Field of the Invention
Provided herein are the "substituted aromatic compounds", which have peroxisome proliferation activated receptor (PPAR) modulating activity, and hence can be used as anti-diabetic agents. They can be used as therapeutic agents for the treatment of diseases and conditions mediated through any of the isoforms of PPAR, diabetes and diabetes-associated complications, diseases or conditions in which insulin resistance is the central pathophysiological mechanism and diseases or conditions such as Type II diabetes, dyslipidaemia, hypertension, coronary heart disease, cardiovascular disease, atherosclerosis, nephrosclerosis, polycystic ovarian syndrome, eating disorders, diabetes nephropathy, glomerulonephritis, glomerularsclerosis, nephrotic syndrome, psoriasis or obesity. Process for the preparation of compounds disclosed herein, pharmaceutical compositions thereof, and the methods for treating diabetes mellitus and the diseases and conditions mediated through insulin resistance are also provided.
Background of the Invention
Type II insulin-resistant diabetes mellitus [also known as non insulin-dependent diabetes mellitus] afflicts an estimated 6% of the adult population in western society and is expected to grow at a rate of 6% per annum worldwide. Type II diabetes is a complex metabolic disorder and is characterized by hyperglycemia. This results from contribution of impaired insulin secretion from pancreas and insulin resistance mainly in muscle and liver. Insulin resistant individuals in addition to being hyperglycemic, exhibit a variety of closely related clinical indications, which include obesity, hypertension, dyslipidemia, premature atherosclerosis. In fact, 80% of diabetic mortality arises from atherosclerotic cardiovascular disease (ASCVD). Uncontrolled hyperglycemia can further lead to late stage complications such as nephropathy, neuropathy and retinopathy.
Non-pharmacological approaches to lower high blood sugar include a strict control of diet followed by vigorous exercise. Presently, several pharmacological agents are also available as hypoglycemic agents including insulin secretagogues e.g., sulphonyl ureas (for example, glimeperide) and non sulphonyl ureas (for example, repaglinide)- which increase insulin secretion from pancreatic cells; biguanides (metformin) which lower hepatic glucose production; and a-glucosidase inhibitors (acarbose) which delays intestinal absorption of carbohydrate.
PPARs (Peroxisome-Proliferator-Activated Receptor) are ligand activated transcription factors (members of nuclear receptor family), which offer promising therapeutic
approaches to Type II diabetes mellitus. PPAR exists in three-subtype forms a, y and 8 (or P). PPAR y is abundantly expressed in adipose tissues. Direct activation of PPAR y leads to induction of adipocyte genes, such as for fatty acid transporter 1, which in turn contributes to lowering of triglycerides and free fatty acid (FFA) level. As FFA is a potential mediator of insulin resistance, lowering of FFA levels contributes to efficacy of PPAR y activation in increasing insulin sensitivity and consequently glucose uptake in skeletal muscle cell. Glitazones (for example, rosiglitazone and pioglitazone) belong to this class of drug and are now proven insulin sensitisers (Moller, D.E.; Nature, (2001), 414. 6865, 821-827).
WO 01/21602 and U. S. patent no. 6,414,002 discloses oxa and thiazole derivatives, which have been described to be useful as antidiabetic and antiobesity agents. WO 02/040481 discloses adenine-based inhibitors of adenylyl cyclase, pharmaceutical compositions and method of use thereof. WO 04/004655 discloses substituted heterocyclic derivatives that have been said to be useful as antidiabetic and antiobesity agents. WO 03/082841 discloses 5-substituted l,l-dioxo-l,2,5 thiazolidine-3-one derivatives that have been said to be useful as PTPASE inhibitors.
Summary of the Invention
Generally provided herein are the "substituted aromatic compounds", which have peroxisome proliferation activated receptor (PPAR) modulating activity, and hence can be used as anti-diabetic agents, and process for the synthesis of these compounds.
Pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, racemates, stereoisomers, tautomeric forms, N-oxides or metabolites of these compounds having the same type of activity are also provided.
Pharmaceutical composition containing one or more compound(s) of Formula I, optionally together with pharmaceutically acceptable carriers or diluents, which can be used for the treatment of diseases and conditions mediated through any of the isoforms (a, y or 5) of PPAR, diabetes mellitus and the disease or condition mediated through insulin resistance.
Other objects will be set forth in accompanying description which follows and in the part will be apparent from the description or may be learnt by the practice of the invention.
In one aspect, there are provided compounds having the structure of Formula I,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof, wherein, Het can be selected from:
(Formula Removed)
wherein:
X1-X11 can be each independently CH, C, CH2, N, NH, O, S, S(=O) or S(=O)2; X12 and X13 can be each independently CR1 or N, wherein R1 is hydrogen or alkyl; X14 can be (CH2)X (where, x =0-2), NR', O, S, S(=O), S(=O)2, wherein R' is the same as defined above;
X15 can be CH or N; X16 and V can be each independently O, NR' or S; D and E can be substituted or unsubstituted alkyl, aryl or a bond;
R1-R5 and R10-R17 can be each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, aryloxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, hydroxy, alkoxy, halogen, optionally substituted amino; A can be N(CH3), O, C(O), NH, S, or a bond;
R6-R9 can be each independently hydrogen, hydroxyl, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, alkoxy, halogen, optionally substituted amino; can be optional double bond; Ri8 can be hydrogen, halogen, nitro, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, COOR20, C(=V)R2] (wherein, V is as defined earlier), OR20, SR20 or N(R22)2 {[wherein R20 can be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl], [R21 can be R20, N(R20)2 (wherein R20 is the same as defined above)], [R22 can be R20, COOR20, C(=V)R21, S(O)qR23, wherein, V, R20 and R21 are the same as defined above and R23 can be R20 except hydrogen and q can be an integer 1 or
2]);
Ri9 can be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, COOR20, C(=V)R21, C(=V)(NR20)2, SO2R23, C(=V)NR'SO2-R23, C(=V)NR"R'" {[wherein, V, R20, R21 R1 and R23 are the same as defined earlier], [R" and R'" together with nitrogen to which they are attached can form a ring which may contain additional one or more heteroatom(s) like O, S or N and the ring so formed may further be substituted with SO2R23 (wherein R23 is the same as defined earlier), alkyl, aryl, heteroaryl]; X can be CH, N or N(-O); Z can be 0, S, NH, N-Me or a bond; Y can be COOR28 or CON(R22)2 (wherein R' and R22 are the same as defined above); A1, A2 or A3 can be substituted or unsubstituted CM alkylene.
In an embodiment, there are provided compounds having the structure of Formula II or Formula III,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof wherein, Het, A1-A3, Z, Y, R18 and R19 are the same as defined for Formula I.
In a second aspect, there is provided a method for the treatment of mammal suffering from diabetes and diabetes-associated complications, comprising administering to a patient, a therapeutically effective amount of a compound disclosed herein.
In a third aspect, there is provided a method for the treatment of mammal suffering from diseases or conditions in which insulin resistance is the central pathophysiological mechanism, comprising administering to a patient, a therapeutically effective amount of a compound disclosed herein.
In a fourth aspect, there is provided a method for the treatment of mammal suffering from diseases or conditions such as Type II diabetes, dyslipidaemia, hypertension, coronary heart disease, cardiovascular disease, atherosclerosis, diabetes nephropathy, glomerulonephritis, glomerularsclerosis, nephrotic syndorme, hypertensive nephrosclerosis, polycystic ovarian syndrome, and eating disorders, as aldose reductase inhibitors and for improving cognitive functions in dementia, psoriasis or obesity, comprising administering to a patient, a therapeutically effective amount of a compound disclosed herein.
In a fifth aspect, there is provided process for preparing compounds disclosed herein.
The compounds disclosed herein can also be used in combination with another type(s) of anti-diabetic agent(s) and/or hypolipidemic agent(s) and/or anti-hypertensive agent(s) and/or platelet aggregation inhibitor(s) and/or anti-osteoporosis agent(s) for the treatment of mammal suffering from diseases and conditions disclosed herein. Other agents like PPAR agonists (biguanides, protein tyrosine phosphate-IB inhibitors, dipeptidyl peptidase inhibitors), insulin or insulin mimetics, sulphonylureas, α-glucosidase inhibitors, cholesterol lowering agents (HMG-CoA reductase inhibitors, sequesterants, nicotinyl alcohol, nicotinic acid or salt thereof, PPAR a agonists, PPAR a/y agonists, inhibitors of cholesterol absorption, Acyl CoA: cholesterol acyl tranferase inhibitors, antioxidants), PPAR 8 agonists, antiobesity compounds, an ideal bile acid transporter inhibitor, agents intended to be used in inflammatory for the treatment of mammal suffering from diseases and conditions disclosed herein.
The following definitions apply to terms as used herein.
The term "alkyl" unless and otherwise specified refers to a monoradical branched or unbranched saturated hydrocarbon having from 1 to 20 carbon atom(s). It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, a phenylene, sulphinyl, sulphonyl group and -NRa-, where Ra can be hydrogen, alkyl, alkenyl, alkynyl cycloalkyl or aryl. Groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, n-hexyl, n-decyl, tetradecyl, cyclopentyl, cycolhexyl, phenyl, biphenyl, naphthyl and the like exemplify this term.
The term "substituted alkyl" herein refers to the alkyl substituted with substituent(s) selected from alkenyl, alkynyl, cycloalkyl, aryl (for R6-R9, alkyl is not substituted with aryl), heterocyclyl, heteroaryl, alkoxy, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, -S(O)aRb wherein Rb can be alkyl, aryl or heteroaryl, and a is an integer from 0-2.
Unless otherwise constrained, all substituents may optionally be further substituted by substituent(s) chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino and cyano or an alkyl group as defined above that has both substituents as defined above and is also interrupted by atom(s) or group(s) as defined above.
