filtration, washed with IN HCl, saturated aqueous Na2SC4, and hexanes. L-2-(4'-{[4-(cyclopropanecarbonyl-amino)-3-methyl-benzofuran-2-carbonyl]amino}-biphenyl-4-sulfonylamino)-3-mcthyI-butyric acid methyl ester was obtained in 26% yield (50 mg). 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.1,7.3 Hz, 10 H) 1.9 (m, 2 H) 2.7 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3.7.1 Hz, 1 H) 7.2 (d, 81 WO 2005/061477 PCT/US2003/040835 J=7.6 Hz, 1 H) 7.5 (t, J=8.1 Hz, 1 H) 7.5 (m, 1 H) 7.8 (m, 4 H) 7.9 (m, 2 H) 8.0 (d, J=8.6 Hz, 2 H) 8.3(d, J=9.3 Hz, 1 H) 10.1 (s, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L-2-(4'-{ [4-(cyclopropanecarbonyl-arnino)-3-methyl-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfony]amino)-3-methyl-butyric acid methyl ester was done according to Example 20, Step 5 to give L-2-(4'-{[4-(cyclopropanecarbonyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino) -biphenyl-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (m, 10 H) 1.9 (s, 1 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.5 (dd, J=9.5, 6.2 Hz, 1 H) 7.2 (d, J=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.0 (d, 7=9.6 Hz, 1 H) 10.1 (s, 1 H) 10.6 (s, 1 H). Example 48: L-2- {4'-[(4-Acelylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-snlfonylamino}-3-methyI-butyric acid Step 1: Coupling of 3-mcthyl-4Mrifluorornethanesulfonyloxy-bcnzofuran-2-carboxylic acid ethyl ester (Example 20, Step 1) with acetamide to give 4-acetylamino-3-methyJ-benzofuran-2-carboxylic acid ethyl ester, was done according to Example 47, Step 1 to provide 4-acctylamino-3-mcthyI-bcnzofuran-2-carboxylic acid ethyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d*) 5 ppm 1.3 (t, .7=7.2 Hz, 3 H) 2.1 (s, 3 H) 2.6 (s, 3 H) 4.4 (q, 7=7.1 Hz, 2 H) 7.2 (d, 7=8.1 Hz, 1 H) 7.5 (m, 2 H) 9.8 (s, 1 H). Step 2: Hydrolysis of 4-acetylamino-3-methyl-benzofuran-2-carboxylic acid ethyl ester to 4-Acety]amino-3-methyl-benzofuran-2-carboxylic acid was done according to Example: 20, Step 3 to provide 4-acetylamino-3-methy]-benzofuran-2-carboxylic acid in quantira(iv*e~"yiel(l. *H NMR (400 MHz, DMSO-d6) 5 ppm 2.1 (s, 3 H) 2.6 (s, 3 H) 7.2 (d, J=7.3 Hz, 1 H) 7.5 (m, 2 H) 9.8 (s, 1 H) 13.4 (s, 1H). Step 3: Coupling of 4-acetylarnino-3-mcthyl-benzofuran-2-carboxyIic acid with L-2-(4-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3 to provide L-2-{4'-[(4-acetylamino-3-methyl-benzofuran-2-carbonyl)- 82 WO 2005/061477 PCT/US2003/040835 amino]-biphenyl-4-sulfonylamino}-3-mcthyl-butyric acid methyl ester in 50% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.8, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.1 (s, 3 H) 2.7 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3, 7.3 Hz, 1 H) 7.2 (d, J=7.8 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H) 7.8 (m, 4 H) 7.9 (d, J=8.8 Hz, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 9.8 (s, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L-2- {4'-[(4-acetylamino-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-su]fony]amino}-3-methyl-butyric acid methyl ester was done according to Example 20, Step 5 to provide L-2- {4'-[(4-acetylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-3-methy]-butyric acid in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.5, 6.7 Hz, 6 H) 2.0 (m, 1 H) 2.1 (s, 3 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.2 (d, 7=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=9.1 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 9.8 (s, lH)10.6(s, 1 H) 12.6 (s, 1 H). Example 49: L-3-Methyl-2- {4'-[(3-me(hyI-4-propionylamino-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid Step 1: Coupling of 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (Example 20, Step ]) with propionamide to give 3-methyl-4-propionylamino-benzofuran-2-carboxyIic acid ethyl ester was done according to Example 47, Step 1 in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.1 (t, J=7.6 Hz, 3 H) 1.3 (t, J=7.2 Hz, 3 H) 2.4 (q, J=7.5 Hz, 2 H) 2.6 (s, 3 H) 4.4 (q, J=7.2 Hz, 2 H) 7.2 (d, J=7.3 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H) 9.8 (s, 1 H). Step 2: Hydrolysis of 3-methyl-4-propionylamino-benzofuran-2-carboxylic acid ethyl ester to 3-methyl-4-propionylamino-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, in quantitative yield. 'H NMR (400 MHz, DMSO-d6) dppm 1.1 (t, J=7.3 Hz, 3 H) 2.4 (q, J=8.0 Hz, 2 H) 2.6 (s, 3 H) 7.2 (d, J=7.3 Hz, 1 H) 7.5 (m, 2 H) 9.7 (s, 1 H) 13.5 (s,lH). Step 3: Coupling of 3-methyl-4-propionylamino-benzofuran-2-carboxylic acid wjth L-2-(4 -amino-biphenyl-4-sulfonylarnino)-3-methyl-butyric acid methyl was done according to Example 47, Step 3, to provide ester L-3-methyl-2- {4'-[(3-methyl-4-propionylamino- 83 WO 2005/061477 PCT/US2003/040835 bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester in 67% yield. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=14.8, 6.7 Hz, 6 H) 1.1 (t, J=7.6 Hz, 3 H) 1.9 (m, 1 H) 2.4 (q, J=7.5 Hz, 2H) 2.7 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.2 (d, J=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H) 7.8 (m, 4 H) 7.9 (m, 2 H) 8.0 (d, J=9.1 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 9.7 (s, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L-3-methy)-2-{4'-[(3-methyl-4-propionylamino-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was done according to Example 20, Step 5, to provide L-3-methyl-2-{4'-[(3-methyl-4-propionylamino-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid in quantitative yield. 'HNMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 1.1 (t, 7=7.5 Hz, 3 H) 2.0 (m, 1 H) 2.4 (q, 7=7.6 Hz, 2 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.2 (d, 7=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 9.7 (s, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 50: L-2- {4'-((4-Isobutyrylamino-3-methyl-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfonylarnino)-3-rnethyl-butyric acid Step 1: Coupling of 3-mcthyl-4-trifIuoromethanesulfonyloxy-benzofuran-2-carboxyIic acid ethyl esler (Example 20, Step 1) with isobutyramide to give 4-isobutyrylamino-3-methyl-benzofuran-2-carboxylic acid elhyl ester, was done according to Example 47, Step 1 in 95% yield. 'HNMR (400 MHz, DMSO-d6 ) **ppm 1.2 (d, J=6.8 Hz, 6 H) 1.3 (t, J=7.1 Hz, 3 H) 2.6 (s, 3 H) 2.7 (m, 1 H) 4.4 (q, J=7.1 Hz, 2 H) 7.2 (d, J=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m, 1 H) 9.1 (s, 1 H). Step 2: Hydrolysis 4-isobutyrylamino-3-methyI-benzofuran-2-carboxylic acid ethyl ester to 4-isobutyryIamino-3-methyl-benzofuran-2-carboxylic acid was done according to Example20, Step 3, in 71% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.2 (d, J=6.8 Hz, 6 H) 2.6 (s, 3 H) 2.7 (m, 1 H) 7.2 (dd, J=7.6, 0.5 Hz, 1 H) 7.5 (m, 2 H) 9.7 (s, 1 H) 13.4 (s, 1 H). Step 3: Coupling of 4-isobutyryJarnino-3-methyl-benzofuran-2-carboxylic acid with L-2-(4-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2-{4- 84 WO 2005/061477 PCT/US2003/040835 ((4-Isobutyrylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3 in 84% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=12.4, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.4 (s, 3 H) 2.5 (s, 3 H) 3.6 (dd, J=9.3, 5.8 Hz, 1 H) 6.8 (s, 1 H) 7.5 (dd, J=7.6, 1.0 Hz, 1 H) 7.7 (dd, J=8.3, 7.3 Hz, 1 H) 7.8 (m, 4 H) 7.9 (m, 3 H) 8.0 (d, J=8.8 Hz, 2 H) 8.1 (d, J=9.3 Hz, 1 H) 10.7 (s, 1 H). Step4: Hydrolysis of L-2-{4'-[(4-isobutyrylamino-3-mcthyl-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonylamino}-3-methyl-butyric acid methyl ester to L-2-{4'-[(4-isobuiyr)']amino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid was done according to Example 20, Step 5 in quantitative yield. 'II NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.6,6.8 Hz, 6 H) 1.2 (d, 7=6.8 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 4 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.2 (d, 7=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.5 (m. 2 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 51: L- 2-{4'-[(4-CycIopropylmethox7-3-methy!-benzofuran-2-carbonyl)-amino]-biphenyl-4-su)fonylamino}-3-methyl-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (300 mg, 1.36 mmol, 1 eq) under nitrogen was added potassium carbonate (377 mg, 2.73 mmol, 2 eq), 5 mL of DMF and bromomcthylcyclopropane (145 uL, 1.50 mmol, 1.1 eq) and the reaction was stirred at room temperature for 16h. After work-up and flash column chromatography. 4-cyclopropylmethoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was obtained in 94% yield (350 mg). 'H NMR (400 MHz, DMSO-d6 ) dppm 0.4 (m, 2 H) 0.6 (m, 2 H) 1.3 (m, 1 H) 1.3 (d, J=14.4 Hz, 3 H) 2.7 (d, 3 H) 4.0 (d, J=6.8 Hz, 2 H) 4.3 (q, J=7.1 Hz, 2 H) 6.8 (dd, J=8.1, 0.5 Hz, 1 H) 7.2 (dd, J=8.3, 0.5 Hz, 1 H) 7.4 (t, J=8.2 Hz, 1 H). Step 2: Hydrolysis 4-cyclopropyJmethoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester to 4-cyclopropylmethoxy-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3 in 96% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.4 (m, 2 H) 0.6 (m, 2 H) 1.3 (m, 1 H) 2.7 (s, 3 H) 4.0 (d, J=6.8 Hz, 2 H) 6.8 (d, J=8.1 Hz, 1 H) 7.2 (dd, J=8.5,0.6 Hz, 1 H)7.4(m, lH)13.3(s, 1H). 85 WO 2005/061477 PCT/US2003/040835 Step 3: Coupling of 4-cyclopropylmethoxy-3-methyl-benzofuran-2-carboxylic acid with L-2-(4',-amino-biphenyI-4-suIfonyJamino)-3-methyl-butyric acid methyl ester to obtain L-2-{4'-[(4-cyclopropylmethoxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-suifonyIamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3 in quantitative yield. !H NMR (400 MHz, DMSO-d6 ) dppm 0.4 (m, 2 H) 0.6 (m, 2 H) 0.8 (dd, 7=14.8,6.7 Hz, 6 H) 1.3 (m, 1 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, 7=9.3, 7.1 Hz, 1 H) 4.0 (d, 7=6.6 Hz, 2 H) 6.8 (d, 7=8.6 Hz, 1 H) 7.2 (d, 7=7.8 Hz. 1 H) 7.4 (m. 1 H) 7.8 (dd, 7=12.0, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H). Step 4: Hydrolysis of L-2-{4'-[(4-cyclopropylmethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino}-3-mcthyl-butyric acid methyl ester to obtain L-2-{4'.[(4-cyclopropylmethoxy-3-methy]-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-mcthyl-butyric acid was done according to Example 20, Step 5, in quantitative yield. The product was purified by recrystalization from ethyl acetate/hexanes. *H NMR (400 MHz, DMSO-d6 ) dppm 0.4 (d, 7=4.8 Hz, 2 H) 0.6 (d, 7=8.1 Hz, 2 H) 0.8 (dd, 7=12.5,6.7 Hz, 6 H) 1.3 (m, 1 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.5, 6.2 Hz, 1 H) 4.0 (d, 7=6.8 Hz, 2 H) 6.8 (d, 7=8.3 Hz, 1 H) 7.2 (d, 7=8.3 Hz, 1 H) 7.4 (t, 7=8.1 Hz, l'H) 7.8 (d, 7=8.6 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.1 Hz, 1 H) 10.5 (s, 1 H) 12.6 (s, 1 H). Example 52: L- 2-{4'-[(lH-Benzoimidazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid Step 1: Coupling of commercially available lH-benzoimidazole-2-carboxylic acid with L-2- (4-amino-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester to obtain L- 2-{4'-[(lH-benzoimidazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3 in 37% yield. JH NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=15.0, 6.7 Hz, 6 H) 1.9 (m, 1 H) 3.3 (s, 3 H) 3.6 (dd, J=9.5, 7.2 Hz, 1 H) 7.4 (m, 2 H) 7.6 (d, J=8.1 Hz, 1 H) 7.8 (m, 5 H) 7.9 (m, 2 H) 8.1 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 11.1 (s, 1 H) 13.5 (s, 1 H). Step 2: Hydrolysis of L- 2-{4'-[(lH-benzoimidazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L- 2-{4'-{(lH-benzoimidazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid was done according to 86 WO 2005/061477 PCT/US2003/040835 Example 20, Step 5 in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.9, 6.8 $Jz, 6 H) 2.0 (m, 1 H) 3.6 (dd, 7=9.5, 5.9 Hz, 1 H) 7.4 (d, 7=6.6 Hz, 2 H) 7.8 (m, 8 H) 8.1 (dd, 7=11.1, 9.1 Hz,3 H) 11.1 (s, 1 H) 12.6(s, 1 H) 13.5 (s, 1 H), Example 53: L- 2-{4'(4-sec-Butoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-me!hy!-buiyric acid Step 1: Alkylation of 4-hydroxy-3-methyI-benzofuran-2-carboxyJic acid ethyl ester with 2-bromobuiane fo give 4-sec-butoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was done according to Example 51, Step 1, in 80% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.0 (t, J=7.5 Hz, 3 H) 1.3 (m, 6 H) 1.7 (m, 2 H) 2.7 (s, 3 H) 4.3 (q, J=7.1 Hz, 2 H) 4.6 (m, 1 H) 6.8 (d, J=8.1 Hz, 1 H) 7.2 (dd, J=8.3,0.5 Hz, 1 H) 7.4 (t, J=8.2 Hz, 1 H). Step 2: Hydrolysis of 4-sec-butoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester to 4-sec-butoxy-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3 in quantitative yield. 'H NMR <400 MHz, DMSO-d6 ) dppm 1.0 (t, J=7.5 Hz, 3 H) 1.3 (d, J=6.1 Hz, 3 H) 1.7 (m, 2 H) 2.7 (s, 3 H) 4.6 (m, 1 H) 6.8 (d, J=8.1 Hz, 1 H) 7.1 (m, 1 H) 7.4 (t, J=8.2 Hz, 1H). Step 3: Coupling of 4-sec~butoxy-3-methyl-benzofuran-2-carboxyIic acid with L-2-(4 -amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L- 2-{4'-[(4-sec-butoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3 in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=14.7,6.8 Hz, 6 H) 1.0 (t, J=7.5 Hz, 3 H) 1.3 (d, 7=6.1 Hz, 3 H) 1.7 (m, 2 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, 7=8.7,7.7 Hz, 1 H) 4.6 (d, 1 H) 6.9 (d, 7=8.3 Hz, 1 H) 7.2 (d, 7=8.1 Hz, 1 H) 7.4 (t, 7=8.2 Hz, I H) 7.8 (dd, 7=12.3, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=S,8 Hz, 2 H) 8.3 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H). Step 4: Hydrolysis of L- 2-{4-[(4-sec-butoxy-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester to L- 2-{4'-[(4-scc-butoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyIamino J-3-methyl-butyric acid was done according to Example 20, Step 5, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) ** 87 WO 2005/061477 PCT/US2003/040835 ppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 1.0 (t, 7=7.5 Hz, 3 H) 1.3 (d, 7=6.1 Hz, 3 H) 1.7 (m, 2 H) 2.0 (m,..WH) 2.7 (s, 3 H) 3.6 (dd, 7=9.3,6.1 Hz, 1 H) 4.6 (q, 7=6.1 Hz, 1 H) 6.9 (d, 7=8.1 Hz, 1 H) 7.2 (d, 7=8.1 Hz, 1 H) 7.4 (t, 7=8.2 Hz. 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8:o (d, 7=9.1 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H) 12.6 (s, 1 H). Example 54: L- 3-Methyl-2- {4'-t(3-phenyI-benzofuran-2-carbonyl)-anuno]-biphenyl-4-sulfonylamino)-butyric acid Step 1: Coupling of 3-phenyI-benzofuran-2-carboxylic acid with L-2- (4-amino-biphenyl-4-su]fonylamino)-3-mcthyl-butyric acid methyl ester to obtain L- 3-methyl-2- {4'-((3-phenyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was done according to Example 47, Step 3, in 83% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.5, 6.7 Hz, 6 H) 1.9 (m, 1 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.5 (m, 4 H) 7.6 (m, 1 H) 7.7 (m, 3 H) 7.8 (m, 5 H) 7.9 (m, 4 H) 8.3 (d, J=9.3 Hz, 1 H) 10.7 (s, 1 H). Step 2: Hydrolysis of L- 3-mcthyl-2-{4 -[(3-phenyl-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester to L- 3-methyl-2-{4'-[(3-phenyl-benzofuran-2-carbonyl)-aminoJ-bipheny1-4-sulfonylamino}-butyric acid was done according to Example 20, Step 5, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.6,6.8 Hz, 6 H) 1.9 (m, 1 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.5 (m, 2 H) 7.5 (m, 2 H) 7.6 (m, 1 H) 7.7 (m, 3 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 5 H) 7.9 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.7 (s, lH)12.6(s, IH). 88 WO 2005/061477 PCT/US2003/040835 Example 55: L- 2-(4'-{[4-(Acetyl-methyl-amino)-3-mcthyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-suIfonylaniino)-3-methyl-butyric acid Step 1: To 4-acetylamino-3-methyl-benzofuran-2-carboxylic acid ethyl ester (300 mg, 1.15 mmo), 1 cq, prepared according to Example 48, Step 1) under nitrogen was added 5 mL of DMF, iodomethane (79 uL, 1.26 mmol, 1.1 eq), and sodium hydride (60%, 51 mg, 1.26 inmol, 1.1 eq). The reaction mixture was stirred at room temperature for 4h. After work up and flash column chromatography (5-40% ethyl acctate/hexanes), 4-(acetyl-methyl-amino)-3-methyl-benzofuran-2-carboxylic acid ethyl ester was obtained in 35% yield (112 mg). 'H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, 1=1.2 Hz, 3 H) 1.7 (s, 3 H) 2.5 (s, 3 H) 3.2 (s, 3 H) 4.4 (m, 2 H)" 7.3 (dd, J=7.6,0.8 Hz, 1 H) 7.6 (dd, J=8.5, 7.7 Hz, 1 H) 7.8 (dd, J=8.5, 0.9 Hz, 1 H). Step 2: Hydrolysis of 4-(acetyl-methyI-amino)-3-methyl-benzofuran-2-carboxylic acid ethyl ester to 4-(acety]-methyl-amino)-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, in, 55% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.7 (s, 3 H) 2.5 (s, 3 H) 3.2 (s, 3 H) 7.3 (dd, J=7.7, 0.9 Hz, 1 H) 7.6 (dd, J=8.6, 7.6 Hz, 1 H) 7.7 (m, 1 H) 13.6 (s,lH). Step 3: Coupling of 4-(acetyl-methyJ-amino)-3-methyl-benzofuran-2-carboxylic acid with L-2- (4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2-(4-{[4-(acetyl-mcthyl-amino)-3-methyl-bcnzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3, in 85% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.7, 6.8 Hz, 6 H) 1.7 (s, 3 H) 1.9 (m, 1 H) 2.5 (s, 3 H) 3.2 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.3 (m, 1 H) 7.6 (m, 1 H) 7.8 (m, 5 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3"(d, J=9.3 Hz, 1 H) 10.7 (s, 1 H). Step 4: Hydrolysis of L-2-(4'-{[4-(acetyI-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester to obtain L-2-(4'-{[4-(acetyl-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-amJno}-biphenyl-4-sulfonyIamino)-3-methyl-butyric acid was done according to 20, Step 5, in quantitative yield. The product was purified via trituration with ethyl acetate. 'H NMR (400 MHz, DMSO-d6 ) ** 89 WO 2005/061477 PCT/US2003/040835 ppm 0.8 (dd, 7=12.6,6.8 Hz, 6 H) 1.7 (s, 3 H) 1.9 (m, 1 H) 2.5 (s, 3 H) 3.2 (s, 3 H) 3.6 (dd, 7=9.1,6.1 Hz, 1 H) 7.3 (dd, 7=7.6,0.8 Hz, 1 H) 7.6 (m, 1 H) 7.8 (m, 3 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2H) 8.1 (d, 7=9.3 Hz, 1H) 10.7 (s, 1 H) 12.6 (s, 1 H). Example 56: L-3-MethyI-2- (4'-{[3-methyl-4- (2H-(etrazol-5-yl)-benzofuran-2.carbonyl]-amino}-biphenyI-4-suIfonylamino)-butyric acid Step 1: To L- 2-{4'-[(4-cyano-3-mcthyl-bcnzofuran-2-carbony])-amino]-biphenyl-4-su]fony)amino}-3-methyl-butyric acid methyl ester (45 mg, 0.082 mmol, Example 20, Step 4) was added trimethylsilyl azide (40 uL, 0.03 mmol, 3.65 eq), dibutyJtin oxide (10 mg, cat.) and 1 mJL of toluene, then the reaction was heated at 120cC in a pressure tube for 72h. L- 3-Methyl-2-(41- {[3-mcthyl-4-(2H-tctrazol-5-yl)-benzofuran-2-carbonyl]-amino} -biphenyl-4-sulfonylamino)-butyric acid methyl ester was obtained and used in crude form. JH NMR (400 MHz, DMSO-d6 ) d5 ppm 0.8 (ra, J=14.8, 6.7 Hz, 6 H) 1.9 (m, 1 H) 2.4 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.6 (dd, J=7.6,1.0 Hz, 1 H) 7.7 (dd, J=8.3, 7.3 Hz, 1 H) 7.8 (dd, J=8.6, 5.6 Hz, 4 H) 7.9 (dd, 3 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.7 (s, 1 H) Step 2: Hydrolysis of L-3-mcthyl-2-(4'-{[3-methyl-4-(2H-tetrazol-5-yl)-bcnzofuran-2-carbonyl]-amino}-biphenyl-4-suIfonyIamino)-butyric acid methyl ester to obtain L-3-mcthyl-2-(4'-J[3-methyl-4-(2H-tetrazol-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid was done according to Example 20, Step 5, in quantitative yield. The product was-purified via prep-HPLC. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=20.7, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.5 (s, 3 H) 3.5 (s, 1 H) 7.5 (m, 2 H) 7.6 (m, 7=7.3, 2.0 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 10.5 (s, 1 H). Example 57: L-2-(4'-{[4-(3,3-Dimethyl-but3'l)-3-inethyl-benzoruran-2-carbonyI]-amino}-biphenyl-4-suIfonylamino)-3-melhyI-butyricacid WO 2005/061477 PCT/US2003/040835 Step 1: L-2- (4'-{l4-(3,3-dimethyl-but-l-yny])-3-mcihyl-ben3ofuran-2-carbonyl]-amino)-bjphenyl-4-sulfonylamino)-3-methy]-butyric acid methyl esier (65 mg, 0.11 mmol, prepared according to Example 34, Step 3) was reduced to L-2- (4'-{[4-(3,3-dimethyI-butyI)-3-methyI-benzofuran-2-carbony]]-amino}-bipheny]-4-sulfony]amino)-3-methyl-butyric acid methyl ester following the procedure of Example 32, Step 1. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=14.7, 6.8 Hz, 6 H) 1.0 (s, 9 H) 1.5 (m, 2 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.0 (m, 2H) 3.4 (s, 3 H) 3.6 (dd, 7=9.5. 7.2 Hz, 1 H) 7.1 (dd, 7=7.5, 0.9 Hz, 1 H) 7.4 (dd, 7=8:3, 7.3 Hz, 1 H) 7.5 (m, 1 H) 7.8 (dd, 7=11.2, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.3 (d, 7=9.6 Hz, 1 H) 10.5 (s, 1 H) Step 2: Hydrolysis of L-2-(4-{[4-(3,3-dimethyl-butyl)-3-methyl-benzofuran-2-carbonyl]-amJno}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2-(4'-{[4-(3,3-dimethyl-butyl)-3-methyl-bcnzofuran-2-carbony]]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid was done according to Example 20, Step 5, in quantitative yield. The product was purified via prep-HPLC. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=13.4, 6.8 Hz, 6 H) 1.0 (s, 9 H) 1.5 (m, 2 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.0 (m, 2 H) 3.5 (s, 1 H) 7.1 (d. 7=7.3 liz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 3 H) 10.5 (s, 1 H). 91 WO 2005/061477 PCT/US2003/040835 Example 58: L- 2-{4'-[(3-Ethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulLonyJamino}-3-rnethyI-butyricacid Step 1: (2-PropionyI-phenoxy)-acetic acid methyl ester (432 mg, 1.94 mmol, 1 eq.) was added to a solution of sodium methoxide (105 mg, .94 mmo], 1 eq.) in methanol (10 mL) and the reaction was heated at 60°C for 4h. The reaction was acidified using IN HC1, diluted with water, extracted twice with ethyl acetate, and the combined organic layers were washed with, saturated aqueous NaHCO3. The aqueous layers were extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulfate, and concentrated in vacuo. 3-Ethyl-benzofuran-2-carboxylic acid methyl ester is obtained in 38% yield after flash column chromatography purification (1-5% ethyl acetatc/hexancs). !H NMR (400 MHz, DMSO-d6 ) dppm 1.2 (t, J=7.6 Hz, 3 H) 3.1 (q, J=7.6 Hz, 2 H) 3.9 (s, 3 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.7 (m, 1 H) 7.9 (dd, J=7.8,0.8 Hz, 1 H). Step 2: Hydrolysis of 3-ethyl-benzofuran-2-carboxylic acid methyl ester to 3-ethyI-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, in 98% yield. *H NMR (400 MHz, CD3OD) 8 ppm 1.2 (d, J=7.6 Hz, 3 H) 3.0 (q, J=7.4 Hz, 2 H).7.2 (m, 1 H) 7.4 (m, 1 H) 7.4 (m, 1 H) 7.6 (m, 1 H). Step 3: Coupling of 3-cthyl-benzofuran-2-carboxyIic acid with L-2- (4'-amino-biphenyI-4-sulfonylamino)-3-methyI-butyric acid methyl ester to obtain L- 2-{4'-[(3-ethyl-benzofuran-2-carbony])-amJno]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3 in 85% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.7, 6.8 Hz, 6 H) 13 (t, J=7.6 Hz, 3 H) 1.9 (m, 1 H) 3.2 (q, J=7.7 Hz, 2 H) 3.4 (s, 3 H) 3.6 (dd, J=9.3,7.1 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.7 (d, J=9.1 Hz, 1 H) 7.8 (dd, J=10.5, 8.7 Hz, 4 H) 7.9 (d, J=7.3 Hz, 1 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.6 Hz, 1 H) 10.6 (s, 1 H). Step 4: Hydrolysis of L- 2-{4'-[(3-ethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester to obtain L- 2-{4'-[(3-ethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyi-bufyfic acid was done according to Example 20, Step 5, in quantitative yield. The product was purified by trituration with 25% ethyl acetate/ hexane. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, j=16.9, 6.8 Hz, 6 H) 1.3 (t, 92 WO 2005/061477 PCT/US2003/040835 7=7.5 Hz, 3 H) 2.0 (m, 1 H) 3.2 (q, J=7.7 Hz, 2 H) 3.5 (s, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.7 (d, 7=8.5 Hz, 1 H) 7.8 (m. 7 H) 8.0 (d, J=8.8 Hz, 2 H) 10.6 (s, 1 H). Example 59: L- 2-{4'-[(4-tcrt-Butoxycarbony)amino-3-mctliyl-bcnzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonyJamino}-3-methyJ-butyricacid Step 1: Coupling of 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester to tert-buty] carbamate to give 4-tert-butoxycarbonyIamino-3-methyl-benzofuran-2-carboxylic acid ethyl ester, was done according to Example 47, Step 1 in 60% yield, *H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, J=7.1 Hz, 3 H) 1.5 (s, 9 H) 2.6 (s, 3 H) 4.4 (q, J=7.1 Hz, 2 H) 7.1 (d, J=7.6 Hz, 1 H) 7.5 (m, 2 H) 9.1 (s, 1 H). Step 2: Hydrolysis of 4-tert-butoxycarbonylamino-3-methyl-benzofuran-2-carboxylic acid ethyl ester to give 4-tcrt-butoxycarbonyIamino-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3. Yield: 98%. 'H NMR (400 MHz, CD3OD) 5 ppm 1.4 (s, 9 H) 2.6 (s, 3 H) 7.1 (m, 1 H) 7.3 (m, 2 H) 8.7 (s, 1 H). Step 3: Coupling of 4-tert-butoxycarbonylamino-3-mcthyl-benzofuran-2-carboxylic acid with L-2- (4'-amino-biphcnyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to give L- 2-{4'-[(4-tert-butoxycarbonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3in 85% yield. !H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.8,6.7 Hz, 6 H) 1.5 (dd, 9 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.3 (s, 3 H) 3.6 (dd, J=9.3, 7.1 Hz, 1 H) 7.2 (dd, J=7.6 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (dd, J=10.2, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, J=9.1 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H)9.1 (s, 1H) 10.5 (s,lH). Step 4: Hydrolysis of L-2- {4'-[(4-tert-butoxycarbonylamino-3-methy]-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-su]fonyIamino}-3-methyl-butyric acid methyl ester to obtain L- 2-{4-[(4-tert-butoxycarbonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid was done according to Example 20, Step 5, in quantitative 93 WO 2005/061477 ' PCT/US2003/040835 yield. The product was purified by trituration with 25% ethyl acetate/hexane. