Field of the Invention
Provided herein are substituted aromatic compounds, which are tRNA synthetase inhibitors, and hence can be used as antimicrobial agents. Compounds disclosed herein can be used for the treatment or prevention of a condition caused by or contributed to by gram positive, gram negative, anaerobic bacteria or fungal organisms, more particularly against bacterium, for example, Staphylococci, Enterococci, Streptococci, Haemophilus, Moraxalla, Escherichia, Chlamydia, Rickettsiae, Mycoplasm, Legionella, Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae, and fungal organisms, for example, Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus, Epidermophyton, Hendersonula, Histoplasma, Microsporum, Paecilomyces, Paracoccidiodes, Pneumocystis, Trichophyton, or Trichosporium. Processes for the preparation of these compounds, pharmaceutical compositions thereof, and method of treating microbial infections are also provided.
Background of the Invention
Antibiotics are of immense value for combating infectious diseases. In recent decades, the effectiveness of antibiotics has been threatened by an inexorable rise in the prevalence of microbial drug resistance. Some important pathogens have serious resistance problems. Staphylococcus aureus is perhaps the most significant of these pathogens. It causes community and hospital acquired infections and is associated with high morbidity and mortality rates. Vancomycin has been used as the antibiotic of last resort to treat methicillin-resistance Staphylococcus aureus infections (MRSA) with multiple resistance. Strains with some level of resistance to vancomycin (Vancomycin-intermediates-resistant S. aureus, VISA) have been known since 1996, but the newly identified highly resistant strain (VRSA) heralds a new stage in the battle with this pathogen. Other serious treatment problems include multidrug resistance in tuberculosis, vancomycin resistant enterococci (VRE), resistance owing to extended spectrum p-lactamases (ESBLs) in Enterobacteriaceae and Pseudomonas aeruginosa, and penicillin resistance in Streptococcus pneumoniae.
A nation wide epidemic of multi drug resistant Salmonell typhi occurred in 1990 and has not yet fully subsided. Antimicrobial resistance among respiratory pathogens has become a common clinical problem, currently over 90% of Morexella catarrhalis and 25% of Haemophilus influenzae produce P lactamases, requiring treatment with a P lactamase stable cephalosporin or combination drugs. In the last several years, there has been a rapid increase in the number of strains resistant to penicillin, cephalosporins, macrolides and fluoroquinolones.
These circumstances have prompted efforts to develop new antibiotics that overcome the emerging antibiotic resistance bacteria. The amino acyl tRNA synthetases are essential enzymes found in all living organisms. These enzymes have emerged as an attractive target for the development of new antibiotics. Amino acyl tRNA synthetases charge tRNA molecules with their corresponding amino acid, an essential step in protein synthesis. There are 20 tRNA synthetases, most of which correspond to attractive broad-spectrum antibacterial targets. This is a validated target class in that pseudomonic acid A, also known as mupirocin, a natural product from Pseudominas fluorescens, inhibits isoleucyl tRNA synthtase and is marketed as a topical antibiotic Bactropan. Other known natural products directed against amino acyl tRNA synthetases include borrelidin, furanomycin, granaticin, indolmycin, ochartoxin A, and cispentacin, none of them has been developed as antibiotic compounds.
U.S. Patent Application Nos. 20040224981 and 20030013724 disclose tRNA synthetase inhibitors. WO 00/18772 discloses condensed imidazolidinone as tRNA synthetase inhibitors. U.S. Patent Nos. 5,191,093 and 4,916,155 disclose crystalline pseudomonate, process for its production and its use in human and veterinary medicines. U.S. Patent No. 4,916,155 discloses crystalline calcium pseudomonate or the hydrate thereof, and their use in human and veterinary medicine.
Novel synthetic compounds, which target tRNA synthetases, offer clear advantages as useful therapeutic agents to curb the threat of drug resistance.
Summary of the Invention
Accordingly, this invention provides substituted aromatic compounds, which are tRNA synthetase inhibitors, and hence can be used for the treatment of microbial infections, and processes for the synthesis of these compounds. Pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites, polymorphs and N-oxides of these compounds having same type of activity are also provided. Pharmaceutical compositions containing the disclosed compounds (Formula I) together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of microbial infections. Other aspects will be set forth in the accompanying description which follows and in 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, stereoisomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy can be cycloalkyl or heterocyclyl; X and Z can be alkylene; Y can be NR1 (wherein R1 can be hydrogen, alkyl or OCOalkyl); XrX4 can be CH or N; R can be OR2, OCONHR2, OCONHSO2R2, SR3 (wherein R2 can be aryl or heteroaryl and R3 can be hydrogen, alkyl, cycloalkyl, heterocyclyl, heteroaryl or aryl) or NR4R5 {wherein R4 and R5 can be independently hydrogen, SO2R6, COR6, CSR6, or COOR6 [wherein R6 can be alkyl, aryl, heteroaryl, heterocyclyl, aralkyl, heteroarylalkyl, heterocycloalkyl, OR7, NHR7, NHSO2R7, NHCOR7, NHCSR7, or NH2C=NHSO2R7 (wherein R7 can be alkyl, aryl, heteroaryl or heterocyclyl)]}. Also, R4 and R5 can, together with the nitrogen to which they are attached, form a heterocyclic ring.
In a second aspect, there is provided a method for treating or preventing a subject suffering from a condition caused by or contributed to by Gram positive, Gram negative, anaerobic bacteria or fungal organisms, comprising administering to said subject, a therapeutically effective amount of a compound or a pharmaceutical composition disclosed herein.
Bacterium, for example, Staphylococci, Enterococci, Streptococci, Haemophilus, Moraxalla, Escherichia, Chlamydia, Rickettsiae, Mycoplasm, Legionella, Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae may cause the bacterial infections.
Organisms, for example, Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus, Epidermophyton, Hendersonula, Histoplasma, Microsporum, Paecilomyces, Paracoccidiodes, Pmumocystis, Trichophyton, or Trichosporium, Enterobactericeae may cause the fungal infections.
The conditions may be, for example, community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, and other bacterial infections, for example, mastitis, catheter infection, foreign body, prosthesis infections or peptic ulcer disease.
In a third aspect, there are provided processes for the preparation of compounds as disclosed herein.
The following definitions apply to terms as used herein:
The term "alkyl," unless otherwise specified, refers to a monoradical branched or unbranched saturated hydrocarbon chain having from 1 to 20 carbon atoms. This term can be exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-decyl, tetradecyl, and the like. Alkyl groups may be substituted further with one or more substituents selected from alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, carboxy, carboxyalkyl, aryl, heterocyclyl, heteroaryl, arylthio, thiol, alkylthio, aryloxy, nitro, aminosulfonyl, aminocarbonylamino, -NHC(=O)Rf, -NRfRq, -C(=O)NRfRq, -NHC(=O)NRfRq,, -C(=O)heteroaryl, C(=O)heterocyclyl, -O-C(=O)NRfRq {wherein Rf and Rq are independently selected from alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl}, nitro, or -SO2R6 (wherein R6 is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl, heterocyclyl, heteroaryl, heteroarylalkyl or heterocyclylalkyl). Unless otherwise constrained by the definition, alkyl substituents may be further substituted by 1 -3 substituents selected from alkyl, carboxy, -NRfRq, -C(=O)NRfRq, -OC(=O) NRfRq, -NHC(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), hydroxy, alkoxy, halogen, CF3, cyano, and -SO2R6, (wherein R6 are the same as defined earlier); or an alkyl group also may be interrupted by 1-5 atoms of groups independently selected from oxygen, sulfur or -NRa- {wherein Ra is selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, acyl, aralkyl,-C(=O)ORf (wherein Rf is the same as defined earlier), SO2R6 (where R6 is as defined earlier), or -C(=O)NRfRq (wherein Rf and Rq are as defined earlier)}. Unless otherwise constrained by the definition, all substituents may be substituted further by 1 -3 substituents selected from alkyl, carboxy, -NRfRq, -C (=O)NRfRq, -O-C(=O)NRfRq (wherein Rf and Rq are the same as defined earlier) hydroxy, alkoxy, halogen, CF3, cyano, and -SO2R6 (where R6 is same as defined earlier); or an alkyl group as defined above that has both substituents as defined above and is also interrupted by 1-5 atoms or groups as defined above.
The term "alkylene" herein refers to -(CH)n- wherein n can be an integer of from 0 to 4 and one or more hydrogen can optionally be substituted with alkyl, hydroxy, halogen or oximes. Alkylene can also be optionally interrupted by -CONH-, -C=O or -C=NOH.
The term "cycloalkyl," unless otherwise specified, refers to cyclic alkyl groups of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may optionally contain one or more olefmic bonds, unless otherwise constrained by the definition. Such cycloalkyl groups can include, for example, single ring structures, including cyclopropyl, cyclobutyl, cyclooctyl, cyclopentenyl, and the like, or multiple ring structures, including
adamantanyl, and bicyclo [2.2.1] heptane, or cyclic alkyl groups to which is fused an aryl group,
for example, indane, and the like. Spiro and fused ring structures can also be included.
Cycloalkyl groups may be substituted further with one or more substituents selected from alkyl,
alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy,
alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, carboxy,
carboxyalkyl, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl,
aminocarbonylamino, -NRfRq, -NHC (=O) NRfRq, -NHC (=O) Rf, -C (=O) NRfRq, -O-C
(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, or SO2-R6 (wherein R6 is same as defined earlier). Unless otherwise constrained by the definition, cycloalkyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, carboxy, hydroxy, alkoxy, halogen, CF3, -NRfRq, -C(=O)NRfRq, -NHC(=O)NRfRq, -OC(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), cyano or -SO2R6 (where R6 is same as defined earlier). "Cycloalkylalkyl" refers to alkyl-cycloalkyl group linked through alkyl portion, wherein the alkyl and cycloalkyl are the same as defined earlier.
The term "aryl," unless otherwise specified, refers to carbocyclic aromatic groups, for example, phenyl, biphenyl or napthyl ring and the like, optionally substituted with 1 to 3 substituents selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, acyl, aryloxy, CF3, cyano, nitro, COORe (wherein R6 is hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, heterocyclylalkyl, heteroarylalkyl), NHC(=O)Rf, -NRfRq, -C(=O)NRfRq, -NHC(=0)NRfRq, -O-C(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), -SO2R6 (wherein R6 is same as defined earlier), carboxy, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl or amino carbonyl amino. The aryl group optionally may be fused with a cycloalkyl group, wherein the cycloalkyl group may optionally contain heteroatoms selected from O, N or S.
The term "heteroaryl," unless otherwise specified, refers to an aromatic ring structure containing 5 or 6 ring atoms, or a bicyclic aromatic group having from 8 to 10 ring atoms, with one or more heteroatom(s) independently selected from N, 0 or S optionally substituted with 1 to 4 substituent(s) selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, carboxy, aryl, alkoxy, aralkyl, cyano, nitro, heterocyclyl, heteroaryl, -NRfRq, CH=NOH, -(CH2)wC(=O)Rg (wherein w is an integer from 0-4 and Rg is hydrogen, hydroxy, ORf, NRfRq, -NHORZ or -NHOH}, -C(=O)NRfRq and -NHC(=O)NRfRq , -SO2R6, -O-C(=O)NRfRq, -O-C(=O)Rf, -O-C(=O)ORf (wherein Re, Rf and Rq are as defined earlier, and Rz is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, heteroarylalkyl or heterocyclylalkyl). Unless
otherwise constrained by the definition, the substituents are attached to a ring atom, i.e., carbon or heteroatom in the ring. Examples of heteroaryl groups include oxazolyl, imidazolyl, pyrrolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, thiazolyl, oxadiazolyl, benzoimidazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, isoxazolyl, triazinyl, furanyl, benzofuranyl, indolyl, benzothiazolyl, or benzoxazolyl, and the like.