The term "alkylene" refers to the divalent radical of the above defined alkyl. It may optionally be substituted with the substituents as defined for alkyl.
The term "alkenyl" unless and otherwise specified refers to a monoradical of a branched or unbranched unsaturated hydrocarbon having from 2 to 20 carbon atoms with either cis or trans geometry. It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, phenylene, sulphinyl, sulphonyl and -NRa-, where Ra can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl. Groups such as ethenyl or vinyl (CH=CH2), 1-propylene or allyl (-CH2CH=CH2), iso-propylene (-C(CH3)=CH2), bicyclo[2.2.1]heptene, and the like, exemplify this term. In the event that alkenyl is attached to the heteroatom, the double bond cannot be alpha to the heteroatom.
The term "substituted alkenyl" herein refers to alkenyl substituted with substituent(s) selected from alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl, alkoxy, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aryl, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, -S(O)aRb wherein Rb can be alkyl, aryl or heteroaryl, and a is an integer of form 0-2.
Unless otherwise constrained by the definition, all substituents may optionally be further substituted by substituent(s) chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CFs, amino, substituted amino and cyano.
The term "alkynyl" unless and otherwise specified refers to a monoradical of an unsaturated hydrocarbon having from 2 to 20 carbon atoms. It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, phenylene, sulphinyl, sulphonyl and -NRa-, where Ra can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl. Groups such as ethynyl, (-C=CH), propargyl (or propynyl, -CH2C≡CH), and the like exemplify this term. In the event that alkynyl is attached to the heteroatom the triple bond cannot be alpha to the heteroatom.
The term "substituted alkynyl" herein refers to alkynyl substituted with substituent(s) selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro and -S(O)aRb wherein a and Rb are the same as defined earlier.
Unless otherwise constrained by the definition, all substituents may optionally be further substituted by substituent(s) chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino and cyano.
The term "cycloalkyl" refers to (un) saturated cyclic alkyl of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings. Groups such cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, cyclopropylene, cyclobutylene, and the like exemplify single ring structures. Groups such as adamantanyl, bicyclo [2.2.1]heptane, and the like exemplify fused ring structures. Cycloalkyl can also be fused with an aryl, for example indane, and the like.
The term "substituted cycloalkyl" herein refers to cycloalkyl substituted with substituent(s) selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, alkoxy, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro and -S(O)aRb wherein a and Rb are the same as defined earlier.
Unless otherwise constrained by the definition, all substituents may optionally be further substituted by substituent(s) chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino and cyano.
The term "alkoxy" herein refers to ORc wherein Rc can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl.
The term "halogen" refers to fluorine, chlorine, bromine or iodine.
The term "optionally substituted amino" herein refers to NRgRh [(wherein Rg and RH can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, -S(O)aRb or CORd (wherein a and Rd are the same as defined earlier)].
The term "aryl" herein refers to aromatic system having 6 to 14 carbon atoms, wherein the ring system can be mono, bi or tricyclic. Groups such as phenyl, naphthyl, anthryl, biphenyl, and the like exemplify this term.
The term "heteroaryl" unless and otherwise specified refers to aromatic ring system having from 2 to 14 carbon atoms and heteroatom(s) independently selected from nitrogen, oxygen and sulphur, wherein the ring system can be mono, bi or tricyclic. Groups such as pyridinyl, pyridazinyl, pyrimidinyl, pyrrolyl, oxazolyl, thiazolyl, thienyl, isoxazolyl, triazinyl, furanyl, benzofuranyl, indolyl, benzothiazolyl, benzoxazolyl, benzthiazinyl, benzthiazinonyl, benzoxazinyl, benzoxazinonyl, quinazonyl, carbazolyl phenothiazinyl, phenoxazinyl and the like exemplify this term.
The term 'heterocyclyl" unless and otherwise specified refers to non-aromatic, aromatic fused with non-aromatic ring system having heteroatom (s) in either the aromatic or the non-aromatic part wherein the said hetero atom(s) can be nitrogen, sulphur or oxygen and the ring system includes mono, bi or tricyclic. Carbonyl or sulfonyl group can replace carbon atom(s) of heterocyclyl. Groups such as benzoxazinyl, benzthiazinyl, imidazolyl, benzimidazolyl, tertazolyl, carbazolyl, indolyl, phenoxazinyl, phenothiazinyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranyl, and the like exemplify this term.
The term "substituted aryl, substituted heteroaryl and substituted heterocyclyl" herein refers to aryl, heteroaryl and heterocyclyl, respectively, substituted with substituent(s) selected from alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, halogen, hydroxy, alkoxy, cyano, nitro, COORd, CORd (wherein Rd can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl), (CH2)o-3C(=O)NReRf [(wherein Re and Rf can be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or -S(O)aRd (wherein a and Rd are the same as defined earlier)], -NRgRh [(wherein Rg and Rh, are the same as defined earlier)], -CSRf, -OCORf (wherein Rf can be hydrogen, alkyl, alkenyl, alkynyl or cycloalkyl), -S(O)aRb, [(wherein a and Rb are the same as defined earlier or -NRgRh (wherein Rg and RH are the same as defined earlier)].
The term "pharmaceutically acceptable solvates" refers to solvates with water (i-e hydrates, hemihydrate or sesquihydrate) or pharmaceutically acceptable solvents, for example solvates with common organic solvents as ethanol and the like. Such solvates are also encompassed within the scope of the disclosure.
The present invention also includes, within its scope, prodrugs of these agents. In general, such prodrugs will be functional derivatives of these compounds, which are readily convertible in vivo into the required compound. They may be carrier-linked or bioprecursors. The carrier-linked prodrugs may be bipartite, tripartite or mutual prodrugs. Prodrugs are intended to improve drug efficacy by improving solubility and consequently absorption and distribution as desired.
Conventional procedure for the selection and preparation of suitable prodrug derivatives are described, for example, in "design of prodrugs", ed. H Bundgaard and, Elsevier, 1985. The present invention provides prodrugs of Formula la
(Formula Removed)
Het, A1-A3, Z, X, R18 and R19 are the same as defined above; W is a group that is easily removed under physiological conditions during or after administration to a mammalian patient to yield a compound having Formula I, or the carboxylate anion thereof, or a pharmaceutically acceptable salt and is selected from the group comprising of-OR25, -OCH2OR25, -OCH(CH3)OR25, -OCH2OC(O)R25, -OCH(CH3)OC(O)R25, -OCH2OC(O)OR25, -OCH(CH3)OC(O)OR25 and -N(R26)2 wherein R25 is independently selected from C1-6 alkyl optionally substituted with one or two groups selected from -C02H, -CONH2, -NH2, -OH, -OAc, -NHAc and phenyl and wherein R2e is independently selected from H and R25.
The disclosed compounds may get metabolized in vivo and these metabolites are also encompassed within the scope of this invention.
The term "polymorphs" includes all crystalline form as well as amorphous form for compounds described herein and as such are intended to be included in the present invention.
The phrase "pharmaceutically acceptable carriers" is intended to include non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
The term "pharmaceutically acceptable salts" refer to a salt prepared from pharmaceutically acceptable monovalent, divalent or trivalent non-toxic metal or organic base. Examples of such metal salts include, but are not limited to, lithium, sodium, potassium, calcium, magnesium, zinc, aluminum and the like. Examples of such organic bases include, but are not limited to, amino acid, ammonia, mono-alkyl ammonium, dialkyl ammonium, trialkyl ammonium and N-methyl glucamine and the like. The free acid forms of compounds of the present invention may be prepared from the salt forms, if desired, by contacting the salt with dilute aqueous solution of an acid, such as hydrochloric acid. The base addition salts may differ from the free acid forms of the compounds of this invention in such physical characteristics as solubility and melting point.
The salt forms differ from the compound described herein in certain physical properties such as solubility, but the salts are otherwise equivalent for purposes of this invention.
The compounds of present invention include stereoisomers. The term "stereoisomer" refers to compounds, which have identical chemical composition, but differ with regard to arrangement of the atoms and the groups in space. These include enantiomers, diastereomers, geometrical isomers, atropisomer and conformational isomers as defined by the IUPAC 1974 Recommendations for Section E. All these stereoisomers are intended to be included within the scope of this invention.
The phrase "modulate" refers to the ability of a modulator for a member of the nuclear hormone receptor superfamily to either directly (by binding to the receptor as a ligand) or indirectly (as precursor for a ligand or an inducer which promotes production of ligand from a precursor) induce expression of gene(s) maintained under hormone expression control, or to repress expression of gene(s) maintained under such control.
The term "pharmaceutically acceptable" means approved by regulatory agency of the federal or a state government or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.
Detailed Description of the Invention
The compounds described herein may be prepared by techniques well known in the
art and familiar to the average synthetic organic chemist. In addition, the compounds of the
present invention may be prepared by the following reaction sequences as depicted in
Scheme I.
(Scheme Removed)
The compound of Formula VIII can be prepared according to Scheme I. Thus, reacting a compound of Formula IV with either a compound of Formula:
(a) Het-A1-OH or
(b) Het-A1-L1 (wherein, L1 is a leaving group selected from Cl, Br, I, 4-
methylbenzenesulfonate, 4-bromo benzenesulfonate, 4-nitrobenzenesulfonate,
methanesulfonate, trifloromethanesulfonate and the like), to give a compound of Formula V,
which on treatment with a compound of Formula H2NCHR-COOR28. HC1 (wherein R28 is
(un)substituted alkyl or aryl) gives a compound of Formula VI (wherein R is the same as
defined earlier) which on reacting with a compound of Formula R19-Cl or R19-N=C=W
(wherein, W is O or S) gives a compound of Formula VII, which is finally subjected to
hydrolysis to give a compound of Formula VIII (wherein Het, A1, Z, R18, and R19 are the same as defined for Formula I).