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=13.6,6.8 Hz, 6 H) 1.5 (s, 9 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.5 (m, 1H) 7.2 (d, 7=7.6 Hz, 1 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=9.1 Hz, 3 H) 9.1 (s, 1 H) 10.5 (s, 1H), Example 60: L-3-Methyl-2- {4-(3-methyI-4-methyIamino-benzofuran-2-carbonyl)-amino3-biphenyl-4-sulfonylamino}-butyric acid Step 1: To 4-tert-butoxycarbony]amino-3-methyI-benzofuran-2-carboxylJc acid ethyl ester (624 ing, .1.95 mmol, prepared according to Example 59, Step 1) was added 1,2-dichloroethane (12 mL) and trifluoroacetic acid (TFA, 6 mL). The reaction was stirred at room temperature for 2 hours. Solvent was removed in vacuo to provide 4-amino-3-methyl-benzofuran-2-carboxylic acid ethyl ester in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) d ppm 1.3 (t, J=7.1 Hz, 3 H) 2.7 (s, 3 H) 4.3 (q, J=7.1 Hz, 2 H) 6.5 (dd, J=7.8,0.8 Hz, 1 H) 6.8 (d, J=8.3 Hz, 1 H) 7.2 (t, J=8.1 Hz, 1 H). Step 2: To 4-amino-3-methyl-benzofuran-2-carboxylie acid ethyl ester (500 mg, 2.28 mmol, 1 eq.) was added iodomethane (310 uL, 6.16 mmol, 2.7 eq.), sodium carbonate (314 mg, 2.96 mmol, 1.3 eq.), and ethanol (10 mL) and reaction was heated at reflux for 16 hours. 3-Methyl-4-methyIamino-benzofuran-2-carboxylic acid ethyl ester was obtained in 17% yield after flash column chromatography, eluting with ethyl acetate/hexanes. (90 mg) 'HNMR (400 MHz, DMSO-d6 ) **ppm 1.3 (t, J=7.1 Hz, 3 H) 2.7 (s, 3 H) 4.3 (q, J=7.1 Hz, 2 H) 6.5 (dd, J=7.8,0.8 Hz, 1 H) 6.8 (d, J=8.3 Hz, 1 H) 7.2 (t, J=8.1 Hz, 1 H). Step 3: Hydrolysis of 3-methyl-4-methylamino-benzofuran-2-carboxylic acid ethyl ester to give 3-methyl-4-methy]ainino-benzofuran-2-carboxyHc add was done according to Example 20, Step 3, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 2.7 amino]-biphenyl-4-sulfonylamino)-butyric acid methyl ester to obtain L-3-methyl-2-{4'-[(3-methyl-methylamino-benzofurah-2-carbonyl)-amino]-biphenyl-4-suIfonyiamino)-butyric acid was done according to Example 20, Step 5, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.5, 6.7 Hz, 6 H) 2.0 (m, 1 H) 2.8 (m, 6 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 5.7 (d, 7=4.5 Hz, 1 H) 6.3 (d, 7=7.8 Hz, 1 H) 6.9 (d, 7=7.8 Hz, 1 H) 7.3 (t, 7=8.1 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 4 II) 8.0 (d, 7=8.8 Hz. 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.4 (s, 1 H). Example 61: L-2- {4'-[(4-Amino-3-methyl-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfonyIamino}-3-methyl-butyric acid To L- 2-{4'-[(4-tert-butoxycarbony]amino-3-methyl-benzofuran-2-carbony])-ainino]-bipbenyl-4-sulfonylamino}-3-methyl-butyric acid (84 mg, prepared according to Example 59, Step 4), 1,2-dichlorocthane (2 mL) and TFA (1 mL) were added, and stirred at room temperature for 3 hours. The solvent was removed in vacuo to give L-2- {4-[(4-amino-3-methyl-benzofuran-2-carbonyl)-aminol'biphenyI-4-sulfonylamino)-3-methyl-butyric acid in quantitative yield. NMR: 'H NMR (400 MHz, DMSO-d6 ) **ppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 5.5 (s, 2II) 6.5 (dd, 7=8.0, 0.6 Hz, 1 H) 6.8 (d, 7=8.8 Hz, 1 H) 7.1 (t, 7=8.1 Hz, 1 H)7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 4 H) 8.0 (d, 7=9.1 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.3 (s, 1 H). 95 WO 2005/061477 PCT/US200J/040835 Example 62: L-2- {4'-l(4-Dimethylamino-3-melhyl-benzofuran-2-carbonyl)-amino]-biphenyi-4-sulfonyIarnino}-3-rnethyl-butyrie acid Step 1: To 4-amino-3-methyl-benzofuran-2-carboxyJic acid ethyl ester (500 mg, 2.28 mmol 1 eq. prepared according to Example 60, Step 1), ethanol (8 mL), iodomethane (500 uL, 7.98 mmol, 3.5 eq.), and potassium carbonate (946 mg, 6.84 mmo), 3 eq.) were added under argon in a sealed tube and the mixture was heated at 80°C for 16 hours. After work-up and flash column chromatography, 4-dimeihylamino-3-methyJ-bcnzofuran-2-carboxyJic acid ethyl ester was obtained in 44% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, J=7.2 Hz, 3 H) 2.7 (t, 3 H) 2.8 (s, 6 H) 4.3 (m, J=7.1,7.1, 7.1 Hz, 2 H) 6.9 (dd, J=7.8,0.8 Hz, 1 H) 7.3 (dd, J=8.3,1.0 Hz, 1 H) 7.4 (m, 1 H). Step 2: Hydrolysis of 4-dimethylamino-3-methyl-benzofuran-2-carboxylic acid ethyl ester to give 4-dimethyJamino-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, in quantitative yield. 1H NMR (400 MHz, DMSO-d6 ) dppm 2.7 (s, 3 H) 2.8 (s, 6 H) 6.9 (d, J=7.6 Hz, 1 H) 7.2 (d, J=7.6 Hz, 1 H) 7.4 (t, J=8.1 Hz, 1 H) 13.2 (s, 1 H). Step 3: Coupling of 4-dimethyIamino-3-methyl-benzofuran-2-carboxyHc acid with L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2- {4'-{(4-dimethylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3, in quantitative yield. Step 4: Hydrolysis of L-2- {4'-{(4-dimethylamino-3-methyl-benzofuran-2-carbony])-aminoJ~biphenyl-4-su]fonyJamino}-3-methyl-butyric acid methyl ester to L-2- {4'-[(4-dimethylainino-3-methyl-benzofuran-2-carbonyl)-arnino]-biphenyl-4-su]fonylarnino}-3-rnethyl-butyric acid was done according to Example 20, Step 5. Purification by preparative HPLC gave the desired product in 50% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, .7=12.6, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.8 (m, 9 H) 3.6 (dd, 7=9.3, 5.8 Hz, 1 H) 6.9 (dd, 7=7.8,0.8 Hz, 1 H) 7.3 (dd, 7=8.3,0.8 Hz, 1 H) 7.4 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.0 (d, 7=9.1 Hz, 1 H) 10.5 (s, 1 H). 96 WO 2005/061477 PCT/US2003/040835 Example 63: L-3-Methyl-2- {4'-[(3-methyl-pyrrolidin-l-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acdd Step 1: To 4-amino-3-methyl-benzofuran-2-carboxylic acid ethyl ester (500 mg, 2.28 mmol, 1 eq., prepared according to Example 60, Step 1) were added toluene (3 mL), 1,4-dibromobutane (272 uL, 2.28 mmol, 1 eq.), and NN-diisopropylethylamine (953 uL, 5.47 mmol, 2.4 eq.) under argon in a sealed tube and the mixture was heated at 110°C for 16 hours. After work-up and flash column chromatography, 3-mcthyl-4-pyrrolidjn-l-yl-bcnzofuran-2-carboxylic acid ethyl ester was obtained in 48% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, J=7.1 Hz, 3 H) 1.9 (m. 4 H) 2.7 (s, 3 H) 3.1 (m, 4 H) 4.3 (q, J=7.1 Hz, 2 H) 6.8 (dd, J=8.0, 0.6 Hz, 1 H) 7.2 (dd, J=8.3,0.8 Hz, 1 H) 7.3 (m, 1 H). Step 2: Hydrolysis of 3-methyl-4-pyrrolidin-l-yl-benzofuran-2-carboxylic acid ethyl ester to give 3-methyI-4-pyrrolidin-l-yl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, in 73% yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.9 (m, 4 H) 2.7 (s, 3 H) 3.1 (m, 4 H) 6.8 (dd, J=7.8,0.8 Hz, 1 H) 7.2 (dd, J=8.1,0.8 Hz, 1 H) 7.3 (m, 1 H) Step 3: Coupling of 3-methyl-4-pyrrolidin-l-yl-benzofuran-2-carboxylic acid with L-2-(4'-amJno-biphenyl-4-sulfonyJamino)-3-methyl-butyric acid methyl ester to obtain L-3-Methyl-2- {41-[(3-melhyl-4-pyrrolidin-l-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was done according to Example 47, Step 3, in 27% yield. !H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (m, 6 H) 1.9 (s, 5 H) 2.8 (d, 7=1.5 Hz, 3 H) 3.2 (s, 4 H) 3.4 (d, 7=1.5 Hz, 3 H) 3.6 (t, 7=8.0 Hz, 1 H) 6.9 (d, 7=7.8 Hz, 1 H) 7.2 (dd, 7=9.3, 13 Hz, 1 H) 7.4 (m, 1 H) 7.8 (m, 4 H) 7.9 (m, 2 H) 8.0 (dd, 7=8.6, 1.5 Hz, 2 H) 8.3 (d, 7=9.6 Hz, 1 H) 10.4 (s, 1 H). Step 4: Hydrolysis of L-3-mcthyI-2- {4'-[(3-methy]-4-pyrroljdin-l-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester to L-3-methyl-2- {4'-[(3-methyl-4-pyrrolidin-l-y)-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid was done according to Example 20, Step 5, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=45.5,6.8 Hz, 6 H) 1.9 (m, 4 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 2.9 (d, 7=2.8 Hz, 1 H) 3.2 (m, 4 H) 6.9 (dd, 7=7.8, 0.8 Hz, 1 H) 7.2 (dd, 7=8.1,0.8 Hz, 1 H) 7.4 (m. 1 H) 7.8 (m, 6 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.5 (s, 1 H) 10.4 (s, 1 H). 97 WO 2005/061477 PCT/US2003/040835 Example 64: L-2- ({4'-[(4-Methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-suIfonyl}-methyI-amino)-3-methyl-butyricacid Step 1: Coupling of 4-methanesulfonylamino-3-methyl-benzofuran-2-carboxyic acid (prepared according to Example 36, Step 2) with L- 2-((4*-amino-biphenyl-4-sulfonyl)-methyl-amino]-3-methyl-butyric acid methyl ester to obtain L-2- ({4'-[(4-methancsulfonylamino-3-methyl-ben2ofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl}-methyl-arnjno)-3-rnethyl-butyric acid methyl ester was done according to Example 47, Step 3, in 43% yield. The product was purified by prep-HPLC. Step 2: Hydrolysis of L-2- ({4-[(4-methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl }-methyl-amino)-3-methyl-butyric acid methyl ester to L-2- ({4-[(4-rnethanesulfonylamino-3-rncthyl-benzofuran-2-carbonyl)-arnino]-biphenyl-4-suJfony]}-rnethyl-amino)-3-methyl-butyric acid was done according to Example 20, Step 5, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.9 (dd, 7=21.0, 6.6 Hz, 6 H) 2.0 (m, H) 2.8 (s, 3 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 4.0 (d, 7=10.4 Hz, 1 H) 7.3 (dd, 7=7.7,0.9 Hz, 1 H) 7.5 (m, 1 H) 7.6 (m,.l H) 7.8 (dd,7=13.3, 8.7 Hz, 4 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H)9.5 (s, 1 H) 10.6 (s, 1 H). Example 65: L-3-Hydroxy-2- {4'-[(4-methancsulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyI-4-suifonyIamino)-butyricacid Step 1: L-2- (4'-Amino-biphenyl-4-su]fonylamino)-3-tert-butoxy-butyric acid methyl 98 WO 2005/061477 PCT/US2003/040835 ester was prepared according to the procedure of Example 39, Steps 1-3, using O-t-butyl-threonine methyl ester and 4-(4,4,5,5-tetramethyl -[l,3,2]dioxaborolan-2-yl)-phenylarnine. Coupling of 4-meihanesulfonyJamino-3-methyl-benzofuran-2-carboxy]ic acid (prepared according to Example 36, Step 2) with L-2- (4'-amino-bipheny]-4-sulfonylamino)-3-tert-butoxy-butyric acid methyl ester to obtain L-3-tert-butoxy-2- {4'-[(4-methanesulfonylamino-3-methyI-benzofuran-2-carbonyl)-arnino]-biphenyI-4-su]fonylamino)-butyric acid methyl ester was done according to Example 47, Step 3, in 38% yield. !H NMR (400 MHz, DMSO-d6 ) dppm 1.0 (m, 12 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.4 (s, 3 H) 3.8 (dd, J=9.7, 3.7 Hz, 1 H) 4.0 (dd, J=10.2. 6.4 Hz, 1 H) 7.3 (d, J=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.6 (d, J=8.3 Hz, 1 H) 7.8 (d, 3=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2 H) 8.0 (d, 1=9.9 Hz, 1 H) 9.5 (s, 1 H) 10.6 (s, 1 H). Step 2: Deprotection of L-3-tert-butoxy-2- {4'-[(4-methanesulfonylamino-3-rnethyl-benzofuran-2-carbonyl)-amino]-b)phenyl-4-sulfonylamino}-butyric acid methyl ester to obtain JL-3-hydroxy-2- {4'-[(4-methanesulfonylamJno-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino}-butyric acid methyl ester was done according to Example 61, Step 1, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.0 (d, J=6.3 Hz, 3 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.4 (s, 3 H) 3.8 (dd, J=9.3, 4.0 Hz, 1 H) 4.0 (m, 1 H) 7.3 (d, J=7.6 Hz, 1 H) 7.5 (m, 1 H) 7.6 (d, J=7.6 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, J=8.8 Hz, 2 H) 8.0 (d, J=9.1 Hz, 1 H) 9.5 (s, 1 H) 10.6 (s, 1 H). Step 3: Hydrolysis of L-3-hydroxy-2- {4-[(4-methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino}-butyric acid methyl ester to L-3-hydroxy-2- {4-[(4-methanesulfonylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid was done according to Example 20, Step 5, in quantitative yield. !H NMR (400 MHz, DMSO-d6 ) dppm 1.0 (d, J=6.3 Hz, 3 H) 2.8 (s, 3 H) 3.1 (s, 3 H) 3.7 (dd, J=9.3, 3.5 Hz, 1 H) 4.0 (s, 1 H) 4.8 (d, J=5.3 Hz, 1 H) 7.3 (d, J=7.8 Hz, 1 H) 7.5 (m, 1 H) 7.6 (d, J=8.3 Hz, 1 H) 7.7 (d, J=9.3 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (s, 4 H) 8.0 (d, J=8.8 Hz, 2 H) 9.5 (s, 1 H)10.6(s, 1H). 99 Example 66: (S)-3-Methyl-2-(4'.{[4-meUjyI-2-(4-trifluoromethyI-phenyl)-thiazole-S-carbonyl)-amino}-biphenyl-4-sulfonyJamlno)-butyrie acid WO 2005/061477 PCT/US200J/040835 Step 1. Coupling of the 4-methyl-2-(4-uifluoromethyl-phenyl)-thiazole-5-carboxylic acid (comercially available) with L-2-(4'-amino-bjphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was canied out according to the procedure described in Example 21, Step 3. The (S)-3-methyl-2-(4-{[4-methyl-2-(4-trifluoromethyI-phenyl)-thia2ole-5-carbonyl]-amino}-biphenyl-4-su]fonylamino)-butyric acid methyl ester was obtained as a white solid in 75% yield. Step 2. Hydrolysis of (S)-3-methyl-2-(4-4-methyl-2-(4-trifluoromethy-phenyl)-thiazole-5-carbonyl]-amino}-biphenyl-sulfonylamino)-butyric acid methyl ester according to the procedure described in Example 20, Step 5, afforded (S)-3-methyl-2-(4'-{[4-melhyl-2-(4-trifluoromethyJ-phcnyJ)-thiazole-5-carbonyl]-ainino}-bipheny]-4-suIfonylamino)-butyricacidas a while solid. MS: cac'd for [M+H]+: 618.67. found: 618.17. Example 67: L-3-Methyl-2- (4'-{[3-methyl-4- (2,2,2-trifIuoro-acetyIainino>benzofuran-2-carbonyl]-amino)-biphenjl-4-sulfonylamino)-butyric acid Step 1: Coupling of 3-methyl-4- (2,2,2-trifluoro-acetylamino)-benzofuran-2-carboxylic acid with L-2- (4'-amino-biphenyl-4-suIfonylamino)-3-methyl-butyric acid methyl ester to obtain L-3-methyl-2- (4'-{ [3-methyl-4- (2,2,2-trifluoro-acctylamino)-benzofuran-2-carbonyl]-amino)-bipheny]-4-sulfonylamino)-butyric acid methyl ester was done according to Example 47, Step 3, in 61% yield. 'H NMR (400 MHz, DMSO-d6 ) **5 0.8 (dd, J=14.7, 6.6 Hz, 6 H) 1.9 (m, 1 H) 2.6 (s, 3 H) 3.4 (s, 3 H) 3.6 (dd, J=9.5, 7.2 Hz, 1 H) 7.3 (d, J=7.8 Hz, 1 H) 7.6 (m, 1 H) 7.7 (d, J=8.3 Hz, 1 H) 7.8 (m, 4 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.6 (s, 1 H) 11.5(s, 1H). Step 2: Hydrolysis of L-3-methyI-2- (4'-{[3-methyI-4- (2,2,2-trifluoro-acetylamino)-benzofuran-2-carbonyl]-amino}-biphenyJ-4-sulfonylamino)-butyric acid methyl ester to L-3-methyl-2- (4'-{ [3-methyl-4- (2,2,2-trifluoro-acetylamino)-benzofuran-2-carbonyl]-amino}-biphenyl-4-suIfonylamino)-butyric acid was done according to Example 20, Step 5, in 25% yield. The product was purified via prep-HPLC. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=13.4, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.6 (s, 3 H) 3.5 (m, 1 H) 7.3 (d, J=7.8 Hz, 1 H) 7.6 (m, 1 H) 7.7 (d, J=7.6 Hz, 1 H) 7.8 (d, J=8.8 Hz, 2 H) 7.9 (m,4 H) 8.0 -2-earboriyl]-amino}-. biphenyl-4-sulfonylamino)-butyric acid was done according to Example 20, Step 5, and the product was purified by ethyl acetate trituration. Yield: 78%. JH NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=12.8,6.7 Hz, 6 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, J=9.3, 6.1 Hz, 1 H) 6.8 (dt J=7.8 Hz, 1 H) 7.2 (dd, J=5.1,3.8 Hz, 1 H) 7.4 (m, 1 H) 7.5 (dd, J=3.8, 1.3 Hz, 1 H) 7.6 (dd, J=8.1 Hz, 1 H) 7.8 (d, J=8,a Hz, 2 H) 7.9 (m, 4 H) 8.0 (m, 3 H) 8.1 (d, J=9.1 Hz, 1 H) 10.2 (s, 1 H)10.6(s, 1H). Example 73; L-2- (4'-{[4-(l,l-Dioxo-I&&6-isoihiazolidin-2-yI)-3-methyl-ben2ofuran-2-carbonyl]-amino}-biphenyl-4-sulfonytemino)-3-methyl-butyricacid Step 1:4-(3-Chloro-propane-l-sulfonylamino)-3-rnethyl-benzofuran-2-carboxyJic acid ethyl ester was prepared from 4-amjno-3-methyJ-benzofuran-2-carboxylic acid ethyl ester (Example 60, Step 1), and 3-chloropropanesulfonyl chloride according to the procedure of Example 68, Step 1. Yield: 70%. *H NMR (400 MHz, DMSO-d6 ) dppm 1.4 (m, 3 H) 2.2 (m, 2 H) 2.8 (s, 3 H) 3.3 (m, 2 H) 3.8 (t, J=6.4 Hz, 2 H) 4.4 (q, J=7.2 Hz, 2 H) 7.2Jd, J=7.3 Hz, 1 H) 7.5 (m, 1 H) 7.7 (m, 1 H) 9.7 (s, 1 H). Step 2: To 4-(3-chloro-propane-l-suIfonylamino)-3-mcthyl-bcnzofuran-2-carboxylic acid ethyl ester (246 mg, 0.68 mmol, leq.) in THF (l0mL) cooled to <0 °C was added sodium hydride (60%, 30 mg, 0.75 mmol, 1.1 eq.). The reaction was allowed to slowly warm to room 106 WO 2005/061477 PCT/US2003/040835 temperature, then transferred to a pressure tube and heated at 74 °C for 16 hours. After work-up and flash column chromatography, 4-(l,l-dioxo-lX6-isothiazo)idin-2-yl)O-rnethyl-benzofuran-2-carboxylic acid ethyl ester was obtained. Yield: 64%. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, J=7.1 Hz, 3 H) 2.5 (m, 2 H) 2.7 (s, 3 H) 3.5 (m, 2 H) 3.7 (dd, J=6.8 Hz, 2 H) 4.4 (q, J=7.1 Hz, 2 H) 7.4 (dd, J=7.8,0.8 Hz, 1 H) 7.6 (m, 1 H) 7.7 (dd, J=8.3, 0.8 Hz, 1 H). Step 3: Hydrolysis of 4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-rnethyl-bcnzofuran-2-carboxylic acid ethyl ester to give 4-(l,l-dioxo-R6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, to give 4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carboxylic acid. Yield: 94%. !H NMR (400 MHz, DMSO-d6 ) dppm 2.5 (dd, J=14.7, 7.6 Hz, 2 H) 2.7 (s, 3 H) 3.5 (m, 2 H) 3.7 (t, J=6.8 Hz, 2 H) 7.4 (m, 1 H) 7.6 (m. 1 H) 7.7 (d, J=8.6 Hz, 1 H). Step 3: Coupling of 4-(l,l-dioxo-lXs-isothiazolidin-2-yl)-3-mcthyl-benzofuran-2-carboxylic acid with L-2- (4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2- (4-{[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-melhyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamjno)-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3. Yield: 89%. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 3.5 (m, 2 H) 3.6 (dd, J=9.5,7.2 Hz, 1 H) 3.8 (t, J=6.8 Hz, 2 H) 7.5 (dd, J=7.8, 0.8 Hz, 1 H) 7.6 (m, 1 H) 7.8 (m. 5 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.6 (s, 1 H). Step4: Hydrolysis of L-2- (4-{[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester to obtain L-2- (4-|[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amJno)-3-methyl-butyric acid was done according to Example 20, Step 5, and the product was purified by ethyl acetate trituration. Yield: 67%. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.9, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.5 (m, 2 H) 3.6 (dd, 7=9.3, 5.8 Hz, 1 H) 3.8 (t, 7=6.8 Hz, 2 H) 7.5 (dd, 7=7.7, 0.9 Hz, 1 H) 7.6 (m, 1 H) 7.7 (dd, 7=8.2, 0.9 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). Example 74: D-3-Methyl-2-{4'-t(3-niethyI-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfonylaminoj-butyric acid 107 WO 2005/061477 PCT/US2003/040835 temperature, then transferred to a pressure tube and heated at 74 °C for 16 hours. After work-up and flash column chromatography, 4-(l,l-dioxo-lX6-isothiazo)idin-2-yl)O-rnethyl-benzofuran-2-carboxylic acid ethyl ester was obtained. Yield: 64%. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, J=7.1 Hz, 3 H) 2.5 (m, 2 H) 2.7 (s, 3 H) 3.5 (m, 2 H) 3.7 (dd, J=6.8 Hz, 2 H) 4.4 (q, J=7.1 Hz, 2 H) 7.4 (dd, J=7.8,0.8 Hz, 1 H) 7.6 (m, 1 H) 7.7 (dd, J=8.3, 0.8 Hz, 1 H). Step 3: Hydrolysis of 4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-rnethyl-bcnzofuran-2-carboxylic acid ethyl ester to give 4-(l,l-dioxo-R6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, to give 4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carboxylic acid. Yield: 94%. !H NMR (400 MHz, DMSO-d6 ) dppm 2.5 (dd, J=14.7, 7.6 Hz, 2 H) 2.7 (s, 3 H) 3.5 (m, 2 H) 3.7 (t, J=6.8 Hz, 2 H) 7.4 (m, 1 H) 7.6 (m. 1 H) 7.7 (d, J=8.6 Hz, 1 H). Step 3: Coupling of 4-(l,l-dioxo-lXs-isothiazolidin-2-yl)-3-mcthyl-benzofuran-2-carboxylic acid with L-2- (4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2- (4-{[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-melhyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamjno)-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3. Yield: 89%. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 3.5 (m, 2 H) 3.6 (dd, J=9.5,7.2 Hz, 1 H) 3.8 (t, J=6.8 Hz, 2 H) 7.5 (dd, J=7.8, 0.8 Hz, 1 H) 7.6 (m, 1 H) 7.8 (m. 5 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.6 (s, 1 H). Step4: Hydrolysis of L-2- (4-{[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester to obtain L-2- (4-|[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amJno)-3-methyl-butyric acid was done according to Example 20, Step 5, and the product was purified by ethyl acetate trituration. Yield: 67%. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.9, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.5 (m, 2 H) 3.6 (dd, 7=9.3, 5.8 Hz, 1 H) 3.8 (t, 7=6.8 Hz, 2 H) 7.5 (dd, 7=7.7, 0.9 Hz, 1 H) 7.6 (m, 1 H) 7.7 (dd, 7=8.2, 0.9 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). 107 Example 74: D-3-Methyl-2-{4'-t(3-niethyI-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfonylaminoj-butyric acid WO 2005/061477 PCT/US2003/040835 temperature, then transferred to a pressure tube and heated at 74 °C for 16 hours. After work-up and flash column chromatography, 4-(l,l-dioxo-lX6-isothiazo)idin-2-yl)O-rnethyl-benzofuran-2-carboxylic acid ethyl ester was obtained. Yield: 64%. 'H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (t, J=7.1 Hz, 3 H) 2.5 (m, 2 H) 2.7 (s, 3 H) 3.5 (m, 2 H) 3.7 (dd, J=6.8 Hz, 2 H) 4.4 (q, J=7.1 Hz, 2 H) 7.4 (dd, J=7.8,0.8 Hz, 1 H) 7.6 (m, 1 H) 7.7 (dd, J=8.3, 0.8 Hz, 1 H). Step 3: Hydrolysis of 4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-rnethyl-bcnzofuran-2-carboxylic acid ethyl ester to give 4-(l,l-dioxo-R6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carboxylic acid was done according to Example 20, Step 3, to give 4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carboxylic acid. Yield: 94%. !H NMR (400 MHz, DMSO-d6 ) dppm 2.5 (dd, J=14.7, 7.6 Hz, 2 H) 2.7 (s, 3 H) 3.5 (m, 2 H) 3.7 (t, J=6.8 Hz, 2 H) 7.4 (m, 1 H) 7.6 (m. 1 H) 7.7 (d, J=8.6 Hz, 1 H). Step 3: Coupling of 4-(l,l-dioxo-lXs-isothiazolidin-2-yl)-3-mcthyl-benzofuran-2-carboxylic acid with L-2- (4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester to obtain L-2- (4-{[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-melhyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamjno)-3-methyl-butyric acid methyl ester was done according to Example 47, Step 3. Yield: 89%. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=14.7, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.3 (s, 3 H) 3.5 (m, 2 H) 3.6 (dd, J=9.5,7.2 Hz, 1 H) 3.8 (t, J=6.8 Hz, 2 H) 7.5 (dd, J=7.8, 0.8 Hz, 1 H) 7.6 (m, 1 H) 7.8 (m. 5 H) 7.9 (m, 2 H) 8.0 (d, J=8.8 Hz, 2 H) 8.3 (d, J=9.3 Hz, 1 H) 10.6 (s, 1 H). Step4: Hydrolysis of L-2- (4-{[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester to obtain L-2- (4-|[4-(l,l-dioxo-lX6-isothiazolidin-2-yl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amJno)-3-methyl-butyric acid was done according to Example 20, Step 5, and the product was purified by ethyl acetate trituration. Yield: 67%. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.9, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.8 (s, 3 H) 3.5 (m, 2 H) 3.6 (dd, 7=9.3, 5.8 Hz, 1 H) 3.8 (t, 7=6.8 Hz, 2 H) 7.5 (dd, 7=7.7, 0.9 Hz, 1 H) 7.6 (m, 1 H) 7.7 (dd, 7=8.2, 0.9 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H). Example 74: D-3-Methyl-2-{4'-t(3-niethyI-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfonylaminoj-butyric acid 107 WO 2005/061477 PCT/US2003/040835 Step 1: Amide coupling of 3-mcihyl-benzofuran-2-carboxylic acid with 4-(4,4,5,5-tetramethyl-[l ,3,2]dioxaboroJan-2-yl)-phenylamine was done according to Example 20, Step 4, to give 3-methyl-benzofuran-2-carboxylic acid (4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yj)-phenyl]-amide in 55% yield. 'H NMR (400 MH2, DMSO-d6 ) dppm 1.3 (s, 12 H) 2.6 (s, 3 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.7 (m, 3 H) 7.8 (d, 7=7.3 Hz, 1 H) 7.9 (d, 7=8.6 Hz, 2 H) 10.5 (s, 1 H). Step 2: To H-D-Val-OtBu-HC! (22.5 g. 0.107 mol, 1 eq.) in 400 ml_ of dichloromethane under argon, cooled using an ice-ethanol bath, was added 4-bromobenzene sulfonyl chloride (27.4 g, 0.107 mo), Ieq.). Then N,N-diisopropylethyJamine (43 mL, 0.247 mo], 2.3 eq.) was added via an addition funnel, and the reaction was stirred for 3 hours with slow warming to room temperature. After work-up, D-2-(4-bromo-benzencsu]fonylamino)-3-melhyl-butyric acid ten-butyl ester was obtained in 94 % yield. !H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=l 1.4, 6.8 Hz, 6 H) 1.2 (s, 9 H) 1.9 (m. I H) 3.5 (dd, J=9.5,6.2 Hz, 1 H) 7.7 (d, J=8.8 Hz, 2 H) 7.8 (m, 2 H) 8.2 (d, J=9.6 Hz, 1 H). Step 3: Suzuki coupling of 3-methyl-benzofuran-2-carboxylic acid [4-(4,4,5,5-fetramethy]-[l,3,2)dioxaDorolan-2-yl)-phenyl]-amide with D-2-(4-bromo-benzenesuifonyIamino)-3-methyI-butyric acid tert-butyl ester was carried out according to Example 38, Step 3, to give D-3-methyl-2-{4'-[(3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyJamino}-butyric acid tcrt-butyl ester in 66% yield. JH NMR (400 MHz, CDCh) 5 ppm 0.9 (d, 7=6.8 Hz, 3 H) 1.0 (d, 7=6.8 Hz, 3 H) 1.2 (s, 9 H) 2.1 (m, 1 H) 2.7 (s, 3 H) 3.7 (dd, 7=10.0, 4.4 Hz, 1 H) 5.1 (d, 7=9.9 Hz, 1II) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.5 (rn, 1 H) 7.6 (d, 7=8.6 Hz, 2 H) 7.7 (d, 7=8.6 Hz, 3 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (d, 7=8.6 Hz, 2 H) 8.5 (s, 1 H). Step 4: Removal of t-butyl ester of D-3-methyl-2-{4-[(3-methyJ-bcnzoruran-2-carbony])-amino]-biphenyJ-4-sulfonyJamino}-butyric acid tert-butyl ester was done according to Example 1, Step 3, in quantitative yield. 'H NMR (400 MHz, CD3OD) 5 ppm 0.8 (dd, J=24.1, 6.7 Hz, 6 H) 1.9 (m, 1II) 2.6 (s, 3 H) 3.6 (d, J=5.8 Hz. 1 H) 7.3 (t, J=7.6 Hz, I H) 7.4 (m, 1II) 7.5 (d, J=8.3 Hz, 1 H) 7.6 (m, 3 H) 7.7 (d, J=8.3 Hz, 2 H) 7.8 (m, 4 H) 10.1 (s, 1 H). 108 Example 75: D-2-{4'-[(Benzofuran-2-carbony!)