The term 'heterocyclyl," unless otherwise specified, refers to a non-aromatic monocyclic or bicyclic cycloalkyl group having 5 to 10 atoms wherein 1 to 4 carbon atoms in a ring are replaced by heteroatoms selected from O, S or N, and optionally are benzofused or fused heteroaryl having 5-6 ring members and/or optionally are substituted, wherein the substituents are selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, aryl, alkoxy, alkaryl, cyano, nitro, oxo, carboxy, heterocyclyl, heteroaryl, -O-C(=O)Rf, -O-C(=O)ORf, -C(=O)NRfRq, SO2R6, -O-C(=0)NRfRq, -NHC(=O)NRfRq, -NRfRq (wherein Re, Rf and Rq are as defined earlier) or guanidine. Heterocyclyl can optionally include rings having one or more double bonds. Unless otherwise constrained by the definition, the substituents are attached to the ring atom, i.e., carbon or heteroatom in the ring. Also, unless otherwise constrained by the definition, the heterocyclyl ring optionally may contain one or more olefinic bond(s). Examples of heterocyclyl groups include oxazolidinyl, tetrahydrofuranyl, dihydrofuranyl, dihydropyridinyl, dihydroisoxazolyl, dihydrobenzofuryl, azabicyclohexyl, dihydroindolyl, pyridinyl, isoindole 1,3-dione, piperidinyl or piperazinyl.
The groups "aryl, heteroaryl and heterocyclyl11 can optionally be substituted with substituent(s) selected from alkyl, haloalkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heteroarylalkyl, heterocycloalkyl, halogen, hydroxy, alkoxy, cyano, nitro, aryloxy, haloalkoxy, CORb, CSRb, COORb, S(O)aRb, OCOORb, NHSO2Rb, NHCORb, NHCSRb, (CH)o.2C(=O)NRcRd or NRcRd (wherein Rb, RC and Rd are independently selected from hydrogen, alkyl, aryl, heteroaryl, heterocyclyl and a is an integer of from 0-2. Unless otherwise constrained, all substituents may optionally be further substituted by substituent(s) defined earlier.
The term "pharmaceutically acceptable solvates" refers to solvates with either water (e.g., 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. 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. As used herein the term "prodrugs" refers to the compounds that are rapidly transformed in vivo to yield the parent compound of Formula I, for example by hydrolysis in blood.
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 forms for compounds described herein and as such are 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 term "pharmaceutically acceptable salts" can further refer to salts prepared from pharmaceutically acceptable non-toxic inorganic or organic acids. Examples of such inorganic acids include, but are not limited to, hydrochloric, hydrobromic, hydroiodic, nitrous, nitric, carbonic, sulfuric, phosphoric acid, and the like. Appropriate organic acids include, but are not limited to aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of organic acids, for example, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic, methanesulfonic, ethanesulfonic, benzenesulfonic, panthenic, toluenesulfonic, 2-hydroxyethanesulfonic acid and the like.
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 included within the scope of this invention.
The term "subject" as used herein refers to human or lower mammal.
The term "treatment", as used herein, unless otherwise indicated, includes the treatment or prevention of a bacterial or fungal infection as provided in the method of the present invention
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 disclosed 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 Schemes I, la-Id, II, Ha, lib, III, IV, V, VI, VII, VIII and IX.
Scheme I
(Scheme Removed)
The sulfonamide of Formula 5 can be prepared according to Scheme I. Thus, reacting a compound of Formula 2 with a compound of Formula 3 gives a compound of Formula 4, which on oxidation gives sulfonamide of Formula 5 (wherein X1-X4 and R6 are the same as defined earlier).
The reaction of a compound of Formula 2 with a compound of Formula 3 to give a compound of Formula 4 can be carried out in one or more organic bases, for example, pyridine, triethylamine, trimethylamine, tributylamine, or 4-N-dimethylaminopyridine. The oxidation of a compound of Formula 4 to give a compound of Formula 5 can be carried out in the presence of one or more oxidizing agents, for example, Dess-Martin periodinane, 2-iodoxybenzoic acid, N-chloro succinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and
dimethylsulfoxide), Jones Oxidation reagent (chromic acid, aqueous sulfuric acid and acetone), pyridinium dichromate, l-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride or in mixtures thereof, in one or more solvents, for example, chlorinated solvents (chloroform, dichloromemane, carbon tetrachloride or dichloroethane), polar aprotic solvents (dimethylsulfoxide, dimethylformamide, acetone, tetrahydrofuran, acetonitrile) or in mixturex thereof. N-Chlorosuccinamide can be used in combination with dimethyl sulphide and 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride can be used in combination with dimethylsulfoxide.
The compound of Formula 8 can be prepared according to Scheme la. Thus, reacting a compound of
(a) Formula 6 (when R6 is 4-fluorophenyl) with a compound of Formula RgH gives a
compound of Formula 7, which on oxidation gives a compound of Formula 8
(wherein Rg is optionally substituted aryl, heteroaryl or heterocyclyl).
(b) Formula 6 (when R6 is 4-nitrophenyl) with a reducing agent gives the
corresponding amine, which on reaction with a compound of Formula 2,5-
dimethoxytetrahydrofuran or 2,5-dimethoxy-3-formyltetrahydrofuran gives a
compound of Formula 7, which is finally oxidized to give a compound of
Formula 8 (wherein R8 is 5-membered nitrogen containing heteroaryl).
The reaction of a compound of Formula 6 (wherein R6 is 4-fluorophenyl) with a compound of Formula R8H can be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium acetate or cesium carbonate, in one or more polar aprotic solvents, for example, N-methyl-2-pyrrolidinone, dimethlyformamide or dimethylsulfoxide. The reduction of a compound of Formula 6 (when R6 is 4-nitrophenyl) to give an amine compound can be carried out in the presence of one or more reducing agents, for example, Raney Nickel in hydrazine hydrate, zinc, tin or iron in the presence of hydrochloric acid or lithium aluminium hydride. The amine compound thus formed can be converted to a compound of Formula 7 by reaction with 2,5-dimethoxytetrahydrofuran in one or more polar protic solvents, for example, water, methanol, ethanol or acetic acid. The oxidation of a compound of Formula 7 to give a compound of Formula 8 can be carried out using the procedures described in Scheme I.
Scheme Ib
(Scheme Removed)
The compound of Formula 10 can be prepared according to Scheme Ib. Thus, reacting a compound of Formula 9 with a compound of Formula R8B(OH)2 gives a compound of Formula 9a, which on oxidation gives a compound of Formula 10 (wherein R8 is optionally substituted aryl, heteroaryl or heterocyclyl and X1-X4 are the same as defined earlier).
The reaction of a compound of Formula 9 with a compound of Formula R8B(OH)2 to give a compound of Formula 9a can be carried out in one or more polar protic solvents, for example, methanol, ethanol, propanol, isopropanol, t-butanol or water. The reaction of a compound of Formula 9 to give a compound of Formula 9a can be carried out in the presence of copper (I) iodide, palladium catalyst, for example, palladium (II) acetate, palladium (II) trifluoroacetate, palladium (II) propionate, tetra kis(triphenylphosphine) palladium (0), tris(dibenzylidineacetone) palladium (0) or bis(triphenylphosphine) palladium (II) chloride in one or more inorganic bases, for example, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium acetate or cesium carbonate. The oxidation of a compound of Formula 9a to give a compound of Formula 10 can be carried out using the procedures described in Scheme I.
Scheme Ic
(Scheme Removed)
The compound of Formula 14 can be prepared according to Scheme Ic. Thus, reacting a compound of Formula 11 with a compound of Formula R6COOH to give a compound of Formula 12 (wherein R9 is a protecting group, for example, tert-butyldimethylsilyl, trimethylsilyl, 4-benzyloxybutyryl, l,4-diazabicyclo[2.2.1]octane or tert-butyldiphenylsilyl), which on deprotection gives a compound of Formula 13, which is finally oxidized to give a compound of Formula 14 (wherein X1-X4 and R6 are the same as defined earlier).
The reaction of a compound of Formula 11 with a compound of Formula R6COOH to give a compound of Formula 12 can be carried out in the presence of one or coupling agents, for example, 1-hydroxybenzotriazole, l-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimodazole or N,N'-carbonyldiimidazole in one or more aprotic solvents, for example, N-methyl-2-pyrrolidinone, dimethylformamide or dimethylformamide. The deprotection of a compound of Formula 12 to give a compound of Formula 13 can be carried out in the presence of tetra-n-butylammonium fluoride in one or more solvents, for example, ethers (tetrahydrofuran, dioxane or ether) or aprotic solvents (dimethylsulfoxide, dimethylformamide or acetone). The oxidation of a compound of Formula 13 to give a compound of Formula 14 can be carried out using the procedures described in Scheme I.
Scheme Id
(Scheme Removed)
The compound of Formula 18 can be prepared according to Scheme Id. Thus, reacting a compound of Formula 11 with imidazole gives a compound of Formula 15, which on treatment with a compound of Formula R6CH2OH gives a compound of Formula 16 (wherein R9 is a protecting group, for example, tert-butyldimethylsilyl, trimethylsilyl, 4-benzyloxybutyryl, 1,4-diazabicyclo[2.2.1]octane or tert-butyldiphenylsilyl), which on deprotection gives a compound of Formula 17, which is finally oxidized to give a compound of Formula 18.
The reaction of a compound of Formula 11 with imidazole to give a compound of Formula 15 can be carried out in the presence of one or more coupling agents, for example, N,N-carbonyldiimidazole, N,N-dicyclohexylcarbodiimide or l-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride in one or more solvents, for example, chlorinated solvent (chloroform, dichloromethane, dichloroethane or tetrachloromethane), polar aprotic solvents (dimethylformamide, dimethylformamide or acetone) or in mixtures thereof. The reaction of a compound of Formula 15 with a compound of Formula R6CH2OH to give a compound of Formula 16 can be carried out in one or more solvents, for example, chlorinated solvent
(dichloromethane, dichloroethane, chloroform or tetrachloromethane), aprotic solvents
(dimethylformamide or dimethylformamide) or in mixtures thereof. The deprotection of a
compound of Formula 16 to give a compound of Formula 17 can be carried out in the presence
of tetra-n-butylammonium fluoride in one or more solvents, for example, ethers
(tetrahydrofuran, dioxane or ether), polar aprotic solvents (dimethylsulfoxide,
dimethylformamide or acetone) or in mixtures thereof. The oxidation of a compound of
Formula 17 to give a compound of Formula 18 can be carried out using the procedures described
in Scheme I. SchemeII
(Scheme Removed)
The compound of Formula 24 can be prepared according to Scheme II. Thus, reacting a compound of Formula 19 with a compound of Formula 20 gives a compound of Formula 21, which on treatment with tosyl chloride gives a compound of Formula 22, which on reaction with a compound of Formula Cy-Ha gives a compound of Formula 23 (wherein Ha is halogen), which is finally deprotected to give a compound of Formula 24 (wherein Cy is the same as defined earlier).
The reaction of a compound of Formula 19 with a compound of Formula 20 to give a compound of Formula 21 can be carried out in one or more solvents, for example, chlorinated solvent (chloroform, dichloromethane, carbon tetrachloride or dichloroethane), polar aprotic solvent (dimethylsulfoxide or dimethylformamide) or in mixtures thereof. The reaction of a compound of Formula 21 with tosyl chloride to give a compound of Formula 22 can be carried out in one or more solvents, for example, ethers (ether, dioxane, or tetrahydrofuran), chlorinated solvent (dichloromethane, dichloroethane or chloroform) or in mixtures thereof. The reaction of a compound of Formula 21 with tosyl chloride can be carried out in alkali or alkaline metal hydroxide, for example, potassium hydroxide, sodium hydroxide, calcium hydroxide or in mixtures thereof. The reaction of a compound of Formula 22 with a compound of Formula Cy-Ha to give a compound of Formula 23 can be carried out in the presence of magnesium (in dry ether) in one or more solvents, for example, ethers (ether, dioxane or tetrahydrofuran), chlorinated solvent (dichloromethane or chloroform) or mixture thereof. The deprotection of a compound of Formula 23 to give a compound of Formula 24 can be carried out in the presence
of one or more mineral acids, for example, hydrochloric, hydrobromic or hydroiodic acid in one
or more solvents, for example, a polar protic solvent (water, methanol, ethanol, propanol, isopropanol or tert-butanol).
Scheme Ila
(Scheme Removed)
The compound of Formula 26 (Formula 24, wherein Cy is cyclohexyl) can also be prepared according to Scheme Ila. Thus, a compound of Formula 25 can be reduced to give a compound of Formula 26.
The reduction of a compound of Formula 25 to give a compound of Formula 26 can be carried out in one or more reducing agents, for example, platinum oxide in the presence of one or more organic acids, for example, acetic or trifluoroacetic acid.
Scheme lib
(Scheme Removed)
The compound of Formula 31 (Formula 24, wherein Cy is piperidine) can also be prepared according to Scheme IIb. Thus reacting a compound of Formula 27 with nitroethane gives a compound of Formula 28, which on dehydration gives a compound of Formula 29, which on hydrogenation gives a compound of Formula 30, which on reduction gives a compound of Formula 31, which is finally protected to give a compound of Formula 32.