The reaction of a compound of Formula IV with a compound of Formula Het-A1-OH to give a compound of Formula V can be carried out in a solvent, for example, tetrahydrofuran, dimethylformamide, dichloromethane, toluene, diethylether, dioxane, ethylacetate, acetonitrile or benzene.
The reaction of compound of Formula IV to give a compound of Formula V can be carried out in the presence of a redox couple agent, which may be any one of those known to a person skilled in the art of organic synthesis. The oxidizing part of the redox couple is selected from the group comprising of diisopropylazodicarboxylate (DIAD), diethylazo-dicarboxylate (DEAD), N,N,N',N'-tetramethylazodicarboxamide (TMAD), 1,1'-(azodicarbonyl)dipiperidine (ADDP), cyanomethylenetributylphosphorane (CMBP), 4,7-dimethyl-3,5,7-hexahydro-l,2,4,7-tetrazocin-3,8-dione (DHTD) or N,N,N'N'-tetraisopropyl -azodicarboxamide (TIP A). The reduction part of the redox couple is a phosphine selected from the group comprising of trialkylphosphine (such as tributylphosphine), triarylphosphine (such as triphenylphosphine), tricycloalkylphosphine (such as tricyclohexylphosphine), triheteroarylphosphine or 4-(diphenylphosphino)-N,N'-dimethyl-aniline. The phosphine reagent with a combination of aryl, alkyl or heteroaryl substituents may also be used (such as diphenylpyridylphosphine).
The reaction of a compound of Formula IV with a compound of Formula Het-Ai-Li to give a compound of Formula V can be carried out in a solvent, for example, acetone, diethyl ether, tetrahydrofuran, dimethylformamide, dimethylsulfoxide or acetonitrile.
The reaction of compound of Formula IV with a compound of Formula Het-Aj-Li to give a compound of Formula V can be carried out in the presence of an organic base, for example, triethylamine, diethylamine, tributylamine, diisopropylamine, 4-dimethylaminopyridine 1,8-diazabicyclo [5,4,0]-undec-7-ene, 1,4-diazabicyclo [2,2,2] octane, N-methylmorpholine, diisopropylethylamine, pyridine, sodium hydride or in the presence of inorganic base such as potassium carbonate or cesium carbonate.
The reaction of compound of Formula V with a compound of Formula RCH(NH2)COOR28.HCl to give a compound of Formula VI can be carried out in a solvent, for example, dichloromethane, dichloroethane, tetrahydrofuran, dimethylformamide, toluene, diethylether, dioxane, ethylacetate or acetonitrile.
The reaction of a compound of Formula V to give a compound of Formula VI can be carried out in the presence of an organic base, for example, triethylamine, pyridine or 4-dimethylaminopyridine.
The reaction of compound of Formula V to give a compound of Formula VI can be carried out in the presence of a reducing agent, for example, sodium borohydride, sodium triacetoxy borohydride, sodium cyanoborohydride or any method known to the art.
The reaction of compound of Formula VI with a compound of Formula R19-Cl or R19-N=C=W (wherein, W is the same as defined earlier) to give a compound of Formula VII can be carried out in a solvent, for example, dichloromethane, dichloroethane tetrahydrofuran, dimethylformamide, toluene, diethylether, dioxane, ethylacetate or acetonitrile.
The reaction of a compound of Formula VI to give a compound of Formula VII can be carried out in the presence or absence of a base, when the base is present it can be selected from a group comprising of triethylamine, pyridine, 4-dimethylaminopyridine or diisopropylethylamine and the like.
The hydrolysis of compound of Formula VII to give a compound of Formula VIII can be carried out in the presence of an inorganic base, for example, lithium hydroxide, sodium hydroxide or potassium hydroxide in a solvent, for example, tetrahydrofuran, methanol, water, dimethylformamide, diethylether, or mixture thereof.
In the above scheme, where the specific base, solvents, reducing agents etc., are mentioned it is to be understood that other bases, solvents, reducing agents etc., known to those skilled in the art may be used. Similarly the reaction temperature and duration may be adjusted according to the desired needs.
An illustrative list of compounds of the invention is given below: Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl] glycinate (Compound No. 1); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl] glycinate (Compound No. 2); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-fluorophenoxy)carbonyl]glycinate (Compound No. 3); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl} glycinate (CompoundNo. 4); Ethyl N-[(4-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycinate (Compound No. 5); Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate (Compound No. 6); Ethyl N-(4- {2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methoxy-phenoxy) carbonyl]glycinate (Compound No. 7); Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycinate (Compound No. 8); Ethyl N-(4-{2-[1,3-
benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy)carbonyl]glycinate (Compound No. 9); Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy }benzyl)-N-{[3-(trifluoromethyl)phenoxy]carbonyl}glycinate (Compound No. 10); Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-methylphenoxy) carbonyl] glycinate (Compound No. 11); Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy }benzyl)-N-benzoyl glycinate (Compound No. 12); Ethyl N-4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-(3-methoxybenzoyl) glycinate (Compound No. 13); Ethyl N-(4-{2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl) glycinate (Compound No. 14); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy) carbonyl]glycinate (Compound No. 15); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl] glycinate (Compound No. 16); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-fluorophenoxy)carbonyl] glycinate (Compound No. 17); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate (Compound No. 18); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl] glycinate (Compound No. 19); Ethyl N-[(benzyloxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate (Compound No. 20); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy)carbonyl]glycinate (Compound No. 21); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methoxy phenoxy)carbonyl]glycinate (Compound No. 22); Ethyl N-benzoyl-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate (Compound No. 23); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(2-fluorobenzoyl)glycinate (Compound No. 24); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(4-fluorobenzoyl)glycinate (Compound No. 25); Ethyl N-benzoyl-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)glycinate (Compound No. 26); Ethyl N-(2-fluorobenzoyl)-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy}benzyl)glycinate (Compound No. 27); Ethyl N-(4-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)glycinate (Compound No. 28); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(phenoxycarbonyl)glycinate (Compound No. 29); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl] glycinate (Compound No. 30); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(3-methylphenoxy)carbonyl] glycinate (Compound No. 31); Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate (Compound No. 32); Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate (Compound No. 33); Ethyl N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycinate (Compound No. 34); Ethyl N-[(3-
methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl) glycinate (Compound No. 35); Ethyl N-[(benzyloxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl) glycinate] (Compound No. 36); Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl }-N-(phenoxy carbonyl)glycinate (Compound No. 37); Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 38); Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxor2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl} glycinate (Compound No. 39); Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-(phenoxycarbonyl) glycinate (Compound No. 40); Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate (Compound No. 41); Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate (Compound No. 42); Ethyl N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate (Compound No. 43); Ethyl N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate (Compound No. 44); Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate (Compound No. 45); Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-[(4-methylphenoxy) carbonyl]glycinate (Compound No. 46); Ethyl N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy] benzyl}glycinate (Compound No. 47); Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} -N- {[3-(trifluoromethyl)phenoxy] carbonyl}glycinate (Compound No. 48); Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate (Compound No. 49); Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate (Compound No. 50); Ethyl N-(3-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4.fl)-yl) ethoxy]benzyl}glycinate (Compound No. 51); Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl}glycinate (Compound No. 52); Ethyl N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 53); Ethyl N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 54); Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 55); Ethyl N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (CompoundNo. 56); Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-
yl)ethoxy] benzyl}glycinate (Compound No. 57); Ethyl N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 58); Ethyl N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 59); Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 60); Ethyl N-(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 61); Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl}glycinate (CompoundNo. 62); Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-(2-fluorobenzoyl) glycinate (Compound No. 63); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-methoxyphenoxy) carbonyl] glycinate (Compound No. 64); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate (Compound No. 65); Ethyl N-(4-{2-[1,3-benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(3 -chlorophenoxy) carbonyl] glycinate (Compound No. 66); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate (Compound No. 67); Ethyl N-[(4-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 68); Ethyl N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 69); Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}-N-(phenoxy- carbonyl) glycinate (Compound No. 70); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-chlorophenoxy) carbonyl]glycinate (Compound No. 71); Ethyl N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate (CompoundNo. 72); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate (Compound No. 73); Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate (Compound No. 74); Ethyl N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate (CompoundNo. 75); Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate (Compound No. 76); Ethyl N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate (Compound No. 77); Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate (Compound No. 78); Ethyl N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-
yl)ethoxy]benzyl}glycinate (Compound No. 79); Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} -N- {[3-(trifluoromethyl)phenoxy]carbonyl} glycinate (Compound No. 80); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycinate (Compound No. 81); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-fluorophenoxy) carbonyl] glycinate (Compound No. 82); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate (CompoundNo. 83); Ethyl N-(4-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-[(2,5-dichlorophenoxy)carbonyl] glycinate (Compound No. 84); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy)carbonyl]-D-alaninate (Compound No. 85); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate (Compound No. 86); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methylphenoxy) carbonyl] glycinate (Compound No. 87); Ethyl N- {3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(3-methylphenoxy) carbonyl] glycinate (Compound No. 88); Ethyl N-[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxy benzyl}glycinate (Compound No. 89); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methylphenoxy) carbonyl]glycinate (Compound No. 90); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-
N-[(4-methoxyphenoxy)carbonyl]-L-alaninate (Compound No. 91); E thyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl]-L-alaninate (Compound No. 92); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(phenoxy carbonyl)-L-alaninate (Compound No. 93); Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl)-L-alaninate (Compound No. 94); Ethyl N-[(2-methoxyphenoxy) carbonyl]-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)-L-alaninate (Compound No. 95); N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl) amino]ethoxy}benzy 1)-L-alanine (Compound No. 96); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate (Compound No. 97); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy)carbonyl]glycinate (Compound No. 98); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate (Compound No. 99); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate (Compound No. 100); Ethyl N-(3- {2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate (Compound No. 101); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate (Compound No. 102); Ethyl N-(3-{2-[l,3-
benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycinate (Compound No. 103); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl]glycinate (CompoundNo. 104); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy)carbonyl]glycinate (Compound No. 105); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(2-methoxyphenoxy) carbonyl]glycinate (Compound No. 106); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbony^ (Compound No. 107); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate (Compound No. 108); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate (Compound No. 109); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate (Compound No. 110); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy) carbonyl]glycinate (CompoundNo. Ill); Ethyl N-(3 - {2- [ 1,3 -benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(3 -chlorophenoxy) carbonyl]glycinate (Compound No. 112); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate (Compound No. 113); Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate (CompoundNo. 114); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-methylphenoxy) carbonyl] glycinate (Compound No. 115); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate (Compound No. 116); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(phenoxycarbonyl)glycinate (Compound No. 117); Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methylphenoxy) carbonyl]glycinate (Compound No. 118); Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}glycinate (Compound No. 119); Ethyl N- {3 - [2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} -N- [(4-methylphenoxy) carbonyl]glycinate (Compound No. 120); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl]glycinate (Compound No. 121); Ethyl N-[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate (Compound No. 122); Ethyl N- [(2-chlorophenoxy)carbonyl] -N- {3 - [2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycinate (Compound No. 123); Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(isobutoxycarbonyl)glycinate (Compound No. 124); Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate (Compound No. 125); Ethyl N-(2-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)
glycinate (Compound No. 126); Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(2-methoxybenzoyl)glycinate (Compound No. 127); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(4-methoxyphenoxy)carbonyl]glycine (CompoundNo. 128); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl]glycine (Compound No. 129); N- {4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} -N-[(4-fluorophenoxy)carbonyl] glycine (Compound No. 130); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl) phenoxy]carbonyl] glycine (Compound No. 131); N-(4-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine (Compound No. 132); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methoxyphenoxy) carbonyl]glycine (CompoundNo. 133); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine (CompoundNo. 134); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine (Compound No. 135); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycine (Compound No.136); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-methylphenoxy) carbonyl] glycine (Compound No.l37);N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl) glycine (Compound No.138); N-(4-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-(3-methoxybenzoyl) glycine (Compound No. 139); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl) glycine (Compound No. 140); N- {3 - [2-(5-ethylpyridin-2-yl)ethoxy] benzyl} -N- [(4-methoxyphenoxy)carbonyl] glycine (Compound No. 141); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl]glycine (Compound No. 142); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-fluorophenoxy)carbonyl]glycine (Compound No. 143); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl} glycine (Compound No.144); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl]glycine (CompoundNo.145); N-[(benzyloxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycine (Compound No. 146); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy)carbonyl]glycine (Compound No. 147); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methoxyphenoxy) carbonyl]glycine (Compound No. 148); N-benzoyl-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}glycine (Compound No. 149); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(2-fluorobenzoyl)glycine (Compound No. 150); N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-(4-fluorobenzoyl)glycine (Compound No. 151); N-benzoyl-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)glycine (Compound No. 152);
N-(2-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)glycine (Compound No. 153); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(2-methoxy benzoyl)glycine (Compound No. 154); N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-(phenoxycarbonyl)glycine (Compound No. 155); N-{4-[2-(5-ethylpyridin-2-yl) ethoxy] benzyl }-N-[(4-methyl phenoxy)carbonyl]glycine (Compound No. 156); N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(3-methyl phenoxy)carbonyl]glycine (Compound No. 157); N-[(benzyloxy)carbonyl]-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}glycine (Compound No. 158); N-(4-{2-[methyl(pyridin-2-yl) amino]ethoxy}benzyl)-N-(phenoxycarbonyl)glycine (Compound No. 159); N-(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl) amino]ethoxy}benzyl) glycine (Compound No. 160); N-[(3-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl) amino]ethoxy}benzyl) glycine (Compound No. 161); N-[(benzyloxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)glycine (Compound No. 162); N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}-N-(phenoxycarbonyl)glycine (Compound No. 163); N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycine (Compound No. 164); N-[(4-methoxyphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycine (CompoundNo. 165); N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycine (Compound No. 166); N-[(2-methoxyphenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine (Compound No. 167); N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine (Compound No. 168); N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine (Compound No. 169); N-[(4-chlorophenoxy)carbonyl] -N- {4- [2-(2-methyl-4-oxoquinazolin-3 (4H)-yl)ethoxy] benzyl}glycine (Compound No. 170); N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine (Compound No. 171); N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl }-N-[(4-methylphenoxy) carbonyl]glycine (Compound No. 172); N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine (Compound No. 173); N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycine (Compound No. 174); N-(isobutoxycarbonyl)-N-{4-[2-(2-methyl-4-oxoquinazolin-3 (4H)-yl)ethoxy]benzyl}glycine (Compound No. 175); N-[(benzyloxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl} glycine (Compound No. 176);
N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(3-methylphenoxy) carbonyl]glycine (Compound No. 177); N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl}glycine (Compound No. 178); N-[(3-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (Compound No. 179); N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl} glycine (Compound No. 180); N-[(benzyloxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (Compound No. 181); N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (CompoundNo. 182); N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (Compound No. 183); N-(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (CompoundNo. 184); N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (Compound No. 185); N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine (CompoundNo. 186); N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycine (Compound No. 187); N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycine (Compound No. 188); N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(2-fluorobenzoyl)glycine (Compound No. 189); N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methoxy phenoxy)carbonyl]glycine (Compound No. 190); N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy} benzyl)-N-[(4-chlorohenoxy) carbonyl] glycine (Compound No. 191); N-(4-{2-[1,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(3-chlorohenoxy) carbonyl]glycine (Compound No. 192); N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(4-methylhenoxy) carbonyl]glycine (Compound No. 193); N-[(4-chlorophenoxy)carbonyl] -N- {4- [2-(3 -oxo-2,3 -dihydro-4H-1,4-benzothiazin-4-yl) ethoxy]benzyl}glycine (Compound No. 194); N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine (Compound No. 195); N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}-N-(phenoxycarbonyl) glycine (Compound No. 196); N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(2-chlorophenoxy) carbonyl]glycine (Compound No. 197); N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycine (CompoundNo. 198); N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycine (Compound No. 199); N-
(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} glycine (Compound No. 200); N-(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine (Compound No. 201); N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} glycine (Compound No. 202); N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine (Compound No. 203); //-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl}glycine (Compound No. 204); N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine (Compound No. 205); N-{4-[2-(3-oxo-2,3 -dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl} -N- {[3 -(trifluoromethyl)phenoxy] carbonyl}glycine (Compound No. 206); N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl] glycine (Compound No. 207); N-(4-{2-[ 1,3 -benzothiazol-2-yl(methyl) amino] ethoxy} benzyl)-N- [(4-fluorophenoxy)carbonyl] glycine (Compound No. 208); N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-![3-(trifluoromethyl) phenoxyjcarbonyl}glycine (Compound No. 209); N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(2,5-dichlorophenoxy)carbonyl] glycine (Compound No. 210); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}-4-methoxybenzyl)-N-[(4-methoxy phenoxy)carbonyl]-L-alanine (Compound No. 211); N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-{[3-(trifluoromethyl) phenoxy] carbonyl]glycine (Compound No. 212); N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-[(4-methylphenoxy) carbonyl] glycine (Compound No. 213); N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-[(3-methylphenoxy) carbonyl] glycine (Compound No. 214); N-[(3-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxy benzyl} glycine (Compound No. 215); N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}-4-methoxy benzyl)-N-[(4-methyl phenoxy)methyl]glycine (Compound No. 216); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]-L-alanine (Compound No. 217); N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-methyl phenoxy)carbonyl]-L-alanine (Compound No. 218); N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(phenoxy carbonyl)-L-alanine (Compound No. 219); N-(phenoxycarbonyl)-N-[4-(2-pyridin-2-ylethoxy)benzyl]-L-alanine (Compound No. 220); N-[(2-methoxyphenoxy) carbonyl]-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)-L-alanine (Compound No. 221); N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-L-alanine (Compound No. 222); N-(3-{2-[l,3-benzoxazol-2-yl (methyl)amino]ethoxy} benzyl)-N-[(4-methoxyphenoxy)carbonyl]glycine (Compound No. 223); N-(3-{2-[l,3-
benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(2-methoxyphenoxy) carbonyl] glycine (CompoundNo. 224); N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine (Compound No. 225); N-(3-{2-[l,3-benzoxazol-2-yl (methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycine (Compound No. 226); N-(3-{2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl] glycine (Compound No. 227); N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycine (Compound No. 228); N-(3-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine (Compound No. 229); N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy)carbonyl]glycine (Compound No. 230); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine (CompoundNo. 231); N-(3-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine (Compound No. 232); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine (Compound No. 233); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-(isobutoxycarbonyl) glycine (Compound No. 234); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy} benzyl-N- [(4-chlorophenoxy) carbonyl] glycine (Compound No. 235); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl)glycine (CompoundNo. 236); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine (Compound No. 237); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl]glycine (Compound No. 238); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycine (Compound No. 239); N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycine (Compound No. 240); N-(3-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycine (Compound No. 241); N-(3 - {2- [ 1,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- {[3-(trifluoromethyl) phenoxy]carbonyl}glycine (Compound No. 242); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(phenoxycarbonyl)glycine (CompoundNo. 243); N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methylphenoxy) carbonyl]glycine (Compound No. 244); N- [(4-methoxyphenoxy)carbonyl] -N- { 3 - [2-(2 -methyl -4-oxoquinazo lin-3 (4H)-yl)ethoxy] benzyl}glycine (Compound No. 245); N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-[(4-methylphenoxy) carbonyl]glycine (Compound No. 246); N-{3-[2-(5 -ethylpyridin-2-yl)ethoxy]benzyl} -N- [(3-methylphenoxy)carbonyl] glycine (Compound No. 247);N-[(3-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycine
(Compound No. 248); N-[(2-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycine (Compound No. 249); N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(isobutoxycarbonyl)glycine (Compound No. 250); N-[(4-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycine (Compound No. 251); N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycine (Compound No. 252); N-(4-fluorophenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycine (Compound No. 253); N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(l-oxido-3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycine (Compound No. 254), or
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides or metabolites.