-methyI-aminoJ-biphenyI-4-suIfonylamino}-3-methyl-butyric acid WO 2005/061477 PCT/US2003/0408J5 Step 1: Amide coupling of benzofuran-2-carboxylic acid with 4-(4,4,5,5-tetraniethyl-[l,3,2]dioxaborolan-2-yl)-phenylamine was done according to Example 20, Step 4 to give benzofuran-2-carboxyJic acid [4-(4,4,5,5-tetramcthyI-[l,3,2]dioxaborolan-2-yl)-phenyl]-amide in 83% yield. *H NMR (400 MHz, DMSO-d6 ) dppm 1.3 (s, 12 H) 7.4 (m, 1 H) 7.5 (m, 1 H) 7.7 (d, J=8.3 Hz, 2 H) 7.7 (dd, 7=8.5,0.9 Hz, 1 H) 7.8 (m, 4 H) 10.6 (s. 1 H) Step 2: To a solution of benzofuran-2-carboxylic acid [4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-amide (195 mg, 0.54 mmol, 1 eq) in 3.5 mL of DMFunder nitrogen atmosphere was added NaH (60% in mineral oil, 23 mg, 0.58 mrnol, 1.1 eq). After 30 min of reaction, iodomethane (0.05 mL, 0.8 mmol, 1.5 eq) was added and the reaction was allowed to go for 12h. After work up and column chromatography, benzofuran-2-carboxylic acid methyl-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-amJde (83 mg) was obtained in 41% yield. ]H NMR (400 MHz, Benzene-de) 5 ppm 1.3 (s, 12 H) 3.4 (s, 3 H) 6.9 (d, 7=0,8 Hz, 1 H) 7.0 (m, 4 H) 7.2 (m, 2 H) 8.1 (d, 7=8.3 Hz, 2 H). Step 3: Suzuki coupling of benzofuran-2-carboxylic acid methyl-[4-(4,4,5,5-tetramethyl-[l,3,2]djoxaboro]an-2-yl)-phenyl]-amidewithD-2-(4-bromo-benzenesulfonylamino)-3-methyl-butyric acid tert-butyl ester was carried out according to Example 38, Step 3 to give D-2-{4-t(benzofuran-2-carbonyl)-methyl-amino]-biphenyI-4-sulfonylamino}-3-methyI-butyric add tert-butyl ester in 77% yield. 'H NMR (400 MHz, CD3OD) 5 ppm 0.8 (m, 6 H) 1.1 (s, 9 H) 1.9 (m, 1 H) 3.4 (s, 3 H) 3.5 (d, 7=5.8 Hz, 1 H) 6.6 (s, 1 H) 7.1 (m, 1 H) 7.2 (m, 2 H) 7.3 (d, 7=8.8 Hz, 2 H) 7.4 (d, 7=7.8 Hz, 1 H) 7.6 (d, 7=8.8 Hz, 2 H) 7.7 (d, 7=8.6 Hz, 2 H) 7.8 (m, 2 H). Step 4: Removal of t-butyl ester was done according to Example 1, Step 3, in quantitative yield. 'H NMR (400 MHz, DMSO-d6 ) d ppm 0.8 (dd, J=12.1,6.8 Hz, 6 H) 1.9 (m, 1 H) 3.5 (dd, J=9.3,6.1 Hz, 1 H) 5.1 (s, 2 H) 7.1 (d, J=8.8 Hz, 2 H) 7.5 (m, 1 H) 7.6 (d, J=7.6 Hz, 1 H) 7.7 (d, J=8.8 Hz, 2 H) 7.8 (s, 4 H) 7.9 (dd, J=7.8,1.3 Hz, 1 H) 8.0 (d, J=9.3 Hz, 1 H). 109 Example 76: 4.{5-[(Benzofuran-2-carbon}I)-arnino]-pyridin-2-yI}-benzenesulfon)l-L-valine WO 2005/061477 PCT/US2003/040835 Step I: 4~Bromo-benzenesulfonyl-L-vaIine-r-butyl ester, prepared from L-valine-t-butyl ester and 4-bromobenzenesulfonyl chloride according to the procedure of Example 38, Step 1, (10.2 mmol) was dissolved in DMSO (40 mL). To the solution was added PdCl2(dppf) (0.51 mmol), KOAc (30.6 mmol), bis(pinacolato)diboron (13.3 mmol), and dppf (0.51 mmol). The reaction mixture was de-gassed and stirred overnight at 75°C. The mixture was diluted with BOAc and washed with brine (3x). The organic layer was separated and dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography to afford 1.57 g of 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-benzenesulfonylJ-L-valine-f-butyl ester. Step 2: The ester from Step 1 (0.45 mmol) was dissolved in 1,4-dioxane (2 mL). To the solution was added Pd(PPh3)4 (0.022 mmol), K3PO4 (0.90 mmol), and 2-bromo-5-nitro-pyridine (0.48 mmol). After degassing, the mixture was stirred at 80°C for 16h. The mixture was diluted with ethyl acetate and washed with brine (3x). The organic layer was separated and dried over anhydrous sodium sulfate, and then concentrated. The crude product was purified by flash chromatography to afford 4-(5-nitro-pyridin-2-yl)-benzenesulfonyl-L-vaIine-/-butyl ester in 56 % yield. Steps 3-6: The nitro group of the product was reduced to the amino group using the procedure for Example 2, Step 4. The resulting product was acylated with benzofuran-2-carbonyl chloride using the same procedure as that for N-({4-[(l-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl fluoride to give 4-{5-[(bcnzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonyl-L-valine-r-butyl ester. The tert-butyl group was removed using the procedure of Example 1, Step 3 to give 4-{5-f(benzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonyl-L-vaIine. LCMS MH*(m/z) 494. 'H NMR (300MHZ, CDCl3/CD3OD): 8 9.0 ppm (d, 1H, J=2.5 Hz), 8.45 ppm (dd, 1H, J,=S.6 Hz, J2=2.6 Hz), 8.08-7.93 ppm (dm, 4H), 7.85 ppm (d, 1H, J=9.0 Hz), 7.77-7.62 ppm (m, 3H), 7.54-7.48 ppm (m, 1H), 7.39-7.33 ppm (m, 1H), 4.43 ppm (s, 1H), 3.75 ppm (d, 1H, J=5.2 Hz), 2.17 ppm (m, 1H), 1.01 ppm -N-methyl-D-valjne. Yield 77.9%. m.p. 239-24rC;-MS 505.1(M-H) 111 WO 2005/061477 PCT/US2003/040S35 Example 78: N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-}sulfonyl)-N-methyl-L-valine According to the same general method as Example 77,0.2g of L-valinc methyl ester hydrochloride provided 0.13g of N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyI)-N-methyl-L-valine. Yield 77.6%. m.p. 237-239°C; MS 505.0(M-H) Example 79: N-({4'-[(l-Benzofuran-2-yIcarbony!)amino]-l,r-biphenyl-4-yl}sulfonyl)-N-methylglycine According to the same general method as Example 77,0.14g of sarcosine methyl ester hydrochloride provided O.lg of N-({4'-[(l-bcnzofuran-2-ylcarbonyl)amino]-l,r-biphenyl-4-yl}sulfonyl)-N-methylglycine. m.p. 226-228°C; MS 463.1(M-H) Example 80: (S)-2-{4'-[(l,3-Dimethyl-lH-thleno[2,3-c]pyrazoIe-5-carbonyl)-amino]-biphenyI-4-sulfonylamino}-3-methyI-butyric acid Step 1. Coupling of l,3-dimethyl-lH-thieno(2,3-c]pyrazolc-5-carboxylic acid (commercially available) with L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester was carried out according to the procedure described in Example 21, Step 3. The (S)-2-{4'-[(l,3-dimethyl-lH-thieno[2,3-c]pyrazole-5-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-rnethyl butyric acid methyl ester was obtained as a white solid in 75% yield. 112 WO 2005/061477 PCT/US2003/040835 Step 2. Hydrolysis of (S)-2-{4>-l(l,3-dimethyl-lH-thieno[2,3:c]pyrazole-5-carbonyl)-amino-biphenyl-4-su]fonylamino}-3-methyl-butyric acid methyl ester according to the procedure described in Example 20, Step 5 afforded (S)-2-{4*-[(l,3-300°C; MS 562.3 (M+H)+. Example 86: N-[(4'-{[(5-EthyI-4-methoxy-3-inethyl-l-benzofuran-2-yl)carbonyl]amino}-l,r-biphenvI-4-yl)sulfonyl]-L-valine Step 1: To a solution of 2.0g (II. 1 mmol) of 2,6-dihydroxy-3-ethyl-acetophenone in 21 mL of acetone was added 2.45g (17.8 mmol) of potassium carbonate and 1.35 mL (12.2 mmol) of ethyl bromoacetate. The resulting mixture was refluxed for 3.5h and then cooled to room temperature and filtered. The filtrate was diluted with water, acidified with IN HO and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:10) to provide 2. Ig of ethyl (2-acetyJ-4-ethyl-3-hydroxyphenoxy)acetate. Step 2: To a solution of 1.92g (7.22 mmol) of ethyl (2-acetyl-4-ethy]-3-hydroxyphenoxy)acetate in 35 mL of absolute ethanol was added 0.54g (7.94 mmol) of sodium ethoxide. The reaction was heated at reflux for 3h and then cooled to room temperature, acidified with IN HCI, and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/heaxnes (1:9) to provide 0.9g of ethyl 3-methyl-4-hydroxy-5-ethylbenzofuran-2-carboxyJate. Step 3: To a solution of 0.25g (1.01 mmol) of ethyl 3-methyJ-4-hydroxy-5-ethylbenzofuran-2-carboxyJate in 3.0 mL of DMF was added 0.417g (3 eq) of potassium carbonate and 0.63 mL (10 eq) of iodomethane and the reaction was stirred at room temperature for 14h. The reaction was then diluted with ether and water. The organic layer was washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eJuting with ethyl acetate/hexanes (1:10) to provide 0.24g of ethyl 3-methyl-4-methoxy-5-ethylben2ofuran-2-carboxylate. 115 WO 2005/061477 PCT/US2003/040835 Step 4: To a solution of 0.22g (0.82 mmol) of ethyl 2-methyl-3-methoxy-4-cthylbj?nzofuran-2-carboxylate in 4.1 mL of methanol and 4.1 mL of THF was added 4.1 mL of IN sodium hydroxide solution. The reaction was stirred for 12h at room temperature and then acidified with IN HC1 and extracted with ethy] acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo to provide 0.201 g of 3-methyl-4-methoxy-5-ethylbenzofuran-2-carboxylic acid. Step 5: To 0.094g of 3-methyl-4-methoxy-5-cthylbenzofuran-2-carboxylic acid, 0.27g of ben20triazole-l-yloxytri(pyrroHdjnophosphonium)hexaf]uorophosphate and 0.145g of L-2-(4-amino-biphenyl-4-sulfonylamJno)-3-methyl-butyric acid methyl ester (Example 2A, Step 4), in 1.5mL DMF, cooled in an ice bath, was added N,N-diisopropylethylamine and the resulting mixture was stirred at 0°C for 5 minutes. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was concentrated in vacuo, and the residue was extracted with djchJoromethane and water. The organic layer was washed with water and brine, dried over Na2SO4, filtered, concentrated in vacuo, and purified by column chromatography eluting with hexane.ethyl acetate (3:2) to provide 0.17g of methyl N-((4'-{ [(5-ethyl-4-methoxy-3-methyl-l-benzofuran-2-yl)carJbonyl]amino}-l,r-biphenyl-4-yI)sulfonyl]-L-valinate. Yield 73.9%. m.p.l70-172°C; MS: 579.3 (M+H)+. Step 6: According to the procedure of Example 2A, Step 6, 0.16g of methyl N-[(4'-{ [(5-ethyl-4-methoxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino)-l,r-biphenyl-4-yl)sulfonyl]-L-valinate provided 0.1 lg of N-[(4*-{[(5-ethyl-4-methoxy-3-methyl-l-bcnzofuran-2-yl)carbonylJamino}-l)r-biphenyJ-4-yl)sulfonyl]-L-valine. Yield 70.5%. m.p. 225-22S°C; MS 565.3 (M+H)+. Example 87: N-[(4'-{[(4-Ethyl-3-mcthyl-l-benzofuran-2-y])carbonyl]amino}-l,l'-biphenyl-4-yI)sulfonyI]-L-vaIine Step 1: To a solution of 2.48g (7.05 mmol) of 3-methyl-4-trifIuoromethanesulfonyloxy-benzofuran-2-carboxylic acid ethyl ester (Example 20, Step 2) in 30 mL of DMF was added 2.16 mL (7.40 mmol) of vinyl tributyltin, 0.S98g (21.1 mmol) of lithium chloride and 0.247g (0.352 mmol) of tctrakis(triphenylphosphine)palladium(0). The reaction was heated to 90°C for 3h and then cooled to room temperature. The reaction was diluted with water and extracted with ether. The combined organics were washed with water and brine, dried over magnesium sulfate, 116 WO 2005/061477 PCT/US2003/040835 filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl cctate/hexanes (1:25) to provide 1.22g of 3-methyl-4-vinylbenzofuran-2-carboxylic acid ethyl ester. Step 2: To a solution of 0.40g (1.74 mmol) of 3-methyl-4-vinylbenzofuran-2-carboxylic acid ethyl ester in 25 mL of ethyl acetate under nitrogen was added 0.050g of 10% palladium on carbon. The reaction was shaken on a Parr hydrogenator under 40 psi of hydrogen for 4h. The reaction was then filtered through a pad of celite. The celite was washed with an additional 150 mL of ethyl acetate and the filtrate was concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetaie/hexanes (1: 30) to provide 0.395 of 3-methyl-4-ethylbenzofuran-2-carboxylic acid ethyl ester. Step 3: To a solution of 0.380g (1.64 mmol) of 3-inethyl-4-ethylbenzofuran-2-carboxylic acid ethyl ester in 8 mL of methanol and 8 mJL of THF was added 8.2 mL of IN sodium hydroxide solution and the reaction was stirred for 14h at room temperature and then acidified with IN HC1 and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo to provide 0.321 g of 3-methyl-4-ethylbenzofuran-2-carboxyJic acid. ' Step 4: According to the procedure of Example 86, Step 5,0.082g of 3-methyI-4-ethylbenzofuran-2-carboxylic acid and 0.15g of L-2-(4'-amino-biphenyl-4-sulfonylamuno)-3-methyl-butyric acid methyl ester provided 0.19g of methyl N-[(4'-{[(4-ethyl-3-methyl-l-ben2ofuran-2-yl)carbonyJ]amin0}-1,1 -biphenyl-4-yl)suJfonyl]-L-vaJinate. Yield 86.3%. m.p.183-185°C; MS; 549.2 (M+H)+. Step 5: According to the procedure of Example 2A, Step 6,0.16g of methyl N-[(4-{[(4-ethyl-3-methyl-l-benzofuran-2-yl)carbonyl]amino)-l,r«bJphenyl-4-yl)sulfonyl]-L-vaJinate provided 0.075g of N-[(4-{ [(4-ethy]-3-methyl-I-benzofuran-2-yl)carbonyl]amino}-l,1 -biphenyl-4-y))sulfonyl]-L-vaIine. Yield 48.1%. m.p. 239-241°C; MS 535.3 (M+H)+. Example 88: N-[(4*-{[(5-Ethyl-4-isopropoxy-3-metbyl-l-benzofuran-2-yl)carbonynamino}-l,l'-biphenyl-4-yl)sulfonyll-L-valine Step 1: According to the procedure of Example 86, Step 3 0.200g<0.81 mmol) of 3-roethyl-4-hydroxy-5-ethylbenzofuran carboxylic acid ethyl ester (Example 86, Step 2) and 0.379 117 WO 2005/061477 PCT/US2003/040835 mL (4.03 mmol) of 2-bromopropane gave 0.21 lg of 5-ethyl-4-isopropoxy-3-methylbenzofuran-2-carbwylic acid ethyl ester after chromatography on silica gel cluting with ethyl acetate/hexanes (1:20). Step 2: According to the procedure of Example 86, Step 4, 0.170g (0.586 mmol) of 5-ethyl-4-isopropoxy-3-methyl-l-benzofuran-2-carboxylic acid ethyl ester provided O.142g of 5-ethyl-4-isopropoxy-3-methylbenzofuran-2-carboxylic acid, purified by washing with hcxanes. Step 3: According to the procedure of Example 86, Step 5,0.052g (0.2mmol) of 5-ethyl-4-isopropoxy-3-methylbenzofuran-2-carboxylic acid and 0.073g of L-2-(4-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester provided 0.1 lg of methyl N-[(4'-{ [(5-ethyl-4-isopropoxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino)-l,r-biphenyl-4-yl)sulfonyl]-L-valinate. Yield 89.3%. m.p. 182-184°C; MS: 607.3 (M+H)Step 4: According to the procedure of Example 2A, Step 6, O.O55g of methyl A'-((4 -{[(5-ethyl-4-isopropoxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino}-l,r-biphenyl-4-yl)sulfonyl]-L-valinate provided 0.053g of N-[(4'-{[(5-ethyl-4-isopropoxy-3-methyl-l-benzofuran-2-yl)carbonynamino)-l,r-biphenyl-4-yl)sulfonyl]-L-valinc. Yield -100%. m.p. 159-162°C; MS 591.3 (M-H)Example 89:/V-{[4'-({[4-(Benzyloxy)-5-ethyI-3-mcthyI-l-bcnzofuran-2-yl]carbonyl}amino)-l,l'-biphenYl-4-ynsulronyl]-L-valine Step 1: According to the procedure of Example 86, Step 3,0.250g (1.01 mmol) of 3-methyl-4-hydroxy-5-ethylbenzofuran carboxylic acid ethyl ester (Example 86, Step 2) and 0.599 mL (5.04 mmol) of benzyl bromide gave 0.34lg of 5-ethyl-4-benzyloxy-3-methylbenzofuran-2-carboxylic acid ethyl ester after chromatography on silica gel eluting with ethyl acetate/hexanes (1:20). Step 2: According to the procedure of Example 86, Step 4 .307g (0.908 mmol) of 5-cthyl-4-bcnzyloxy-3-methyl-l-benzofuran-2-carboxylic acid ethyl ester provided 0.219g of 5-ethyl~4-benzyloxy-3-methylbenzofuran-2-carboxylic acid, purified by washing with hexanes. Step 3: According to the procedure of Example 86, Step 5, 0.155g (0.5mmol) of 5-ethyl-4-benzyloxy-3-methylbenzofuran-2-carboxylic acid and 0.18g of L-2-(4-amino-biphenyl-4-su]fonylamino)-3-methyl-butyric acid methyl ester provided 0.21g of methyl N-{[4'-({[4- 118 PCT/US2003/040835 WO 2005/061477 (benzyloxy)-5-ethyI-3-methyl-l-benzofuran-2-yl]carbonyl }amino-l,1-bipbenyI-4-ylsulfonyl}-L-valinate. Yield 63.6%. m.p. 191-193°C; MS: 655.2 (M+H)+ Step 4: According to the procedure of Example 2A, Step 6,0.06g of methyl N-{[4'-({[4-(benzyioxy)-5-ethyI-3-methyl-1 -benzofuran-2-yl]carbonyl} amino)-1,1 '-biphenyM-ylJsulfonyl }-L-valinate provided 0.054g of N-{ [4'-({[4-(benzy]oxy)-5-ethyl-3-methyl-l-bcnzofuran-2-yl]carbonyl}amino)-1,1-biphenyl-4-yl]sulfonyl}-L-valine. Yield 86%. m.p. 224-226°C; MS 639.2 (M-H)Example 90:N-[(4'-{(5-Ethyl-hydroxy-3-rnethyl-l-bcnzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-yl)sulfonyl]-L-valine Step I: To O.lg (0.15mmol) of methyl N-{[4 -({[4-(benzy?oxy)-5-ethyl-3-methyl-I-benzofuran-2-yl]carbonyl}amino)-l,1-biphenyl-4-yl3sulfonyl}-L-valinate from Example 89, dissolved in 20 mL of methanol and l0mL of THF was added 0.2g of 10% palladium on active carbon and the mixture was hydrogenated in a Parr hydrogenator at 40 psi for 4hours. The reaction mixture was then filtered through cclite and the celite pad was washed with with methanol. The filtrate was concentrated in vacuo to provide 0.11g of methyl N-[(4'-{ [(5-ethyl-4-hydroxy-3-methyyl-benzofuran-2-yJ)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonylJ-L--valinatc. Yield - 100%, m.p. 75-80°C MS: 565.2 (M+Hf. Step 2: According to the procedure of Example 2A, Step 6,0.098g of methyl N-[(4'-{[(5-ethyl-hydroxy-3-methyl-l-benzofuran-2-yl)carbonyl]arnino}-l,r-biphenyl-4-yl)sulfonyI]-L-valinate provided 0.054g of N-[(4 -|[(5-ethyl-4-hydroxy-3-methyl-l-benzofuran-2-y])carbonyl3amion}-l,1-biphenyl-4-yl)su]fonyl]-L-valine. Yield 56.8%. m.p. 122-125°C; MS 549.2 (M-H)-. 119 Example 91: N-|[4''({[4-(2,2-DJmethyl-l,3-dioxolan-4-yl)-3-mehyl-l-benzofuran-2-yI]carbonyl}amino)-l,1-biphenyl-4-yl]sulronyl}-L-valine WO 2005/061477 PCT/US2003/040835 Step: To-a solution of 0.146g (1.25 nunol) of N-methylmorpholine N-oxide in 1 ml- of THF and 3 mL of water was added 0.272 mL of osmium tetroxide (2.5 weight % in t-butano), 0.022 mmol) followed by 0.250g (.087 mmol) of 3-methyl-4-vinylbenzofuran-2-carboxylic acid ethyl ester (Example 87, Step I) dissolved in 1 mL of THF. The reaction was stirred for 2h at room temperature and then quenched with excess aqueous sodium hydrosulfite solution. The resulting mixture was extracted with ethyl acetate, and the combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:1) to provide 0.202g of 4-(l,2-dihydroxyethyl)-3-methylbenzofuran-2-carboxylic acid ethyl ester. Step 2: To a solution of 0.150g (0.568 mmol) of 4-(l,2-dihydroxyethyl)-3-methylbenzofuran-2-carboxylic acid ethyl ester dissolved in 5 mL of acetone was added O.OlOg of p-tolucncsulfonic acid and the reaction was stirred at room temperature overnight. Saturated sodium bicarbonate was added and the acetone was removed in vacuo. The residue was extracted with ether, the organics were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:5) to provide 0.172g of 4-(2,2-dimethyl-l,3-dioxolan-4-yl)-3-methylbenzofuran-2-carboxy]ic acid ethyl ester. Step 3: According to the procedure of Example 86, Step 4,0.172 g (0.566 mmol) of 4-(2,2-dimethyI-l,3-dioxolan-4-yJ)-3-mcthylbenzofuran-2-carboxylic acid ethyl ester provided 0.147g of 4-(2,2-dimethyl-l,3-dioxolan-4-yl)-3-methylbenzofuran-2-carboxyJic acid as a white solid after purification by washing with ether/hexanes (1:1). Step 4: According to the procedure of Example 86, Step 5, 0.116g (0.41 mmol) of 4-(2,2-dimethyl-l,3-dioxolan-4-yl>3-methylbenzofuran-2-carboxylic acid and O.lSg of L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-rnethyl-butyric acid methyl ester provided 0.18g of methyl N-{[4-({(4-(2,2-dimethyl-l,3-dioxolan-4-yI)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-],l -biphenyl-4-yl]sulfonyl}-L-valinate. Yield 89.4%. m.p. 192-194°C; MS: 619.3 (M-HT. Step 5: According to the procedure of Example 2A, Step 6,0.157g of methyl N-{[4-({[4-(2,2-dimethyl-l,3-dioxolan-4-yl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,l'-biphenyl-4-yl]suJfonyl}-L-vaIinate provided 0.084g of N-{[4-({[4-(2,2-dimethyl-l,3-dioxo]an-4-yl)-3-methyl-1 -benzofuran-2-yl]carbonyl Jamino)-1,1 -biphcnyI-4-y]]sulfonyl}-L-valine. Yield 54.97o. m.p. 240°C(d). MS 605.2 (M-H)120 WO 2005/061477 PCT/US2003/040835 Exarample 92:N-{[4'.({[4-(Hydroxymethyl)-3-methyl-l-benzofuran-2.yl]carbonyl}amJno)-l,1-biphenyl-4-yl]sulfonyI}-L-valine Step 1: To a solution of 0.250g (1.087 mmol) of 3-mcthyl-4-vinylbcnzofuran-2-carboxylic acid ethyl ester (Example S7, Step 1) in 7.5 mL of dioxane and 2.5 mL of water was added 0.272 mL of 2.5 weight % osmium tetroxide in t-butanol (0.022 mmol) and the reaction was stirred for 10 minutes at room temperature, turning yellow-brown in color. Sodium periodate (0.4S8g, 2.282 mmol) was then added in several portions over 30 minutes and a white precipitate formed. The reaction was stirred at room temperature for 2h and then diluted with water and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel cluting with ethyl acetate/hexanes (1:10) to provide 0.225g of 4-carbonyl-3-methylbenzofuran-2-carboxyIic acid ethyl ester. Step 2: To a solution of 0.123g (0.530 mmol) of 4-carbonyl-3-methylbenzofuran-2-carboxylic acid ethyl ester in 10 mL of ethanol was added 0.019g (0.505 mmol) of sodium borohydride. The reaction was stirred at room temperature for 2h and than diluted wuth water and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel cluting with ethyl acetate/hexanes (1:3) to provide 0.113g of 4-hydroxymethyl-3-methy)benzofuran-2-carboxylic acid ethyl ester. Step 3: To a solution of 0.220g (0.940 mmol) of 4-hydroxymethyJ-3-methylbenzofuran-2-carboxylic acid ethyl ester in 5 mL of DMF was added 0.156g (1.034 mmol) of t-butyldimethylsilyl chloride and 0.160g (2.350 mmol) of imidazole and the reaction was stirred at room temperature for 14h. The reaction mixture was diluted with water and extracted with ether. The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:10) to provide 0.315g of 4-tert-butyl(dimethyl)silyloxymethyl-3-methylbenzofuran-2-carboxylic acid ethyl ester. Step 4: According to the procedure of Example 86, Step 4, 0.277 g (0.796 mmol) of 4-tert-buty](dimethyl)siJyloxymethyl-3-methylbenzofuran-2-carboxylic acid ethyl ester provided 121 WO 2005/061477 PCT/US2003/040835 0.054g of 4- tert-butyl(dimethy))sily]oxymcthyl-3-methy]benzofuran-2-carboxylic acid after chromatography on silica gel eluting with ethyl acetate/hexanes (1:3). Step 5: According to the procedure of Example 86, Step 5,0.115g of 4-({ [tert-butyl(dimethyl)silyl]oxy}methyl)-3-methyl-l-benzofuran-2-carboxylic acid and 0.13g of L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester provided 0.20g of methyl N-{[4-({[4-({[tert-butyl(dimcthyl)silyl]oxy}methyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,r-biphenyl-4-yl]sulfonyl)-L-valinate. Yield 84.5%. m.p. 204-206°C; MS: 663.4 (M-H)Step 6: According to the procedure of Example 2A, Step 6, 0.18g of methyl N-{[4'-({[4-({[tert-butyl(dimethyl)si]yl]oxy}methyl)-3-rnethyl-l-benzofuran-2-yl]carbonyl}amino)-l,l'-biphcnyl-4-yl]suIfonyl}-L-valinatc provided 0.13g of N-{[4'-({[4-(hydroxymethyl)-3-mcthyl-l-benzofuran-2-y]]carbonyl}amino)-l,l -biphenyl-4-yl]sulfonyl}-L-valine. Yield 73.3%. m.p. . 272°C(d). MS 535.12 (M-H)Example 93: N-[(4'-{[(3,4-DimethyI-l-bcnzofuran-2-yl)carbonyI]amlno}-l,l'-biphcnyI-4-yI)sulfonyl]-L-valine Step 1: To a solution of 0.200g (0.855 mmo!) 4-hydroxvmethyl-3-rnethylbenzofuran-2-carboxylic acid ethyl ester (Example 92, Step 2) in 5 mL of THF was added 0.336g (1.28 mmol) of triphenylphosphine and O.355g (1.07 mmol) of carbon tctrabromide. The reaction was stirred at room temperature for lh and then concentrated in vacuo. The residue was diluted ith 20 mLof ether and filtered. The filtrate was concentrated in vacuo and chromatographed on silica gel eluting with ethyl acetate/hexanes (1:10) to provide 0.196g of 4-bromomethyl-3-methylbenzofuran-2-carboxylic acid ethyl ester. Step 2: To a solution of 0.291 g (0.98 mmol) of 4-bromornethyl-3-rnethylbenzofuran-2-carboxylic acid ethyl ester in 5 mL of DMSO was added 0.074g (1.96 mmol) of sodium borohydridc and the reaction was stirred at room temperature for 2h. The reaction was diluted with water and extracted with ether. The organics were washed with water and brine, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:10) to provide 0.209g of 4-methyl-3-methylbenzofuran-2-carboxylic acid ethyl ester. 122 WO 2005/061477 PCT/US2003/040835 Step 3: According to the procedure of Example 86, Step 4, 0.206g (0.95 mmol) of 4-rnethyl-3-methylbenzofuran-2-carboxylic acid ethyl ester provided 0.175g of 4-methyl-3-methylbcnzofuran-2-carboxylic acid. Step 4: According to the procedure of Example 86, Step 5, 0.067g of 4-methyl-3-inethylbenzofuran-2-carboxylic acid and 0.13g of L-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester provided 0.14g of methyl N-[(4-{l(3,4-dimethyl-l-benzofuran- 2-yl)carbonyl]amino}-l,r-biphenyI-4-yl)sulfonyl]-L-valinate. Yield 53.8%. m.p.l99-200°C; MS: 535.1 (M+H)+. Step 5: According to the procedure of Example 2A, Step 6,0.12g of methyl N-[(4-{[(S^-dimethyl-benzofuran-ylarbonynarnino)-11,-biphenyl-yt)sulfonyl]L-valinate provided 0.12g of N-[(4'-{[(3,4-dimethyl-l-benzofuran-2-yl)carbonyl]amJno}-l,1-biphenyl-4-yl)su]fonyl]-L-valine. Yield -100%. m.p. 250-252°C; MS 519.2 (M-H)". Example 94: N-[(4-{t(4-Acetyl-3-methyl-l-benzofuran-2-yl)carbonyl]amino}-l,l'-bJphenyl-4-yl)sulfonyl]-L-valine Step 1: To a solution of 2.061 g (5.86 mmol) of 3-rncthyl-4-trifluoromethanesuifonyloxy-benzofuran-2-carboxylic acid ethyl ester (Example 20, Step 2) in 26 mL of DMF was added 3.0 mL of butyl vinyl ether, 1.6 mL of triethylaminc, 0.077g of palladium acetate, and0.139g of 1,3-bis(dipheny!phosphino)propane. The resulting mixture was heated to 60°C for 24h and then cooled tor room temperature. The mixture was diluted with water and extracted with ether. The organics were washed with water and brine, filtered and concentrated in vacuo. The residue was filtered through a pad of silica gel eluting with ethyl acetate/hexanes (1:10) to provide a mixture of 4-acetyl-3-methylbenzofuran-2-carboxyJic acid ethyl ester and ethyl 4-(l-butoxyvinyl)-3-methyl-l-benzofuran-2-carboxylatc. The mixture was dissolved in 12.9 mL of acetic acid and 8.6 mL of 3N HC1 and stirred at room temperature for lh. The reaction was diluted with water and extracted with ether. The organics were washed with water and brine, filtered and concentrated in vacuo. The residue was filtered through a pad of silica gel eluting with ethyl acetate/hexanes (1:20) to provide 1.16g of 4-acetyl-3-methylbenzofuran-2-carboxylic acid ethyl ester. 