The reaction of a compound of Formula 27 with nitroethane to give a compound of Formula 28 can be carried out in the presence of one or more inorganic base, for example, sodium hydroxide, potassium hydroxide, cesium hydroxide, calcium hydroxide or sodium hydrogen carbonate. The dehydration of a compound of Formula 28 to give a compound of Formula 29 can be carried out in the presence of acetic anhydride and sodium acetate. The hydrogenation of a compound of Formula 29 to give a compound of Formula 30 can be carried out in the presence of a hydrogenating agent, for example, sodium, Platinum/hydrogen or palladium-carbon/hydrogen in one or more protic polar solvents, for example, methanol,
ethanol, isopropanol or water. The protection of a compound of Formula 31 to give a compound
of Formula 32 can be carried out in the presence of an N-protecting agent, for example, di-tert-Butyl dicarbonate in one or more polar aprotic solvents, for example, methyl isobutyl ketone, acetone, dimethylformamide or dimethylsulfoxide and in the presence of one or more inorganic bases, for example, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, cesium carbonate or calcium carbonate.
Scheme III (Scheme Removed)
The compound of Formula 32 can be prepared according to Scheme III. Thus, reacting a compound of Formula 5 with a compound of Formula 24 gives a compound of Formula 33 (wherein Cy, X1-X4 and R6, are the same as defined earlier).
The reaction of a compound of Formula 5 with a compound of Formula 24 to give a compound of Formula 32 can be carried out in the presence of one or more reducing agents, for example, sodium cyanoborohydride, sodium borohydride or sodium triacetoxyborohydride in one or more polar protic solvents, for example, methanol, ethanol, propanol, isopropanol or water.
Scheme IV
(Scheme Removed)
The compound of Formula 33 can be prepared according to Scheme IV using the procedures described in Scheme III.
Scheme V
(Scheme Removed)
The compound of Formula 34 can be prepared according to Scheme V using the procedure described in Scheme III.
Scheme VI
(Scheme Removed)
The compound of Formula 39 can be prepared according to Scheme VI. Thus, protecting a compound of Formula 35 with a protecting agent R9Hal (wherein Hal is halogen) gives a compound of Formula 36 (wherein R9 is tert-butyldimethylsilyl, trimethylsilyl, di-tert-Butyl dicarbonate, 4-benzyloxybutyryl, l,4-diazabicyclo[2.2.1]octane or tert-butyldiphenylsilyl), which on reduction gives a compound of Formula 37, which on reaction with a compound of Formula R6NCO gives a compound of Formula 38, which on deprotection gives a compound of Formula 39.
The protection of a compound of Formula 35 to give a compound of Formula 36 can be carried out in the presence of one or more organic bases, for example, triethylamine, trimethylamine, pyridine or tert-butylamine in one or more chlorinated solvents, for example, dichloromethane, dichloroethane, chloroform or tetrachloromethane. The reduction of a compound of Formula 36 to give a compound of Formula 37 can be carried out in the presence of a reducing agent, for example, Raney Nickel in hydrazine hydrate, zinc, tin or iron in the presence of hydrochloric acid or lithium aluminium hydride. The reaction of a compound of Formula 37 with a compound of Formula R6NCO to give a compound of Formula 38 can be carried out in one or more chlorinated solvents, for example, dichloromethane dichloroethane, chloroform or tetrachloromethane. The deprotection of a compound of Formula 38 to give a compound of Formula 39 can be carried out in the presence of one or more mineral acids, for example, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, methanol, ethanol, propanol or isopropanol.
Scheme VII
(Scheme Removed)
The compound of Formula 41 can be prepared according to Scheme VII. Thus, reacting a compound of Formula 37 with thiophene-2-sulphonylchloride gives a compound of Formula 40, which on deprotection gives a compound of Formula 41 (wherein Cy and X1-X4 are the same as defined earlier).
The reaction of a compound of Formula 37 with a thiophene-2-sulphonylchloride to give a compound of Formula 40 can be carried out in the presence of one or more organic bases, for example, pyridine, triethylamine or trimethylamine. The deprotection of a compound of Formula 40 to give a compound of Formula 41 can be carried out in the presence of one or more mineral acids, for example, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, methanol, propanol or isopropanol.
(Scheme Removed)
The compounds of Formula 44 and 46 can be prepared according to Scheme VIII. Thus, deprotecting a compound of Formula 35 with thiophenol or thioglycolic acid in the presence of a base, for example, potassium carbonate, sodium carbonate or cesium carbonate gives a compound of Formula 42, which on
(1) reaction with a compound of Formula 42a gives a compound of Formula 43,
which on deprotection gives a compound of Formula 44, or on
(2) reaction with a compound of Formula R6NCO gives a compound of Formula 45,
which on deprotection gives a compound of Formula 46.
The deprotection of a compound of Formula 35 to give a compound of Formula 42 can be carried out in the presence of one or more inorganic bases, for example, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate or calcium carbonate in one or more solvents, for example, acetonitrile, ethyl acetate, polar aprotic solvents (acetone, dimethylsulfoxide or dimethylformamide) or in mixtures thereof. The reaction of a compound of Formula 42 with a compound of Formula 42a to give a compound of Formula 43 can be carried out in the presence of one or more organic bases, for example, pyridine, triethylamine or trimethylamine. The reaction of a compound of Formula 42 with a compound of Formula R6NCO to give a compound of Formula 45 can be carried out in one or more chlorinated solvents, for example, dichloromethane, dichloroethane, chloroform or tetrachloromethane.
The deprotection of compounds of Formula 43 and 45 to give compounds of Formula 44 and 46, respectively, can be carried out in the presence of one or more mineral acids, for example, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, methanol, ethanol, propanol, isopropanol or butanol.
Scheme IX
(Scheme Removed)
The compound of Formula 51 can be prepared according to Scheme IX. Thus, reacting a compound of Formula 47 with a compound of Formula 24 gives a compound of Formula 48, which on protection gives a compound of Formula 49, which on reaction with a compound of Formula R6NCO gives a compound of Formula 50, which is finally deprotected to give a compound of Formula 51.
The reaction of a compound of Formula 47 with a compound of Formula 24 to give a compound of Formula 48 can be carried out in the presence of one or more reducing agents, for example, sodium cyanoborohydride or sodium borohydride, one or more organic acids, for example, acetic or trifluoroacetic acid in one or more polar protic solvents, for example, methanol, ethanol, propanol, isopropanol or butanol. The protection of a compound of Formula 48 with a protecting agent, for example, di-tert-Butyl dicarbonate can be carried out in one or
more chlorinated solvents, for example, dichloromethane, dichloroethane, chloroform or tetrachloromethane. The reaction of a compound of Formula 49 with a compound of Formula R6NCO to give a compound of Formula 50 can be carried out in the presence of one or more organic bases, for example, triethylamine, trimethylamine or pyridine in one or more chlorinated solvents, for example, dichloromethane, dichloroethane or chloroform. The deprotection of a compound of Formula 50 to give a compound of Formula 51 can be carried out in the presence of one or more mineral acids, for example, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, methanol, ethanol, propanol or isopropanol.
In the above schemes, where the specific bases, oxidizing agents, reducing agents, coupling agents, solvents, etc., are mentioned, it is to be understood that other bases, oxidizing agents, reducing agents, coupling agents, solvents, 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.
The compounds disclosed herein possess antimicrobial activity against gram-positive, gram-negative, anaerobic bacteria and fungal infections. They are useful as antimicrobial agents for the treatment of infections diseases in human and animal.
Compounds of the present invention useful for such purpose are listed below:
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2,3,4,5,6-pentafluorobenzenesulfonamide (Compound No. 1);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-methoxyphenyl)thiophene-2-sulfonamide (Compound No. 2);
5-( 1 -benzothien-2-yl)-N- [2-( {[(1S)2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] thiophene-2-sulfonamide (Compound No. 3);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-(3,4-dimethoxyphenyl)thiophene-2-sulfonamide (Compound No. 4);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide (Compound No. 5);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl) thiophene-2-sulfonamide (Compound No. 6);
N-[2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5 -(2,5 -dimethoxyphenyl) thiophene-2-sulfonamide (Compound No. 7);
5-(3-acetylphenyl)-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide (Compound No. 8);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(l-hydroxyethyl) phenyl]thiophene-2-sulfonamide (Compound No. 9);
5-(3-acetylphenyl)-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide (Compound No. 10);
N-[2-( {[(1S)-2-cyclohexyl-1 -methyl ethyl]amino} methyl)phenyl]-5-(2,5-dimethoxyphenyl) thiophene-2-sulfonamide (Compound No. 11);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide (Compound No. 12);
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide (Compound No. 13);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(3,4-dimethoxyphenyl) thiophene-2-sulfonamide (Compound No. 14);
6-chloro-N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] imidazo[2,1 -b][l,3]thiazole-5-sulfonamide (Compound No. 15);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (Compound No. 16);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thiophene-2-sulfonamide (Compound No. 17);
N~ [2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methy l)pheny 1] - 5- [ 5-(trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfonamide (Compound No. 18);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methy l)phenyl] -5- [ 1 -methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide (Compound No. 19);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(trifluoromethoxy) phenyl]thiophene-2-sulfonamide (Compound No. 20);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl) isoxazol-3-yl]thiophene-2-sulfonamide (Compound No. 21);
N-[2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -5- [5-(trifluoromethy 1) isoxazol-3-yl]thiophene-2-sulfonamide (Compound No. 22);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide (Compound No. 23);
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5- [ 1 -methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide (Compound No. 24);
N-[2-({[(lS)'2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thiophene-2-sulfonamide (Compound No. 25);
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-[4-(trifluoromethoxy) phenyl]thiophene-2-sulfonamide (Compound No. 26);
5 -chloro-N- [2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -3-methyl-1 -benzo thiophene-2-sulfonamide (Compound No. 27);
methyl 5-({[2-({[(1 S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)-4-methylthiophene-2-carboxylate (Compound No. 28);
methyl 4-({[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2,5-dimethyl-3-furoate (Compound No. 29);
5-chloro-N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1,3 -dimethyl-1H-pyrazole-4-sulfonamide (Compound No. 30);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2,2'-bithiophene-5 -sulfonamide (Compound No. 31);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-furyl)thiophene-2-sulfonamide (Compound No. 32);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -5-phenylthiophene-2-sulfonamide (Compound No. 33);
N- [2-( {[(1R)-2-cyclohexyl-1 -(hydroxymethyl)ethyl] amino} methyl)phenyl]thiophene-2-sulfonamide (Compound No. 34);
methyl 5-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-4-methylthiophene-2-carboxylate (Compound No. 35);
5-chloro-N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -3-methyl-1 -benzothiophene-2-sulfonamide (Compound No. 36);
5-chloro-N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -1,3 -dimethyl-1H-pyrazole-4-sulfonamide (Compound No. 37);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2,2'-bithiophene-5-sulfonamide (Compound No. 38);
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5-(3-furyl)thiophene-2-sulfonamide (Compound No. 39);
N-[2-({[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5 -(3 -furyl)thiophene-2-sulfonamide (Compound No. 40);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5-phenylthiophene-2-sulfonamide (Compound No. 41);
5 -bromo-N- [2-( {[(1S)2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]thiophene-2-sulfonamide (Compound No. 42);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]thiophene-2-sulfonamide (Compound No. 43);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]thiophene-2-sulfonamide (Compound No. 44);