In another aspect, the present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one of the disclosed compound or a pharmaceutically acceptable salt together with a pharmaceutically acceptable carrier or diluents. Compounds disclosed herein may be administered to human or animal for treatment by any route, which effectively transports the active compound to the appropriate or desired site of action, such as oral, nasal, pulmonary, transdermal or parenteral (rectal, subcutaneous, intravenous, intraurethral, intramuscular, intranasal), though preferred route is oral. The pharmaceutical composition of the present invention comprises a pharmaceutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. The term "pharmaceutically acceptable carriers" is intended to include non-toxic, inert solid, semi-solid or liquid filler, diluents, encapsulating material or formulation of any type.
Solid form preparation for oral administration includes capsules, tablet, pills, powder, granules, sachets and suppository. For solid form preparation, the active compound is mixed with at least one inert, pharmaceutically acceptable excipients or carrier such as sodium citrate, dicalcium phosphate; binders such as carboxymethyl cellulose, alginates, gelatins, polyvinylpyrolidinone, acacia; disintegrating agents such as agN-agar, calcium carbonate, alginic acid, certain silicates and sodium carbonate; absorption acceptors such as quaternary ammonium compounds; wetting agents such as cetyl alcohol, glycerol monostearate; adsorbents such as kaolin; lubricants such as talc, calcium stearate, magnesium stearate, solid polyethyleneglycol, sodium lauryl sulphate and mixture thereof. In the case of capsules, tablets, pills, the dosage form may also comprise buffering agents.
The solid preparation of tablets, capsules, pills, granules can be prepared with coating and shells such as enteric coating and other coatings well known in the pharmaceutical formulating art.
Liquid form preparation of oral administration includes pharmaceutically acceptable emulsions, solution, suspensions, syrup and elixir. For liquid preparation, the active compound is mixed with water or other solvent, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (such as cottonseed, groundnut, corn, germ, olive, custard sesame oil), glycerol, and fatty acid esters of sorbitan and mixture thereof. Besides inert diluents, the oral composition can also include adjuvant such as wetting agents, emulsifying agents, suspending agents, sweetening agents, flavoring agents and perfuming agents.
Injectible preparations such as sterile injection or aqueous solution may be formulated according to the art using suitable dispersing or wetting and suspending agent. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solutions, and isotonic sodium chloride.
The formulation of the present invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known to the art.
Examples set forth below demonstrate the general synthetic procedure for the preparation of representative compounds. The examples are provided to illustrate particular aspect of the disclosure and do not constrain the scope of the present invention as defined by the claims.
Experimental Detail
Preparation of compound of Formula V
In a dry two-necked round bottom flask containing dry tetrahydrofuran and fitted with
a septum and nitrogen balloon were charged an aldehyde, triphenyl phosphine and a heterocycle (in a ratio of 1.0:1.4:1.2 respectively). Upon cooling the solution to -5°C to 0°C, diisopropylazodicarboxylate was added (1.3 equiv. with respect to aldehyde) drop wise under stirring. After complete addition the resultant mixture was allowed to come to room temperature and stirred overnight. The volatile matters were removed under reduced pressure and the residue was purified over silica column using mixture of ethyl acetate and hexane as a mobile phase.
Preparation of compound of Formula VI
The compound of Formula V and hydrochloride salt of a compound of Formula RCH(NH2)COOEt (in a ratio of 1.0:2.25) were placed under vacuum for about 20 minutes and then dissolved in dry dichloromethane followed by the addition of dry triethylamine (2.5 equiv.). Upon stirring the resultant mixture for about 1-2 hours at room temperature sodium triacetoxy borohydride (3.0 equiv.) was added at once and the stirring was continued overnight at room temperature under inert atmosphere. The mixture was then poured into water and the organic parts were extracted with dichloromethane. The dichloromethane layer was washed with brine and dried over anhydrous sodium sulfate and concentrated under reduced pressure. The product was purified by column chromatography over silica gel column using either a mixture of ethyl acetate and hexane or methanol and dichloromethane as eluent.
Preparation of compound of Formula VII
To a cold stirred solution (0°C to -5°C) of the compound of Formula VI and triethylamine in dichloromethane was added compound of Formula R19-Cl either in dry dichloromethane or neat drop wise and the resulting mixture was left for stirring overnight allowing it to come to room temperature. The dichloromethane was removed on rotavapor, and the residue was purified over silica gel column using ethyl acetate and hexane as mobile phase to give the desired carbamate ester.
The following compounds were prepared following the above procedure Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl] glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy) carbonyl] glycinate; Ethyl N-{4-[2-(4-ethylphenyl)ethoxy]benzyl}-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-[(4-chlorophenoxy)methyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methoxy-phenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycinate; Ethyl N-(4-{2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methyl phenoxy) carbonyl]glycinate;
Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-benzoylglycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(3-methoxybenzoyl) glycinate; Ethyl N-(4-{2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl) glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy) carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-fluorophenoxy)carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl]glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy) carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methoxy phenoxy)carbonyl]glycinate; Ethyl N-benzoyl-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(2-fluorobenzoyl)glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(4-fluorobenzoyl)glycinate; Ethyl N-benzoyl-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl)glycinate; Ethyl N-(2-fluorobenzoyl)-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)glycinate; Ethyl N-(4-fluorobenzoyl)-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(4-methylphenoxy) carbonyl] glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(3-methylphenoxy)carbonyl] glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycinate; Ethyl N-(4-{2-[methyl(pyridin-2-yl)ammo]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate; Ethyl N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycinate; Ethyl N-[(3-methylphenoxy) carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycinate; Ethyl N-[(benzyloxy)carbonyl] -N-(4- {2- [methyl(pyridin-2-yl)amino] ethoxy} benzyl) glycinate]; Ethyl
N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}-N-(phenoxycarbonyl) glycinate; Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate;Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-(phenoxycarbonyl) glycinate; Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-
oxoquinazolin-3(4H)-yl)ethoxy] benzyl }glycinate; Ethyl N-(2-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl ^ -[(4-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate; Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl }-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy] benzyl}glycinate; Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-[(3-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethoxy] benzyl} -N- {[3-(trifluoromethyl) phenoxy] carbonyl}glycinate; Ethyl N-[(4-fluorophenoxy)carbonyl]-7Vr-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl} glycinate; Ethyl N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l ,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycinate; Ethyl N-[(4-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(4-methylphenoxy)carbonyl]-N- {4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl ^ -[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(2-fluorobenzoyl) glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy)carbonyl] glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-
2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(2-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}-N-(phenoxy-carbonyl) glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-chlorophenoxy) carbonyl]glycinate; Ethyl N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate; Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} glycinate; Ethyl N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l ,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy] benzyl}glycinate; Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl] glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy]carbonyl} glycinate; Ethyl N-(4-{2-[l, 3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2,5-dichlorophenoxy)carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy)carbonyl]-D-alaninate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] -4-methoxybenzyl} -N- {[3-(trifluoromethyl)phenoxy] carbonyl} glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methylphenoxy) carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(3-methylphenoxy) carbonyl] glycinate; Ethyl N-[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxy benzyl} glycinate; Ethyl N-(3-12-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]-L-alaninate; E thyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methyl phenoxy)carbonyl]-L-alaninate; Ethyl N-{4-[2-(5-ethylpyridin-2-y^ ethoxyJbenzylJ-N-^ henoxy carbonyl)-L-alaninate; Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl)-L-alaninate; Ethyl N-[(2-methoxyphenoxy)
carbonyl]-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)-L-alaninate; N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-L-alanine; Ethyl N-(3- {2- [ 1,3 -benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl] glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(benzyloxy)carbonyl] glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy)carbonyl] glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy }benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-berizothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoroniethyl)phenoxy] carbonyl}glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(phenoxycarbonyl)glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methylphenoxy) carbonyl]glycinate; Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy]benzyl} glycinate; Ethyl N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl]glycinate; Ethyl N-[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-[(2-chlorophenoxy)
carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N- {3 - [2-(5 -
ethylpyridin-2-yl)ethoxy]benzyl}-N-(isobutoxycarbonyl)glycinate; Ethyl N-(4-{2-
[methyl(pyridin-2-yl)amino] ethoxy} benzyl)-N- {[3 -(trifluoromethyl)phenoxy] carbonyl}
glycinate; Ethyl N-(2-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)
glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(2-methoxybenzoyl)
glycinate;
Preparation of compound of Formula VIII
The compound of Formula VII and lithium hydroxide (1:2.1) in a mixture of tetrahydrofuran, methanol & water (3:1:1 v/v) were stirred overnight at room temperature. After removing the volatile matters under reduced pressure the residue was dissolved in water. The non-polar impurities were washed with hexane successively followed by the acidification of the water layer to pH 4.0-5.0 using IN hydrochloric acid and then the compound was extracted with ethyl acetate. Ethyl acetate layer was concentrated and the residue was washed with hexane to give chromatographically homogenous and spectroscopically pure acid.