123 WO 2005/061477 PCT/US2003/040835 Step 2: According to the procedure of Example 86, Step 4,0.200g of 4-acetyl-3-methylbenzofuran-2-carboxylic acid ethyl ester provided 0.165g of 4-acetyl-3-methylbenzofuran-2-carboxylic acid. Step 3; According to the procedure of Example 86, Step 5,0.165g of 4-acetyl-3-methyl-l-benzofuran-2-carboxylic acid and 0.27g of L-2-(4-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester provided 0.20g of methyl N-[(4-{[(4-acetyl-3-methyl-l-benzofuran-2-y3)carbonyl]amino}-l,l-bipbenyl-4-y])su3fonyl3-L-valinate. Yield 47.6%. m.p.l97-199°CMS: 535.1 (M+H)+. Step 4: According to the procedure of Example 2A, Step 6, 0.23g of inethy] N-I(4'-{[(4-acety]-3-meth'yl-l-benzofuran-2-yl)carbonyl]amino}-l,r-bipheiiyl-4-yl)su]fonyl]-L-valinate provided O.Hg of N-[(4-{ [(4-acetyl-3-methyl-l-benzofuran-2-y])carbonyl}amino}-l,l-biphenyl-4-yl)sulfonyl]-L-valine. Yield 50.1%. m.p. 228-235 °C; MS: 547.2 (M-H)Example 95: N-{[4'-({[4-(l-Hydroxethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,l'-biphenyI-4-yI]sulfonyl}-L-valine To a solution of 0.05g of N-[(4-{[(4-acetyl-3-methyI-l-benzofuran-2- yl)carbon)'3]amino}-l,l-biphenyl-4-yl)sulfony]]-L-valine, the product of Example 94, Step 3, in 18 mL of ethanol was added O.Olg of sodium borohydride and the reaction was stirred at room temperature for 2 hours. The reaction was quenched with IN HO, adjusting to ~pH3. The reaction mixture was concentrated in vacuo and the residue was then extracted with ethyl acetate. The. organic layer was washed with water, brine, dried over Na2SC4, filtered, and concentrated to provide 0.037g of N-{ [4'-({[4-(l-hydroxyethyl)-3-methyI-l-benzofuran-2-yl]carbonyl}amino)-l,r-biphenyl-4-yl]sulfony]}-L-va]ine. Yield 74%. m.p. 148°C(d); MS: 549.1(M-H)-. 124 Example 96: N-[(4'-{[(3-methyl-4-vinyl-l-benzofuran-2-yl)carbonyl]amino}-l5l'-biphenyl-4-yl)sulfonyl]-L-valine WO 2005/061477 PCT/US2003/040835 Step 1: According to the procedure of Example 36, Step 4,0.300g (1.304 mmol) of 3-methyl-4-vinyl-benzofuran-2-carboxylic acid ethyl ester (Example 87, Step 1) provided 0.256g of 3-methyl-4-vjnyl-benzofuran-2-carboxylic acid after chromalography on silica gel eluting with ethyl acctatc/hexanes (1:3). Step 2: According to the procedure of Example 86, Step 5, 0.08 lg of 3-methyl-4-vinyl-benzofuran-2-carboxylic acid and 0.15g of L-2-(4'-amino-biphenyl-4-sulfonylajruno)-3-methyl-butyric acid methyl ester provided 0.18g of methyl N-[(4'-{[(3-methyl-4-vinyl-l-benzofuran-2-yJ)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valinate. Yield 82%. m.p. 185°C (d);MS: 547.3 (M+H)+. Step 3: According to the procedure of Example 2A, Step 6,0.16g of methyl N-[(4-{[(3-rnethyl-4-vinyl-1 -benzofuran-2-yl)carbonyl]amino} -1,1 -biphenyl-4-yl)sulfonyl]-L-valinate p rovided O.065g of N-[(4 - {{(3-methyl-4-vinyl-l -bcnzofuran-2-yl)carbonyl]amino}-1,1 -biphcnyl-4-yl)suIfonyl]-L-valine. Yield 42%. m.p. 285°C (d); MS 531.2 (M-H)". Example 97: N-{[4-({[4-(l,2-dihydrox7ethyI)-3-methyI-l-benzofuran.2-yI]carbonyl)amino)-l,l'-biphenyl-4-yl]sulfonyJ}-L-vaIine Step 1: To a solution of N-methyl morphoIine-M-oxide (50% wt solution in wafer, 0.103g, 0.44mmol) in THF and water (lmL/OJmL) was added 0.096mL (0.38mrool) of osmium tctroxide (2.5 wt % in t-butanol). To that solution was quickly added 0.21 g (0.38mmol) of methyl N-[(4'-:{[(3-methyl-4-vinyl-l-benzofuran-2-yI)carbonyl]amJno}-l,r-biphenyl-4-y])sulfonyl]-L-va!inate (Example 96, Step 2).The reaction was stirred at room temperature for 2 hours and then quenched with excess sodium hydrosulfitc in water. The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water.and brine, dried over Na2SO4, filtered, and concentrated to provide 0.19g of methyl N-{ [4*-({ [4-(l,2-dihydroxyethyl)-3-methyI-1 -benzofuran-2-yl Jcarbonyl} amino)-1,1 -biphenyl-4-yI]sulfonyl }-L-valinate. Yield 85.2%. m.p. 90-95°C MS: 581.2 (M+H)+. Step 2: According to the procedure of Example 2A, Step 6,0.18g of methyl N-{ [4'-({[4-(1,2-dihydroxyethyl)-3-methyl-l -benzofuran-2-yl]carbonyl} amino)-l ,1 '-biphenyl-4- 125 WO 2005/061477 PCT/US2003/040835 yl]sulfony)}-L-valinate provided 0.llg of N-{4-{[4-(1,2-dihydroxyethyl-3-methyl-l-benzofuran-2-yl]carbonyllarnino-1,1-biphenyl4-yl]sulfonyl}-L-valine. Yield 61.9%. m.p. 165°C (d). MS 565.3 (M-H)'. Example 98: N-methyl-N-[(4'-{[(3-methyl-4-vinyM-benzofuran-2-y])carbony)]amino}-l,l'-biphenyl-4-yl)su)fonyl]-L-valine Step I: To a solution of 0.077g (0.14mmol) of the product of Example 96, Step 2, methyl N-[(4'-{[(3-methyl-4-vinyl4-benzofuran-2-yl)carbonyl]amino}-l,r-biphcnyl-4-yI)sulfonyl]-L-valinate, in lmL of DMF, 0.05g of potassium carbonate were added, followed by 0.018mL of iodomethane. The reaction was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was extracted with dichloronocthanc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated to provide O.lg of methyl N-methyl-N-[(4'-{ [(3-methyl-4-vinyl- l-benzofuran-2-yl)carbonyl]amino}-1,1-biphenyl-4-yl)sulfonyl]-L-valinate. Yield 63.4%. MS: 561 (M+H)+. Step 2: According to the procedure of Example 2A, Step 6,0.05g of methyl N-methyl-N-1(4- {[(3-methyl-4-vinyl- l-benzofuran-2-yl)carbonyl]amino} -1,1 -biphenyl-4-yl)sulfonyl]-L-valinatc provided 0.033g of N-methyl-N-[(4'-{[(3-methyl-4-vinyl-l-bcnzofuran-2-yl)carbonyl]amino)-l,l-biphenyl-4-yl)sulfonyl]-L-valine. MS: 547.2 (M+H)Example 99: N-{[4'-({[4-(l,2-dihydroxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl)amino)-l,1-biphenyl-4-yl]sulfonyl}-N-methyl-L-valine Step 1:'According to the procedure of Example 97, Step 1, 0.14g (025mmol) of methyl N-methyl-N-[(41-{[(3-methyl-4-vinyl-l-benzofuran"2-yl)carbonyl]amino)-l,r-biphenyl-4-yl)sulfonyl]-L-valinate was oxidized to provide 0.09g of methyl N-{[4-({[4-(],2- 126 WO 2005/061477 PCT/US2003/040835 dihydroxyethyl)-3-methyl-l -benzofuran-2-yl]carbonyl} amino)-l,l '-biphenyl-4-yl]sulfonyl} -N-metthyl-L-vaIinate. Yield 60.8%. m.p. 182-185°C; MS: 595.3 (M+H)+. Step 2: According to the procedure of Example 2A, Step 6,0.07g of methyl N-{[4-({[4-(l,2-dihydroxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl)amino)-l,1-biphenyl-4-y]]suJfonyJ}-N-methyl-L-valmate provided 0,049g of N-{[4'-({[4-(l,2-dihydroxyethyl>3-methy]-1 -benzofuran-2-yI]carbonyI} amino)-1, F-biphenyl-4-yi]sul'fonyI} -N-rnethyl-L-valine. Yield 71.9 %. m.p. 222-225°C; MS: 579.1 (M-H)-. Example 100: N-{[4'-({[4-(methoxymethyl)-3-methyl-benzofuran-2-yl]carbonyl}amino)-3,l'-bipbenyl-4-yI]sulfonyl}-L-vaIine Stepl: To a solution of 0.19g <0.81mmole) of ethyl 4-(hydroxymethyl)~3-inethyl-l-benzofuran-2-carboxylate (Example 92, Step 2) in 2 mL of chloroform was added silver (IT) oxide (0.34g, 1.46mmol, l.Seq) and 2 mL of iodomethane and the mixture was heated in sealed tube at ~ 55°C for 4.5days.The reaction was filtered and concentrated in vacuo to provide 0.20g of ethyl 4-(methoxymethyl)-3-methyl-l-benzofuran-2-carboxylate. Yield: -93.8% m.p. 45-47°C; MS:249.1(M+H)+. Step 2: According to the procedure of Example 86, Step 4,0.21g (O.SSmmole) of ethyl 4-(methoxymethyl)-3-methyl-l-benzofuran-2-carboxylate provides 0.18g of 4-(methoxymethyl)-3-methyl-l-benzofuran-2-carboxylic acid. Yield: 100% m.p. 164-166° C; MS: 219.0 (M-H)", Step 3: According to the procedure of (Example 86, Step 5) 0.066g (0.3mmole) of 4- (methoxymethyl)-3-methyl-l-benzofuran-2-carboxylic acid and 0.109g (0.3mmole) of methyl N- [(4-amino-l,r-biphenyl-4*yl)sulfonyl3-L-valinate, after purification by column chromatograph eluting with hexane/ethyl acetate (1:1) provided 0.12g of methyl N-{[4 -({{4-(methoxymethyl)- 3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,l-biphenyl-4-yl]sulfonyl}-L-valine. Yield: 71.0%m.p. 144-146° QMS: 565.3 (M+H)+. . Step 4: According to the procedure of (Example 2A, Step 6), 0.09g of methyl N-{ [4-({[4-(methoxymethyl)-3-methyl-l-benzofuran-2-yl]carbonyl)amino)-l,r-biphenyl-4-yl]sulfonyl}-L-valine provided 0.076g of N-{[4'r({[4-(methoxymethyl>3-methyM-ben2ofuran- 127 WO 2005/061477 PCT/US2003/040835 2-yI]carbonyi}amino)-l,l'- biPhenyl-4-yI]sulfonyl}-L-va1ine. Yield: 86.3% m.p. 227-230 °C; MS: 551.2 (M-H)"; Example 101: N-{[4'-{{[4-(l"melhoxyelhyI)-3-methyH-benzofuran-2-yl]carbonyI}amino)-l,l'-biphenyI-4-yl]sulfonyl}-L-vaIine Step 1: According to the procedure of Example 92, Step 2,1.065 (4.33 mmol) of 4-acetyl-3-methylbenzofuran-2-carboxylic acid ethyl ester (Example 94, Step 1) provided 0.75 g of ethyl 4-(l-hydroxyethyl)-3-methyl-l-benzofuran-2-carboxylate. Step 2: According to the procedure of (Example 100, Step 1), 0.2Ig of ethyl 4-(l-hydroxyethyl)-3-methy]-l-benzofuran-2-carboxyJaie after heating with iodomethane for 8 days provided 0.22 g of ethyl 4-(l-methoxyethyl)-3-methyl-l-benz.ofuran-2-carboxylate. Yield: -100 % m.p. 67-69°C; MS: 263.2 (M+H)+. Step 3: According to the procedure of (Example 86, Step 4), 0.17g of ethyl 4-(l-methoxyethyl)-3-rnethyl-l-benzofuran-2-carboxylate provided 0.15 g of 4-(l-methoxyethyl)-3-methyl-l-benzofuran-2-carboxylic acid. Yield 100% m.p. 113-115 °C; MS: 233.1 (M-H)". Sep 4: According to the procedure of (Example 86, Slep 5), 0.09g (0.4mmole) of 4-(l-methoxyethyl)-3-methyl-l-benzofuran-2-carboxylic acid and 0.15 g (0.4mmole) of N-[(4-amino-l,F-biphenyl-4-yl)sulfonyl]-L-valinate, after purification by column chromatography eluting with hexane/ethyl acetate (1:1) provided 0.19g of methyl N-{[4-({[4-(l-methoxyethyl)~ 3-methyl-1 -benzofuran-2-yl]carbonyl} amino)-1,1 -biphenyI-4-yl Jsulfonyl} -L-valinate. Yield 82.6% m.p. 186-188°C; MS: 579.3(M+H)+. Step 5: According to the procedure of (Example 2A, Step 6)), 0.I6g of methyl N-{ [4-({[4-(l -methoxyethy))-3-methyl-1 -benzofuran-2-yl]carbonyl} amino)- 1,1 -biphenyl-4-yl]sulfonyl}-L-valinate provided 0.12 g of N-{[4'-({[4-(l-methoxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,r-biphenyl-4-yl]sulfonyl}-L-valine. Yield 76.9% m.p. 97°C(d); MS: 563.3 (M-H)'. 128 WO 2005/061477 PCT/US2003/040835 Example 102: N-{[4>-({[4-(2-methox>ethyI)-3.methyM-benzofuran-2-y}]carbonyI}ainino)-l,l'-biphenyI-4-yl]sulfonyl}-L-valinate Step 1: To a solution of 0.35g (1.5mmol) of 3-methyl-4-vinyl-l-benzofuran-2-carboxylate (Example 87, Step 1) in 3mL of THF, cooled in an ice bath, was added lmL (1 mmol) of borane-THF complex (1.0M solution in THF). The reaction was stirred at room temperature for 2 hours. The reaction was cooled in an ice bath and 1.5 mL of water was added. Next 0.61g of sodium percarbonate was added in one portion. The reaction was heated at ~50°C for lhour, then cooled to room temperature. Water was added and the resulting mixture was extracted with ethyl acetate. The organic layer washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with hexane/ethyl acetate (2:1) to provide 0.20g of ethyl 4-(2-hydroxyethyl)-3-methy]-l-benzofuran-2-carboxylate. Yield 54%. m.p. 88-90°C; MS 249.1 (M+H)+. Step 2: According to the procedure of (Example 100, Step 1), 0. 16g (0.65mmol) of ethyl 4-(2-hydroxyethyl)-3-methyl-l-benzofuran-2-carboxylate was heated at ~55°C for 7 days to provide 0.17 g of ethyl 4-(2-methoxyethvl)-3-methyl-l-benzofuran-2-carboxylate. Yielcl -100%; MS: 263.1 (M+H)+. Step 3: According to the procedure of (Example 86, Step 4), 0.16g of ethyl 4-(2-methoxyethyl)-3-methyl-l-benzofuran-2-carboxylate provided 0.14g of 4-(2-methoxyethyl)-3-rnethyJ-l-benzofuran-2-carboxylic acid. Yield 100%; m.p. 138-140°C; M: 233.1 (M-H)". Step 4: According to the procedure of (Exampl 86, Step 5), 0.13g (0.56 mmol) of 4-(2-methoxyethyl)-3-rnethyl-l-benzofuran-2-carboxylic acid and 0.20g (0.56 mmol) of N-[(4-amino-l,r-biphenyl-4-yl)sulfonyl]-L-valinate, after purification by column chromatography eluting with hexane/ethyl acetate (1:1) provided 0.2lg of methyl N-{[4'-(U4-(2-methoxyethyl)-. 3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,r-biphenyl-4-yl]sulfonyl}-L-vaIinate. Yield 66% m.p. 67-70°C; MS: 579.1(M+H)+ Step 5: According to the procedure of (Example 2A, Step 6), 0.16g of methyl N-{[4-({[4-(2-methoxyethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,r-biphenyl-4-yljsulfonyl }-L-valinate provided 0.144g of N-{ [4'-({ [4-(2-methoxyethyl)-3-methyl-l- 129 WO 2005/061477 PCT/US2003/040835 benzofuran-2-y]]carbony]}amino)-l,r-biphenyl-4-yl]sulfony]}-L-valine. Yield 93%; m.p. 100-110°C;MS:563.2(M-H)Example 103: N-[(4'-{[(4-Isopropoxy-l-benzofuran-2-yl)carbonyI]amino}-l,l'-biphenyl-4-yl)su]fonyl]-L-valine Stepl: To a solution of 0.41g (2.13 mmol) of 4-hydroxy-2-benzofurancarboxylic acid methyl ester in 7mL of DMF was added 0.80mL (8.54mmol) of 2-bromopropane and 1.18g (8.54mmol) of potassium carbonate. The reaction was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo, and the residue was extracted with ethyl acetate. The organic layer washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 0.49g of methyl 4-isopropoxy-l-benzofuran-2-caTboxylate. Yield -100%; m.p. 43^5°C; MS: 235.1 (M+H)+. Step 2: To 0.15g (0.62mmole) of 4-isopropoxy-l-benzofuran-2-carboxylate in 2.5mL of methanol and 2.5mL of THF was added 3mL of IN sodium hydroxide solution. The solution was stirred at room temperature for 45 minutes. The reaction mixture was concentrated in vacuo, the residue was diluted with water and neutralized with IN HC1 to pH -3-4, and then extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 0.13g of 4-isopropoxy-l-benzofuran-2-carboxylic acid. Yield 94%. m.p. 148-150°C. MS: 219.1(M-H)Step 3: According to the procedure of (Example 86, Step 5), 0.1 Ig (0.5 mmol) of 4-isopropoxy-l-benzofuran-2-carboxylic acid and 0.18 g (0.5 mmol) of N-[(4 -amino-1,1'-biphenyl-4-yl)sulfonyl]-L-valinate, after purification by column chromatography eluting with hexane/ethyl acetate (1:1) provided 0.14g of methyl N-[(4'-{[(4-isopropoxy-l-benzofuran-2-yl)carbonyl]aminoj-l,l -biphenyl-4-yl)su]fonyl]-L-valinate. Yield 52%; m.p. 226-229°C; MS: 563.3(M-H)". 130 WO 2005/061477 PCT/US2003/040835 Step 4: According to the procedure of (Example 2A, Step 6), 0.14g of methyl N-[(4'-{[(4-isopropoxy-l-benzofuran-2-yl)carbonyl]amino}-l,r-biphenyl-4-yI)sulfonyl]-L-vaJinate provided 0.07g of N-[(4'-{ [(4-isopropoxy-l-benzofuran-2-yl)carbonyl]amino}-l,l-biphenyl-4~ yl)sulfonyl]-L-valine. Yield 50%; m.p. 132°C(d); MS: 549.2 (M-H)Example 104: N-[(4'-{[(5-methoxy-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-yI)su!fonyI]-L-valine Step 1: According to the procedure of (Example 86, Step 5), 0.24g (0.6 mmol) of 5-methoxy-2-benzofurancarboxylic acid and 0.44g (0.6 mmol) of N-[(4 -amino-1,1 -biphenyl-4-yl)sulfonyl]-L-valinate, after purification by column chromatography eluting with hexane/ethyl acetate (1:1) provided 0.33g of methyl N-[(4'-{[(5-methoxy-l-benzofuran-2-yl)carbonyl]amino}-l,l*-biphenyl-4- yl)sulfonyl]-L-vaIinate. Yield: 53%; m.p. 234-235 °C; MS: 537.3 (M+H)+ Step 2: According to the procedure of (Example 2A, Step 6), 0.31g of methyl N-[(4'-{[(5-methoxy-l-benzofuran-2-yl)carbonyl]amino}-l,1 -biphenyl-4- yl)sulfonyl]-L-valinate provided 0.17 gofN-[(4-{t(5-methoxy-l-benzofuran-2-yl)carbonyl]amino}-l,r-biphenyl-4-yl)sulfonyl]-L-valine. Yield 53% m.p. 257-259 °C; MS: 521.2 (M-H)". Example 105: (S)-2-{4'-[(4-Methoxy-3-methyl-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyricacid Step 1:4-Hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (200mg) was mixed with iodomethane (0.5mL), K2CO3 (200mg) and 2mL of DMF. The mixture was stirred at 131 WO 2005/061477 PCT/US2003/040835 room temperature overnight. The mixture was mixed with brine and extracted with ethyl acetate, and the combined ethyl acetate layers were washed with brine. Removal of the solvent gave the crude product that was purified by column chromatographt to give I62mg (76% yield) of 4-methoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as amber colored oil. Step 2: To 150mg of 4-methoxy-3-rnethyl-benzofuran-2-carboxylic acid ethyl ester dissolved in lmL of THF was added 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 120mg (91% yield) of 4-methoxy-3-rnethyl-benzofuran-2-carboxylic acid as white solid. Step 3: To 110mg (0.53mmol) of 4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 2mL of oxalyl chloride and the resulting mixture was refluxed for 4h in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in 2mL of dichloromethane and was added to a mixture of 232mg (0.64mmol)of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were removed under vacuum. Column chromatography on silica gel gave 95mg (33% yield) of (S)-2-{4-[(4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as off white solid. Step 4: To a solution of 80 mg of (S)-2-{4 -[(4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylarnino}-3-methyl-butyric acid methyl ester dissolved in lmL of THF was added 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room iemperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum and triturated with acetonitrile to give 63mg (81% yield) of (S)-2-{4 -[(4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid, obtained as white solid. ]H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.5, 6.7 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3,5.8 Hz, 1 H) 3.9 (s, 3 H) 6.9 (d, 7=8.1 Hz, 1 H) 7.2 (d, 7=7.8 Hz, 1 H) 7.4 (t, 7=8.2 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1H)12.6(S,1H). 132 WO 2005/061477 PCT/US2003/040835 EXAMPLE 106: (S)-2-{4'-t(4-ethoxy-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyl-sulibnylamino}-3-rnethyl-butyricacid Step 1: 4-Hydroxy-3-methyl-benzofuran-2-carboxyIic acid ethyl ester (200mg) was mixed with ethyl iodide (0.5mL), K2CO3 (200mg) and 2mL of DMF. The mixture was stirred a room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent under vacuum gave the crude product, which was purified by column chromatography to give 175mg (77% yield) of 4-ethoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as white solid. Step 2: To a solution of 160mgof 4-ethoxy-3-methyl-benzofuran-2-carboxylic acid eth> ester dissolved in lmL of THF was added 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature overnight The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum t< give 130mg (92% yield) of 4-ethoxy-3-methyl-benzofuran-2-carboxylic acid was obtained as white solid. Step 3: A solution of 115mg (0.46mmol) of 4-ethoxy-3-methyl-benzofuran-2-carboxylic acid in 2mL of oxalyl chloride was refluxed for 4h in the presence of a catalytic amount of DMI then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in 2mL of dichloromethane and was added to a mixture of 201mg (0.56mmol) of (S)-2-(4-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, and 2mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were then removed under vacuum. Column chromatography with silica gel gave 237mg (93% yield) of (S)-2-{4'-[(4-ethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as an off white solid. 133 WO 2005/061477 PCT/US2003/040835 Step 4: io 100 mg or (S-2-4-(4-etnoxy-3-metnyl-Denzoruran-2-carDonyi)-aminoj-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester dissolved in imLof THFwas added 3mL of LiOH solution (3.6g LiOH/50raL MeOH/50mL H2O). The mixture was stin-ed room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filter© The solid product was dried under vacuum and triturated with acetonitrile to give 89mg (91% yield) of (S)-2-{4-[(4-ethoxy-3-methyl-benzofuran-2-carbonyl)-arrjino3-biphenyl-4-sulfonylamino}-3-methyl-butyric acid as a white solid. 'H NMR (400 MHz, DMSO-d6 ) dpprr 0.8 (dd, J=12.6,6.6 Hz, 6 H) 1.4 (t, 7=6.9 Hz, 3 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.6 (m, 1 H) 4.2 (« J=6.9 Hz, 2 H) 6.8 (d, 7=8.3 Hz, 1H) 7.2 (d, 7=8.3 Hz, 1 H) 7.4 (t, J=8.2 Hz, 1 H) 7.8 (d, 7=8. Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.1 Hz, 1 H) 10.5 (s, 1 H) 12.6 (s, 1H). Example 107: (S)-3-MethyI-2-{4}-[(3-methyI-4-propoxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid Step 1:4-Hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (200mg) was . mixed with iodopropane (0.5mL), K2CO3 (200mg) and 2mL of DMF. The mixture was stirred room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent ga^ the crude product, which was purified by column chromatography to give 176mg of 3-methyl-* propoxy-benzofuran-2-carboxylic acid ethyl ester as white solid. Step 2: To a solution of 160mg of 4-propoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester dissolved in imL of THFwas added 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum t give 124mg (87% yield) of 4-propoxy-3-methyl-benzofuran-2-carboxylic acid, obtained as whi solid. 134 WO 2005/061477 PCT/US2003/040835 Step 3: A solution of 110mg (0.47mmol) of 4-ethoxy-3-methyl-benzofuran-2-carboxyIic acid in 4mL of oxalyl chloride was refluxed for 4h in the presence of a catalytic amount of DMF. The excess oxalyl chloride was then removed under vacuum. The residue was dissolved in 2mL of dichloromethane and was added to a mixture of 204mg (0.56mmol) of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, and 2mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were removed under vacuum. Column chromatography on silica gel gave 152mg (57% yield) of (S)-2-{4'.[(3-methyl-4-propoxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fony]aminp}-3-methyl-butyric acid methyl ester as a white solid. Step 4: To 100 mg of (S)-2-{4'-[(4-ethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fonyIamino}-3-methyl-butyric acid methyl ester dissolved in lmL of THF was added 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 84mg (86% yield) of (S)-3-methyl-2-{4 -{(3-methyl-4-propoxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-butyricacid. obtained as white solid. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, J=12.9, 6.8 Hz, 6 H) 1.1 (t, 7=7.3 Hz, 3 H) 1.8 (m, 2 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.1, 6.1 Hz, 1 H) 4.1 (t, 7=6.2 Hz, 2 H) 6.8 (d, 7=8.1 Hz, 1 H) 7.2 (d, 7=8.1 Hz, 1 H) 7.4 (t, 7=8.2 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H) 12.6 (s, 1 H). Example 108: (S)-2-{4'-[(4-Isopropoxy-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonylamino}-3-methyl-butyric acid Step 1: To4-hydroxy-3-methyl-benzofuran-2-carboxylic acid terf-butyl ester (200mg, 0.8mmol) in 4mL of DMF was added 2-bromopropane (0.5mL), and K2CO3 (200mg). The mixture was stirred at room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The'combined ethyl acetate layers were washed with brine. 135 WO 2005/061477 PCT/US2003/040835 tert-buty] ester as colorless crystals. Step 2: To 220mg of 4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid rert-butyl ester was added 3mL of TFA/dichloromethane (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and the residue was triturated witl acetonitrile. Filtration of the precipitate gave 210mg of 4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid as a white solid. Step 3: To 200mg (0.91mmol) 4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid in 4mL of DMF was added 329mg (1 eq) of (S)-2-(4'-amino-biphenyI-4-suIfonylamino)-3-methyl-butyric acid methyl ester, 482mg (1.2eq) of BOP, and 0.19mL of N,N-diisopropylethylamine. The mixture was stirred at room temperature overnight. Brine was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and water. Removal, of the solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 395mg (69% yield) of (S)-2-{4'-[(4-Isopropoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyI-butyric acid methyl ester as colorless oil. Step 4: To 370 mg (S)-2-{4-[(4-isopropoxy-3-methyl-benzofuran-2-carbonyl)-amino]- • bipheny]-4-sulfonylamino}-3-methy]-butyric acid methyl ester dissolved in 2mL of THF was added 3mL of liOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 6 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 286mg of (S)-2-{4'-[(4-isopropoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid, obtained as white solid. ]H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=13.5,6.7 Hz, 6 H) 1.4 (d, 7=6.1 Hz, 6 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.5 (t, .7=7.2 Hz, 1 H) 4.8 (m, 1 H) 6.9 (d, 7=8.6 Hz, 1 H) 7.2 (d, 7=8.6 Hz, 1 H) 7.4 (t, 7=8.2 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 4 H) 8.0 (m, 3 H) 10.5 (s, 1H). 136 WO 2005/061477 PCT/US2003/040835 Example 109: (S)-3-Methyl-2-{4'-[(3-methyl-4-phenyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert butyl ester (l00mg, 0.4mmol) was added N,Ndiisopropylethylamine (130mg, 1 mmol) and 2mL of dichloromettiane. The solution was cooled to <-10°C. Trifluormethanesulfonic anhydride (O.lniL, 0.6mmol) was added dropwise. The reaction mixture was stirred at -10°C for 2h and was then poured into water. The mixture wasextracted with dichloromethane and the combined organic layers were washed with water and dried over sodium sulfate. Removal of the solvent gave 145mg (95% yield) of 3-methyl-4-trifluoromethanesulfonyIoxy-benzofuran-2-carboxylic acid tert-butyl ester. Step 2: 3-Methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid tert-butyl ester (85mg, 0.25mmol) was mixed with K2CO3 (68mg, 0.5mmol), phenylboronic acid (3lmg, 0.25mmol), Pd(Phs)4 (14mg, O.Olmmol), lmL of 1,2-dimethoxyethane and 2 drops of water. The mixture was heated and stirred in an 85°C oil bath for 2h. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with.water and dried over sodium sulfate. Filtration followed by removal of the solvent in vacuo gave the crude product (71mg), which was purified by column chromatography to give 53mg (77% yield) of 3-methyl-4-phenyl-benzofuran-2-carboxylic acid tert-butyl ester, obtained as white solid. Step 3: 3-Methyl-4-pbenyl-benzofuran-2-carboxylic acid tert-butyl ester was dissolved in 2mL of TFA/dichloromethane (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 66mg of 3-methyl-4-phenyl-benzofuran-2-carboxylic acid as white solid. Step 4: To 60mg (0.24mmol) 3-methyl-4-phenyl-benzofuran-2-carboxylic acid was added lmL of oxalyl chloride and the mixture was refluxed for lh in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in lmL of dichloromethane and was added to a mixture of 129mg (0.36mmol) of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, 87mg (0.714mmol) of 4-(dimethylamino)pyridine and 2mL of in an ice/water bath. The mixture was stirred at room 137 WO 2005/061477 PCT/US2003/040835 temperature overnight. A]] the solvents were removed under vacuum. Column chromatography on silica gel gave 41mg (29% yield) of (S)-3-methyl-2-{4'-[(3-methyl-4-pheny]-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fonylamlno}-butyric acid methyl ester as white solid. Step 5: To 38mg of (S)-3-methyl-2-{4'-[(3-methyl-4-phenyl-benzoFuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester dissolved in 0.5mL of THF was added 2mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 12mg of (S)-3-methyl-2-{4 '-[(3-methyl-4-phenyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid, obtained as pals brown solid.'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=13.6, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.2 (s, 3 H) 3.5 (m, 1 H) 7.2 (dd, 7=7.3,1.0 Hz, 1 H) 7.5 (m, 5 H) 7.6 (dd, 7=8.3,7.3 Hz, 1 H) 7.7 (dd, 7=8.3,1.0 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 4 H) 8.0 (m, 3 H) 10.6 (s, 1 H). Example 110: (S)-3-Methyl-2-(4'-{[3-methy]-4-(3-nitro-pheny])-benzofuran-2-carbonyl]-amino}-biph enyl-4-sulfonylamino)-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester (l00mg, 0.4mmol) was added N,N-diisopropylethylamine (130mg, lmmol) and 2mL of dichloromethane. The solution was cooled to <-10°C. Trifluoromethanesulfonic anhydride (0.lmL, 0.6mmol) was added dropwise. The reaction mixture was stirred at -10°C for 2h and was poured into water. The mixture was extracted with dichloromethane and the combined organic layers were washed with water and dried over sodium sulfate. Removal of the solvent gave 145mg (95% yield) of 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxyIic acid tert-butyl ester. Step 2: 3-Methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid terr-butyl ester (380mg, lmmol) was mixed with K2CO3 (280mg, 2mmol), 3-nitro-phenylboronic acid (334mg, 2mmol), Pd(Ph3)4 (115mg, 0,lmmol), 4mL of 1,2-dimethoxyethane and 5 drops of water. The mixture was heated and stirred in an 85 °C oil bath for 3h. The reaction mixture was 138 WO 2005/061477 PCT/US2003/040835 poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over sodium sulfale. Removal of solvent gave the crude product, which was purified by column chromatography to give 310mg (88% yield) of 3-methyl-4-(3-nitro-phcnyl)-benzofuran-2-carboxylic acid ferr-butyl ester, obtained as white solid. Step 3: To 300mg of 3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carboxyIic acid rerr-butyl ester was added 4mL of TFA/djchloromethane (1:1). The solution was stirred at room temperature for 5h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 232mg (92% yield) of 3-methyl-4-(3-nitro-phenyl>benzofuran-2-carboxylic acid as white solid. Step 4: To lOOmg (0.34mmol) of 3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carboxylic acid was added 2mL of oxalyl chloride and the resulting mixture was refluxed for 2h in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in lmL of dichloromethane and was added to a mixture of 183mg (0.5mmol) of (S)-2-(4'-amino-biphenyI-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were removed under vacuum. Column chromatography on silica gel gave 41mg of (S)-3-meihyl-2-(4 -{[3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid methyl ester as white solid. Step 5: To 4 lmg of (S)-3-methyl-2-(4-{[3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-butyric acid methyl ester dissolved in O.5Lof THF was added 2mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 29mg of (S)-3-methyl-2-(4'-{ [3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carbonyl]-amino)-biphenyl-4-sulfonylamino)-butyric acid, obtained as pale brown solid. JH NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.4, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.2 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.3 (dd, 7=7.3, 0.8 Hz, 1 H) 7.6 (dd, 7=8.3,7.3 Hz, 1 H) 7.8 (m, 8 H) 8.0 (d, 7=8.8 Hz, 3 H) 8.1 (d, 7=9.3 Hz, 1 H) 8.3 (t, 7=1.9 Hz, 1 H) 8.3 (m, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). 139 WO 2005/061477 PCT/US2003/040835 Example 111: (S)-3-melhyl-2-{4'-[(3-methyl-4-pyridin-3-yl-benzoofuran-2-carbonyl)-amino biphenyl-4-sulfonylamino}-butyric acid Step 1: To 4-hydioxy-3-methyl-benzofuran-2-carboxylic acid /en-butyl ester (lOOmg, 0.4mmol) was added N,N-diisopropylethylamine (130mg, lmmol) and 2mL of dichloromethane The solution was cooled to <-10cC. Trifluoromcthanesulfonic anhydride (O.lmL, 0.6mmol) was added dropwise. The reaction mixture was stirred at -10cC for 2h and was then poured into water. The mixture was extracted with dichloromethane and the combined organic layers were washed with water and dried over sodium sulfate. Removal of the solvent gave 145mg (95% yield) of 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid lerr-butyl ester. Step 2: To 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid tert-butyl ester (285mg, 0.75mmol) in 3mL of 1,2-dimethoxyethane was added K2CO3 (363mg, 3.5eq), pyridine-3-boronic acid (138mg, 1.13mmol), Pd(Ph3)4 (43mg, O.OSeq), and 0.5mL of water. The mixture was heated and stirred in an 85°C oil bath for 3h. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over sodium sulfate. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography to give 202mg of 3-mcthyl-4-pyridin-3-yl-benzofuran-2-carboxylic acid lert-butyl ester, obtained as white solid. Step 3: To 185mg of 3-methyl-4-pyridin-3-yl-benzofuran-2-carboxylic acid rerr-butyl ester was added 4mL of TFA/dichloromethane (1:1). The solution was stirred at room temperature for 5h. The solvents were removed under vacuum and the residue was triturated wit) ether. Filtration gave 136mg of desired of 3-methyl-4-pyridin-3-yl-benzofuran-2-carboxylic acid as white solid. Step 4: To 3-methyl-4-pyridin-3-yl-benzofuran-2-carboxyHc acid (123mg, 0.49mmol) in 4mL of DMF was added (S)-2-(41-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (352mg, 0.97mmol), BOP (429mg, 0.97mmol), and TvyV-diisopropylethylamine (0.17mL, 0.97mmol). The mixture was stirred at room temperature overnight. The reaction 140 WO 2005/061477 PCT/US2003/040835 mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine and water. Removal of solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 115mg of (S)-3-methyl-2-{4 -[(3-methyl-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyricacid methyl ester, obtained as white solid. Step 5: To lOOmg of (S)-3-methyl-2-{4-[(3-methyl-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was dissolved in imL of THF was added 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The pH of the solution was adjusted to 7 and the resulting suspension was filtered. The solid product was dried under vacuum to give 75mg of (S)-3-rnethyl-2-{4'-[(3-methyl-4-pyridin-3-yl-benzofuran-2-carbonyl)-amJno]-biphenyl-4-sulfonylamino}-butyric acid, obtained as white solid. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.2 (s, 3 H) 3.6 (dd, 7=9.3 Hz, 1 H) 7.3 (dd, 7=7.3, 1.0 Hz, 1 H) 7.5 (m, 1 H) 7.6 (dd, 7=8.3, 7.6 Hz, 1 H) 7.8 (m, 3 H) 7.9 (m, 4 H) 7.9 (m, 1 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.1 Hz, 1 H) 8.7 (m, 2 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 112: (S)-3-Methyl-2-{4'-[(3-methyl-4-pyridin-4-yl-benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfony!amJno)-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid rerr-butyl ester (lOOmg, 0.4mmol) was added A^-diisopropylethylamine (130mg, lmmol) and 2mL of dichloromethane. The solution was cooled to <-10°C. Trifluoromethancsulfonic anhydride (O.lmL, 0.6mmol) was added dropwise. The reaction mixture was stirred at -10°C for 2h and was then poured into water. The mixture was extracted with dichloromethane and the combined organic solution was washed with water and dried over sodium sulfate. Removal of the solvent gave 145mg (95% yield) of 3-methyl-4-trifluoromethanesulfonyloxy-bcnzofuran-2-carboxyIic acid ten-butyl ester. 141 WO 2005/061477 PCT/US2003/040835 Step 2: 3-Methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid tert-buty] ester"{258mg. 0.68mrr,ol) was mixed with K2CO3 (207rag, 2.2eq), pyridine-4-boronic acid (1 lOmg, 1.3eq), Pd(Ph3)4 (43mg, 0.05eq), 3mL of 1,2-dimethoxyethane and 0.5mL of water. The mixture was heated and stirred in an 85°C oil bath for 5h. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over sodium sulfate. Removal of solvent gave the crude product, which was purified by column chromatography to give 156mg of 3-methyl-4-pyridin-4-yl-benzofuran-2-carboxylic acid tert-butyl ester, obtained as white solid. Step 3: To 141mg of 3-methy]-4-pyridin-3-yl-benzofuran-2-carboxylic acid rerr-butyl ester was added 4mL of TFA/dichloromethane (1:1). The solution was stirred at room temperature for 5h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 98mg of 3-methyl-4-pyridin-4-yl-benzofuran-2-carboxylic acid as a white solid. Step 4: To 3-methyl-4-pyridin-4-yI-benzofuran-2-carboxylic acid (88mg, 0.35mmol) in 4mL of DMF was added (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (252mg, 0.7mmol), BOP (307mg, 0.7mmol), and N,N-diisopropylethylamine (0.12mL, 0.7mmol). The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine and water. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 172mg of (S)-3-methyl-2-{4'-[(3-methyl-4-pyridin-4-yl-benzofuran-2-carbonyl)-amJno]-biphenyl-4-sulfonylamino)-butyric acid methyl ester, obtained as white solid. Step 5: To l60mg of (S)-3-methyl-2-{4'-[(3-methyl-4-pyridin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was added lmL of THF and 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The pH of the solution was adjusted to 7 and the resulting suspension was filtered. The solid product was dried under vacuum to give 132mg of (S)-3-methyl-2-{4'-[(3-methy]-4-pyridin-4-yl-benzofuran-2-carbonyl)-amino3-biphenyl-4-sulfonylamino}-butyric acid, obtained as white solid. !H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=21.5, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.2 (s, 3 H) 3.4 (s, 1 H) 7.3 (dd, 7=7.3, 1.0 Hz, 1 H) 7.5 (m, 2 H) 7.6 (dd, 7=8.3, 7.3 Hz, 1 H) 7.8 (m. 5 H) 7.9 (m, 2 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.7 (m, 2 H) 10.6 (s, 1 H). 142 WO 2005/061477 PCT/US2003/040835 Example 113: (S)-2-{4'-[(4-Furan3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxy]ic acid rert-butyl ester (lOOmg, 0.4mmol) was added N,N-diisopropylethylamine (130mg, Immol) and 2mL of dichloromethane. The solution was cooled to <-10°C. Trifluoromethanesulfonic anhydride (O.lmL, 0.6mniol) was added dropwise. The reaction mixture was stirred at -10°C for 2h and was then poured into water. The mixture was extracted with dichloromethane and the combined organic layers were washed with water and dried over sodium sulfatc. Removal of the solvent gave 145mg (95% yield) of 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid tcrt-butyl ester. Step 2: 3-Methyl-4-trifluoromethanesuIfonyloxy-benzofuran-2-carboxylic acid tert-butyl ester (285mg, O.75mmol) was mixed with K2CO3 (207mg, 2.2eq), furan-3-boronic acid (lOlmg, 1.2eq), Pd(Ph3)4 (43mg, 0.05eq), 3mL of 1,2-dimethoxyethane and 0.5mL of water. The mixture was heated and stirred in a 85°C oil bath for 2h. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over sodium sulfate. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography to give 153mgof 4-furan-3-yI-3-methyl-benzofuran-2-carboxylic acid rerr-butyl ester, obtained as white solid. Step 3: To 174mgof 4-furan-3-yl-3-methyl-benzofuran-2-carboxylic acid terr-butyl ester was added 4mL of TFA/dichloromethane (1:1). The solution was stirred at room temperature for 2h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 124mg of of 4-furan-3-yl-3-methyl-benzofuran-2-carboxylic acid as a white solid. Step 4: To 4-furan-3-yl-3-methyl-benzofuran-2-carboxylic acid (114mg, 0.47mmo]) was added (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (170mg, 0.47mmol), BOP (249mg, 1.2eq), N,N-diisopropyIethylamine (O.lmL, 1.2eq) and 4mL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine 143 WO 2005/061477 PCT/US2003/040835 and water. Removal of the solvent gave the crude product, which was purified by column chronfatography on silica gel to give 258mg of (S)-2-{4'-[(4-furan-3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester, obtained as white solid. Step 5: To 240mg of (S)-2-{4'-[(4-furan-3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino}-3-methyl-butyric acid methyl ester was added 2mL of THF and 4mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified to pH2 and the resulting suspension was filtered. The solid product was dried under vacuum to give 171mg of (S)-2-{4-[(4-furan-3-yl-3-methyl-ben2ofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methy]-butyric acid was obtained as white solid. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=13.1, 6.8 Hz, 6 H) 2.4 (s, 3 H) 3.5 (m, 1 H) 6.8 (dd, 7=1.9,0.9 Hz, 1 H) 7.2 (dd, 7=7.3,1.0 Hz, 1 H) 7.5 (dd, 7=7.6 Hz, 1 H) 7.7 (dd, 7=8.5, 0.9 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.8 (m, 4 H) 7.9 (m, 2 H) 7.9 (dd, 7=1.5,0.8 Hz, 1 H) 8.0 (m, 3 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 114: (S)-3-methyl-2-{4'-[(3-methyl-4-morpholin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyI-4-suIfonylamino}-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-bnty] ester (lOOmg, 0.4mmol) was added N,N-diisopropylethylamine (130mg, lmmol) and 2mL of dichloromethane. The solution was cooled to <-10°C. Trifjuoromethanesulfonic anhydride (O.lmL, 0.6mmol) was added dropwise. The reaction mixture was stirred at -10°C for 2h and was then poured into water. The mixture was extracted with dichloromethane and the combined organic layers were washed with water and dried over sodium sulfate. Removal of the solvent gave 145mg (95%' yield) of 3-methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid tert-butyl ester. 144 WO 2005/061477 PCT/US2003/040835 Step 2: To 3-methyl-4-trifIuoromethanesu]fonyloxy-bcnzofuran-2-carboxylic acid tert-butyl ester (190mg, 0.5mmol) was added K3PO4 (I59mg, 0.75mmol), morpholine (52mg, 0.6mmol), Pd(OAc)2 (10mg) and 4rnL of dioxane. The mixture was heated and stirred in an 85°C oil bath overnight. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over sodium sulfate. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography to give 96mg of 3-methyl-4-rnorpholin-4-yl-benzofuran-2-carboxylic acid tert-butyl ester, obtained as white solid. Step 3: To 140mg 3-methyl-4-morpholin-4-yl-benzofuran-2-carboxylic acid ferr-butyl ester was added 4mL of TFA/dichloromethane (1:1). The solution was stirred at room temperature for 5h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 107mg of 3-methyl-4-morpholin-4-yl-bcnzofuran-2-carboxylic acid as a white solid. Step 4: To 3-mcthyl-4-morpholin-4-yl-benzofuran-2-carboxylic acid (97mg, 0.37mmol) was added (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (268mg, 0.74mmol), BOP (327mg, O.74mmol), /v\N-diisopropylethylamine (0.13mL, 0.74mrnol) and 4mL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine and water. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 184mg of (S)-3-methyl-2-{4'-[(3-methyl-4-morpholin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester, obtained as an off-white solid. Step 5: To 160mg of (S>3-methyl-2-{4'-[(3-methyl-4-morpholin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester was added lmLof THF and 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 150mg of (S)-3-methyl-2-{4'-[(3-methyl-4-morpholin-4-yl-benzpfuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid, obtained as an off-white solid. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=14.1, 6.8 Hz, 6 H) 2.0 (dd, 7=12.1,6.8 Hz, 1 H) 2.8 (s, 3 H) 3.0 (m, 4 H) 3.5 (m, 1 H) 3.8 (m, 4 H) 7.0 (d, 7=7.8 Hz, 1 H) 7.4 (d, J=8.3 Hz, 1 H) 7.4 (m, 1 H) 7.8 (d, 7=8.6 Hz, 2 H) 7.8 (m, 4 H) 8.0 (d, 7=9.1 Hz, 3 H) 10.5 (s, 1 H). 145 WO 2005/061477 PCT/US2003/040835 Example 115: (S)-2-{4'-[(5-Chloro-4-isopropoxy-3-methyl-benzofuran-2-carbonykl)-amino]-biphenyl-4-sulfonylamino}-3-rnethyl-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (O.5g, 2.27 mmol) was added 5 mL of carbon tetrachloride, and the mixture was cooled with an ethanol/ice bath while 1 equivalent of N-chlorosuccinimide was added in small poroom tcmperaturcions. After stirring at -10°C for 3h, the reaction mixture was filtered and the filtrate was loaded onto a silica column and chromatographed to give 259 mg (48% yield) of 5-chloro-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as an off-white solid. Step 2: To 5-chloro-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (1 lOmg) was added 2mL of isopropylbromide, 150mg of K2CO3 and 4mL of DMF. The mixture was stirred at room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent in vacuo gave 134mg of 5-chloro-4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as a thick colorless oil (100% yield). Step 3: To 1 lOmg of 5-chloro-4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added lmL of THF and 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O) was added. The mixture was stirred at room temperature overnight The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and resulting suspension was filtered. The solid product was dried under vacuum to give 94mg (94% yield) of 5-chloro-4-isopropoxy-3-methyl-benzofuran-2-carboxy)ic acid. Step 4: To 80mg of 5-chJoro-4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid was added 121mg of (S)-2-(4'-ainino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid ferr-butyl ester, 159mg of BOP, 46mg of N,N'-diisopropylethylamine and 4mL of DMF. The mixture was stirred at room temperature for 48h. The mixture was addedbrine and was extracted with ethyl acetate. The combined ethyl acetate solution was washed with brine. Removal of the solvent and purification of the residue by column chromatography on silica gel gave 178mg (98% yield) of 146 WO 2005/061477 PCT/US2003/040835 (S)-2-{4-[(5-chloro-4-isopropoxy-J-metny]-benzofuran-2-carbonyl)-amino]-bipheny]-4-su)fony]amino}-3-methyl-butyric acid /err-butyl ester as a colorless semi-solid. Step 5: To 160mg of (S)-2-{4'-((5-chloro-4-isopropoxy-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamlno}-3-methyl-butyric acid tert-buty\ ester was added 3mL of TFA/dichloromethane (J:l) and the solution was stirred at room temperature for 9h. When the reaction was done, the solvents were removed under vacuum and the residue was triturated with acetonitrile. The mixture was freeze-dried to yield 120mg (77% yield) of (S)-2-{4-[(5-chloro-4-isopropoxy-3-niethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid as a white solid. !H NMR (400 MHz, DMSO-d6 ) d8 ppm 0.8 (dd, 7=12.4,6.8 Hz, 6 H) 1.3 (d, 7=6.1 Hz, 6 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3,6.1 Hz, 1 H) 4.7 (m, 1 H) 7.5 (d, 7^8.8 Hz, 1 H) 7.6 (m, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m/4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 116: (S)-2-{4'-[(5-Chloro-4-methoxy-3-me(hyI-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonylamino}-3-methyl-butyric acid Step 1: To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester 0.5g (2.27 mmol) was added 5 mL of carbon tetrachloride, and the mixture was cooled with an ethanol/ice bath while 1 equivalent of N-chlorosuccinimide was added in small portions. After stirring at-10°C for 3h, the reaction mixture was filtered and the filtrate was loaded onto a silica gel column. Chromatography gave 259 mg (48% yield) of 5-chloro-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as an off-white solid. Step 2: To 5-chloro-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (120mg, 0.47mmol) was added 0.3mL (4.7mmol) of iodomethane, 130mg (2eq) of K2CO3 and 4mL of DMF. The mixture was stirred at room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined organic solution was washed with 147 WO 2005/061477 PCT/US2O03/040835 brine and water. Removal of the solvent in vacuo gavel 19mg (94% yield) of 5-chloro-4-methoxy-3~methyl-benzofuran-2-carboxylic acid ethyl ester as a white solid. Step 3: To 105mg of 5-chloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added imL of THF and 3mL of LiOH solution (3.6g IiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was triturated with dichloromethane and dried under vacuum to give 82mg (87% yield) of 5-chIoro-4-methoxy-3-methyl-benzofuran-2-carboxylieacid.. Step 4: To 80mg (O.33mmol) of 5-chloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 2 mL of oxalyl chloride and the mixture refluxed for 2h, then stirred room temperature overnight. The excess oxalyl chloride was removed under vacuum. The residue was dissolved in 2mL of dichloromethane and was added to a mixture of 181mg (0.5mmol) of (S)-2-(4-amino-biphenyi-4-sulfonylamino)-3-methyl-butyric acid methyl ester and imLof pyridinein an ice/water bath. The mixture was stirred at 0°C overnight. The reaction mixture was diluted with dichloromethane and was washed with 2N HC1, and water. Removal of the solvent in vacuo gave the crude product which was purified by column chromatography to give 168mg (86% yield) of (S)-2-{41-[(5-chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyIamiiioJ-3-rnethyl-butyric acid methyl ester as a white solid. Step 5: To lOOmg of (S)-2-{4'-[(5-chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl~butyric acid methyl ester was added 2mL of THF and 2mL of LiOH solution (3.6g LiOH/50mLMeOH/50mL H2O) was added. The mixture was stirred at room temperature for 3 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 60mg (62% yield) of (S)-2-{4'-[(5-chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid. 'H NMR (400 MHz, DMSO-d6 ) dppm 0.8 (dd, 7=12.4,6.8 Hz, 6 H) 2.0 (dd, J=13.1,6.6 Hz, 1 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3,6.1 Hz, 1H) 3.9 (s, 3 H) 7.5 (d, 7=8.6 Hz, 1 H) 7.6 (m, 1H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1H) 10.6 (s, 1 H) 12.6 (s, 1H). 148 WO 2005/061477 PCT/US2003/040835 Example 117: (S)-2-{4'-[(5,7-DichIoro-4-methoxy-3-melhyl-benzofuran-2-carbonyI)-amino]-bipheny!-4-sulfony)amino}-3-rnethyl-butyricacid Step 1: To 4-hydroxy-3-mcthyl-benzofuran-2-carboxylic acid ethyl ester (O.5g, 2.27 mmol) was added 5 mL of carbon tetrachloride, carbon telrachloride, and the mixture was cooled with an cthanol/ice bath while 1 equivalent of N-chlorosuccinimide was added in small portions. After stirring at -10cC for 3h, the reaction mixture was filtered and the filtrate was loaded onto a silica gel column. Chromatography gave 190 mg (30% yield) of 5,7-dichloro-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as an off-white solid. Step 2: To 120mg of 5,7-dichloro-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added lmL of iodomethane, 200mg of K2CO3 and 4mL of DMF. The mixture was stirred at room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate solution was washed with brine. Removal of the solvent in vacuo gave 125mg (99% yield) of 5,7-dichloro-4-mcthoxy-3-mcthyl-benzofuran-2-carboxylic acid ethyl ester as off-white solid. Step 3: To 1 lOmg of 5,7-dichloro-4-mcthoxy-3-rnethyl-bcnzofuran-2-carboxylic acid ethyl ester was added lmL of THF and 3mL of IiOH solution (3.6g LiOH/50mL Me0H/50mL H2O). The mixture was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 96mg (96% yield) of 5,7-dichIoro-4-methoxy-3-methyI-benzofuran-2-carboxylic acid, obtained as a white solid. Step 4: To 80mg of 5,7-dichloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 120mg of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester, 154mg of BOP, 50mg of N,N-diisopropylethyJamine and 4mL of DMF. The mixture was stirred at room temperature for 48h. The mixture was washed with brine and was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent 149 WO 2005/061477 PCT/US2003/040835 in vacuo and purification of the residue by column chromatography on silica gel gave 1 lOmg (60% yield) of (S)-2-{4-[(5,7-dich]oro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-bipheny)-4-su)fonylamino)-3-methyl-butyric acid /erf-butyl ester as an off-white solid. Step 5: To 102mgof (S)- 2-{4'-[(5,7-dichloro-4-mcthoxy-3-methyl-benzofuran-2-carbony))-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl ester was added 3mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for 3h. When the reaction was done, the solvents were removed under vacuum and the residue was triturated with ether/chloroform. Filtration of the suspension gave 67mg (72% yield) of (S)-2-{4'-[(5,7-dichloro-4-methoxy-3-methyI-benzofuran-2-carbonyl)-amJno]-biphenyl-4-sulfonylamino)-3-methyl-butyric acid as a white solid. *H NMR (400 MHz, DMSO-d*) 8 ppm 0.8 (dd, 7=12.4, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, .7=9.3, 6.1 Hz, 1 H) 3.9 (s, 3 H) 7.8 (m, 5 H) 7.9 (m, 2 H) 7.9 (d, 7=8.6 Hz, 2 H) 8.1 (d, 7=9.6 Hz, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 118: (S)-2-{4':[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyJ)-amino]-biphenyl-4-su)fonylamino}-3-methyl-butyric acid Step 1: To 200mg (0.81 mmol) of 4-hydroxy-3-methyl-benzofuran-2-cajboxylic acid ten butyl ester was added 2 mL of carbon tetrachloride. The mixture was cooled with water/ice bath while 1 equivalent of N-bromosuccinimidc was added in small portions. After stirring at 0°C for 6h, the reaction mixture was filtered and the filtrate was loaded onto a column and purified by column chromatography to give 225 mg (85% yield) of 5-bromo-4-hydroxy-3-methyl-benzofuran-2-carboxyIic acid tert-butyl ester as a white solid. Step 2: To 220mg (0.67mmol) of 5-bromo-4-hydroxy-3-rnethyl-benzofuran-2-carboxylic acid tert-butyl ester was added 0.42mL (6.7mmol) of iodomethane, 185mg (1.34mmol) of K2CO and 2mL of DMF. The mixture was stirred at room temperaturc-over night. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were 150 WO 2005/061477 PCT/US2003/040835 washed with brine. Removal of the solvent gave 230mg (100% yield) of 5-bromo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester as a colorless oil. Step 3: To 220mg of 5-bromo-4-methoxy-3-methyl-benzofuran-2-carboxyiic acid tert-butyl ester was added 3mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for lOh. When the reaction was done, the solvents were removed by vacuum and the residue was triturated with hexane/dichloromethane. Filtration of the suspension gave 141mg (77% yield) of 5-bromo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid as a white solid. Step 4: To 40mg (0.14mmol) of 5-bromo-4-methoxy-3-methyl-benzofuran-2:carboxylic acid was added 0.5mL of oxalyl chloride and the mixture was refluxed for 2h, then the excess oxalyl chloride was removed by vacuum. The residue was dissolved in 0.5mL of dichloromethane and was added to a mixture of 92mg (O.25mmol) of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, 34mg (0.28mmol) of 4-(dimethylamino)pyridine and lmL of dichloromethane in an ice/water bath. The mixture was stirred at 0°C for overnight. The mixture was diluted with dichloromethane and was washed with 2N HC1, and water. Removal of the solvent from the organic solution gave 20mg (23% yield) of (S)-2-{4'-[(5-bromo:4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino]-3-methyl-butyric acid methyl ester as an off-white solid. Step 5: To 18 mg of (S)-2-{4'-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was added 0.5mL of THF and 0.5mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 6 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 8mg (39% yield) of (S)72-{4'-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid. 'H NMR (400 MHz, DMSO-d6) **ppm 0.8 (dd, 7=12.9,6.8 Hz, 6 H) 2.0 (m, 1H) 2.7 (s, 3 H) 3.6 (dd, J=9.0,5.9 Hz, 1 H) 3.9 (s, 3 H) 7.5 (d, 7=8.8 Hz, 1H) 7.7 (d, 7=8.8 Hz, 1H) 7.8 (d, 7=8.6 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.1 Hz, 1 H) 10.6 (s, 1H) 12.6 (s, 1 H). 151 WO 2005/061477 PCT/US2003/040835 Example 119: (R)-2-{4'-[(5-Bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyricacid Step 1: To 2g (0.81 mmol) of 44-hydroxy-3-methyl-bcnzofuran-2-carboxylic acid ethyl ester was added 20 mL of carbon tetrachloride, and the mixture was cooled with a water/ice bath while 1 equivalent of N-bromosuccinimide was added in small portions. After stirring at 0°C for 3h, the reaction mixture was filtered and the filtrate was loaded onto a column and purified by column chromatography to give 1.6 mg (59% yield) of 5-bromo-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as a white solid. Step 2: To 200mg (0.67mmol) of 5-bromo-4-hydroxy-3-mcthyl-bcnzofuran-2-caiboxylic acid ethyl ester was added 0.5mL of iodomcthanc, 200mg of K2CO3 and 2mL of DMF. The mixture was stirred at room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent in vacuo gave 185mg (88% yield) of 5-bromo~4-methoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as a white solid. Step 3: To 170mg of 5-bromo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added lmL of THF and 3mL of LiOH solution (3.6g LiOHy50mL MeOH/50mL H2O). The mixture was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 156mg (100% yield) of 5-bromo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid, obtained as a white solid. Step 4: To 75mg (0.263mmol) of 5-bromoo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 2mL of oxalyl chloride and the mixture was refluxed for 2h in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed by vacuum. The residue was dissolved in 0.5mL of dichloromethane and was added to a mixture of 143mg (0.39mmol) of (R)-2-(4'-amino-biphenyl-4-sulfony]amino)-3-methyl-butyric acid methyl ester, 152 WO 2005/061477 PCT/US2003/040835 2mL ol pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. The solvent was removed under vacuum. Column chromatography on silica gel gave 89mg (54% yield) of (R)-2-{4'-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino)-3-methyl-butyric acid methyl ester as an off-white solid. Step 5: To 89 mg of (R)-2-{4'-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylarnino)-3-mcthyl-butyric acid methyl ester was added lmLof THF and 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum and triturated with 0.5mL of chloroform to give 49mg (56% yield) of (R)-2-{4 -[(5-bromo-4-methoxy-3-methyl-bcnzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, ;=12.4,6.8 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3. 6.1 Hz, 1 H) 3.9 (s, 3 H) 7.7 (d, 7=8.8 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (ra, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 8.3 (s, 1 H) 10.6 (s, 1 H) 12.6 (s, 1 H). Example 120: (S)-2-{4'-[(5-Iodo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-3-rncthyl-butyric acid Step 1: To 4.4g (17.7 mmol) of 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester was added 40 mL of carbon tetrachloride, the mixture was cooled with an water/ice bath while 1 equivalent of N-iodosuccinimide was added in small portions. After stirring at 0cC for3h, the reaction mixture was loaded onto a column and purified by column chromatography to give 2.55gmg(38% yield) of 5-iodo-4-hydroxy-3-rnethyl-benzofuran-2-carboxylic acid ten-butyl ester as a white solid. Step 2: To 748mg (2 mmol) of 5-iodo-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid /erf-butyl ester was added 1.42g(10 mmol) of iodomethane, 553mg (4 mmol) of K2CO3 and 153 WO 2005/061477 PCT/US2003/040835 lOmL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent in vacuo gave 790mg (100% yield) 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid rert-butyl ester as a pale brown oil. Step 3: To 140mg (0.36 mmol) of 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid /err-butyl ester was added 3mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for 2.5h. When the reaction was done, lhe solvents were removed by vacuum and the residue was triturated with hexane/dichloromethane. Filtration of the suspension gave 120mg (100% yield) of 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid as a white solid. Step 4: To 1 lOmg (0.33mmol) of 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 132 mg (lleq) of (S)-2-(4'-amino-biphenyM-sulfonylarnino)-3-methyl-butyric acid methyl ester, BOP (34mg, 1.2eq), NTV-diisopropylethylamine (52mg,l .2eq) and 4mL of DMF. The mixture was stirred at room temperature for 48h. Brine was added and the mixture was extracted" with ethyl acetate. The combined organic solution was washed with 2N HC1 and water. Concentration of the organics in vacuo gave the crude product which was purified by column chromatography on silica gel to give 106mg (47% yield) of (S)-2-{4'-[(5-iodo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was obtained as an off-white solid. Step 5: To 96 mg of (S)-2-{4'-[(5-iodo-4-methoxy-3-rnethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamJno)-3-methy]-butyric acid methyl ester was added 0.5mL of THF and 2mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O. The mixture was stirred at room temperature for 3 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 60mg (63% yield) of (S)-2-{4'-[(5-iodo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylarnino}-3-methyl-buryric acid. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=13.9, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.5 (m, 1 H) 3.9 (s, 3 H) 7.3 (d, 7=8.6 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 5 H) 8.0 (d, 7=9.1 Hz, 3 H) 10.6 (s, 1 H). 154 WO 2005/061477 PCT/US2003/040835 Example 121: (S)-2-{4'-[(5-Acetyi-4-methoxy-3>melhyJ-benzofuran-2-carbonyI)-amino]-biphenyl-4-suIfonyJamino}-3-methyl-butyricacid Step 1: To 4-hydroxy-3-methy!-benzofuran-2-carboxylic acid tert-butyl ester (300mg, 1.21mmol) was added iodomethane (0.75mL, lOeq), K2CO3 (332mg, 2.4mmol) and 2mLbf DMF. The mixture was stirred at room temperature overnight. The mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate solution was washed with brine. Removal of the solvent gave 312mg (98% yield) of 4-methoxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester as an amber colored oil. Step 2: To 4-methoxy-3-methyl-benzofuran-2-carboxylic acid rm-butyl ester (310mg, 1.18mmol) dissolved in 9mL of chlorobenzene was added acetyl chloride (0.3mL, 3.6eq). The solution was cooled to <0°C while titanium tetrachloride (0.61 mL, 4.8eq) was added dropwise. The reaction mixture was stirred at 0eC and below for 6h and then heated in an 85CC oil bath for 3.5h. The reaction mixture was poured into ice/water, and the mixture was extracted with ethyl acetate. The combined organic solution was washed with 2N HC1 and water. Removal of the solvents in vacuo gave 167mg (57% yield) of 5-acetyl-4-methoxy-3-methyI-benzofuran-2-carboxylic acid. Step 3: To 75mg (0.3mmo!) of 5-acctyl-4-mcthoxy-3-metiiyl-benzofuran-2-carboxylic acid was added lmL of oxalyl chloride and the mixture was refluxed for 2.5h in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in lmL of dichloromcthane and was added to a mixture of 163mg (0.46mmol) of (S)-2-(4'-amino-biphenyl~4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight All the solvents were removed under vacuum. Column chromatography on silica gel gave 54mg (31% yield) of (S)-2-{41-[(5-acetyI-4-methoxy-3-methyl-benzofuran-2-carbonyI}z. amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as an off-white solid. 155 WO 2005/06,477 PCT/US2003/040835 Step 4: To (S)-2-{4'-[(5-acetyl-4-methoxy-3-methyl-benzofuran-2-carbony])-amino]-biphen^-4-su]fonylarruno}-3-methyl-butyric acid methyl ester (89mg) was added lmLof THF and 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 2 days. The solvents were removed under vacuum and the residue was triturated with 4mL of 2N HC1 and filtered. The solid product was dried under vacuum to give 54mgof (S)-2-[4'-I(5-acetyl-4-methoxy-3-methyl-bcnzofuran-2-carbonyl)-amino]-biphenyl-4- sulfonylamino}-3-methyl-butyric acid was obtained as an off-white solid. 3H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.9,6.S Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 2.9 (s, 3 H) 3.6 (dd, 7=9.3.6.1 Hz, 1 H) 4.0 (s. 3 H) 7.0 (d, 7=8.8 Hz, 1 H) 7.8 -amJno-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were removed under vacuum. Column chromatography on silica gel gave 36mg (20% yield) of (S)-2-(4'-{[5-(l-chloro-vinyJ)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester as an off-white solid. Step 4: To (S)-2-(4'-{[5-(l-chloro-vinyl)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-mcthyl-butyric acid methyl ester (29mg) was added 0.5mL of THF and 2mL of LiOH solution (3.6g IJOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 3 days. The solvents were removed under vacuum and the residue was triturated with 2mL of 2N HC1 and filtered. The.solid product was dried under vacuum. 23mg of desired (S)-2-(4>-{[5-(l-chloro-vinyl)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-arnino}-biphenyl-4-sulfonyIamino)-3-methyl-butyric acid, obtained as an off-white solid. *H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd. 7=12.9, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 4.0 (s, 3 H) 5.9 (d, 7=2.3 Hz, 1 H) 6.7 (d, 7=2.3 Hz, 1 H) 7.0 (d, 7=8.6 Hz, 1 H) 7.7 (d, 7=8.6 Hz. 1 H) 7.8 (m, 8 H) 8.1 (d, 1 H) 10.3 (s, 1 H) 12.6 (s, 1 H). Example 123: (S)-2-{4J-[(5-AcetyI-4-hydroxy-3-methyl-benzofuran-2-carbonyI)-amino]-biphenyl-4-suIfonyIamino}-3-methyI-biityricacid Step 1. To 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester 0.5g (2.27mmol) was added 15mL of chlorobenzene, 0.27g (3.4mmol) of aceryl chloride and 0.63mL 157 WO 2005/061477 PCT/US2003/040835 (5.7mmol) of titanium tetrachloride. The mixture was sealed in a pressure tube and the tube was placed% 95°C oil bath for 5h with stirring. The reaction mixture was washed with 0.5N HC1 and was extracted with ethyl acetate. Removal of the solvents gave the crude product, which was purified by column chromatography to give 0.33g (59% yield) of 5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester as a white solid. Step 2. To lOOmg of 5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added lmL of THF and 3mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and resulting suspension was filtered. The solid product was dried under vacuum to give 82mg (92% yield) of 5-bromo-4-methoxy-3-methy]-benzofuran-2-carboxylic acid. Step 3: To 70mg (0.3mmol) of 5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added 115mg (2eq) EDCI, 109mg (leq) of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2mL of DMF. The mixture was stirred at 65°C overnight. The reaction mixture was poured into brine, and extracted with dichloromethane. The organic solution was washed with 2N HC1 and water. Removal of the solvents under vacuum gave crude product, which was purified by column chromatography on silica gel to give 20mg (10% yield) of (S)-2-{4'-[(5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as a white solid. Step 4: To (S)-2-{4'-[(5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carbonyl)-amin6]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester (15 mg) was added 0.5mL of THF and 2mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 4 days. The solvents were removed under vacuum and 2mL of water was added. The aqueous solution was acidified and the resulting solid was collected through filtration to give 7mg of (S)-2-{4'-[(5-acetyI-4-hydroxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methy]-butyric acid as an off-white solid. 'HNMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.4, 6.8 Hz, 6 H) 1.9 (m, 1 H) 2.7 (s, 3 H) 2.8 (s, 3 H) 3.6 (dd, 7=9.3, 6.1 Hz, I H) 7.3 (d, 7=9.1 Hz, 1 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (dd, 7=9.1, 3.8 Hz, 2 H) 10.5 (s, 1 H) 13.7 (s, 1 H). 158 WO 2005/061477 PCT/US2003/040835 Example 124: (S)-2-{4'-[(5-Cyano-4-methoxy-3-methyl-benzofuran-2-carbonyI)-amino]-bipheny)-4-su)fonyJamino}-3-rnethyl-butyricacid Step 1: To 4.4g (17.7 mmol) of 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester was added 40 mL of carbon tetrachloride, and the mixture was cooled with a water/ice bath while 1 equivalent of N-iodosuccinimide was added in small portions. After stirring at 0°C for 3h, the reaction mixture was loaded onto a column and purified by column chromatography to give 2.55g mg (38% yield) of 5-iodo-4-hydroxy-3-methyl-bcnzofuran-2-carboxylic acid tert-butyl ester as a white solid. Step 2: To 748mg (2 mmol) of 5-iodo-4-hydroxy-3-rnethyl-benzofuran-2-carboxylic acid rerr-butyl ester was added 1.42g (10 mmol) of iodomethane, 553mg (4 mmol) of K2CO3 and lOmL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent gave 790mg (100% yield) of 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester as a pale brown oil. Step 3. To 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester (490mg, 1.26mmol) was added 356mg (3mmol) of Zn(CN)2,140mg of Pd(PPh3)4 and 4mL of DMF. The mixture was stirred at 90°C for 3h. After cooling to room temperature the reaction mixture was loaded onto a silica gel column and was purified by column chromatography to give 260mg (72% yield) of desired 5-cyano-4-methoxy-3-mcthyl-benzofuran-2-carboxylic acid tert-butyl ester was obtained as a white solid. Step 4: To 150mg of 5-cyano-4-methoxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester was added 4mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for 3h. When the reaction was done, the solvents were removed under vacuum and the residue was triturated with hexane/dichloromcthane. Filtration of the suspension gave 121mg (100% yield) of 5-cyano-4-methoxy-3-methyl-benzofuran-2-carboxylic acid as a white solid. 159 WO 2005/001477 PCT/US2003/040835 Step 5: To llOmg (0.48mmol) of 5-cyano-4-methoxy-3-methyl-benzofuran-2-caiboxylic acid was added 207 mg (1.2eq) of (S)-2-(4-anuno-biphenyl-4-su]fonylamino)-3-methyl-butyric acid methyl ester, BOP (252mg, 1.2cq), NN-diisopropylethylamine (74mg,1.2eq) and 4mL of DMF. The mixture was stirred at room temperature for 48h. Brine was added and the mixture was extracted with ethyl acetate. The combined organic solution was washed with 2N HC1 and water. Concentration of the organics in vacuo gave crude product, which was purified by column chromatography on silica gel to give 89mg (32% yield) of (S)-2-{4'-l(5-cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-arnino]-biphcnyl-4-sulfonylamino)-3-methyl-butyricacid methyl ester as an off-white solid. Step 6: To 70 mg of (S)-2-{4'-[(5-cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amJno]-biphcnyl-4-sulfony)amino}-3-methyl-butyric acid methyl ester was added 1.5mL of THF and 2mL of LiOH solution (3.6g LiOH/50mL MeOH/50mL H2O). The mixture was stirred at room temperature for 3 days. The solvents were removed under vacuum and the residue was dissolved in 5mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 42mg (61% yield) of (S)-2-{4'-[(5-cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyIamino)-3-methyl-butyric acid 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6,6.8 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.6 (dd, 7=9.5, 5.9 Hz, 1 H) 4.2 (s, 3 H) 7.6 (d, 7=8.6 Hz, 1 H) 7.8 (m, 7 H) 8.0 (d, 7=8.8 Hz, 2 H) 8.1 (d, 7=9.1 Hz, 1 H) 10.7 (s. 1 ID-Example 125: (S)-2-{4'-[(5-Melhyl-4-methoxy-3-methyI-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonylamino}-3-methy)-butyric acid Step 1: To 1.24g (5mmol) of 4-hydroxy-benzofuran-2-acid rerr-butyl ester was added 9.5g of magnesium methoxide/methanol solution (6-10 weight %) and 25mL of toluene. The mixture was heated at reflux for 45 minutes. Methanol was distilled off. An additional lOmL of toluene was then added for further distillation to ensure the complete removal of the methanol. 160 WO 2005/061477 PCT/US2003/040835 2.4g of paraformaldehyde was added in small portions over 35 min. The reaction mixture was stirrediff 130°C for another 30min. The reaction mixture was washed with 2N HC1, and extracted with ethyl acetate. Removal of the solvents gave the crude product which was purified by column chromatography to give 440mg of 5-formyl-4-hydroxy-3-methyl-benzofuran-2- carboxylic acid tert-butyl ester. Step 2: To 5-formyl-hydroxy-3-methyl-benzofuran-2-carboxylic acid /erf-butyl ester (430mg, 1.56mmol) was added 8mL of THF, and sodium cyanoborohydride (117mg, 1.87mmol) was added in one portion. The solution was stirred at room temperature for lh and then placed in a 65°C oil bath overnight. The solvent was removed under vacuum and water was added. The mixture was extracted with ethyl acetate. Removal of the solvent gave the crude product, which was purified by column chromaiography to give 70mg of 4-hydroxy-3,5-dimethyl-benzofuran-2-carboxylic acid ferr-butyl ester as a white solid. Step 3. To 80mg of 4-hydroxy-3,5-dimcthyl-benzofuran-2-carboxylic acid tert-butyl ester was added lmL of iodomethane,-80mgof K2CO3 and lmLofDMF. The mixture was stirred at room temperature overnight. The reaction mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate solution was washed with brine. Removal of the solvent gave 82mg of 4-methoxy-3,5-dimethyl-benzofuran-2-carboxylic acid tert-butyl ester as a pale yellow solid. Step 4: To 80mg of 4-methoxy-3,5-dimcthyi-bcnzofuran-2-carboxylic acid ferr-butyl ester was added 2mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for 3h. When the reaction was done, the solvents were removed under vacuum and the residue was triturated with hcxane/dichloromethane. Filtration of the suspension gave 55mg of 4-rnethoxy-3,5-dimethyl-benzofuran-2-carboxylic acid as a pale brown solid. Step 5: To 45mg (0.2mmol) of 4-methoxy-3,5-dimethyl-benzofuran-2-carboxyIic acid was added 124 mg (1.5eq) of (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester, BOP (106mg, 1.2eq), NN-diisopropylethylamine (31mg,1.2eq) and 2mL of DMF. The mixture was stirred at room temperature for 24h. Brine was added and the mixture was extracted with ethyl acetate. The combined organic solution was washed with 2N HC1 and water. Removal of the solvent from the organic solution gave the crude product, which was purified by column chromatography on silica gel to give 89mg of (S)-2-{4'-[(4-methoxy-3,5- dimethyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-su]fonylamino)-3-mcthyl-butyric acid tert-butyl ester as an off-white solid. Step 6: To 80mg of (S)-2-{4'-[(4-methoxy-3,5-dimethyl-benzofuran-2-carbonyl)-arnino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl ester was added 2mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for 3h. When the 161 WO 2005/061477 PCT/US2003/040835 reaction was done, the solvent was removed under vacuum and the residue was triturated with acetomtrile. Filtration of the suspension gave 64mg of (S)-2-{4'-[(4-methoxy-3,5-dimcthyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid as a white solid. 'H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, J=12A, 6.8 Hz, 6 H) 2.0 (m, 1 H) 2.3 (s, 3 H) 2.7 (s, 3 H) 3.6 (dd, .7=9.3, 5.8 Hz, 1 H) 3.8 (s, 3 H) 7.4 (m, 2 H) 7.8 (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8.0 (d, .7=8.8 Hz, 2 H) 8.1 (d, 7=9.3 Hz, 1 H) 10.5 (s, 1 H). Example 126: (S)-2-{4'.[(5-Hydroxymethyl-4-methoxy.3-methyl-benzofuran-2-carbonyl)-amino]-biphcnyl-4-sulfonyIamino}-3-methyl-butyricacid Step I: To 1.24g (5mmol) of 4-hydroxy-bcnzofuran-2-acid tert-buly] ester was added 9.5g of magnesium methoxide/methanol solution (6-10 weight %) and 25mL of toluene. The mixture was heated at reflux for 45 minutes. Methanol was distilled off. An additional l0mL of toluene was then added for further distillation to ensure the complete removal of the mcthanol. Next, 2.4g of paraformaJdehyde was added in small portions over 35 min. The reaction mixture was stirred at 130°C for another 30min. The reaction mixture was washed with 2N HC1, and extracted with ethyl acetate. Removal of the solvents gave the crude product which was purified by column chromatography to give 440mg of 5-formyl-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester. Step 2: To 5-formyl-4-hydroxy-3-rnethyl-benzofuran-2-carboxylic acid /err-butyl ester (430mg, I.56mmol) was added 8mL of THF, followed by sodium cyanoborohydride (117mg, 1.87mmol) in one portion. The solution was stined at room temperature for lh and then placed in a 65°C oil bath overnight. The solvent was removed under vacuum and water was added. The mixture was extracted with ethyl acetate. Removal of the solvent gave the crude product, which was purified by column chromatography to give 200mg of 4-hydroxy-5-hydroxymethyl-3-methyl-benzofuran-2-carboxylic acid /err-butyl ester was obtained as a yellow semi-solid. 