N-[2-({[(\ S)-2-cyclohexy 1-1 -methy lethyl] amino} methy l)phenyl] isonicotinamide (Compound No. 45);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]nicotinamide (Compound No. 46);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2,2'-bithiophene-5-sulfonamide (Compound No. 47);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -3,5-bis(trifluoromethyl) benzenesulfonamide (Compound No. 48);
2-({[(lS)-2-cyclohexyl-l -methylethyl] amino }methyl)phenyl [(2-methylphenyl)sulfonyl] carbamate hydrochloride salt (Compound No. 49);
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -6-phenoxypyridine-3-sulfonamide (Compound No. 50);
5-bromo-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-furamide (Compound No. 51);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2-furamide (Compound No. 52);
N~[2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methy l)phenyl] -1 -benzothiophene-3-sulfonamide (Compound No. 53);
N~ [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl]thiophene-2-carboxamide (Compound No. 54);
N-[2-({[(1S)-2-cycloheptyl-l -methylethyl] amino }methyl)phenyl]thiophene-2-carboxamide hydrochloride salt (Compound No. 55);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-ruramide hydrochloride salt (Compound No. 56);
5-bromo-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl] amino} methy l)phenyl]-2-furamide hydrochloride salt (Compound No. 57);
5-(3-acetylphenyl)-N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide (Compound No. 58);
5-( 1,3 -benzodioxol-5 -yl)-N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] thiophene-2-sulfonamide (Compound No. 59);
N-[2-({ [(1 S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-3,3'-bithiophene-5-sulfonamide (Compound No. 60);
N-[2-({[(\ S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5-(3 -methoxyphenyl) thiophene-2-sulfonamide (Compound No. 61);
methyl 3-({[2-({[(1 S)-2-cyclohexyl-1 -methyl ethyl]amino}methyl)phenyl]amino} sulfonyl)-4-(isopropylsulfonyl)thiophene-2-carboxylate (Compound No. 62);
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-(3 -fluorophenyl) thiophene-2-sulfonamide (Compound No. 63);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(hydroxymethyl) phenyl]thiophene-2-sulfonamide (Compound No. 64);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(hydroxymethyl) phenyl]thiophene-2-sulfonamide (Compound No. 65);
methyl 5 -({[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-4-methylthiophene-2-carboxylate (Compound No. 66);
methyl 4-( {[2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-2,5 -dimethyl-3-furoate (Compound No. 67);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (Compound No. 68);
N-[2-({[(1S)-2-cyclopentyl-l -methylethyl] amino }methyl)phenyl]- 5 -(3 -fluorophenyl) thiophene-2-sulfonamide (Compound No. 69);
N-[2-({ [(1S)-2-cycloheptyl-l -methylethyl]amino}methyl)phenyl]-5-(3-fluorophenyl) thiophene-2-sulfonamide (Compound No. 70);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide (Compound No. 71);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-methylthiophene-2-carboxamide (Compound No. 72);
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -5-methylthiophene-2-carboxamide (Compound No. 73);
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]nicotinamide (Compound No. 74);
N-[2-({[(1S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]nicotinamide (Compound No. 75);
N-[3-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)pyridin-2-yl]thiophene-2-sulfonamide (Compound No. 76);
N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]thiophene-2-sulfonamide (Compound No. 77);
N- [3-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)pyridin-2-yl] -4-fluorobenzene sulfonamide (Compound No. 78);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 79);
N-[2-({[(\ S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 80);
methyl 5-({[2-({[(1 S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)-1 -methyl-1H-pyrrole-2-carboxylate (Compound No. 81);
methyl 5 -({[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-1 -methyl-1H-pyrrole-2-carboxylate (Compound No. 82);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide (Compound No. 83);
N-[2-({[(1S)-2-cyclohepty 1-1 -methylethyl] amino} methyl)pheny 1] -1 -methyl-1H-imidazole-4-sulfonamide (Compound No. 84);
5 -bromo-N- [2-( {[(1 S)-2-cyclohepty 1-1 -methylethyl] amino} methy l)phenyl] -2-furamide (Compound No. 85);
N-[2-({[(\ S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -3,5 -bis(trifluoromethyl) benzenesulfonamide (Compound No. 86);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide (Compound No. 87);
N-[2-({[(1S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]isonicotinamide (Compound No. 88);
5 -chloro-N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -1,3 -dimethyl-1H-pyrazole-4-sulfonamide (Compound No. 89);
(1 -benzothien-2-yl)-N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] thiophene-2-sulfonamide (Compound No. 90);
5-( 1 -benzothien-2-yl)-N- [2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] thiophene-2-sulfonamide (Compound No. 91);
N- [2-( {[(1 S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -5-(3,4-dimethoxyphenyl) thiophene-2-sulfonamide (Compound No. 92);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(4-methoxyphenyl) thiophene-2-sulfonamide (Compound No. 93):,
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] isonicotinamide (Compound No. Ill);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide (Compound No. 112);
methyl 3-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl) thiophene-2-carboxylate (Compound No. 113);
methyl 3-({[2-({[(1 S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]amino}sulfonyl) thiophene-2-carboxylate (Compound No. 114);
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -4-(1H-imidazol-1 -yl) benzenesulfonamide (Compound No. 115);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -2-(2-thienylsulfonyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 116);
N-[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-6-phenoxypyridine-3-sulfonamide (Compound No. 117);
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -6-phenoxypyridine-3 -sulfonamide (Compound No. 118);
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-pyrrol-1 -yl) benzenesulfonamide (Compound No. 119);
N- [2-( {[(1 S)-2-cyclopenty 1-1 -methylethyl] amino} methy l)pheny 1] -4-(1H-pyrrol-1 -y 1) benzenesulfonamide (Compound No. 120);
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -4-(1H-1,2,4-triazol-1 -yl) benzenesulfonamide (Compound No. 121);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide (Compound No. 122);
N- [2-( {[(1tS)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -1H-imidazole-4-sulfonamide (Compound No. 123);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide (Compound No. 124);
N-[2-({ [(1S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide (Compound No. 125);
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -5 - {3-[( 1 E)-N-hydroxy ethanimidoyl]phenyl}thiophene-2-sulfonamide (Compound No. 126);
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5- {3 -[(1E)-N-methoxy ethanimidoyl]phenyl}thiophene-2-sulfonamide (Compound No. 127);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2-furamide (CompoundNo. 128);
2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl (4-methoxyphenyl)carbamate (Compound No. 129);
N- [2-( {[(1 5)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5 -(phenylsulfonyl) thiophene-2-sulfonamide (Compound No. 130);
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5-(phenylsulfonyl) thiophene-2-sulfonamide (Compound No. 131);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(phenylsulfonyl)thiophene-2-sulfonamide (Compound No. 132);
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl] [(2,2-dimethylpropanoyl)oxy] amino} methyl) phenyl] -2-(2-thienylsulfonyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 133);
N-[2-( {[(1S)2-cyclohexyl-1 -methylethyl] [(2,2-dimethylpropanoyl)oxy] amino} methyl) phenyl] -2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 134);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] [(2,2-dimethylpropanoyl)oxy] amino} methyl) phenyl] -l,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 135);
5 -(1,3-benzodioxol-5 -yl)-N- [2-( {[(1 S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] thiophene-2-sulfonamide (Compound No. 136);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-imidazol-1 -yl)benzenesulfonamide (Compound No. 137);
N- [2-( {[(1S)2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] -4-(1H-imidazol-1 -yl)benzenesulfonamide (Compound No. 138);
N-[2-({[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5-( 1,3 -oxazol-2-yl)thiophene-2-sulfonamide (Compound No. 139);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]thiophene-2-carboxamide (Compound No. 140);
N-(4-acetylphenyl)-N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl]urea (Compound No. 141);
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide (Compound No. 142);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-pyridin-4-ylthiophene-2-sulfonamide (Compound No. 143);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-pyridin-3-ylthiophene-2-sulfonamide (Compound No. 144);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -3,3 '-bithiophene-5 -sulfonamide (Compound No. 94);
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -3,3 '-bithiophene-5-sulfonamide (Compound No. 95);
N-[2-({ [(1S)-2-cyclopentyl-1 -methylethyl]amino}methyl)phenyl]-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 96);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 97);
5-(l,3-benzodioxol-5-yl)-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide (Compound No. 98);
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2-[4-(4-methoxyphenyl) piperazin-l-yl]acetamide (Compound No. 99);
5-chloro-N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] -3 -methyl-1 -benzothiophene-2-sulfonamide (Compound No. 100);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide (Compound No. 101);
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2-methyl-l,3-thiazol-4-yl)thiophene-2-sulfonamide (Compound No. 102);
N-[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(2-methyl-l,3-thiazol-4-yl)thiophene-2-sulfonamide (Compound No. 103);
ethyl 3-[5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate (Compound No. 104);
ethyl 3-[5-({[2-({[(1S)-2-cyclopentyl-1 -methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate (Compound No. 105);
ethyl 3-[5-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate (Compound No. 106);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide (Compound No. 107);
N- [2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2,4-dimethyl-1,3-thiazole-5 -sulfonamide (Compound No. 108);
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -2,4-dimethyl-1,3-thiazole-5-sulfonamide (Compound No. 109);
N-[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5 -methylthiophene-2-carboxamide (Compound No. 110);
2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl (4-acetylphenyl)carbamate (Compound No. 145);
N-[2-({ [(1S)2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]-4-(1H-1,2,4-triazol-1 -yl)benzenesulfonamide (Compound No. 146);
N-[2-( {[(1 S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl]-4-( 1H-1,2,4-triazol-1 -yl)benzenesulfonamide (Compound No. 147);
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide (Compound No. 148);
6-( {[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]amino} sulfonyl)-N-(4-methoxyphenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide (Compound No. 149);
6-( {[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-N-isopropyl-3,4-dihydroisoquinoline-2(1H)-carboxamide (Compound No. 150);
N- [2-( ([(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-(1H-imidazol-1 -ylcarbonyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 151);
N-[2-( {[(1S)-2-cyclohexyl-1 -methyl ethyl]amino} methyl)phenyl] -4-( {[(4-methoxyphenyl) amino]carbonyl}amino)benzenesulfonamide (Compound No. 152);
4-( {[(4-acetylphenyl)amino] carbonyl} amino)-N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino }methyl)phenyl]benzenesulfonamide (Compound No. 153);
N-[4-( {[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino }methyl)phenyl] amino} sulfonyl) phenyl]thiophene-2-sulfonamide (Compound No. 154);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1 -pyrimidin-2-yl-1H-imidazole-4-sulfonamide (Compound No. 155);
N~ [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1 -benzofuran-2-carboxamide (Compound No. 156);
N-[2-({ [(1S)-2-cyclopentyl-l -methylethyl] amino }methyl)phenyl]-1 -benzofuran-2-carboxamide (Compound No. 157);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl] amino }methyl)phenyl]-l-benzofuran-2-carboxamide (Compound No. 158);
N-{3-[5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2-thienyl]phenyl}acetamide (Compound No. 159);
N- {3- [5 -({[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-2-thienyl]phenyl}acetamide (Compound No. 160);
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-(2,3,4-trimethoxy phenyl)thiophene-2-sulfonamide (Compound No. 161);
N-[2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxy phenyl)thiophene-2-sulfonamide (Compound No. 162);
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide (Compound No. 163);
N- [2-( {[(1 5)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-fluorobenzamide (Compound No. 164);
4-amino-N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]benzamide (Compound No. 165);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-isopropylurea (Compound No. 166);