The following compounds were prepared following the above procedure N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl]glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-fluorophenoxy)carbonyl]glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl] glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine;N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methoxyphenoxy) carbonyl]glycine; N-(4-{2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(benzyloxy)carbonyl] glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(4-fluorophenoxy)carbonyl]glycine; N-(4-{2-[l ,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- {[3 -(trifluorom ethyl) phenoxy] carbonyl} glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl] glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl)glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(3-methoxybenzoyl)glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl)glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl] glycine; N- {3 - [2-(5 -ethylpyridin-2-yl)ethoxy]benzyl} -N-[(4-fluorophenoxy)carbonyl] glycine; N-{3- [2-(5 -ethylpyridin-2-yl)ethoxy]benzyl} -N- {[3 -
(trifluoromethyl)phenoxy] carbonyl} glycine; N- {3 - [2-(5 -ethylpyridin-2 -yl)ethoxy] benzyl} -N-[(4-methylphenoxy)carbonyl]glycine; N-[(benzyloxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy)carbonyl]glycine;N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methoxyphenoxy) carbonyl]glycine; N-benzoyl-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(2-fluorobenzoyl)glycine;N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(4-fluorobenzoyl)glycine; N-benzoyl-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycine; N-(2-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)glycine;
N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(2-methoxybenzoyl)glycine;N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-(phenoxycarbonyl)glycine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-methyl phenoxy)carbonyl]glycine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl]glycine; N-[(benzyloxy)carbonyl]-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}glycine; N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl)-N-(phenoxycarbonyl)glycine; N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)glycine; N-[(3-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)glycine; N-[(benzyloxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)aniino] ethoxy}benzyl)glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycine; N-[(2-methoxyphenoxy) carbonyl] -N- {4- [2-(3 -oxo-2,3 -dihydro-4H-1,4-benzoxazin-4-yl)ethoxy] benzyl} glycine; N-[(4-methoxyphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycine; N-[(2-methoxyphenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-[(4-methoxyphenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-[(2-chlorophenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl} glycine; N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl} glycine; N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(4-methylphenoxy) carbonyl]glycine; N-(4-fluorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-{ [3-(trifluoromethyl) phenoxy]carbonyl}glycine; N-(isobutoxycarbonyl)-N-{4-[2-(2-methyl-4-oxoquinazolin-3 (4H)-yl)etnoxy]benzyl}glycine;
N-[(benzyloxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl} glycine;N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(3-methylphenoxy)carbonyl]glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl} glycine; N-[(3-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(benzyloxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-(isobutoxycarbonyl)-N- {4- [2-(3-oxo-2,3 -dihydro-4H-1,4-benzoxazin-4-yl)ethoxy] benzyl} glycine; N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(2,5-dichlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycine; N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy] benzyl} glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(2-fluorobenzoyl)glycine; N-(4-{2-[ 1,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(4-chlorohenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(3-chlorohenoxy) carbonyl]glycine; N-(4-{2-[1,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methylhenoxy) carbonyl]glycine; N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} glycine; N- [(2-chlorophenoxy)carbonyl] -N- {4- [2-(3-oxo-2,3 -dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl} glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}-N-(phenoxycarbonyl) glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(2-chlorophenoxy) carbonyl]glycine; N-[(2,5-dichlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl)glycine; N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl} glycine; N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(3-methylphenoxy) carbonyl]-N-(4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine;
N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl} -N- {[3 -(trifluoro- methyl)phenoxy] carbonyl} glycine; N-(4- {2-[1,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine;N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycine; N-(4-{2-[l ,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(2,5-dichlorophenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino] ethoxy} -4-methoxybenzyl)-N-[(4-methoxy phenoxy) carbonyl]-L-alanine;N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-{[3-(trifluoro methyl)phenoxy] carbonyl]glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-[(4-methylphenoxy) carbonyl] glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-[(3-methylphenoxy) carbonyl] glycine; ^ -[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxy benzyl} glycine; N-(3-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}-4-methoxy benzyl)-N-[(4-methylphenoxy)methyl] glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]-L-alanine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-methyl phenoxy)carbonyl]-L-alanine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-(phenoxy carbonyl)-L-alanine; N-(phenoxycarbonyl)-N-[4-(2-pyridin-2-ylethoxy)benzyl]-L-alanine; N-[(2-methoxyphenoxy) carbonyl]-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)-L-alanine; N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)aniino]ethoxy}benzyl)-L-alanine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl] glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy }benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine; N-(3-{2-[l ,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl)glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl)glycine;N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy)carbonyl] glycine; N-(3- {2-[ 1,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine;N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}
benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine; N-(3-{2-[1,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-(isobutoxycarbonyl)glycine; N-(3-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy)carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N-(phenoxycarbonyl)glycine; N-(3 - {2- [ 1,3 -benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine; N-(3-{2-[l^ -benzothiazol-2 -yl( methyl) amino]ethoxy}benzyl)-N-[(3-chlorophenoxyjcarbonyl] glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl] glycine; N-(3-{2-[l ,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-{[3-(trifluoromethyl)phenoxy]carbonyl}glycine;N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy }benzyl)-N-(4-methylphenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N- {[3-(trifluoromethyl) phenoxy] carbonyl} glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(phenoxycarbonyl)glycine;N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methylphenoxy)carbonyl]glycine; N-[(4-methoxyphenoxy)carbonyl]-N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl} glycine; N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-[(4-methylphenoxy) carbonyl]glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl] glycine; N- [(3 -chlorophenoxy)carbonyl] -N- {3 - [2-(5 -ethylpyridin-2-yl)ethoxy] benzyl} glycine; N- [(2-chlorophenoxy)carbonyl] -N- {3 - [2-(5 -ethylpyridin-2-yl)ethoxy]benzyl}glycine;N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(isobutoxycarbonyl)glycine; N-[(4-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl} glycine; N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycine;N-[(4-fluorophenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)glycine; N-[(4-methylphenoxy)carbonyl]-N-{4-[2-( 1 -oxido-3 -oxo-2,3 -dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl} glycine,
Table I
(Table Removed)
Functional and Binding Assay
Transient Transfection and Transcription Assay: HEK-293 cells, purchased from ATCC (USA) cell bank, maintained in Minimum essential medium (Eagle) withlO % charcoal dextran treated serum, were inoculated in 6-well plates (Ix 106 cells/well) and cultured approximately 18 hours in Minimum essential medium (Eagle) with 2 mM L-glutamine and Earle's BSS adjusted to contain 1.5 g/L sodium bicarbonate, and 1.0 mM sodium pyruvate in 5% CO2 at 37 °C. The cells were transfected with each PPAR expression plasmid, pCMV Script- (PPAR γl/PPARα/PPAR8) full length (2 µg in 2 ml/well), pTAL-PPRE-Luc (4 µg), pAdvantage and pRL-CMV by Lipofection using Lipofectamine-2000 (Invitrogen, Carlsbad, USA) in abovementioned media but without antibiotics. Transfection mixture was replaced by fresh media (without antibiotics) after 5 hours duration. After transfection, the cells were harvested and seeded into 96-well plate (LumiNunc™ Plates, NUNC, Roskilde, Denmark) at a density of 3 x 104 cells /well in 100 µl of medium with Phenol-red free MEM with 10 % charcoal dextran treated serum and other components. After the cells had adhered, 100 µl of Phenol-red free MEM with 10 % charcoal dextran treated serum containing compound/standards were added. No drug controls cells were added with DMSO concentration of 0.3 % as final. After 24 hours, cells were lysed and the luciferase activity was measured in a Luminescence-Scintillation counter (Wallac MicroBeta® TriLux, PerkinElmer, CT, USA) using the Dual-Luciferase Reporter Assay System (Promega, Madison, WI, USA). (1)
Calculation of Transcriptional Activity: The firefly luciferase activity was divided by the sea pansy luciferase activity to adjust for the transfection efficiency, and the value was defined as the normalized luciferase activity. Fold activation is calculated as the ratio of PPN-mediated transcriptional activity in the cells treated with each drug to that in DMSO-treated control cells. Compound EC50 was calculated with GraphPad Prism 4.0 software. % Maximum standard was calculated as the ratio of maximum firefly (standard) reading and firefly test reading multiplied by 100. Rosiglitazone (BRL-49653) and Ragaglitazar (DRF-2725) were used as standards for PPAR yl and PPAR a, respectively.
Reference: Minoura H. et al, (2004). Pharmacological characteristics of a novel nonthiazolidinedione insulin sensitizer, FK614. European Journal of Pharmacology. 494 273-281.