162 WO 2005/061477 PCT/US2003/040835 Step 3. To 190mg of 44iydroxy-5-hydroxymethyl-3-memyl-benzofuran-2-carboxylic acid rert-butyl ester was added lmL of iodomethane, 200mg of K2CO3 and 3mL of DMF. The mixture was stirred at room temperature ovemight.The reaction mixture was washed with brine and extracted with ethyl acetate. The combined ethyl acetate solution was washed with brine. Removal of the solvent gave 200mg of 4-methoxy-5-hydroxymethyl-3-methyl-benzofuran-2-carboxylic acid rert-butyl ester as a pale yellow oil. Step 4: To l90mg of 4-methoxy-5~hydroxymethyl-3-methyl-benzofuran-2-carboxylic acid rerf-butyl ester was added 4mL of TFA/dicblorornethane (1:1) and the solution was stirred at room temperature for 3h. When the reaction was done, the solvents were removed under vacuum and the residue was triturated with acetonitrile. Filtration of the suspension gave 184mg of 4-methoxy-3-methyl-5-(2,2,2-trifluoro-acetoxymethyl)-benzofuran-2-carboxylic acid as a white solid. Step 5: To lOOmg (0.42mmol) of 4-methoxy-3-methyl-5-(2,2,2-trifluoro-acetoxymethyl)-benzofuran-2-carboxylic acid was added 256 mg (1.5eq) of (S)-2~(4 -amino-biphenyl-4-sulfonylamrno)-3-methyl-butyric acid tert-butyl ester, BOP (185mg, leq), Nfl-diisopropylethylamine (54mg,leq) and 4mL of DMF. The mixture was stirred at room temperature for 48h. Brine was added and the mixture was extracted with ethyl acetate. The combined organic solution was washed with 2N HCJ and water. Removal of the solvent from the organic solution gave the crude product, which was purified by column chromatography on silica gel to give S9mg of (S)-2-{4'-[(5-hydroxymethyl-4-methoxy-3-methyi-ben2ofuran-2-carbonyl)-amino]-biphenyl-4~sulfonylamino}-3-methyl-butyric acid zenr-butyl ester as an off white solid. Step 6: To 81mg of (S)-2-{4'-[(5-hydroxymethyl-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl ester was added 2mL of TFA/dichloromethane (1:1) and the solution was stirred at room temperature for 3h. When the reaction was done, the solvents were removed under vacuum and the residue was triturated with acetonitrile/water. Filtration of the suspension gave mixture of (S)- 2-(4'-{[4-methoxy-3-methyl-5-(2,2,2-trifluoro-acetoxymethyl)-benzofuran:2-carbonyI]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid and (S)-2-{4-[(5-hydroxymetbyl-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-bipheriyl-4-su]fonylamino}-3-methyl-butyric acid. To the mixture was added lmL of THF and 2mL of LiOH solution (3.6g of LiOH/50mL of MeOH/50mL of water). The solution was stirred at room temperature overnight. The solvents were removed under vacuum and the residue was dissolved in 3mL of water. The solution was acidified and the resulting suspension was filtered. The solid product was dried under vacuum to give 68mg of (S)-2-{4 -[(5-hydroxymethyl-4-methoxy-3-methyl-ben2ofuran-2-carbonyl)-amino]-biphenyl-4-sulfony3amino}-3-rnethyl-butyric acid as an off-white solid. 'HNMR (400 163 WO 2005/061477 PCT/US2003/040835 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6,6.8 Hz, 6 H) 2.0 (m, 1 H) 2.8 (s, 3 H) 3.6 (dd, J=9.1, 6.1 Hz JL H) 3.9 (s, 3 H) 4.6 (d, 7=5.3 Hz, 2 H) 5.2 (t, 7=5.6 Hz, 1 H) 7.5 (d, 7=8.6 Hz, 1 H) 7.6 (d, 7=8.6 Hz, 1 H) 7.S (d, 7=8.8 Hz, 2 H) 7.9 (m, 4 H) 8-0 (d, 7=9.1 Hz, 2 H) 8.1 (d, 7=9.1 Hz, 1 H) 10.5 (s,lH) 12.6 (s,lH). Example 127: (5)-3-McthyI-2-{4!-[(benzooxazoIe-2-carbonyI)-amino]-bIpheny1-4-sulfonylamindj-butyric acid Step 1: To 2-aminophenol (437mg, 4 mmol) was added ethyl triethoxyacetate (3.5g, 4eq). The mixture was stirred at 11O°C overnight. The reaction mixture was cooled and triturated with hexane. Filtration gave 5l6mg of benzoxazo]e-2-carboxylic acid ethyl ester as a white solid. Step 2: To benzoxazoIe-2-carboxylic acid ethyl ester (437mg, 4mmol) was added 2mL of THF and 4mL of NaOH solution (2N in MeOH). The reaction mixture was stirred at room temperature overnight. The suspension was filtered and the solid was dried under vacuum to give 160mg of benzoxazole-2-carboxyJic acid sodium salt as an off-white solid. Step 3: To benzooxazole-2-carboxyIic acid sodium salt (161mg, Immol) was added (S)-2-(4'-arruno-bipheny]-4-sulfony]amino)-3-methyl-butyric acid tert-butyl ester (405mg, leq), BOP (550mg, 1.2eq), N,N-diisopropyJethylamine (155mg, 1.2eq) and 4mL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic layers were washed with brine and water. Removal of solvent gave the crude product, which was purified by column chromatography on silica gel to give 126mg of (5)-3-methyl-2-{4'-[(benzoxazole-2-carbonyl)-amino]-biphenyI-4-sulfonylamino}-butyric acid tert-butyl ester as a white solid. Step 4: To (5)-3-methyI-2-{4'-[(benzoxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid tert-butyl ester was added_4m]LQf TFA/CH2CI2 (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 90mg of (S)-3-methyl-2-{4'-[(benzooxazoIe-2-carbonyl)-amino3-biphenyl-4-sulfonylaminoj-butyric acid as a white solid. 'HNMR. (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.6, 6.8 Hz, 6 H) 1.9 (m, 1 H) 3.6 (dd, 7=9.3, 6.1 Hz, 1 H) 7.6 (m, 1 H) 7.6 (m, 1 H) 7.8 (m, 6 H) 8.0 (m, 2 H) 8.1 (m, 3 H) 11.4 (s, 1 H). 164 WO 2005/061477 PCT/US2003/040835 Example 128: (5)-3-Methyl-2-{4'-[(4-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylaminoj-butyric acid Step 1: To 2-amino-3-methylphenol (lg, 8.1mmol) was added ethyl triethoxyacetate (5.4g, 3eq). The mixture was stirred at 110°C overnight. The reaction mixture was cooled and triturated with hexane. Filtration gave 1.36g of 4-methyl-benzooxazo]e-2-carboxylic acid ethyl ester as a white solid. Step 2: To 4-methyl-benzooxazole-2-carboxylic acid ethyl ester (140mg) was added 2mL of THF, and 0.93mL (2eq) of NaOH solution (2N in MeOH). The reaction mixture was stirred at room temperature overnight. The suspension was filtered and the solid was dried under vacuum to give 200mg (100%) of 4-methyl-benzooxazole-2-carboxylic acid sodium salt as an off-white solid. Step 3: To 4-methyl-benzooxazole-2-carboxylic acid sodium salt (180mg, 0.93mmol) was added (S)-2-(4'-amino-biphenyl-4-sulfony]amino)-3-methyl-butyric acid terr-butyl ester (450mg, 1.2eq), BOP (490mg, 1.2eq), N,N-diisopropylethylamine (144mg, 1.2eq) and 4mL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted .with ethyl acetate. The combined organic solution was washed with brine and water. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 158mg of (5)-3-methyl-2-{4'-[(4-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid rerr-butyl ester as a white solid. Step 4: To (5)-3-methyl-2-{4'-[(4-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl ester (135mg) was added 4mL of TFA/CH2CI2 (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 140mg of (5)-3-methyl-2-{4'-t(4-methyl-benzooxazole-2-carbonyl)-amin6]-bipheny]-4-sulfonylamino}-butyric acid as white solid. ]H NMR (400 MHz, DMSO-d6) dppm 0.8 (dd, 7=12.4,6.8 Hz, 6 H) 2.0 (m, 1 H) 2.7 (s, 3 H) 3.6 165 WO 2005/061477 PCT/US2003/040835 (dd, J=3,6.1 Hz, 1 H) 7.4 (d, J-8.3 Hz, 1 H) 7.5 (m, 1H) 7.7 (d, J=8.3 Hz, 1H) 7.8 (m, 6 H) 8.1 (t, J=8.8 Hz, 3 H) 11.3 (s, 1 H). Example 129: (5)-3-Methyl-2-{4'-[(5-inethy]-benzooxazole-2-carbonyI)-amino]-WphenyI-4-sulfonylamino}-butyrjc acid Step 1: To 2~amino-4-rnethyIphenoI (Ig, 8.lmmol) was added ethyl triethoxyacetate (5.4g, 3eq). The mixture was stirred at 110°C overnight. The reaction mixture was cooled and triturated with hexane. Filtration gave 850mg (91%) of 5-methyl-benzooxazo]e-2-carboxy]ic acid ethyl ester as a white solid. Step 2: To 5-jnethyl-benzooxazo]e-2-carboxylic acid ethyl ester (170mg) was added 2mL of THF, and 0.83mL (2eq) of sodium hydroxide solution (2N in MeOH). The reaction mixture was stirred at room temperature overnight. The suspension was filtered and the solid was dried under vacuum to give 144mg of 5-methyl-benzooxa2ole-2-carboxylic acid sodium salt as an off-white solid. Step 3: To 5-methy]-benzooxazole-2-carboxyHc acid sodium salt (130mg, O.83mmol) was added (S)-2~(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid rert-butyl ester (400mg, 1.2eq), BOP (430xng, 1.2eq), AyV-diisopropylethylamine (126mg, 1.2eq) and4mLof RMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine and water. Removal of solvent gave the crude product, which was purified by column chromatography on silica gel to give 60mg of (S)-3-methyl-2-{4'-[(5-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-suIfonylamino}-butyric acid tert-butyl ester was obtained as a white solid. Step 4: To (S)-3-methyI-2-{4'-[(5-methy]-benzooxazole-2-carbonyl)'amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl ester (30mg) WEIS added 2mL of TFA/CR2CI2 (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 14mg of (5)-3-methyl-2-{4'-f(5-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid as a white solid. 'H 166 WO 2005/061477 PCT/US2003/040835 NMR(400 MHz, DMSO-d6) dppm 0.76 - 0.93 (m, 6 H) 1.84 - 2.07 (m, 6 H) 3.56 (dd, 1 H) 7.70 - 7.95 (m, 8 H) 7.98 - 8.14 (m, 3 H) 11.32 - 11.41 (m, 1 H). Example 130: (5)-3-Methyl-2-{4'-[(5-chloro-benzothiazo]e-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid Step 1: To 2-amino-4-chloro-benzenethiol (lg) was added ethyl triethoxyacetate (3eq). The mixture was stirred at 110°C overnight. The reaction mixture was cooled and triturated with hexane. Filtration gave 392mg of 5-chloro-benzothiazoIe-2-carboxylic acid ethyl ester as a white solid. Step 2: To 5-chloro-benzothiazole-2-carboxylic acid ethyl ester (200mg, 0.83mmol) was added 3mL of THF, and 0.83mL (2eq) of NaOH solution (2N in MeOH). The reaction mixture was stirred at room temperature overnight. The suspension was filtered and the solid was dried under vacuum to give 170mg of 5-chloro-benzothiazole-2-carboxylic acid sodium salt as an off-white solid. Step 3: To 5-chloro-benzothiazole-2-carboxylic acid sodium salt (150mg, 0.64mmol) was added (S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester (310mg, 1.2eq), BOP (340mg, 1.2eq), N,N-diisopropylethylamine (99mg, 1.2eq) and 4mL of DMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine and water. Removal of solvent gave the crude product, which was purified by column chromalography on silica gel to give 136mg of (S)-3-methyl-2-{4'-[(5-chloro-benzothiazole-2-carbonyl)-arnino]-biphenyl-4-sulfonylamino}-butyric acid rerf-butyl ester was obtained as a white solid. Step 4: To (5)-3-methyl-2-{4'-[(5-chloro-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino)-butyric acid tert-butyl ester (30mg) was added 3mL of TFA/CH2C12 (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and_ the residue was triturated with ether. Filtration gave 105mg of (S)-3-methyl-2-{4'-[(5-chloro-benzothiazole-2-carbonyl)-amino]-biphenyl-4-su]fonylamino}-butyric acid as yellow solid. 'H 167 WO 2005/061477 PCT/US2003/040835 NMR (400 MHz, DMSO-d6) dppm 0.79 - 0.88 (m, 6 H) 1.85 - 2.07 (m, 1 H) 3.56 (dd, 1 H) 7.70 (dd, 1 H) 7.76 - 7.94 (m, 6H) 8.03 - 8.12 (m, 3 H) 8.26 (d, 1 H) 8.35 (d, 1 H) 11.36 -11.40 (m, 1 H). Example 131: (S)-3-Methyl-2-{4'-[(S-trifIuoromethyl-benzothiazo]e-2-carbonyl)-amino]-biphenYl-4-sulfonylamino}-butyricacid Step 1: To 2-amino-4-trifluoromethyI-benzenethiol (0.7g) was added ethyl triethoxyacetate (3eq). The mixture was stirred at 110°C overnight. The reaction mixture was cooled and triturated with hexane. Filtration gave 460mg of 5-trifluoromethy]-benzothiazo]e-2-carboxylic acid ethyl ester as a white solid. Step 2: To 5-trifluoromethyl-benzothiazole-2-carboxylic acid ethy] ester (200mg, 0.73mmo]) was added 3mL of THF, and 0.73mL (2eq) of NaOH solution (2N in MeOH). The reaction mixture was stirred at room temperature overnight. The suspension was filtered and the solid was dried under vacuum to give 270mg of 5-trifluoromethyl-benzothiazo]e-2-carboxylic acid sodium salt as an off-white solid. Step 3: To 5-trif]uoromethyl-benzothiazole-2-carboxylic acid sodium salt (260mg, 0.97mmol) was added (S)-2-(4'-amino-biphenyl-4-sulfony]amino)-3-methyl-butyric acid tert-butyl ester (469mg, 1.2eq), BOP (515mg, 1.2eq) and 5mLof DMF. The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic layers were washed with brine and water. Removal of solvent gave the crude product, which was purified by column chromatography on silica gel to give 230mg of (5)-3-methy]-2-{4'-[(5-trifluoromethyl-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl ester as a white solid. Step 4: To (5)-3-methyl-2-{41-[(5-trifluoromethyl-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid rerr-butyl ester (210mg) was added 3mL of TFA/CH2CI2 (1:1). The solution was stirred at room temperature for 3h. The solvents were removed under vacuum and the residue was triturated with ether. Filtration gave 181mg of (5)-3-methy]-2-{4-[(5-trifluoromethyl-benzothiazo]e-2-carbonyl)-amino3-biphenyl-4-sulfonylamino}-butyric acid 168 WO 2005/061477 PCT/US2003/040835 as a yellow solid. 'H NMR (400 MHz, DMSO-d6) dppm 0.83 (dd, 7=12.63, 6.82 Hz, 6 H) 1.92 -2.00 (m, 1 H) 3.56 (dd, 7=9.35, 6.06 Hz, 1 H) 7.80 - 7.86 (m, 4 H) 7.88 - 7.92 (m, 2 H) 7.97 (dd, 7=8.59, 1.52 Hz, 1 H) 8.05 - 8.07 (m, 1 H) 8.09 (d, 7=2.78 Hz, 1 H) 8.49 (s, 1 H) 8.57 (d, 7=8.59 Hz, 1H) 11.41 (s,lH). Example 132: D-3-Methyl-benzofuran-2-carboxylic acid 4'-(l-carboxy-2-methyl-propylsuIfamoyl)-3,5-dimethyl-biphenyl-4-yI ester Step 1: To 3-methy]-benzofuran-2-carboxylic acid (500mg, 2.84 mmol, leq) in 5 mL of dichloromethane under argon, was added 2,6-dimethyl-4- (4,4,5,5-tetramethyl- [1,3,2] dioxaborolan-2-yl)-phenol (704 mg, 2.84 mmol, leq.), 1,3-dicyclohexylcarbodiimide (1.17g, 5.68 mmol, 2 eq.), and 4-(dimetbylamino)pyridme (173 mg, 1.42 mmol, 0.5 eq.). The resulting mixture was stirred at room temperature for 6h. The reaction was then diluted with water and extracted with ethyl acetate. The organics were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo'. The residue was purified using flash column chromatography on silica gel to provide 3-methyl-benzofuran-2-carboxylic acid 2,6-dimethyl-4-(4,4,5,5-tetramethyl- [1,3,2] dioxaborolan-2-yl)-phenyl ester in 28% yield. ]H NMR (400 MHz, DMSO-d6) d ppm 1.3 (s, 12 H) 2.2 (s, 6 H) 2.7 (s, 3 H) 7.4 (m, 1 H) 7.5 (s, 2 H) 7.6 (m, 1 H) 7.8 (d, J=8.3 Hz, 1 H) 7.9 (m, 1 H). Step 2: To 3-methyl-benzofuran-2-carboxylic acid 2,6-dimethyl-4- (4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenyl ester (310 mg, 0.76 mmol, 1 eq.), D-2- (4-bromo-benzenesu]fonylamino)-3-methy]-butyric acid terf-butyl ester (300 mg, 0.76 mmol, 1 eq., Example 74, step 2), tetrakis(triphenylphosphine)palladium(0) (44 mg, 0.0387 mmol, 0.05 eq.), and ethylene glycol dimethyl ether (10 mL) were added under argon and stirred for 10 minutes. Then potassium carbonate (211 mg, 1.53 mmol, 2 eq.) in water (4 mL) was added. The reaction was heated at reflux for 16 h. After aqueous work-up and ethyl acetate extraction, purification using flash column chromatography provided D-3-methyl-benzofuran-2-carboxylic acid 4 -(1-tert-butoxycarbonyl-2-methyl-propylsulfamoyl)-3,5-dimethyl-biphenyl-4-yl ester in 69% yield. JH NMR (400 MHz, DMSO-d6) d ppm 0.9 (m, 6 H) 1.2 (s, 9 H) 1.9 SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4RS, CN, phenyl, heteroaryl, and C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 aikynyl, each optionally substituted with NR4R5, N[(CH2)2j20, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, 235 WO 2005/061477 PCT/US2003/040835 NHC(=O)OR4, NO2j SO2NR4R5, SO2R4, OR8, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, hetero^loalkyl, phenyl, orheteroaryl; and R8 is selected from H, phenyl, heteroaryl, and C1-C6 alky], optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4,.NR4SO2R5, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl. 37. The method of claim 36 wherein: E is C(H)=C(H); UisO; W is C(H), or C(CH3); M is C(R9), wherein R9 is H, halogen, C1-C6 alky], or CN; and L is C(H)=C(H). 38. The method of claim 28 wherein R1 and R2 are each C1-C6 alkyl. 39. The method of claim 28 wherein R3 is H. 40. The method of claim 28 wherein R4 and R5.are each C1-C6 alky]. 41. The method of claim 28 wherein G and E are each C(H)=C(H). 42. The method of claim 28 wherein U is O or S. 43. The method of claim 28 wherein W is C(H) or C(CH3). 44. The method of claim 28 wherein M is CR6. 45. The method of claim 28 wherein L is CH=CH. 46. The method of claim 28 wherein R7 is other than H. 47. A compound the formula 1: 236 WO 2005/061477 PCT/US2003/040835 wherein: R1 and R2 are, independently, H, CH(OH)R4, phenyl, heteroaryl, or C1-C6 alkyl, with the proviso that when R1 or R2 is CH(OH)R4, then Z is substituted with NR4SO2R5, SO2NR4R5, heterocycloalkyl, heteroaryl, or C3-C6 cycloalkyl; R3 is H or C1-C6 alkyl; R4 and R5 are, independently with respect to each occurrence, a bond to the other, H, Cl-C6 alkyl, or phenyl; G and E are, independently, S, O, N(R4), C(R6)=C(R6), orN=C(R6); R6 is, independently with respect to each occurrence, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2}2NR4, NR4SO2R5, NR4C(=O)R5,NHC(=O)OR4,NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN.phenyl, heteroaryl, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; X is N(R3)C(=O), OC(=O), OS(O)2, NHSO2, OCH2, CH2S(O), or CH2S(O)2; and Z is at least one heteroaryl moiety. 48. The compound of claim 47 wherein R1 is substituted with halogen, CO2R4, C(=O)NR4R5, phenyl, or heteroaryl. 49. The compound of claim 47 wherein R3 is substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl. 50. The compound of claim 47 wherein R6 is each optionally substituted with NR"R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SQ2R5, NR4C(=O)R5, NR4C(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyl, or heteroaryl. 51. The compound of claim 47 wherein Z is a 5 membered ring. 52. The compound of claim 47 wherein Z is bicyclic. 237 WO 2005/061477 PCT/US2003/040835 53. The compound of claim 47 wherein Z is furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, isoxazole, isothiazole, thiazole, 1,2,5-lhiadiazole, 1,2,3-triazoIe, 1,3,4-thiadiazole, 1,2,3-thiadiazole, 1,2,4-ihiadiazole, 1,2,4-triazoIe, 1,2,4-oxadiazole, 1,3,4-oxadjazole, and furazan, or wherein: U is selected from S, O, and N(R4); W is selected from C(R6), and N; M is selected from CCR6), and N; L is selected from C(R6)=C(R6), C(R6)=N, and N(R4); R7 is selected from a bond to R6, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4» NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyl, heteroary], and C1-C6 alky], C2-C6 alkenyl, and C2-C6 alkyny], each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR8, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycJoalkyl, phenyl, orheteroaryl; and R8 is selected from H, phenyl, heteroaryl, and C1-C6 alky], optionally substituted with NR4R5, N[(CH2)2J2O, N[(CH2)2]2NR4, NR4SO2RS, NR4C(=O)R5, NHC(=O)OR4, NO2) SO2NR4R5, SO2R4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyJ, heterocycloalkyl, phenyl, or heteroaryl. wherein: 238 54. The compound of claim 47 wherein Z is: WO 2005/061477 PCT/US2003/040835 U is selected from S, O, and N(R4); W is selected from C(R6), and N; M is selected from C(R6), and N; L is selected from C(R6)=C(R6), C(R6)=N, and N(R4); R7 is selected from a bond to R6, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyl, heteroaryl, and C1-C6 alky], C2-C6 alkenyl, and C2-C6 alkynyl, each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR8, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl; and R8 is selected from H, pheny], heteroaryl, and C1-C6 alkyl, optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5, NR4C(=O)R5, NHC(=0)OR4, NO2, SO2NR4RS, SO2R4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl. 55. The compound of claim 47 wherein: R3 is H; G is C(H)=C(H); E is C(H)=C(H) or N=C(H); X is NHC(=O), or OCH2; and wherein: U is selected from S, O, and N(R4); W is selected from C(R6), and N; M is selected from C(R6), and N; L is selected from C(R6)=C(R6), C(Re)=N, and N(R4); R7 is selected from a bond to R6, H, halogen, NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, OR4, C(=O)R4, COOR4, CONR4R5, CN, phenyl, heteroary], and C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, each optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NHSO2R4, NR4C<=O)R5, 239 WO 2005/061477 PCT/US2003/040835 NHC(=O)OR\ NO2, SO2NR4R5, SO2R4, OR8, C(=O)R4, COOR4, COKR4R5, CN, cycloalkyl, hetejseycloalkyl, phenyl, or heteroaryl; and R8 is selected from H, phenyl, heteroaryl, and C1-C6 alkyl, optionally substituted with NR4R5, N[(CH2)2]2O, N[(CH2)2]2NR4, NR4SO2R5; NR4C(=O)R5, NHC(=O)OR4, NO2, SO2NR4R5, SO2R4, C(=O)R4, COOR4, CONR4R5, CN, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl. 56. The compound of claim 55 wherein: EisC(H)=C(H); UisO; WisC(H),orC(CH3); M is C(R9), wherein R9 is H, halogen, C1-C6 alky], or CN; and LisC(H)=C(H). 57. The compound of claim 47 wherein R1 and R2 are each C1-C6 alkyl. 58. The compound of claim 47 wherein R3 is H. 59. The compound of claim 47 wherein R4 and R5 are each C1-C6 alkyl. 60. The compound of claim 47 wherein G and E are each C(H)=C(H). 61. The compound of claim 47 wherein U is O or S. 62. The compound of claim 47 wherein W is C(H) or C(CH3). 63. The compound of claim 47 wherein M is CR6. 64. The compound of claim 47 wherein L is CH=CH. 65. The compound of claim 47 wherein R7 is other than H. 66. The compound of claim 47 that is N-({4 -[(l-benzofuran~2-ylcarbonyl)ammo]-l,l - biphenyl-4-yl}sulfonyl)glycine; L-2-{4 -[(Benzofuran-2-carbonyl)-amino]-biphenyl-4- sulfonylamino}-3-methyl-butyric acid; N-({4-[(lH-indol-2-ylcarbonyl)amino]-l,r-biphenyl-4- 240 WO 2005/061477 PCT/US2003/040835 y1}su]fony])glyeine; (4'-U(5-chloro-l-benzofuraTi-2-y])carbonyl]amino}-l,l-biphenyI-4-yl)sulfonyl]-L:valine; N-[(4'-{[(7-methoxy-l-benzofuran-2-yl)carbony]]amino}-l,l-bjphenyl-4-y])sulfonyl]-L-valine; N-[(4-{[(5-nitro-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyI-4-y])sulfony]]-L-valine; N-[(4-{[(5-amino-l-benzofuran-2-yl)carbonyl]amino}-l,r-biphenyl-4-yl)sulfonyl3~L-valine; N-({4.-[({5-[(methylsulfonyl)amino]-l-benzofuran-2-y] }carbonyl)amino]-l ,1 -biphenyl-4-yl} sulfonyl)-L-valine; N-{ [4'-({[5-(acety1arhino)-l-benzofuran-a-yl]carbonyl}amino)-1,1-biphenyM-yl]sulfonyl}-L-valine; 4-[(5-Ben2enesuIfony]amino-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine; N-[(4-{[(4-methoxy-l-benzofuran-2-y])carbony]]amino}-l,l -biphenyl4-yl)sulfonyl]-L-valine; 4-[(Benzo[p]thiophene-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine; 4-[(4-Benzyloxy-benzofuran-2-carbony])-amino]-biphenyl-4-su]fonyl-L-valine; 4'-{[4-(l-Carboxy-ethoxy> benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonyl-L-vaIine; N-({4'-[(l-Benzofuran-2-y]carbonyl)amino3-l,l'-biphenyl-4-yl}sulfonyl)-L-Asparagine; L-2-{4'-[(Benzofuran-2-carbonyI)-amino]-biphenyl-4-sulfony]amino}-3-methyJ-butyricacid; N-({4-[(l-Benzofbran-2-ylcaxbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-L-Histidine; N-({4'-[(l-Benzofuran-2-yIcarbonyl)amino3-l,l-bJphenyl-4-yl}sulfonyl)-L-leucine;' L-2-{4'-[(Benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}r3-methyl-butyric acid; L-2-{4'-[(4-Cyano-3-methyl-berizofuraTi-2-carbonyl)-amino3-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2-{4'-f(3-methyl-4-prop-l-ynyl-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfony]amino}-butyric acid; L-2-(4'-{[4-(3-Methoxy-prop-l-yny])-3-methyJ-benzofuran-2-carbonyl]-amino}-biphenyl-4-su]fony]amino)-3-methyl-butyricacid; 2-{4'-[(4-CyclopropyIethynyl-3-methyl-benzofuran-2-carbony3)-amino]-bipheny]-4-sulfonykmino}-3-methy]-butyricacid; L-2-(4-{f4-(2-CyclopTopy]-ethyl)-3-rnethyl-benzofran-2-carbonyl3-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-2-(4'-{ [4-(3-Methoxy-Z-propenyl)-3-methyl-benzofuran-2-carbony]]-amino}-bipheny]-4-sulfonylaraino)-3-methy]-butyric acid; L-2-(4'-{[4-(3-Hydroxy-prop-l-ynyl)-3-metyl]-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L-2-(4'-{[4-(3-Hydroxy-propyl)-3-methyl-benzofiran-2-carbony]]-amino}-biphenyI-4-sulfonylamino)-3-methy]-butyric acid; L-3-Methyl-2-(4 -{[3-methyl-4-(4-methyl-pent-l-ynyl)-benzofuran-2-carbony]3-amino]-biphenyl-4-sulfonylamino)-butyric acid; L-3-Methyl-2-(4'-{[3-methyI-4-(4-methyl-pentyl)-benzofuran-2-carbonyl]-ainino}-b!phenyI-4-su]fony]armno)-butyric acid; L-2-(4'-{[4-(3-Methoxy-propyl)-3-methyl-benzofuran-2-carbony]]-amino}-biphenyl-4-suIfonyIamino)-3-methyl-butyric acid; L-2- (4 -{[4-(3-Dimethy3ai2iino-prop-l-ynyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-su]fonylamino)-3-methyl-butyric acid; L-2- (4-{[4-(3-DimethyIamino-propyI)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonyamino)-3-methyl-butyric acid; L- 2-{4 -[(4-Ethynyl-3-methyl-benzofuran-2-carbonyl)- 241 WO 2005/061477 PCT/US2003/040835 amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L- 2-(4'-{[4-(3,3-Dimethyl-but-l-yny 3,-methyI-benzofuran-2-carbony]]-amino]-biphenyl-4-su]fony]amino)-3-methyl-butyric acid; L- 3-Methyl-2- (4'-{[3-methyl-4- (3-methyl-isoxazol-5-yl)-benzofuran-2-carbonyl]-amin.o}-biphenyl-4-su]fonylamino)-butyric acid; L-2- {4-[(4-Methanesu]fony]amino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyricacid; L-2-(4'-{[4-(Methanesu]fonyl-methyl-amino)-3-methyl-benzofuran-2-carbonyl]-aTnino}-bipheny]-4-sulfonylamino)-3-:rnethy]-butyric acid; L-3-Hydroxy-2-(4-{5-[(4-methanesulfony]amino-3-methyl-benzofuran-2-carbonyI)-amino]-pyridin-2-yl }-benzenesulfony]amino)-butyric acid; L-2-(4-{5_[(4.Methane.su]fony]amino-3-methyl-benzofuran-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonylamino)-3-methyl-butyric acid; L-2-(4-{5-[(4-Cyano-3-methyl-benzofuran-2-carbony])-amino]-pyridin-2-yl}-benzenesulfonylainino)-3-methyl-butyric acid; D-2-(4-[(4-Methanesulfonylamino-3-methyl-benzofuran-2-carbonyI)-arnino]-biphenyl-4-sulfOTiy]aTnirio}-3-methyl-butyric acid; L-2-({4'-[(4-C,yano-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl}-methyl-amino)-3-methyI-butyricacid; (L-3-MethyI-2-{4'-[(3~methyl-4-methy]carbamoy]-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-butyric acid triethylamine salt; 2-{4'-[(4-DimethyIcarbamoyl-3-methyl-benzofuran-2-carbonyl)-amino]-. biphenyl-4-sulfonylamino}-3-inethyl-butyric acid triethylamine salt; L-2-{4'-[(4,6-Dimethoxy-3,7-dimethyl-benzofuran-2-carbonyl)-aTnino]-biphenyl-4-sulfonylamiTio}-3-iTiethyl-butyric acid; 2-{4-[(5-Bromo-3-inethyl-benzofuran-2-carbony])-ainino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-2-{4'-[(4-CarbamoyI-3-inethyl-benzofuraTi-2-carbonyl)-aniino]-bipheny]-4-sulfonylamino}-3-methyl-butyric