N~ [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -N-isopropylthiourea (Compound No. 167);
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-(4-methoxyphenyl)urea (Compound No. 168);
N-(4-acetylphenyl)-6-( {[2-( {[(1S)2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] amino}sulfonyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide (Compound No. 169);
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -1,2,3,4-tetrahydro isoquinoline-6-sulfonamide (Compound No. 170);
N-[2-({ [(1S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]-N-isopropylurea (Compound No. 171);
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] isoxazole-5-carboxamide (Compound No. 172);
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-isoxazol-5-ylthiophene-2-carboxamide (Compound No. 173);
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide (Compound No. 174);
tert-butyl 4-(2- {[2-(2-furoylamino)benzyl]amino}propyl)piperidine-1 -carboxylate (Compound No. 175);
N-[2-({[( 1 iS)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]-4-nitrobenzamide (Compound No. 176);
tert-butyl4-[2-({2-[(4-fluorobenzoyl)amino]benzyl}amino)propyl]piperidine-l-carboxylate (Compound No. 177);
tert-butyl4-[2-({2-[(2-thienylcarbonyl)amino]benzyl}amino)propyl]piperidine-l-carboxylate (Compound No. 178);
N-[2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1 -pyrazin-2-yl-1H-imidazole-4-sulfonamide (Compound No. 179);
N-[2-({[(15,2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]thiophene-2-sulfonamide (Compound No. 180);
N- [2-( {[(15',2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl] amino} methyl)phenyl] -1 -benzofuran-2-carboxamide (Compound No. 181);
tert-butyl4-{2-[(2-{[(5-isoxazol-5-yl-2-thienyl)carbonyl]amino}benzyl)amino]propyl} piperidine-1-carboxylate (Compound No. 182);
N-[2-({[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5-isoxazol-5-ylthiophene-2-sulfonamide (Compound No. 183);
N-(4-chlorophenyl)-N-(2- {[(2-cyclohexy 1-1 -methy lethy l)amino] methyl} pheny l)urea (Compound No. 184);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-phenylurea (Compound No. 185);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(3,4-dichlorophenyl)urea (Compound No. 186);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl)-N-(3,4,5 -trichlorophenyl)urea (Compound No. 187);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(2,4-dichlorophenyl)urea (Compound No. 188);
N-(2-{ [(2-cyclohexyl-1-methylethyl)amino] methyl }phenyl)-N-(4-fluorophenyl)urea (Compound No. 189);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-l-naphthylurea (Compound No. 190);
N-(2-{[(2-cyclohexyl-1-methylethyl)amino]methyl }phenyl)-N-isopropyl urea (Compound No. 191);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-isopropylthiourea (Compound No. 192);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl }phenyl)-N-1 -naphthylthiourea (Compound No. 193);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(trichloromethyl)thiourea (Compound No. 194);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl} phenyl)-4-phenylpiperazine-1 -carboxamide (Compound No. 195);
4-benzyl-N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)piperazine-l-carboxamide (Compound No. 196);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl }phenyl)piperazine-1 -carboxamide (Compound No. 197);
4-(4-chlorophenyl)-N-(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl }phenyl)piperazine-1 -carboxamide (Compound No. 198);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl)-4-methylpiperazine-1 -carboxamide (Compound No. 199);
N-(2- {[(2-cyclohexyl-1 -methy lethyl)amino] methyl }phenyl)morpholine-4-carboxamide (Compound No. 200);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl }phenyl)-4-pyrimidin-4-ylpiperazine-1 -carboxamide (Compound No. 201);
4-chloro-N- {[(2- {[(2-cyc lohexyl-1 -methylethyl)amino]methyl} pheny l)amino] carbony 1} benzenesulfonamide (Compound No. 202);
N- {[(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl)amino] carbonyl} -4-methyl benzenesulfonamide (Compound No. 203);
N- {[(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl} phenyl)amino] carbonyl} benzamide (Compound No. 204);
N- {[(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl)amino]carbonyl} benzene carbothioamide (Compound No. 205);
4-[(4-chlorophenyl)sulfonyl]-N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl) piperazine-1-carboxamide (Compound No. 206);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl} phenyl)-4-(phenylsulfonyl)piperazine-1 -carboxamide (Compound No. 207);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl)-4-[(4-methylphenyl)sulfonyl] piperazine-1-carboxamide (Compound No. 208);
N-(2- {[(2-cyclohexyl-1 -methyl ethyl)amino]methyl} phenyl)-4-(2-thienylsulfonyl)piperazine-1 -carboxamide (Compound No. 209);
N- {(1E)-amino [(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl} phenyl)amino]methylene} -4-chlorobenzenesulfonamide (Compound No. 210);
N-{(1E)-amino[(2- {[(2-cyclohexyl-1 -methylethy l)amino] methyl }phenyl)amino]methylene} -4-methylbenzenesulfonamide (Compound No. 211);
N-{(1E)-amino[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)amino]methylene} methanesulfonamide (Compound No. 212);
N- {(1E)-amino[(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl} phenyl)amino]methylene} thiophene-2-sulfonamide (Compound No. 213);
N-(2- {[(1 -methyl-2-piperazin-1 -ylethyl)amino] methyl }phenyl)benzenesulfonamide (Compound No. 214);
4-methyl-N-(2-{ [(1 -methyl-2-piperazin-1 -ylethyl)amino]methyl}phenyl)benzenesulfonamide (Compound No. 215);
4-chloro-N-(2-{[(l-methyl-2-piperazin-l-ylethyl)amino]methyl}phenyl)benzenesulfonamide (Compound No. 216);
N-(2- {[(1 -methyl-2-piperazin-1 -ylethyl)amino]methyl} phenyl)thiophene-2-sulfonamide (Compound No. 217);
5 -bromo-N-(2- {[(1 -methyl-2-piperazin-1 -ylethyl)amino] methyl} phenyl)thiophene-2-sulfonamide (Compound No. 218);
4-methyl-N- [2-( {[ 1 -methyl-2-(4-phenylpiperazin-1 -yl)ethyl]amino} methyl)phenyl] benzenesulfonamide (Compound No. 219);
N- [2-( {[ 1 -methyl-2-(4-phenylpiperazin-1 -yl)ethyl]amino} methyl)phenyl] benzenesulfonamide (Compound No. 220);
N-[2-( {[ 1 -methyl-2-(4-phenylpiperazin-1 -yl)ethyl]amino} methyl)phenyl]thiophene-2-sulfonamide (Compound No. 221);
5-bromo-N-[2-({[l-methyl-2-(4-phenylpiperazin-l-yl)ethyl]amino}methyl)phenyl]thiophene-2-sulfonamide (Compound No. 222);
4-methyl-N-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl]amino}methyl)phenyl] benzenesulfonamide (Compound No. 223);
4-chloro-N-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl]amino}methyl)phenyl] benzenesulfonamide (Compound No. 224);
N- [2-( {[ 1 -methyl-2-(4-methylpiperazin-1 -yl)ethyl]amino} methyl)phenyl]thiophene-2-sulfonamide (Compound No. 225);
N-(4-chlorophenyl)-N-[2-({ [ 1 -methyl-2-(4-methylpiperazin-1 -yl)ethyl]amino}methyl) phenyl]urea (Compound No. 226);
N-(4-chlorophenyl)-N- [2-( {[ 1 -methyl-2-(4-phenylpiperazin-1 -yl)ethyl] amino} methyl) phenyl]urea (Compound No. 227);
N- {2-[( {[(2-cyclohexyl-1 -methylethyl)amino] carbonyl} amino)methyl]phenyl} methanesulfonamide (Compound No. 228);
N- (2- [({[(2-cyclohexyl-1 -methylethyl)amino] carbonyl} amino)methyl]phenyl} benzenesulfonamide (Compound No. 229);
N- {2-[( {[(2-cyclohexyl-1 -methylethyl)amino] carbonyl} amino)methyl]phenyl} -4-methylbenzenesulfonamide (Compound No. 230);
N-{2-[({ [(2-cyclohexyl-1 -methylethyl)amino] carbonyl} amino)methyl]phenyl} thiophene-2-sulfonamide (Compound No. 231);
5-bromo-N-{2-[( {[(2-cyclohexyl-1-methylethyl)amino]carbonyl} amino)methyl]phenyl} thiophene-2-sulfonamide (Compound No. 232);
4-chloro-N-{2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino)methyl]phenyl} benzenesulfonamide (Compound No. 233);
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl} phenyl)-3 -methoxy-4-piperazin-1 -ylbenzenesulfonamide (Compound No. 234);
N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)-5-(phenylsulfonyl)thiophene-2-sulfonamide (Compound No. 235);
N-(2- {[(2-cyclohexyl- l-methylethyl)amino]methyl}phenyl)-l-benzo fur an-2-carboxamide (Compound No. 236);
N-(2-{[(2-cyclopentyl-l -methylethyl)amino]methyl}phenyl)-2-(l ,3-dioxo-l ,3-dihydro-2H-isoindol-2-yl)acetamide (Compound No. 237);
2- {[(2-cyclohexyl-1 -methylethyl)amino] methyl }phenyl (4-methoxyphenyl)carbamate (Compound No. 238);
N-(2- {[(2-cycloheptyl-1 -methylethyl)amino]methyl} phenyl)-6-(1H-imidazol-1 -yl) nicotinamide (Compound No. 239);
N-(4-{[(2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl)amino]sulfonyl} phenyl)thiophene-2-sulfonamide (Compound No. 240);
N-(2- {[(2-cyclopentyl-1 -methylethyl)amino]methyl}phenyl)-2-( 1H-1,2,4-triazol-1 -yl) acetamide (Compound No. 241);
N-(2- {[(2-cycloheptyl-1 -methylethyl)amino]methyl} phenyl)-2-(4-pyrimidin-2-ylpiperazin-1 -yl)acetamide (Compound No. 242);
2- {[(2-cyclopentyl-1 -methylethyl)amino] methyl }phenyl (4-acetylphenyl)carbamate (Compound No. 243);
N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)isonicotinamide (Compound No. 244);
N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)-4-fluorobenzenesulfonamide (Compound No. 245);
N-(2-{[(2-cyclohexyl-1 -methylethyl)amino]methyl}phenyl)-6-(3-furyl)nicotinamide (Compound No. 246);
N-(2- {[(2-cyclopentyl-1 -methylethyl)amino] methyl} phenyl)-4-( 1H-1,2,3 -triazol-1 -yl) benzenesulfonamide (Compound No. 247);
N-(3-{[(2-cycloheptyl-l-methylethyl)amino]methyl}pyridin-2-yl)-2-furamide (Compound No. 248);
N-(2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl)isonicotinamide (Compound No. 249);
N-(2- {[(2-cyclohex-1 -en-1 -yl-1 -methylethyl)amino] methyl} phenyl)-5 -(1,3 -oxazol-5 -yl) furan-2-sulfonamide (Compound No. 250);
N-(2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl)-N-(3-methylisoxazol-5-yl)urea (Compound No. 251);
2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl [4-(1H-imidazol-1 -yl) phenyl] carbamate (Compound No. 252);
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-5-(3-furyl)nicotinamide (Compound
No. 253);
l-benzofuran-2-ylmethyl (2-{[(2-cyclohexyl-l-methylethyl)amino] methyl }phenyl)carbamate (Compound No. 254);
N-[2-({[ 1 -methyl-2-(4-methylpiperazin-1 -yl)ethyl]amino}methyl)phenyl]thiophene-2-sulfonamide (Compound No. 255);
N-1-benzothien-2-yl-N-[2-({[l-methyl-2-(tetrahydro-2H-pyran-4-yl)ethyl]amino} methyl)phenyl]urea (Compound No. 256);
2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} phenyl [4-(1H-pyrazol-1 -yl)phenyl] carbamate
(Compound No. 257);
2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl [4-(2-furyl)phenyl]carbamate (Compound No. 258);
3,3'-bipyridin-6-yl (2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)carbamate (Compound No. 259);
Pyridin-4-yl(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)carbamate (Compound No. 260);
N-1-benzothien-2-yl-N'-(4-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-3-yl)urea (Compound No. 261);
N-1-benzothien-2-yl-N'-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-3-yl)urea (Compound No. 262);
3- {[(2-cyclohexyl- l-methylethyl)amino]methyl}pyridin-4-yl 1-benzothien-2-ylcarbamate
(Compound No. 263);
3-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-2-yl 1-benzothien-2-ylcarbamate (Compound No. 264);
N-1 -benzothien-2-yl-N-(3-{ [(2-cyclohexyl-1 -methylethyl)amino]methyl}pyridin-2-yl)urea (Compound No. 265);
N-1 -benzothien-2-yl-N-(3 - {[(2-cyclohexyl-1 -methylethyl)amino]methyl} pyridin-4-yl)urea (Compound No. 266);
2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-3-yl 1-benzothien-2-ylcarbamate (Compound No. 267);
4- {[(2-cyclohexyl-1 -methylethyl)amino]methyl} pyridin-3-yl 1 -benzothien-2-ylcarbamate (Compound No. 268);
l-benzothien-2-yl (3-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-2-yl)carbamate (Compound No. 269);
1 -benzothien-2-yl (4-{[(2-cyclohexyl-1 -methylethyl)amino]methyl}pyridin-3-yl)carbamate (Compound No. 270);
1 -benzothien-2-yl (2-{[(2-cyclohexyl-1 -methylethyl)amino]methyl}pyridin-3-yl)carbamate (Compound No. 271);
2-{[(2-cyclopropyl-1 -methylethyl)amino]methyl}phenyl [4-(2-furyl)phenyl] carbamate (Compound No. 272);
2- {[(2-cyclopropyl-1 -methylethyl)amino] methyl} phenyl 1 -benzothien-2-ylcarbamate (Compound No. 273);
1 -benzothien-2-yl [2-( {[ 1 -methyl-2-(tetrahydro-2H-pyran-4-yl)ethyl] amino} methyl) phenyl]carbamate (Compound No. 274);
1 -benzothien-2-yl (3-{[(2-cyclohexyl-1 -methylethyl)amino]methyl}pyridin-4-yl)carbamate (Compound No. 275);
1 -benzothien-2-yl (2- {[(2-cyclopropyl-1 -methylethyl)amino]methyl}phenyl)carbamate (Compound No. 276);
N-(2- {[(2-cyclopropyl-1 -methylethyl)amino]methyl}phenyl)-2-(l ,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide (Compound No. 277);
l-benzothien-2-yl [2-({[l-methyl-2-(tetrahydro-2H-pyran-4-yl)ethyl]amino}methyl)pyridin-3-yl]carbamate (Compound No. 278);
N-(2-{[(2-cyclopentyl-1 -methylethyl)amino]methyl}phenyl)-2-( 1H-1,2,4-triazol-1 -yl) acetamide (Compound No. 279);
1 -benzothien-2-yl (2-{[(1 -methyl-2-piperidin-4-ylethyl)amino]methyl}phenyl)carbamate (Compound No. 280);
3-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl}pyridin-4-yl 1 -benzothien-2-ylcarbamate (Compound No. 281);
N-1 -benzothien-2-yl-N-(2- {[(1 -methyl-2-piperidin-4-ylethyl)amino]methyl}phenyl)urea (Compound No. 282);
N-(2- {[(1 -methyl-2-piperidin-4-y lethy l)amino]methy 1} phenyl)thiophene-2- sulfonamide (Compound No. 283);
N-(2-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl}phenyl)-2-(lH-pyrazol-l-yl)acetamide (Compound No. 284);
N-(2-{[(1 -methyl-2-piperidin-4-ylethyl)amino]methyl}phenyl)isonicotinamide (Compound No. 285); or their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites or N-oxide.