WE CLAIM:
1. Compounds having the structure of Formula I,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof wherein, Het is selected from:
(Formula Removed)
wherein:
X1-X11 are each independently CH, C, CH2, N, NH, O, S, S(=O) or S(=O)2;
X12 and X13 are each independently CR' or N, wherein R1 is hydrogen or alkyl;
X14 is (CH2)X (where, x =0-2), NR', 0, S, S(=O) or S(=O)2 wherein, R' is the same as defined
above;
X15 isCHorN;
X16 and V are each independently O, NR', or S, wherein R' is the same as defined earlier;
D and E are substituted or unsubstituted alkyl, aryl or a bond;
R1-R5 and R10-R17 are each independently hydrogen, substituted or unsubstituted alkyl,
substituted or unsubstituted aryl, aryloxy, substituted or unsubstituted alkenyl, substituted or
unsubstituted alkynyl, hydroxy, alkoxy, halogen, optionally substituted amino;
A is N(CH3), 0, C(O), NH, S or a bond;
R6-R9 are each independently hydrogen, hydroxyl, halogen, substituted or unsubstituted
alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, alkoxy,
halogen, optionally substituted amino; is optional double bond;
R18 is hydrogen, halogen, nitro, cyano, substituted or unsubstituted alkyl, substituted or
unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl,
substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted
or unsubstituted heteroaryl, COOR20, C(=V)R21 (wherein, V is as defined earlier), OR20, SR20 or N(R22)2 {[wherein R2o can be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl], [R21 can be R20, N(R20)2 (wherein R20 is the same as defined above)], [R22 is R20, COOR20, C(=V)R21, S(O)qR23, wherein, V, R20 and R21 are the same as defined above and R23 is R20 except hydrogen and q can be an integer 1 or 2]}; Ri9 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, COOR20, C(=V)R2b C(=V)(NR20)2, SO2R23, C(=V)NRSO2-R23, C(=V)NR'R" {[wherein, V, R20 and R21 are the same as defined earlier], [R1 and R" together with nitrogen to which they are attached form a ring which contain additional one or more heteroatom(s) like O, S or N and the ring so formed is further substituted with SO2R23 (wherein R23 is the same as defined earlier), alkyl, aryl, heteroaryl]; X is CH, N or N(-0); Z is O, S, NH, N-Me or a bond;
Y is COOR28 (wherein R28 is hydrogen or substituted or unsubstituted alkyl) or CON(R22)2 (wherein R22 is the same as defined above); A1, A2 or A3 is substituted or unsubstituted CM alkylene.
2. The compound of claim 1, wherein the compound is:
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof, wherein: Het, A1-A3, Z, Y, R18 and R19 are the same as defined in claim 1.
3. A compound, namely:
Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl] glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2- methoxyphenoxy) carbonyl] glycinate; Ethyl N-{4-[2-(4-ethylphenyl)ethoxy]benzyl}-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-[(4-chlorophenoxy)methyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl (methyl)
amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methoxy-phenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl} glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methyl phenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-benzoyl glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(3-methoxybenzoyl) glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)aminoJethoxy}benzyl)-N-(4-methoxybenzoyl) glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxyJbenzyl}-N-[(4-methoxyphenoxy) carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(4-fluorophenoxy)carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl)phenoxyJ carbonyl}glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl] glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxyJ-4-methoxybenzyl}-N-[(4-methoxy phenoxy)carbonyl]glycinate; Ethyl N-benzoyl-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(2-fluorobenzoyl)glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxyJ benzyl}-N-(4-fluorobenzoyl)glycinate; Ethyl N-benzoyl-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl)glycinate; Ethyl N-(2-fluorobenzoyl)-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)glycinate; Ethyl N-(4-fluorobenzoyl)-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-[(3-methyl-phenoxy)carbonyl] glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate; Ethyl N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl) glycinate; Ethyl N-[(3-methylphenoxy) carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl) glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycinate;
Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}-N-(phenoxy carbonyl)glycinate; Ethyl N-[(2-methoxyphenoxy)carbonyl]-A/'-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-(phenoxycarbonyl)glycinate; Ethyl N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate; Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(4-methylphenoxy)carbonyl]glycinate; Ethyl N-[(4-fluorophenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy] benzyl}glycinate; EthylN-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-{[3-(trifluoromethyl) phenoxy] carbonyl}glycinate; Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate; Ethyl N-[(benzyloxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycinate; Ethyl N-[(3-methoxy- phenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}-N-{[3-(trifluoroniethyl)phenoxy] carbonyl} glycinate; Ethyl N-[(4-fluorophenoxy)carbonyl]-N-(4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy] benzyl}glycinate; Ethyl'N-[(benzyloxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl} glycinate; Ethyl N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l ,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycinate; Ethyl N-[(4-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycinate; Ethyl N-[(2,5-dichlorophenoxy)carbonyl]-
N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl}glycinate; Ethyl N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(2-
fluorobenzoyl) glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(4-methoxyphenoxy) carbonyl] glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy)carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N-[(3-chlorophenoxy)carbonyl] glycinate; Ethyl N-(4- {2- [ 1,3 -benzothiazol-2-yl(methyl)amino] ethoxy} benzyl)-N- [(4-methylphenoxy) carbonyl]glycinate; Ethyl N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-[(2-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycinate; Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}-N-(phenoxy-carbonyl) glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-chlorophenoxy) carbonyl]glycinate; Ethyl N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-(4-{2-[ 1,3-benzothiazol-2-yl (methyl)amino]ethoxy} benzyl)-N-(isobutoxycarbonyl) glycinate; Ethyl N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl} glycinate; Ethyl N-[(4-methylphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl} glycinate; Ethyl N- [(3 -chlorophenoxy)carbonyl] -N- {4- [2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(3-methylphenoxy)carbonyl]-N- {4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy] benzyl}glycinate; Ethyl N-[(2-methoxyphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl}glycinate; Ethyl N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l ,4-benzothiazin-4-yl)ethoxy]benzyl} glycinate; Ethyl N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl} -N- {[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy)carbonyl]glycinate; Ethyl N-(4-{2-[ 1,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-(4-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-[(2,5-dichlorophenoxy)carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy) carbonyl]-D-alaninate; Ethyl N-{3 -[2-(5-ethylpyridin-2-yl)ethoxy] -4-methoxybenzyl} -N- {[3 -(trifluoromethyl)phenoxy] carbonyl}glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(4-methylphenoxy) carbonyl] glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxybenzyl}-N-[(3-methylphenoxy) carbonyl] glycinate; Ethyl N-[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxy benzyl}glycinate; Ethyl N-(3-{2-
[ 1,3-benzothiazol-2-yl(methyl)amino]ethoxy} -4-methoxybenzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]berizyl}-N-[(4-methoxyphenoxy)carbonyl]-L-alaninate; E thyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-
N-[(4-methyl phenoxy)carbonyl]-L-alaninate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(phenoxy carbonyl)-L-alaninate; Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)-N-(phenoxycarbonyl)-L-alaninate; Ethyl N-[(2-methoxyphenoxy) carbonyl]-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl)-L-alaninate; N-[(4-methylphenoxy) carbonyl]-N-(4-{ 2-[methyl (pyridin-2-yl) amino]ethoxy}benzyl)-L-alanine; Ethyl N-(3-{2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl] glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy) carbonyl] glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(3-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl (methyl)amino] ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl] glycinate; Ethyl N-(3-{2-[l ,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-(isobutoxycarbonyl) glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl (methyl)aminoJethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[1,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycinate; Ethyl N-(3-{2-[ 1,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy) carbonyl] glycinate; Ethyl N-(3-{2-[l ,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycinate; Ethyl N-(3- {2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxyjcarbonyl}glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl) ethoxyJbenzyl}-N-(phenoxycarbonyl)glycinate; Ethyl N-(3-{2-[l,3-benzoxazol-2-yl (methyl)
amino]ethoxy}benzyl)-N-[(3-methylphenoxy) carbonyl] glycinate; Ethyl N-[(4-methoxyphenoxy)carbonyl]-N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycinate; Ethyl N-{3-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl}-N-[(4-methylphenoxy) carbonyl]glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl]glycinate; Ethyl N-[(3-chlorophenoxy)carbony 1]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl} glycinate; Ethyl N-[(2-chlorophenoxy)carbonyl]-N- {3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycinate; Ethyl N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(isobutoxycarbonyl)glycinate; Ethyl N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl)-N-{[3-(trifluoromethyl)phenoxy] carbonyl]glycinate; Ethyl N-(2-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)glycinate; Ethyl N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(2-methoxybenzoyl)glycinate; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl} -N- [(4-methoxyphenoxy)carbonyl]glycine; N- {4- [2-(5-ethylpyridin-2-yl)ethoxy] benzyl} -N-[(2-methoxyphenoxy)carbonyl] glycine; N- {4- [2-(5 -ethylpyridin-2-yl)ethoxy] benzyl}-N-[(4-fluorophenoxy)carbonyl]glycine;N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl] glycine; N-(4-{2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine;N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methoxyphenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine;N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-{[3-(trifluoromethyl) phenoxy] carbonyl} glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzoxazol-2-yl (methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl) glycine; N-(4-{2-[l,3-benzoxazol-2-yl (methyl)amino]ethoxy}benzyl)-N-(3-methoxybenzoyl) glycine; N-(4-{2-[l,3-benzoxazol-2-yl (methyl)amino]ethoxy}benzyl)-N-(4-methoxybenzoyl) glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(2-methoxyphenoxy)carbonyl]glycine;N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-fluorophenoxy)carbonyl]glycine;N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl} glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-methylphenoxy)carbonyl] glycine; N-[(benzyloxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl) glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}-4-methoxybenzyl)-N-[(4-niethoxyphenoxy) carbonyl]glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] -4-methoxybenzyl} -N- [(4-methoxyphenoxy)carbonyl] glycine; N-benzoyl-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}glycine;N-{4-[2-(5-ethylpyridin-2-yl)