acid; L-2-(4'-{[4-(Cyc]opropanecarbonyl-amino)-3-methyl-benzofuran-2-carbonyl]-amino}-bipheny]-4-su]fony]amino)-3-methyl-butyric acid; L-2- {4'-[(4-AcetylamiBO-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2-, {4'-[(3-methyl-4-propioTiy]amino-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; L-2- {4'-[(4-Isobutyrylamino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fonylamino}-3-methyl-butyric acid; L- 2-{4-[(4-Cyc]opropyIrnethoxy-3-methy]-benzofuran-2-carbony])-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L- 2-{4'-[(lH-Benzoimidazole-2-carbony])-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L- 2-{4'-[(4-sec-Butoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L- 3-Methyl-2- {4-[(3-phenyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylaiiuno}-butyric acid; L- 2-(4'-{[4-(Acetyl-raethyl-amino)-3-methy]-benzofuran-2-carbonyl]-ainino}-biphenyl-4-sulfony]amino)-3-methyl-butyric acid; L-3-Methyl-2- (4'-{[3-methyl-4- (2H-tetrazol-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylaniino)-butyric acid; L-2-(4'-{[4-(3,3-Dimethyl-butyl)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L- 2- 242 WO 2005/061477 PCT/US2003/040835 {4^[(3_Ethyl-benzofuran-2-carbony])-amino]-bipheny]-4-sulfony]amino}-3-methyl-butyric acid; L-2-{4'-[(4-tert-Butoxycarbonylamino-3-methy]-benzofuran-2-carbonyl)-aminol-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2- {4-[(3-methyl-4-methyIamino-benzofuraT}-2-carbonyl)-amino]-biphenyI-4-sulfonylamino}-butyric acid; L-2: {4-[(4-Amino-3-methy]-benzofuran-2-carbonyl)-amino]-biphenyi-4-sulfonylamino}-3-methyl-butyricacid; L-2-^4'-[(4.DiTnethy]amJno-3-methyl-berizofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2- {4-[(3-methyl-4-pyrrolidin-l-yl-benzofuran-2-carbonyl)-amino]-bipheny]-4-suIfony]amino}-butyric acid; L-2- (|4-[(4-Methanesulfonylamino-3-meth'yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyI }-methyl-amino)-3-methyl-butyric acid; L-3-Hydroxy-2- {4'-[(4-methanesu]fony]amino-3-methy]-benzofuran-2-carbonyl)-ainiiio]-biphenyl-4-sulfonylamino}-butyric acid; (S)-3-Methyl-2-(4'-{[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazo]e-5-carbony]]-amino}-bipheny]-4-sulfonylamino)-butyric acid; L-3-Methyl-2-(4-{[3-methyl-4-(2,2,2-trifluoro-acety']amino)-benzofuran-2-carbonyl]-amino}-bipheny]-4-sulfonylamino)-butyric acid; L-2- {4'-[(4-Ethanesu]fony]amino-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fony]amino}-3-methyI-butyric acid; L-3-Methyl-2-(4'-{[3-methy]-4-(propane-2-su]fony]amino)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amino)-butyric acid; L-2-(4'-{[4-(Ethanesulfony]-methyI-amino)-3-m6thyl-benzofuran-2-carbonyl]-amino}-bipheny]-4-su]fony]amino)-3-methyl-butyric acid; L- 2-{4'-[(4-Benzenesulfonylamino-3-raethyl-benzofuran-2-carbony])-amino]-biphenyI-4-su]fony]arnino}-3-methyl-butyric acid; L-3-Methyl-2-(4-{[3-methyl-4- (thiophene-2-sulfonylamino)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; L-2- (4-{[4-(l,l-Dioxo-lD6-isothiazolidin-2-yl)-3-methy]-benzofuran-2-carbonyl]-amir)o}-biphenyl-4-sulfonylainino)-3-methyl-butyric acid; D-3-Methyl-2-{4'-[(3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; D-2-{4'-[(Benzofuran-2-carbony])-methyl-amino]-bipheriyl-4-sulfonylamino}-3-methy]-butyric acid; 4-{5-[(Benzofuran-2-carbonyl)-arnino]-pyridin-2-yl}-benzenesulfonyl-L-valine; N-({4-[(l-benzofuran-2-ylcarbonyl)amino]-l,l'-biphenyl-4-yl}sulfonyl)-N-methyl-D-valine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,r-bipheny]-4-yl}su]fonyl)-N-methyl-L-valine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,r-biphenyl-4-yl}sulfonyl)-N-methylglycine; (S)-2-{4'-[(l,3-Dimethyl-lH-thieno[2,3-c]pyrazo]e-5-carbonyl)-amino]-bipheny]-4-su]fony]amino}-3-methyl-butyric acid; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l'-biphenyl-4-yl}sulfonyI)-N-(pyridin-3-ylmethyl)-L-valine; N-({4'-[(l-Benzofuran-2-y]carbony])arnino]-l, 1 '-biphenyl-4-yl} suIfonyl)-N-(2-morpholin-4-ylethyl)-L-valine; N-[(4'-{[(3-Methyl-l-benzofuran-2-y])carbonyl]amino}-l,r-biphenyl-4-y])sulfony3]-L-valine; N-[(4'-{[(5-Bromo-l-benzofuran-2-y])carbonyl]amino}-l ,1 -biphenyl-4-yl)sulfonyl]-L-valine; N-[(4'-{[(4-Methyl-3,4,5,6-tetrahydrofuro[4,3,2-ef][3]benzazepm-2-yl)carbonyJ]amino}- 243 WO 2005/061477 PCT/US2003/040835 1 ,l'-biphenyl-4-yl)sulfony]]-L-valine; N-[(4'-{[(5-Ethyl-4-methoxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyl-4-y])sulfonyl]-L-va]ine; N-[(4'-{[(4-Ethy]-3-methyl-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyl-4-yl)sulfonyl]-L-valine; N-[(4'-{[(5-Ethyl-4-isopropoxy-3-methyI-l-benzofuran-2-y])carbony]]amino}-l,1-bipheny]-4-y])sulfony]]-L-va]Jne; N-{ [4'-({ [4-(Benzyloxy)-5-ethy]-3-methy]-l-benzofuran-2-yl]carbony]} amino)-l ,l'-biphenyl-4-y]]sulfonyl)-L-valine; N-[(4-{[(5-Ethyl-4-hydroxy-3-methyl-l-ben2ofuran-2-y])carbony]]amino}-l,1-bipheny]-4-yl)sulfony]]-L-valine; N-{[4-({[4-(2,2-Dimethyl-l,3-dioxolan-4-yl)-3-rnethyl-1 -benzofuran-2-yl]carbony]) amino)-l, 1 -biphenyl-4-y]]su]fonyl} -L-valine; N-{[4'-({[4-(Hydroxymethyl)-3-methy]-l-benzofuran-2-y]]carbony]}amino)-l,l -bipheny]-4-yJ]sulfonyl}-L-vaIine; N-t(4-{[(3,4-Dimethyl-l-benzofuran-2-y])carbonyl]amino}-l,l'-bipheny]-4-y])sulfonyl]-L-va]ine; N-[(4'-{[(4-Acetyl-3-methyI-l-benzofuran-2-yl)carbony]]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-va]ine; N-{[4-({[4-(l-HydroxyethyI)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,1-biphenyl-4-yl]sulfonyl}-L-valine; N-[(4'-{[(3-methyl-4-vinyl-l-benzofuran-2-y])carbonyI]amino}-l,1-biphenyl-4-yl)su]fony]]-L-va]ine; N-{[4'-({[4-(l,2-dihydroxyethyl)-3-methy]-l-benzofuran-2-yl]carbonyl} armno)-l,l -biphenyl-4-y]]sulfonyl}-L-valine; N-methyl-N-[(4'-{[(3-methy]-4-vinyl-l-benzofuran-2-y])carbony]]amino}-l,1-biphenyI-4-yl)sulfonyl]-L-valine; N-{[4'-({[4-(l,2-dihydroxyethyl)-3-methyl-1 -benzofuran-2-yJ]carbonyl}arnino)-1, 1 -biphenyl-4-y]]sulfony] }-N-methy]-L-valine; N-{[4'-({[4-(methoxymethyl)-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l,l'-biphenyl-4-y]]sulfonyl}-L-valine; N-{[4'-({[4-(l-methoxyethy])-3-methy]-l-benzofuran-2-y]]carbony]}amino)-l,1-biphenyl-4-yl]sulfonyl}-L-valine; N-{[4'-({[4-(2-methoxyethyl)-3-methy]-l-benzofuran-2-yl]carbonyl]amjno)-l,1 -biphenyl-4-y]]su]fony]}-L-vaJinate; N-[(4-{[(4-Isopropoxy-1 -benzofuran-2-yl)carbonyl] amino} -1,1 '-biphenyl-4-yl)su]fonyl]-L-valine; N-[(4-{[(5-methoxy-l-benzofuran-2-y])carbony]]amino}-l,l'-biphenyl-4-y])su]fony]]-L-valine; (S)-2-{4'-[(4-Methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amiTio}-3-methyl-butyric acid; (S)-2-{4-[(4-ethoxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-sulfony] amino} -3-methy]-butyric acid; (S)-3-Methy]-2-{4'-[(3-methyl-4-propoxy-benzofuran-2-carbonyl)-anu'no]-biphenyl-4-sulfonylamino}-butyric acid; (S)-2-{4'-[(4-Isopropoxy-3-inethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; (S)-3-Methyl-2-{4'-[(3-methyl-4-phenyl-benzofuran-2-carbonyl)-ainino]-bipheny]-4-su]fony]amino}-butyric acid; (S)-3-Methyl-2-(4'-{ [3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carbonyl3-amino}-biphenyl-4-sulfonylamino)-butyricacid; (S)-3-methyl-2-{4'-[(3-methy]-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino)-butyricacid; (S)-3-Methyl-2-{4-[(3-methyl-4-pyridin-4-yI-benzofuran-2-carbony])-amino]-biphenyl-4-suJfonylamino}-butyric acid; (S)-2-{4'-[(4-Furan-3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4- 244 WO 2005/061477 PCT/US2003/040835 sulfonylamino}-3-methyl-butyrica cid; (S)-3-methyl-2-{4'-[(3-methyl-4-morpholin-4-yl-be^)furan-2-carbony])-amino]-biphenyl-4-sulfonylamino}-butyric acid; (S)-2-{4'-[(5-Chloro-4-isopropoxy-3-inethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylarnino}-3-rnethyl-butyric acid; (S)-2-{4'-[(5-Chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyricacid; (S)-2-{4'-[(5,7-Dichloro-4-methoxy-3-methyl-benzofuran-2-carbony])-ainino]-biphenyl-4-su]fony]ainino}-3-methyl-butyric acid; (S)-2-{4'-[(5-bromo-4-methoxy-3-methy]-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fony]amino}-3-methy]-butyric acid; (R)-2-{4'-[(5-Bramo-4-methoxy-3-methyl-benzofurari-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyI-butyric acid; (S)-2-{4-[(5-Iodo-4-methoxy-3-methyI-benzofuran-2-carbony])-amino]-bipbeny]-4-sulfony]amino}-3-methyl-butyric acid; (S)-2-{4-[(5-Acetyl-4-methoxy-3-methy]-benzofuran-2-carbony])-amino]-biphenyl-4-su]fonylamino}-3-methy]-butyric acid; S)-2-(4'-{ [5-(l-Chloro-vinyl)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amino)-3-inethyl-butyric acid; (S)-2-{4-[(5-Acetyl-4-hydroxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-sulfony]axnino}-3-methyl-butyric acid; (S)-2-{4'-[(5-Cyano-4-methoxy-3-methyl-benzofuran-2-caibonyl)-amino]-biphenyl-4-su3fony]amino}-3-methy]-butyric acid; (S)-2-{4-[(5-Methyl-4-methoxy-3-inethyl-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino}-3-methyl-butyric acid; (S)-2-{4-[(5-Hydroxyrnethy]-4-methoxy-3-inethy]-benzofuran-2-carbonyl)-ainino]-biphenyl-4-su]fonylamino}-3-methyl-butyric acid; (S)-3-Methy]-2-{4'-[(benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-butyric acid; (S)-3-Methy]-2-{4'-[(4-methy]-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-butyric acid; (S)-3-Methyl-2-{4-[(5-methyl-benzooxazo]e-2-carbony])-amino]-bipheny]-4-sulfonylamino]-butyric acid; (S)-3-Methy]-2-{4'-[(5-ch]oro-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylainino}-butyric acid; (S)-3-Methy]-2-{4-[(5-trifluoromethy]-benzothiazo]e-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; D-3-Methyl-benzofuran-2-carboxy]ic acid 4-(l-carboxy-2-methyI-prop'y]su]famoy])-3,5-dimethy]-bipbeny]-4-y] ester; D-Benzofuran-2-carboxylic acid4'-(l-carboxy-2-methyl-propylsulfamoyl)-3,5-dimethyI-biphenyI-4-y] ester; D-3-Methyl-benzofuran-2-carboxylic acid4-(l-carboxy-2-methy]-propylsu]famoy])-biphenyl-4-ylester; Benzofuran-2-carboxylic acid 4'-(l-carboxy-2-metliyl-propylsuIfamoyl)-biphenyl-4-yl ester; D-2-[4'-(5-Bromo-4-methoxy-3-inethy]-benzofuran-2-y]iTiethoxy)-bipheny]-4-sulfonylainino]-3-methy]-butyricacid; D-2-[4-(Benzothiazol-2-y]meth6xy)-biphenyI-4-sulfonylamino]-3-methyl-butyric acid; D-3-Methyl-2-[4'-(l-methy]-lH-benzoimidazp]-2-y]rnethoxy)-bipheny]-4-sulfony]amino]-butyric acid; D-3-Methyl-2-[4'-(3-methyl-benzofuran-2-y]methoxy)-bipheny]-4-suIfony]amino]-butyric acid; D-2-[4-(Benzofuran-2-y]methoxy)-3'-methoxy-bipheny]-4-su]fonylamino]-3-methyl-butyric acid; D-2- [4-(Benzofuran-2-ylmethoxy)-biphenyl-4-sulfonylamino]-3-methyI- 245 WO 2005/061477 PCT/US2003/040835 butyric acid; L-2-[4'-(5-Chloro-4-methoxy-3-methyl benzofuran-2-ylmethoxy)-biphenyl-4-sulfonylamino]-3-methyl butyric acid; L-2-[4'-(5-Cyano-4-methoxy-3-methy] benzofuran-2-ylmethoxy)-biphenyl-4-sulfonylamino]-3-methyl butyric acid; N-{[4'-(2-Furoyloxy)-l,l,-biphenyl-4-yl]sulfony]}-D-va]ine; N-{[4'-(3-Furoy]oxy)~lJ'-bipheny]-4-yl]su]fony]}-D-valine; L-2-[4'-(4-Ethy]-3-methyl benzofuran-2-ylmethoxy)-biphenyl-4-sulfolylamino]-3-methyl butyric acid; N-[(4'-{[4-(3-methoxypropyl)-3~methyl-l-benzofuran-2-yl]methoxy}-l,1-biphenyl-4-yl)su]fony]]-L-valine; N-({4'-[(5-Bromo-4-inethoxy-3-methy]-l-benzofuran-2-yl)methoxy]-l,1 '-biphenyl-4- yl)sulfony])-L-valine; N-({4'-[(5-Bromo-4-isopropoxy-3-methyl-l-benzofuran-2-yl)methoxy]-l.l'-biphenyl- 4-yl} sulfonyl)-D-valine; N-[(4'-{[(5-bromo-4-methoxy-3-methyl-l-benzofuran-2-yl)methyl]amino}-l, 1'- bipheny]-4-y])su]fony]]-L-valine; L-2-{4'-[(Benzothiazo]e-2-carbonyl)-amino]-bipheny]-4-su]fony]amino}-3-methyl-butyric acid; D-2-{4'-[(Benzothia2ole-2-carbony])-ainino]-bipheny]-4-su]fony]amino}-3-methy]-butyric acid; L-3-Methyl-2-{4'-[(naphtho[2,1 -b]furan-2-carbonyl)-amino]-bipheny]-4-sulfonylamino) -butyric acid; L-3-Methyl-2-{4'-[(l-methy]-naphtho[2,l-b]furan-2-carbony])'amino]-bipheny]-4-sulfonylamino}-butyric acid; L-3-Methyl-2-{4'-[(3-methyl-4-phenoxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fonyIamino}-butyric acid; L-2-(4'-{ [4-(l-Methoxycarbony]-l-methyl-ethoxy)-3-methy]-benzofuran-2-carbonyl]-amino}-biphenyl-4-su]fonylamino)-3-methyl-butyric acid; L-2-{4'-[(4-Ethoxycarbony]methoxy-3-methyl-benzofuran-2-carbony])-amino]-biphenyl-4-su]fonylamino}-3-methyl-butyric acid; L-2-{4'-[(4-Methoxycarbony]methoxy-3-methyI-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fony]amino}-3-metbyl-butyric acid; L-2-{4'-[(4-Carboxymethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid; L-3-Methyl-2-(4'-{ [3-methy]-4-(pyridin-3-ylmethoxy)-benzofuran-2-carbonyl]-amino}-bipheny]-4-sulfony]amino)-butyric acid; L-2-{4'-[(4-Hydroxy-3-methyl-benzofuran-2-carbony])-amino]-bipheny]-4-su]fonylanxino}-3-methyl-butyric acid; L-2-(4-{ 5-[(l-Ethyl-lH-benzimidazole-2-carbonyl)-amino]-pyridin-2-yl}-benzenesulfonylamino)-3-methyl-butyric acid; N-({4'-[(l,2,3-thiadiazo]-4-ylcarbony])amino]-l,1-biphenyl-4-yl)sulfonyl)-L-valine; D-2-[4'-(Benzofuran-2-sulfonylmethyl)-biphenyl-4-suIfonylainino]-3-methyl-butyric acid; D-2-[4'-(Benzofuran-2-sulfiny]methy])-biphenyl-4-su]fonylamino]-3-methyl-butyric acid; (S)-2-(4'-{[3-(4-Chloro-phenyl)-isoxazo]e-5-carbonyI]-amino}-biphenyl-4-su]fonylamino)-3-methyl-butyric acid; (S)-3-Methy]-2-{4'-[(l-methyl-3-phenyl-lH-thieno[2,3-c]pyrazo]e-5-carbony])-amino]-biphenyl-4-sulfonylamino}-butyric acid; (S)-3-Methyl-2-{4'-[(5-methyI-l-pheny]-lH-pyrazole-3-carbony])-amino]-bipheny]-4-su]fonylamino}-butyricacid; (S)-3-Methyl-2-{4'-[(2-pyndin-4-yl-thiazole-4-carbony])7amino]-biphenyl-4-sulfonyIamino]-butyric acid; (S)-3-Methyl-2-[4'-(thiophene-2-su]fony]amino)-biphenyl-4-sulfony2amino]-butyric acid; (R)-3-Methyl-2-[4'-(thiophene-2-su]fonylamino)-biphenyl-4-sulfonylamino]-butyric acid; (R)-2- 246 WO 2005/061477 PCT/US2003/040835 {4-[(Furan-2-carbonyl)-amino]-bJphenyl-4-su]fony]amino}-3-methyl-butyric acid; (R)-3-Methyl-2-{4'-[(thiophene-2-carbonyl)-amino]-bipheny]-4-su]fonylamino}-butric acid; (S)-3-Methyl-2-{4'-[(thiophene-2-carbonyl)-amino]-biphenyl-4-su]fonylamino}-butyric'acid; (S)-2-{4'-[(Furan-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-3-methyl-butyric acid; (S)-2-{4 -[(4-Dimethy]carbamoy]methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-3-methyl-butyric acid; (S)-2-(4'-{[4-(2-tert-Butoxycarbonylamirio-ethoxy)-3-methyl-benzofuran-2-carbony]]-amino} -bipheny]-4-sulfony]amino)-3-methyl-butyric acid; (S)-3-Methyl-2-(4'-{[3-methyl-4-(pyridin-2-y]methoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amino)-butyric acid; (S)-3-Methy]-2-(4'-{[3-methyl-4-(pyridin-4-ylmethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfony]amino)-butyric acid; (S)-2-{4'-[(4-Carbamoylmethoxy-3-methy]-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-3-methyl-butyric acid; (S)-2-(4'-{[4-(2-Aniino-ethoxy)-3-methyl-benzofuran-2-carbonyI]-amino}-biphenyl-4-sulfony]amino)-3-naethyl-butyric acid; (S)-2-(4'-{ [4-(2-Dimethylamino-ethoxy)-3-methyl-benzofuran-2-carbony]]-amino}-biphenyl-4-sulfony]amino)-3-jnethyl-butyric acid; N-[(4-{[(5-Chloro-l-benzofuran-2-yl)carbony]]amino}-l,l'-biphenyl-4-yl)sulfonyl]-L-valine; N-({4'-[(5-Bromo-2-furoyl)amino]-l,1 '-biphenyl-4-yl}sulfonyl)-L-valine; N-[(4'-{[(7-Nitro-lH-indol-2-yl)carbonyl]amino}-l,1-biphenyl-4-yl)sulfony]]-L-valine; N-[(4'-{[(2-Pyridin-4-yl-l,3-thiazol-5-y])carbony]]amino}-l,1-biphenyl-4-yl)sulfony]]-L-valine; N-[(4'-{[5-(2-Nitrophenyl)-2-furoyl]amino}-l ,1 -bipheny]-4-y])sulfonyl]-L-valine; N-{ [4-({[2-(2,3-Dihydro-l,4-benzodioxin-2-y])-l,3-thiazol-4-yl]carbonyl}amino)-l,l'-biphenyl-4-yl]sulfonyl}-L-valine; N-[(4-{[(5-Methyl-3-pheny]isoxazol-4-yl)carbony]]amino}-l,1-bipheny]-4-yl)sulfony]]-L-valine; N-[(4'-{[(4-Methyl-l,2,3-thiadiazol-5-yl)carbony]]amino}-l,1-biphen3'l-4-y])su]fony]]-L-va]ine; N-[(4-{[(l-tert-Buty]-3-methy]-]H-pyrazol-5-yl)carbonyl]amJno}-l,l-bipheny]-4-yl)sulfonyl]-L-valine; N-[(4'-{[(3-Ch]oro-l-benzothien-2-y])carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine; N-{ [4'-({ [3-(2-Chlorophenyl)-5-methylisoxazol-4-y]]carbonyl} amino)-l,l -biphenyl-4-y]]suIfonyl}-L-valine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4- -yl}sulfonyl)-D-alanine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1 -biphenyl-4-yl}sulfonyl)-L-valine; N-({4'-[(l-Benzofuran-2-y]carbonyl)amino]-l,l'-biphenyl-4-y]}sulfonyl)-D-valine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-L-norvaline; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-D-norvaline; N-({4-[(l-Benzofuran-2-ylcarbony])amino]-l,l -biphenyl-4-yl}sulfonyl)-L-aspartic acid; N-({4'-[(1-Benzofuran-2-ylcarbonyI)amino]-l,1-biphenyl-4-yl}su]fonyl)-D-aspartic acid; N-2-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-L-glutamine; N~2~-({4'-[(l-Benzofuran-2-y]carbonyl)amJ.np]-l,1-bipheny]-4-yl}sulfonyl)-D-glutamine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-L-histidine; N-({4'-[(l- 247 WO 2005/061477 PCT/US2003/040835 Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-D-histidine; N-({4'-[(l-Bezofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-L-iso]eucine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-1,1 '-biphenyl-4-yl}sulfonyl)-D-isoleurine; N-({4'-[(l-Benzofuran-2-ylcarbony])amino]-l,1-biphenyl-4-yl}sulfony])-L-leudne; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-D-leucine; N-({4'-[(l-Benzofuran-2-yIcarbony])amino]-l,l-biphenyl-4-y]}sulfony])-L-norieucJne; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-D-norleucine; N-({4-[(l-Benzofuran-2-ylcarbonyl)arrano]-l,1-bipheny]-4-yl}sulfony])-L-pheny]alanine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1 -biphenyl-4-yl}sulfonyl)-D-phenylalanine; l-({4 -[(1-Benzofuran-2-ylcarbonyl)amino]-l,L-biphenyl-4-yl}sulfony])-L-proline; l-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl)su]fony])-D-proIine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l-bipheny]-4-y]}sulfony])-L-tryptophan; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-D-tryptophan; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-1,1 '-biphenyl-4-yl}su]fonyl)-N-methy]glycine; N-({4 -[(1 -Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)-2-methylalanine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l, 1 '-biphenyl-4-yl} sulfonyl)-N-methyl-L-alanine; 1 -[({ 4 '-[(l-Benzofuran-2-ylcarbonyl)amino]-l, 1 '-biphenyl-4-yl}sulfonyl)amino]cyclopentanecarboxylic acid; N-({4'-[(1-Benzofuran-2-ylcarbonyl)amino]-l,1 -biphenyl-4-yl} sulfonyl)-N-methylvaline; N-({4'-[(1-Benzofuran-2-ylcarbonyl)amino]-l, 1 -biphenyl-4-yl}sulfonyl)-3-methyl-L-valine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}su]fonyl)-2-methy]leucine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l ,1 -biphenyl-4-yl} sulfonyl)-D-glutamic acid; (2R)-[({4'-[(1-Benzofuran-2-y]carbonyl)amino]-l,1-biphenyl-4-yl}su]fonyl)amino](phenyl)aceticacid; [({4-[(l-Benzofurati-2-ylcarbpnyl)amino]-l,1-biphenyl-4-y]}sulfonyl)amino](thien-2-yl)acetic acid; (2S)-2-[({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl}sulfonyl)amino]-5-methoxy-5-oxopentanoic acid; 3-[({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l'-biphenyl-4-yl }sulfonyl)amino]-3-phenylpropanojc acid; 2-[({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-yl} sulfonyl)amino]-4-phenylbutanoic acid; N-({4'-[(l-Benzofuran-2-yIcarbonyl)amino]-l,1-biphenyl-4-yl}sulfony])-L-tyrosine; N-({4'-[(l-Benzofuran-2-ylcarbonyl)araino]-l,1-biphenyl-4-y]}sulfonyl)-D-tyrosine; (2S)-2-[({4'-[(l-Benzofuran-2-ylcarbonyl)aminoj-l,l -biphenyl-4-yl}sulfonyl)amino]-4-tert-butoxy-4-oxobutanoic acid; (2R)-2-[({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-y]}sulfonyl)amino]-4-tert-butoxy-4-oxobutaTioic acid; (2S)-[({4'-[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl} sulfony])amino](2,3-dihydro-lH-inden-2-yl)acetic acid; N-({4 -[(l-Benzofuran-2-ylcarbonyl)amino]-l,l -biphenyl-4-yl}sulfonyl)-O-methyl-L-tyrosine; [({4-[(l-Benzofuran-2-y]carbonyl)amino]-l, 1 -biphenyl-4-yl }sulfonyl)amino](l-methyl-lH-indol-5-yl)acetic acid; 248 WO 2005/061477 PCT/US2003/040835 [({ 4-[(l-Benzofuran-2-ylcarbony])amino]-l,l -biphenyl-4-y] }sulfonyI)amino](l-benzothien-5-yf)aeetic acid; N-({4 -[(l-Benzofuran-2-y]carbony])amino]-l,l'-bipheny]-4-y]}sulfonyl)-4-nitro^ L-phenylalanine; N-({4'-[(1 -Benzofuran-2-ylcarbonyl)amino]-l, 1 -biphenyl-4-y]}su]fonyl)-3-(2-naphthyl)alanine; N-({4-[(l-Benzofuran-2-y]carbony])amino]-l,l -bipbenyl-4-yl}sulfony])-beta-methylphenylalanine; N-({4-[(l-Benzofuran-2-ylcarbonyl)amino]-l,1-biphenyl-4-y]]sulfonyI)-N-methyl-L-tryptophan; N-2-({4-[(l-Benzofuran-2-ylcarbonyl)amiho]-l,1-bjpheny]-4-yl}sulfonyl)-N~5~-pheny]g]utamine; N-({4-[(l-Benzofuran-2-y]carbonyl)amino]-1,1 -biphenyl-4-yI }sulfonyl)-4,4,4,4',4',4 -hexafluorovaline; 4-Amino-N-({4'-[(l-benzofuran-2-ylcarbonyl)amino]-l, 1 -biphenyl-4-yl} sulfony])-L-phenylalanine; (2R)-2-[({4 -[(1-Benzofuran-2-y]carbony])amino]-l,1-biphenyl-4-yl}suIfony3)amino]-5-(benzyloxy)-5-oxopentanoicacid; N-({ 4-[(l -Benzofuran-2-ylcarbonyl)amino]-l ,1 -biphenyl-4-yl} sulfonyl)-l-benzyl-L-histidine; or N-({4-[(l-Benzofuran-2-y]carbonyl)amino]-l,l -bipheny]-4-y]}su]fonyl)-O-benzyl-L-tyrosine. 67. The compound of claim 47 that is L-2-(4'-{[4-(3-Methoxy-propyl)-3-methyl-benzofuran-2-carbonyI]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid; L- 3-Methy]-2- (4'-{[3-methyl-4-(3-methyl-isoxazol-5-yl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylaniino)-butyric acid; D-2-{4'-[(4-Methanesu]fonylamino-3-methy]-benzofuran-2-carbony])-amino]-biphenyl-4-sulfony]araino}-3-methyl-butyric acid; L- 2-{4'-[(4-Cyclopropylmethoxy-3-methyl-benzofuran-2-carbony])-arnino]-biphenyl-4-sulfony3amino}-3-methyl-butyricacid;L-3-Methyl-2- (4'-{[3-methyl-4- (2H-tetrazol-5-y])-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; L-2- {4 -[(4-Dimethylamino-3-methyl-benzofuran-2-carbony])-amino]-biphenylT4-su]fony]amino}-3-methyl-butyric acid; L- 2-{4'-[(4-Benzenesulfonylamino-3-methy]-benzofuran-2-carbonyJ)-amino]-bipheny]-4-su]fonyIarniho}-3-methyl-butyric acid; L-3-Methyl-2-(4'-{[3-methyl-4- (thiophene-2-sulfonylamino)-benzofuran-2-carbonyl]-amdno}-biphenyI-4-sulfonylamino)-butyric acid; N-[(4'-{[(5-Ethy]-4-methoxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino}-l,1-biphenyl-4-yl)sulfonyl]-L-valine;N-[(4'-{[(4-Ethy]-3-methy]-l-benzofuran-2-yl)carbonyl]amino}-1,1 -bipheny]-4-y])su]fonyl]-L-valine; N-[(4'-{[(5-Ethyl-4-hydroxy-3-methyl-l-benzofuran-2-yl)carbonyl]amino}rl,l--biphenyl-4-yl)sulfonyl]-L-valine; N-{[4'.({[4-(2,2-Dimethyl-l,3-dioxolan-4-y])-3-rnethyl-l-benzofuran-2-y]]carbony]}amino)-lj -biphenyl-4-yl]sulfony]}-L-va]ine;N-[(4'-{[(3,4-Dimethyl-l-benzofuran-2-yl)carbonyl]amino}-l,l'-biphenyI-4-yI)suJfony]]-L-va]jne;N-[(4-{[(4-Acetyl-3-methyl-l-benzpfuran-2-yl)carbony]]amino}-l,1-bipheny]-4-yl)sulfonyI]-L-valine;N-{[4-({[4-(l-Hydroxyethyl)-3-methyI-l-benzofuran-2-yI]carbonyl}amino)-l,1-biphenyl-4-yI]su]fonyl}-L-va]ine;N-[(4'-{[(3-roethy]=4- vinyl-1 -benzofuran-2^1)carbonyll amino} -1,1 -biphenyl-4-yl)sulfonyl]-L-valine; N- 249 WO 2005/061477 PCT/US2003/040835 {[4'-({ [4-(methoxymethy])-3-methyl-l-benzofuran-2-yl]carbonyl}amino)-l ,1'- bipbenyl-4-yl] sfonyl }-L-valine; N-{ [4'-({ [4-(l-methoxyethyl)-3-methyI-l-benzofuran-2-yljcarbonyl }amino)-l,l'-bipheny]-4-yl]sulfonyl }-L-valine; N-{ [4'-({ [4-(2-methoxyethyl)-3-methyl-l-benzofuran-2-y]]carbony]}amino)-l,1-biphenyl-4-yl]sulfonyl}-L-va]jnate;(S)-2-{4'-[(4-ethoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fony]amino}-3-methy]-butyric acid; (S)-3-methyl-2-{4'-t(3-methyl-4-pyridin-3-yI-benzofuran-2-carbonyl)-amino]-bipheny]-4-sulfonylamino}-butyricacid; (S)-3-Methyl-2-{4'-[(3-rnethyl-4-pyridin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylainino}-butyric acid; (S)-2-{4'-[(4-Furan-3-yl-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyI-4-sulfonylamino} -3-methyl-butyric acid; (S)-2-{4-[(5-Chloro-4-methoxy-3-methy]-benzofuran-2-carbonyl)-amJno]-bipheny]-4-sulfonylamino} -3-methyl-butyric acid; (S)-2-{4 -[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carboByl)-amino]-biphenyl-4-su]fony]amino}-3-methyI-butyricacid; (R)-2-{4-t(5-Bromo-4-methoxy-3-methy]-benzofuran-2~carbony])-amino]-bipheny]-4-su]fony]ainino)-3-methy]-butyric acid; (S)-2-{4'-[(5-Iodo-4-methoxy-3Tmethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfony]amino}-3-methyl-butyricacid; (S)-2-{4'-[(5-Cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-su]fonylamino}-3-methy]-butyricacid; (S)-2-{4'-[(5-Methyl-4-inethoxy-3-methy]-benzofuran-2-carbony])-amino]-biphenyl-4-su]fony]amino}-3-methy]-butyric acid; (S)-3-Methyl-2-{4'-[(5-methy3-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; D-2-[4-(5-Bromo-4-methoxy-3-methyl-benzofuran-2-ylmethoxy)-biphenyl-4-su]fony]amino]-3-methy]-butyric acid; L-2-{4 -[(4-Ethoxycarbonylmethoxy-3- " methyl-benzofuran-2-carbonyl)-amiT)o]-biphenyl-4-sulfonylamino} -3-methyl-butyric acid; L-2-{4'-[(4-Carboxymethoxy-3-methy]-benzofuran-2-carbony3)-amino]-biphenyl-4-sulfony]amino}-3-methyl-butyric acid; L-3-Methy]-2-(4 -{[3-methyI-4-(pyridin-3-ylmethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid; (S)-3-Methyl-2-{4'-[(l-methyl-3-phenyl-lH-thieno[2,3-c]pyrazo]e-5-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid; and(S)-3-Methy]-2-(4'-{t3-methyl-4-(pyridin-4-y]inethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid. 68. A composition comprising at least one compound of claim 47 and one or more pharmaceutically acceptable carriers. 69. The method of claim 26, wherein said disease is osteoarthritis, rheumatoid arthritis, asthma, or chronic obstructive pulmonary disease. 250