Because of their antimicrobial activity, the compounds described herein may be administered to an animal for treatment orally, topically, rectally, internasally, or by a parenteral route. The pharmaceutical compositions of the present invention comprise a pharmaceutically effective amount of compounds described herein formulated together with one or more pharmaceutically acceptable carriers.
Solid form preparations for oral administration include capsules, tablets, pills, powders, granules, cachets and suppositories. For solid form preparations, the active compound can be mixed with at least one inert, pharmaceutically acceptable excipients or carrier, for example, sodium citrate, dicalcium phosphate and/or a filler or extenders, for example, starches, lactose, sucrose, glucose, mannitol and silicic acid; binders, for example, carboxymethylcellulose, alginates, gelatins, polyvinylpyrrolidinone, sucrose, or acacia; disintegrating agents, for example, agar-agar, calcium carbonate, potato starch, alginic acid, certain silicates and sodium carbonate; absorption acceletors, for example, quaternary ammonium compounds; wetting agents, for example, cetyl alcohol, or glycerol mono stearate; adsorbants, for example, Kaolin; lubricants , for example, talc, calcium stearate, magnesium stearate, solid polyethyleneglycol, sodium luaryl sulphate and mixture thereof. In the case of capsules, tablets, or pills, the dosage form may also comprise buffering agents.
The solid preparation of tablets, capsules, pills and granules can be prepared with coating and shells, for example, enteric coating and other coatings well known in the pharmaceutical formulating art.
Liquid form preparations for oral administration can include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. For liquid form preparations, the active compound can be mixed with water or other solvent, solubilizing agents and emulsifiers, for
example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol, dimethylformamide, oils, for example, cottonseed, groundnut, corn, germ, olive, castor and sesame oil), glycerol, and fatty acid esters of sorbitan and mixture thereof. Besides inert diluents, the oral composition can also include adjuvants, for example, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavouring agents and perfuming agents.
Injectible preparations, for example, sterile injections, aqueous suspensions 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 solution and isotonic sodium chloride.
Dosage forms for tropical or transdermal administration of compounds provided herein include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active compound can be admixed under sterile condition with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulations, eardrops, eye ointments, powder and solution are also contemplated as being within the scope of this invention.
The pharmaceutical preparation can be provided in a unit dosage form. In such forms, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be packaged preparation, the package containing discrete capsules, powders, in vials or ampoules, and ointments capsule, sachet, tablet, gel, cream itself or it can be the appropriate number of any of these packaged forms.
Examples set forth below demonstrate general synthetic procedures 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.
EXAMPLES
General Procedures Example 1: Preparation of a Compound of Formula 4
To a solution of a compound of Formula 2 (1.2 equiv.) in pyridine, a compound of Formula 3 (1 equiv.) was added portion wise at about 0-5 °C. The reaction mixture was allowed to come at an ambient temperature and stirred overnight. The solvent was evaporated under reduced pressure. Water was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with water, brine, and dried over anhydrous sodium sulfate. The
solvent was evaporated under reduced pressure and the residue was purified by column chromatography to yield the required product.
Example 2: Preparation of Compound of Formula 5
To a solution of compound of Formula 4 (1.0 equiv.) in dichloromethane (20-30 mL) was added Dess Martin Periodinane (1.5 equiv.). The reaction mixture was stirred overnight at an ambient temperature, filtered, and the mother liquor was washed with aqueous sodium bicarbonate solution. The organic layer was dried and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product.
Example 3: Preparation of a Compound of Formula 9a
To a solution of a compound of Formula 9 (10.0 equiv., prepared according to Scheme I) in propanol (15 mL) was added a compound of Formula RgB(OH)2 (12.0 equiv.). The reaction mixture was degassed with argon for about 15 minutes. Tetrakis(triphenyl-phosphine) palladium (0) (1.0 equiv.) was added to the reaction mixture. Sodium carbonate (10.0 equiv.) in water was added to the reaction mixture. The reaction mixture was heated to about 100 °C and stirred for about 5 hours in dark under an argon atmosphere. The reaction mixture was filtered, the residue was concentrated and the product was purified by column chromatography.
Example 4: Preparation of a Compound of Formula 10
The compound of Formula 10 was prepared using the procedure described for compound of Formula 5.
Example 5: Preparation of a Compound of Formula 12
A compound of Formula 11 (1.0 equiv.) and a compound of Formula R6COOH (1.2 equiv.) were taken in dry dimethylformamide (3-10 mL) and cooled to 0 °C. 1-hydroxybenzotriazole (1.2 equiv.) and N-Methylpyrrolidone (3.0 equiv.) were added and stirred for about 15 minutes. l-Ethyl-3-[3-(dimethylamino)propyl]carbodimide (1.5 equiv.) was added and the resulting mixture was stirred at an ambient temperature for about 12 hours. Quenched with water and extracted in dichloromethane. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed under reduced pressure and the residue was purified over silica gel column.
Example 6: Preparation of a Compound of Formula 13
Compound of Formula 12 (1.0 equiv.) was taken in dry tetrahydrofuran and Tetrabutylammonium fluoride (1.2 equiv.) was added. After stirring for about 1 hour at an ambient temperature, solvent was removed under reduced pressure and the residue was extracted in ethyl acetate. Organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column.
Example 7: Preparation of Compound of Formula 14
The compound of Formula 14 was prepared using the procedure described for compound of Formula 5.
Example 8: Preparation of Compound of Formula 16
Compound 11 (1.0 equiv.) was taken in dry dichloromethane (5-10 mL) and imidazole (1.5 equiv.) and N,N'-carbonyldiimidazole (1.5 equiv.) were added. Resulting mixture was stirred at room temperature for about 2 hours, quenched with water and extracted in dichloromethane. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. The solvent was removed and the residue was dissolved in dichloromethane (5-10 mL) and imidazole (1.5 equiv.) and a compound of Formula R2CH2OH (1.2 equiv.) were added. The resulting mixture was stirred at an ambient temperature for about 5 hours, quenched with water and extracted in dichloromethane. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed under pressure and the residue was purified over silica gel column.
Example 9: Preparation of Compound of Formula 17
Compound of Formula 16 (1.0 equiv.) was taken in dry tetrahydrofuran and Tetrabutylammonium Fluoride (1.2 equiv.) was added. After stirring for about 1 hour at an ambient temperature, solvent was removed under reduced pressure and the residue was extracted in ethyl acetate. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column.
Example 10: Preparation of Compound of Formula 18
The compound of Formula 18 was prepared using the procedure described for compound of Formula 5.
Example 11: Preparation of a Compound of Formula 21
To a solution of L-alaniol (1.0 equiv.) in dichloromethane was added di-tert-Butyl dicarbonate (1.1 equiv.) slowly at about 0-5 °C. The reaction mixture was stirred for about 3 hours at an ambient temperature. The reaction mixture was diluted with dichloromethane and washed with water, brine, dried over anhydrous sodium sulfate, and evaporated in vacua. The residue was purified by column chromatography to give the desired product.
Example 12: Preparation of a Compound of Formula 22
To a solution of compound of Formula 21 (1.0 equiv.) in ether (20-30 mL) was added tosyl chloride (1.3 equiv.). The reaction mixture was stirred for about 15 hours and cooled to 0 °C. Potassium hydroxide (about 1.25 equiv., powdered) was added and stirring was continued for about 15 minutes. Additional 1.25 equiv. of potassium hydroxide was added and again the reaction mixture was stirred for additional 15 minutes. The reaction mixture was refluxed at about 40-50 °C for about 3 hours. The reaction mixture was diluted with water and the compound was extracted with ethyl acetate. The organic layer was dried and evaporated under reduced pressure. The product was purified by column chromatography over silica gel to give the desired compound.
Example 13: Preparation of a Compound of Formula 23
In a two-necked round bottom flask Mg (50.3 equiv.) was suspended in ether (100-125 mL), cooled to 0 °C, added slowly a compound of Formula Cy-Ha (50.3 equiv.), and diluted with tetrahydrofuran (100-110 mL). A crystal of iodine was added to titrate the reaction. The reaction mixture was stirred for about 2 hours. The reaction mixture was cooled to about -40 C and added CuBr-Me2S complex (1.0 equiv.) to it. Compound of Formula 22 (10.0 equiv.) dissolved in tetrahydrofuran was added slowly to the reaction mixture. The reaction mixture was stirred for about 2 hours and quenched by adding saturated ammonium chloride solution. The reaction mixture was stirred overnight and was extracted with ethyl acetate. The organic layer was dried and evaporated under reduced pressure. The product was purified by column chromatography.
Example 14: Preparation of a Compound of Formula 24
The deprotection of a compound of Formula 23 to give a compound of Formula 24 was carried out following the methods well known in the art.
Example 15: Preparation of a Compound of Formula 26
(S)-Amphetamine (3.5 equiv.) was dissolved in acetic acid (30-40 mL). Platinum oxide (1.0 equiv.) was added to it and the suspension was stirred at about 50psi (Hz). After about 24 hours platinum oxide (2 g) was added and stirred at about 50psi (Hz) pressure. The reaction mixture was filtered through celite pad. The mother liquor was evaporated to get the final component (lOgm) as the acetate salt. This was used as such for next step without further purification.
Example 16: Preparation of a Compound of Formula 28
Pyridine-4-carboxaldehyde (1 equiv.) and nitro ethane (6.0 equiv.) were taken in a round bottom flask fitted with a magnetic stirrer. To the vigorously stirred reaction mixture at an ambient temperature was added sodium hydroxide (2.0 equiv.) and kept at an ambient temperature for about 3 hours during which a yellowish white solid product separated out. It was filtered and collected for the next reaction as such without purification.
Example 17: Preparation of a Compound of Formula 29
Compound of Formula 28 (1.0 equiv.) was added to a stirred solution acetic anhydride (50-75 mL). The reaction mixture was stirred at an ambient temperature for about 1 hour during which the initially white suspension becomes deep yellow colored solution. Volatiles were removed in vacua and the content was dissolved in dichloromethane (500-600 mL). Washed with aqueous saturated sodium bicarbonate solution. Dried over anhydrous sodium sulfate, column chromatography on silica gel (230-400 mesh) eluant dichloromethane afforded the product as yellowish thick liquid.
Example 18: Preparation of a Compound of Formula 30
Compound of Formula 29 (1.0 equiv.) and platinum oxide (0.32 equiv.) was suspended in glacial acetic acid (30-40 mL). The reaction mixture was subjected to about 55-psi hydrogen pressure for about 16 hours at an ambient temperature. Filtered through a celite pad. Volatiles were removed in vacua to obtain the required product as colorless oil.
Example 19: Preparation of a Compound of Formula 31
Isobutyl methyl ketone (100-125 mL) was added to a flask containing the compound of Formula 30 (1.0 equiv.) and sodium carbonate (2.5 equiv.). The heterogeneous mixture was heated to reflux under nitrogen, and water was removed from the reaction mixture with a Dean-Stark trap. When the imine formation went to completion, the flask was cooled to 0 °C. di-tert-Butyl dicarbonate (1.0 equiv.) was added drop wise into the reaction mixture and kept stirring
for about 1 hour. Reaction mixture was quenched with water. Isobutyl methyl ketone layer separated out was collected, volatiles were removed in vacua to obtain the intermediate imine, which when subjected to heating at about 50 °C with water and n-butanol hydrolyses to the required product.