ethoxy] benzyl}-N-(2-fluorobenzoyl)glycine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy] benzyl}-N-(4-fluorobenzoyl)glycine; N-benzoyl-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycine; N-(2-fluorobenzoyl)-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}-N-(2-methoxy benzoyl)glycine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-(phenoxycarbonyl)glycine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(4-methyl phenoxy)carbonyl]glycine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl]glycine; N-[(benzyloxy)carbonyl]-N-{4-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl}glycine; N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy} benzyl)-N-(phenoxycarbonyl) glycine; N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl (pyridin-2-yl)amino]ethoxy} benzyl) glycine; N-[(3-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl) glycine; N-[(benzyloxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino] ethoxy}benzyl)glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}-N-(phenoxycarbonyl)glycine; ^ -[(2-methoxyphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy]benzyl}glycine; N-[(4-methoxyphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl} glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycine; N-[(2-methoxyphenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-[(4-methoxyphenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-[(2-chlorophenoxy) carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}glycine; N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycine; N-[(3-chlorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl) ethoxy]benzyl}glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(4-methylphenoxy) carbonyl]glycine; N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy]benzyl} glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl) phenoxy]carbonyl}glycine; N-(isobutoxycarbonyl)-N-{4-[2-(2-methyl-4-oxoquinazolin-3 (4H)-yl)ethoxy]benzyl}glycine; N-[(benzyloxy)carbonyl]-N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl} glycine; N-{4-[2-(2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy] benzyl}-N-[(3-methylphenoxy)carbonyl]glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}-N-{[3-(trifluoromethyl)phenoxy]carbonyl}glycine;N-[(3-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl} glycine; N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(benzyloxy)carbonyl]-N-{4-[2-(3-oxo-2,3-
dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(3-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-(isobutoxycarbonyl)-N- {4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethoxy] benzyl} glycine; N-[(4-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyl}glycine; N-[(3-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl)ethoxy] benzyljglycine; N-[(2,5-dichlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzoxazin-4-yl) ethoxy]benzyl}glycine;N-[(4-methoxyphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl} glycine; N-(4-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-(2-fluorobenzoyl)glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino] ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine; N-(4-{2-[l ,3-benzothiazol-2-yl (methyl) amino]ethoxy}benzyl)-N-[(4-chlorohenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(3-chlorohenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl) aminoJethoxyJbenzy^ -N-N-methylhenoxy^ arbonyl] glycine; N-[(4-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(2-chlorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl}glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy] benzyl}-N-(phenoxycarbonyl) glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(2-chlorophenoxy) carbonyl]glycine; N-[(2,5-dichlorophenoxy)carbonyl] -N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazm-4-yl)ethoxy] benzyl}glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycine; N-(isobutoxycarbonyl)-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy] benzyl}glycine; N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(3-chlorophenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(3-methylphenoxy) carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(2-methoxyphenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl) ethoxy]benzyl}glycine; N-[(4-fluorophenoxy)carbonyl]-N-{4-[2-(3-oxo-2,3-dihydro-4H-l,4-benzothiazin-4-yl)ethoxy]benzyl} glycine; N-{4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl} -N- {[3 -(trifluoromethyl)phenoxy] carbonyl} glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine; N-(4-{2-[1,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl)
amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy]carbonyl}glycine; N-(4-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(2,5-dichlorophenoxy)carbonyl] glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}-4-methoxybenzyl)-N-[(4-methoxyphenoxy) carbonyl]-L-alanine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-{[3-(trifluoromethyl) phenoxy] carbonyl}glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-[(4-methylphenoxy) carbonyl] glycine; N-{3-[2-(5-ethylpyridin-2-yl) ethoxy]-4-methoxybenzyl}-N-[(3-methylphenoxy) carbonyl] glycine; N-[(3-chlorophenoxy) carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]-4-methoxy benzyl} glycine; N-(3-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}-4-methoxy benzyl)-N-[(4-methylphenoxy)methyl] glycine; N-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(4-methoxyphenoxy)carbonyl]-L-alanine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl} -N-[(4-methyl phenoxy)carbonyl]-L-alanine; N-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-N-(phenoxy carbonyl)-L-alanine; N-(phenoxycarbonyl)-N-[4-(2-pyridin-2-ylethoxy)benzyl]-L-alanine; N-[(2-methoxy- phenoxy)carbonyl]-N-(4-{2-[methyl (pyridm-2-yl)amino]ethoxy} benzyl)-L-alanine; N-[(4-methylphenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl) amino] ethoxy} benzyl)-L- alanine ;N-(3-{2-[l ,3 -benzoxazol-2-y l(methyl)amino] ethoxy} benzyl)-N-[(4-methoxy- phenoxy)carbonyl]glycine; N-(3-{2-[l ,3-benzoxazol-2-yl(methyl)amino] ethoxy} benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino] ethoxy}benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzoxazol-2-yl (methyl)amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycine; N-(3-{2-[ 1,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl] glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycine;
N-(3 - {2-[ 1,3 -benzoxazol-2-yl (methyl )amino] ethoxy} benzyl)-N- [(benzyloxy)carbonyl] glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl]glycine;N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methoxyphenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy} benzyl)-N-[(2-methoxyphenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy} benzyl)-N-[(4-fluorophenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl) amino]ethoxy}benzyl)-N-(isobutoxycarbonyl) glycine; N-(3-{2-[l,3-benzothiazol-2-yl (methyl)amino]ethoxy}benzyl)-N-[(4-chlorophenoxy) carbonyl]glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-(phenoxycarbonyl) glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(benzyloxy)carbonyl] glycine; N-(3-12-[ 1,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-chlorophenoxy) carbonyl] glycine; N-(3-{2-[l,3-benzothiazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(4-methyl
phenoxy)carbony 1] glycine; N-(3 - {2- [ 1,3 -benzothiazol-2-y l(methyl)amino] ethoxy} benzyl)-N-{[3-(trifluoromethyl) phenoxy]carbonyl} glycine; N-(3-{2-[ 1,3-benzoxazol-2-yl(methyl) amino]ethoxy}benzyl)-N-[(4-methylphenoxy) carbonyl]glycine; N-(3-{2-[ 1,3 -benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N- {[3-(trifluoromethyl) phenoxy] carbonyl} glycine; N- {3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(phenoxycarbonyl)glycine; N-(3-{2-[l,3-benzoxazol-2-yl(methyl)amino]ethoxy}benzyl)-N-[(3-methylphenoxy) carbonyl]glycine; N- [(4-methoxyphenoxy)carbonyl] -N- { 3 - [2-(2-methyl-4-oxoquinazolin-3 (4H)-yl)ethoxy] benzyl} glycine; N- {3 -[2-(2-methyl-4-oxoquinazolin-3 (4H)-yl)ethoxy]benzyl} -N- [(4-methylphenoxy) carbonyl]glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-[(3-methylphenoxy)carbonyl] glycine; N- [(3 -chlorophenoxy)carbonyl] -N- {3 - [2-(5 -ethylpyridin-2-yl)ethoxy]benzyl} glycine; N-[(2-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}glycine; N-{3-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-N-(isobutoxycarbonyl)glycine; N-[(4-chlorophenoxy)carbonyl]-N-{3-[2-(5-ethylpyridin-2-yl)ethoxy] benzyl} glycine; N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-N-{[3-(trifluoromethyl)phenoxy] carbonyl}glycine; N-[(4-fluorophenoxy)carbonyl]-N-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl) glycine; N-[(4-methylphenoxy)carbonyl]-N-{4-[2-(l -oxido-3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy] benzyl} glycine,
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof.
4. A pharmaceutical composition comprising a therapeutically effective amount of a
compound of claim 1 together with pharmaceutically acceptable carriers, excipients or
diluents.
5. A compound according to claim 1 or a pharmaceutical composition of claim 4 is
used as Peroxisome Proliferator Activated Receptor (PPAR) modulating agents.
6. The compound or pharmaceutical composition according to claim 1 or 4 is PPARα,γ
or 8 subtype selective or combination thereof.
7. A method of treating mammal suffering from diabetes and diabetes association
complication, comprising administering to the said mammal, a therapeutically effective
amount of a compound of claim 1 or a pharmaceutical composition of claim 4.
8. A method of treating mammal suffering from the diseases or conditions selected
from the group comprising of Type II diabetes, dyslipidaemia, hypertension,
coronary heart disease, cardiovascular disease, atherosclerosis, diabetes
nephropathy, glomerulonephritis, glomerularsclerosis, nephrotic syndorme,
hypertensive nephrosclerosis, polycystic ovarian syndrome, psoriasis, obesity, eating disorders, for improving cognitive functions in dementia and as aldose reductase inhibitors, comprising administering to the said mammal, a therapeutically effective amount of a compound of claim 1 or a pharmaceutical composition of claim 4. 9. A method for the preparation of compounds of Formula VII,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs, prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof, wherein Het, A1-A3, Z, R, R18, R19 and R28 are the same as defined in Claim 1, the method comprising:
reacting a compound of Formula IV with a compound of Formula Het-Ai-OH or Het-A1-L1
(wherein L1 is a leaving group selected from Cl, Br, I, acetate, 4-methylbenzenesulfonate, 4-
bromobenzenesulfonate, 4-nitrobenzenesulfonate, methanesulfonate, trifloromethanesulfonate
and the like) (Formula Removed)

to give a compound of Formula V,
(Formula Removed)
which on treating with a compound of Formula H2NCHRCOOR28-HC1 gives a compound of Formula VI,
(Formula Removed)
which is finally treated with a compound of Formula R19-Cl or R19-N=C=W to give a compound of Formula VII.
10. A method for the preparation of compounds of Formula VIII,
(Formula Removed)
(Formula I wherein, X=CH, A2=CH2, A3=CHR, Y=COOH)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, polymorphs,
prodrugs, stereoisomers, tautomeric forms, N-oxides and metabolites thereof wherein,
Het, A1-A3, Z, R, R18, and R19 are the same as defined in Claim 1,
the method comprising:
hydrolysis of a compound of Formula VII
(Formula Removed)
to give a compound of Formula VIII.