Example 20: Preparation of a Compound of Formula 32
To a solution of compound of Formula 5 (1.0 equiv.) in methanol (20-30 mL) was added compound of Formula 24 (2.45 equiv.). After stirring for about 1 hour, sodium cyanoborohydride (2.45 equiv.) was added to the reaction mixture. The reaction mixture was stirred overnight and then evaporated the solvent under reduced pressure. The residue was dissolved in dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The product was purified by column chromatography.
Example 21: Preparation of Compound of Formula 33 and 34
To a solution of compound of Formula 14 (1.0 equiv.) or 18 (1.0 equiv.) in methanol (20-30 mL) was added compound of Formula 24 (2.45 equiv.). After stirring for about 1 hour, sodium cyanoborohydride (2.45 equiv.) was added to the reaction mixture. The reaction mixture was stirred overnight and then evaporated the solvent under reduced pressure. The residue was dissolved in dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The product was purified by column chromatography.
Example 22: Preparation of a Compound of Formula 36
The compound of Formula 35 (1.0 equiv.) was taken in dichloromethane (75-100mL)
and to it triethylamine (1.5 equiv.) was added at an ambient temperature. It was cooled to 0 °C and di-tert-Butyl dicarbonate (1.2 equiv.) dissolved in 25 mL was added drop wise and the contents were stirred at an ambient temperature overnight, quenched with water and extracted in dichloromethane. Solvent was evaporated and the crude product was purified over silica gel column.
Example 23: Preparation of a Compound of Formula 37
The compound of Formula 36 (1.0 equiv.) was taken in methanol (10-15 mL) and cooled to 0 °C. To this Raney Nickel (1.0 equiv.) was added, followed by drop wise addition of hydrazine hydrate (10-15 mL). The reaction mixture was stirred at an ambient temperature for about 1 hour and filtered through celite pad. Evaporation of filtrate gave the desired compound.
Example 24: Preparation of a Compound of Formula 39
The compound of Formula 37 (1.0 equiv.) was taken in dichloromethane (5-10mL) and cooled to 0 °C. To this R6NCO (1.2 equiv.) was added and the reaction mixture was stirred at room temperature overnight. It was then filtered and the filtrate was evaporated to give compound of Formula 38. Compound of Formula 38 (1.4 equiv.) was taken in a round bottom flask and cooled to 0 °C. To this mixture, ethanolic hydrochloride (5-10 mL) was added and the reaction mixture was stirred overnight at an ambient temperature. Evaporation of the solvent gave the salt of the amine, which was taken in dichloromethane, cooled and basified using triethylamine to get the free amine. The crude product was purified on preparative thin layer chromatography.
Example 25: Preparation of a Compound of Formula 41
The compound of Formula 37 (1.0 equiv.) was taken in pyridine (5-10 mL) and cooled to 0 °C. To this mixture, thiophene-2-sulphonylchloride (1.2 equiv.) was added in portion wise and the contents were stirred for about 1 hour at 0 °C, quenched with water and extracted in dichloromethane. The organic layer was washed with dilute hydrochloric acid solution, water and brine and evaporated to get the crude product of Formula 40.
Compound of Formula 40 (1.54 equiv.) was taken in a round bottomed flask and cooled to 0 °C. To this ethanolic hydrochloride (5-10 mL) was added and the reaction mixture was stirred overnight at an ambient temperature. Evaporation of the solvent gave the salt of the amine, which was taken in dichloromethane, cooled and basified using triethylamine to get the free amine. The crude product was purified on preparative thin layer chromatography.
Example 26: Preparation of a Compound of Formula 42
The compound of Formula 35 (1.0 equiv.) was taken in acetonitrile (10-20 mL) and to it cesium carbonate (4.0 equiv.) and thiophenol (3.0 equiv.) was added at an ambient temperature. The reaction mixture was heated at about 50 °C for about 4 hours, cooled to an ambient temperature, quenched with water and extracted with ethyl acetate. Evaporation of solvent gave the crude product, which was purified over silica gel column chromatography.
Example 27: Preparation of a Compound of Formula 44
The amine of Formula 43 (1.0 equiv.) was taken in pyridine (5-1 OmL) and cooled to 0 °C. To this a compound of Formula 42a (1.2 equiv.) was added in portion wise and the contents were stirred for about 1 hour at 0 °C, quenched with water and extracted in dichloromethane. The
organic layer was washed with dilute hydrochloric acid solution, water and brine and evaporated to get compound of Formula 43.
Compound of Formula 43 (1.0 equiv.) was taken in a round bottom flask and cooled to 0 °C. To this mixture, ethanolic hydrochloride (5-10 mL) was added and the reaction mixture was stirred overnight at room temperature. Evaporation of the solvent gave the salt of the amine, which was taken in dichloromethane, cooled and basified using triethylamine to get the free amine. The crude product was then purified over preparative thin layer chromatography.
Example 28: Preparation of a Compound of Formula 46
The amine of Formula 42 (1.0 equiv.) was taken in dichloromethane (5-10 mL) and cooled to 0 °C. To this mixture, R6NCO (1.2 equiv.) was added and the reaction mixture was stirred at an ambient temperature overnight. It was then filtered and the filtrate was evaporated to get compound of Formula 45.
Compound of Formula 45 (1.0 equiv.) was taken in an round bottom and cooled to 0 °C. To this mixture, ethanolic hydrochloride (10-15 mL) was added and the reaction mixture was stirred overnight at room temperature for about 5 hours. Evaporation of the solvent gave the salt of the amine, which was taken in dichloromethane, cooled and basified using triethylamine to get the free amine. The crude product was then purified by preparative thin layer chromatography.
Example 29: Preparation of a Compound of Formula 48
Compound of Formula 47 (3.0 equiv.) and compound of Formula 24 (1.0 equiv.) were taken in methanol containing about 1% acetic acid and stirred at an ambient temperature for about 24 hours. Sodium cyanoborohydride (1.5 equiv.) was added and the resulting mixture was stirred at room temperature for about 2 hours. Solvent was removed and the residue was extracted in dichloromethane. Organic layer was washed with aqueous sodium bicarbonate, water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column to get the desired compound.
Example 30: Preparation of a Compound of Formula 49
Compound of Formula 48 (1.0 equiv.) was taken in dry dichloromethane (5-10mL) and di-tert-Butyl dicarbonate (1.2 equiv.) was added. The resulting mixture was stirred at an ambient temperature for about 12 hours. Solvent was removed and the residue was purified over silica gel column to get the desired compound.
Example 31: Preparation of a Compound of Formula 50
Compound of Formula 49 (1.0 equiv.) was taken in dry dichloromethane (5-10mL) and cooled to 0 °C. Triethylamine (2.0 equiv.) and a compound of Formula R6NCO (1.5 equiv.) were added. The resulting mixture was slowly warm to an ambient temperature and stirred for about 3 hours. Quenched with water and extracted in dichloromethane. Organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column.
Example 32: Preparation of a Compound of Formula 51
Compound of Formula 50 (1.0 equiv.) was dissolved in about 20% trifluoroacetic acid solution in dichloromethane (5-10 mL) and stirred for about 3 hours. Quenched with aqueous sodium bicarbonate and extracted in dichloromethane. Organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column.
The following compounds were prepared analogously, following the above general procedures:
Compound No. 1: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2,3,4,5,6-pentafluorobenzenesulfonamide, Mass (m/z): 477.3; m. pt.: 63-64;
Compound No. 2: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-methoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 499.3; m. pt.: Gummy;
Compound No. 3: 5-(l-benzothien-2-yl)-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 525.2; m. pt.: 59-61;
Compound No. 4: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3,4-dimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 529.3; m. pt.: 55-57;
Compound No. 5: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l-benzothiophene-2-sulfonamide, Mass (m/z): 443.1; m. pt.: 49-51;
Compound No. 6:N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 515.2; m. pt.: Gummy;
Compound No. 7: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 543.2; m. pt.: Gummy;
Compound No. 8: 5-(3-acetylphenyl)-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino} methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 497.1; m. pt.: Gummy;
Compound No. 9: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(l-hydroxyethyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 513.1; m. pt.: 52-55;
Compound No. 10: 5-(3-acetylphenyl)-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino} methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 525.2; m. pt.: Gummy;
Compound No. 11: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 529.1; m. pt.: Gummy;
Compound No. 12:N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l-benzothiophene-2-sulfonamide, Mass (m/z): 429.2; m. pt.: Gummy;
Compound No. 13: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-!-benzothiophene-2-sulfonamide, Mass (m/z): 457.2; m. pt.: Gummy;
Compound No. 14: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(3,4-dimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 515.3; m. pt.: 47-48;
Compound No. 15: 6-chloro-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] imidazo[2,l-6][l,3]thiazole-5-sulfonamide, Mass (m/z): 467.1; m. pt.: Gummy;
Compound No. 16: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(trifluoromethyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 537.3; m. pt.: Gummy;
Compound No. 17: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thiophene-2-sulfonamide; Mass (m/z): 541.3; m. pt: 69;
Compound No. 18: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl)isoxazol-3-yl]thiophene-2'Sulfonamide, Mass (m/z): 528.2; m. pt.: 110;
Compound No. 19: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide, Mass (m/z): 541.2; m. pt.: Gummy;
Compound No. 20: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(trifluoromethoxy)phenyl]thiophene-2-sulfonamide, Mass (m/z): 539.1; m. pt.: Gummy;
Compound No. 21:N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfonamide, Mass (m/z): 514.0; m. pt.: Gummy;
Compound No. 22: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfonamide, Mass (m/z): 542.1; m. pt.: Gummy;
Compound No. 23: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide, Mass (m/z): 555.1; m. pt.: Gummy;
Compound No. 24: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide, Mass (m/z): 527.0; m. pt.: Gummy;
Compound No. 25: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thiophene-2-sulfonamide, Mass (m/z): 555.1; m. pt.: Gummy;
Compound No. 26: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(trifluoromethoxy)phenyl]thiophene-2-sulfonamide, Mass (m/z): 553.2; m. pt.: 59;
Compound No. 27: 5-chloro-N-[2-({[(l1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]-3-methyl-l-benzothiophene-2-sulfonamide, Mass (m/z): 491.2; m. pt.: 82-84;
Compound No. 28: methyl 5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)-4-methylthiophene-2-carboxylate, Mass (m/z): 465.2; m. pt.: Gummy;
Compound No. 29: methyl 4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)-2,5-dimethyl-3-fiiroate, Mass (m/z): 463.2; m. pt.: Gummy;
Compound No. 30: 5-chloro-N-[2-({[(lS)-2-cyclohexyl-l -methylethyl]amino}methyl) phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide, Mass (m/z): 439.4; m. pt.: Gummy;
Compound No. 31: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2,2'-bithiophene-5-sulfonamide, Mass (m/z): 475.2; m. pt.: Gummy;
Compound No. 32: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-furyl)thiophene-2-sulfonamide, Mass (m/z): 459.3; m. pt.: Gummy;
Compound No. 33: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-phenylthiophene-2-sulfonamide, Mass (m/z): 469.3; m. pt.: 81-83;
Compound No. 34: N-[2-({[(1R)-2-cyclohexyl-l-(hydroxymethyl)ethyl]amino} methyl) phenyl]thiophene-2-sulfonamide, Mass (m/z): 409.3; m. pt.: 79-80;
Compound No. 35: methyl 5-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-4-methylthiophene-2-carboxylate, Mass (m/z): 479.2; m. pt.: Gummy;
Compound No. 36: 5-chloro-N-[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]-3-methyl-l-benzothiophene-2-sulfonamide, Mass (m/z): 505.2; m. pt.: Gummy;
Compound No. 37: 5-chloro-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide, Mass (m/z): 453.2; m. pt.: Gummy;
Compound No. 38:N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2,2'-bithiophene-5-sulfonamide, Mass (m/z): 489.2; m. pt.: Gummy;
Compound No. 39: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(3-furyl)thiophene-2-sulfonamide, Mass (m/z): 445.2; m. pt.: Gummy;
Compound No. 40: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(3-furyl)thiophene-2-sulfonamide, Mass (m/z): 473.2; m. pt.: Gummy;
Compound No. 41: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-phenylthiophene-2-sulfonamide, Mass (m/z): 455.2; m. pt.: 61-62.5;
Compound No. 42: 5-bromo-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]thiophene-2-sulfonamide, Mass (m/z): 457.1; m. pt.: 135-136.5;
Compound No. 43: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide, Mass (m/z): 379.2; m. pt.: Gummy;
Compound No. 44: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide, Mass (m/z): 407.2; m. pt.: Gummy;
Compound No. 45: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] isonicotinamide, Mass (m/z): 352.3; m. pt.: Gummy;
Compound No. 46:N-[2-({[(lS)-2-cydohexyl-l-methylethyl]amino}methyl)phenyl] nicotinamide, Mass (m/z): 352.3; m. pt.: 113-114;
Compound No. 47: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,2'-bithiophene-5-sulfonamide, Mass (m/z): 461.2; m. pt.: Gummy;
Compound No. 48: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3,5-bis(trifluoromethyl)benzenesulfonamide, Mass (m/z): 523.3; m. pt.: 114-116;
Compound No. 49: 2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl [(2-methylphenyl)sulfonyl]carbamate hydrochloride salt, Mass (m/z): 445.2; m. pt.: 151-152.5;
Compound No. 50: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-6-phenoxypyridine-3-sulfonamide, Mass (m/z): 480.3; m. pt.: 58-60;
Compound No. 51: 5-bromo-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]-2-furamide, Mass (m/z): 419.2; m. pt.: 60-62;
Compound No. 52: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-furamide, Mass (m/z): 341.2; m. pt.: 48-50;
Compound No. 53: N-[2-({[(lS')-2-cyclohexyl-l-methylethyl]ammo}methyl)phenyl]-l-benzothiophene-3-sulfonamide, Mass (m/z): 443.2; m. pt.: 50-52;
Compound No. 54: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-carboxamide, Mass (m/z): 357.2; m. pt.: 48-50;
Compound No. 55: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-carboxamide hydrochloride salt, Mass (m/z): 371.3; m. pt.: 143-145;
Compound No. 56: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-furamide hydrochloride salt, Mass (m/z): 327.3; m. pt.: 174-176;
Compound No. 57: 5-bromo-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]-2-fiiramide hydrochloride salt, Mass (m/z): 405.1; m. pt.: 84-86;
Compound No. 58: 5-(3-acetylphenyl)-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 511.2; m. pt.: Gummy;
Compound No. 59: 5-(l,3-benzodioxol-5-yl)-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl] amino}methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 513.2; m. pt.: Gummy;
Compound No. 60: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3,3'-bithiophene-5-sulfonamide, Mass (m/z): 475.2; m. pt.: Gummy;
Compound No. 61: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(3-methoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 513.2; m. pt.: 34-35;
Compound No. 62: methyl 3-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-4-(isopropylsulfonyl)thiophene-2-carboxylate, Mass (m/z): 557.2; m. pt: 111-112.5;
Compound No. 63: N-[2-({[(l1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-fluorophenyl)thiophene-2-sulfonamide, Mass (m/z): 487.2; m. pt.: 56-58;
Compound No. 64: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(hydroxymethyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 499.0; m. pt.: 62-63;
Compound No. 65: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(hydroxymethyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 199.0; m. pt: 144-146;
Compound No. 66: methyl 5-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-4-methylthiophene-2-carboxylate, Mass (m/z): 451.3; m. pt.: 58-60;
Compound No. 67: methyl 4-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2,5-dimethyl-3-furoate, Mass (m/z): 477.1; m. pt.: 135-136.5;
Compound No. 68: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(trifluoromethyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 551.2; m. pt: 40-41;
Compound No. 69: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(3-fluorophenyl)thiophene-2-sulfonamide, Mass (m/z): 473.2; m. pt: 55-56;
Compound No. 70: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(3-fluorophenyl)thiophene-2-sulfonamide, Mass (m/z): 501.3; m. pt: 62-63;
Compound No. 71: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide, Mass (m/z): 446.0; m. pt: 81-82;
Compound No. 72: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-methylthiophene-2-carboxamide, Mass (m/z): 371.3; m. pt: 118-119;
Compound No. 73: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-methylthiophene-2-carboxamide, Mass (m/z): 385.3; m. pt: Gummy;
Compound No. 74: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] nicotinamide, Mass (m/z): 338.3; m. pt.: 80-82;
Compound No. 75: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]
nicotinamide, Mass (m/z): 366.2; m. pt: 105-107;
Compound No. 76: N-[3-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)pyridin-2 -yl]thiophene-2-sulfonamide, Mass (m/z): 408.3; m. pt.: Gummy;
Compound No. 77: N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]thiophene-2-sulfonamide, Mass (m/z): 394.1; m. pt.: 172-173;
Compound No. 78: N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]-4-fluorobenzenesulfonamide, Mass (m/z): 406.3; m. pt.: 148-149;
Compound No. 79: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 538.1; m. pt.: 68;
Compound No. 80: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]aminolmethyl)phenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 442.1; m. pt.: Gummy;
Compound No. 81: methyl 5-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-l-methyl-1H-pyrrole-2-carboxylate, Mass (m/z): 462.1; m. pt.: Gummy;
Compound No. 82: methyl 5-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-l-methyl-1H-pyrrole-2-carboxylate, Mass (m/z): 434.1; m. pt.: Gummy;
Compound No. 83: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide, Mass (m/z): 377.0; m. pt.: 42-44;
Compound No. 84: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide, Mass (m/z): 405.2; m. pt.: 43-45;
Compound No. 85: 5-bromo-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]-2-furamide, Mass (m/z): 433.0; m. pt.: Gummy;
Compound No. 86: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-3,5-bis(trifluoromethyl)benzenesulfonamide, Mass (m/z): 509.1; m. pt.: 97-98;
Compound No. 87: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-ulfonamide, Mass (m/z): 460.2; m. pt.: 68-69.5;
Compound No. 88: [2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl] isonicotinamide, Mass (m/z): 366.2; m. pt.: Gummy;
Compound No. 89: Chloro-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide, Mass (m/z): 425.0; m. pt.: Gummy;
Compound No. 90: -benzothien-2-yl)-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino} methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 539.2; m. pt.: 128-130;
Compound No. 91: (l-benzothien-2-yl)-N-[2-({[(1S)-2-cyclopentyl-lmethylethyl]amino} methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 511.2; m. pt.: 124-126;
Compound No. 92: [2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(3,4-dimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 543.2; m. pt.: 45-46;
Compound No. 93: [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(4-methoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 485.2; m. pt.: 101-102;
Compound No. 94: [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-3,3'-bithiophene-5-sulfonamide, Mass (m/z): 461.2; m. pt.: Gummy;
Compound No. 95: [2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-3,3'-bithiophene-5-sulfonamide, Mass (m/z): 489.2; m. pt.: Gummy;
Compound No. 96: [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 524.0; m. pt.: 55;
Compound No. 97: [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 428.1; m. pt.: Gummy;
Compound No. 98: (l,3-benzodioxol-5-yl)-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl] amino}methyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 499.0; m. pt.: Gummy;
Compound No. 99: [2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-[4-(4-methoxyphenyl)piperazin-l-yl]acetamide; Mass (m/z): 479.2; m. pt.: Gummy;
Compound No. 100: 5-chloro-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino} methyl) phenyl]-3-methyl-l-benzothiophene-2-sulfonamide; Mass (m/z): 477.08; m. pt.: 74-76;
Compound No. 101: [2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide; Mass (m/z): 574.1; m. pt.: 148-150;
Compound No. 102: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2-methyl-l,3-thiazol-4-yl)thiophene-2-sulfonamide; Mass (m/z): 476.00; m. pt.: 158-159;
Compound No. 103: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(2-methyl-l,3-thiazol-4-yl)thiophene-2-sulfonamide; Mass (m/z): 504.10; m. pt.: 80-82;
Compound No. 104: ethyl 3-[5-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate; Mass (m/z): 533.10; m. pt.: 40-41;
Compound No. 105: ethyl 3-[5-({[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate; Mass (m/z): 519.00; m. pt.: 56-58;
Compound No. 106: ethyl 3-[5-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate; Mass (m/z): 547.10; m. pt.: 54-56;
Compound No. 107:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide; Mass (m/z): 422.0479.2; m. pt.: 56-58;
Compound No. 108:N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide; Mass (m/z): 408.1; m. pt: 60-61;
Compound No. 109: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide; Mass (m/z): 436.0; m. pt.: 53-55;
Compound No. 110: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-methylthiophene-2-carboxamide; Mass (m/z): 357.1; m. pt.: Gummy;
Compound No. 111: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] isonicotinamide; Mass (m/z): 338.2; m. pt.: 70-72;
Compound No. 112: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide; Mass (m/z): 451.2; m. pt.: Gummy;
Compound No. 113: methyl 3-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)thiophene-2-carboxylate; Mass (m/z): 437.0; m. pt.: Gummy;
Compound No. 114: methyl 3-({[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)thiophene-2-carboxylate; Mass (m/z): 465.1; m. pt.: 53-57;
Compound No. 115: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-imidazol-l-yl)benzenesulfonamide; Mass (m/z): 467.1; m. pt.: 62-64;
Compound No. 116: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-(2-thienylsulfonyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide; Mass (m/z): 588.0; m. pt.: 80-81;
Compound No. 117: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-6-phenoxypyridine-3-sulfonamide; Mass (m/z): 494.1 ; m. pt.: Gummy;
Compound No. 118: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-6-phenoxypyridine-3-sulfonamide; Mass (m/z): 466.1; m. pt.: Gummy;
Compound No. 119: N-[2-({[(l,S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-pyrrol-l-yl)benzenesulfonamide; Mass (m/z): 452.1; m. pt.: 207-209;
Compound No. 120: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-pyrrol-l-yl)benzenesulfonamide; Mass (m/z): 438.1; m. pt.: 135-137;
Compound No. 121: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-l,2,4-triazol-l-yl)benzenesulfonamide; Mass (m/z): 454.1; m. pt: 110-112;
Compound No. 122: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide; Mass (m/z): 377.1; m. pt.: 55-56;
Compound No. 123: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide; Mass (m/z): 391.1; m. pt: 51-52;
Compound No. 124: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide; Mass (m/z): 437.2; m. pt.: Gummy;
Compound No. 125: N-[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide; Mass (m/z): 465.3; m. pt: 115-117;
Compound No. 126: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-{3-[(1E)-N-hydroxyethanimidoyl]phenyl}thiophene-2-sulfonamide; Mass (m/z): 526.1; m. pt.: 73-77;
Compound No. 127: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-{3-[(1E)-N-methoxyethanimidoyl]phenyl}thiophene-2-sulfonamide; Mass (m/z): 540.1; m. pt.: 48-50;
Compound No. 128: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]aminolmethyl)phenyl]-2 -furamide; Mass (m/z): 355.2; m. pt.: Gummy;
Compound No. 129: 2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl (4-methoxyphenyl)carbamate; Mass (m/z): 397.1; m. pt.: 56-57;
Compound No. 130: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(phenylsulfonyl)thiophene-2-sulfonamide; Mass (m/z): 547.0; m. pt.: 85-87;
Compound No. 131: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(phenylsulfonyl)thiophene-2-sulfonamide; Mass (m/z): 519; m. pt.: 50-52;
Compound No. 132: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(phenylsulfonyl)thiophene-2-sulfonamide; Mass (m/z): 533.0; m. pt.: 175-177;
Compound No. 133: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl][(2,2-dimethylpropanoyl)oxy] amino}methyl)phenyl]-2-(2-thienylsulfonyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide; Mass (m/z): 688.1; m. pt.: 80;
Compound No. 134: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl][(2,2-dimethylpropanoyl)oxy] amino}methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide; Mass (m/z):638.1;m. pt.: 132;
Compound No. 135: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl][(2,2-dimethylpropanoyl)oxy] amino}methyl)phenyl]-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide; Mass (m/z): 542.1; m. pt.: 93;
Compound No. 136: 5-(l,3-benzodioxol-5-yl)-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl] amino}methyl)phenyl]thiophene-2-sulfonamide; Mass (m/z): 527.1; m. pt.: 53;
Compound No. 137: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-imidazol-l-yl)benzenesulfonamide; Mass (m/z): 453.1; m. pt.: 60-62;
Compound No. 138: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-imidazol-l-yl)benzenesulfonamide; Mass (m/z): 439.1; m. pt: 56-58;
Compound No. 139: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(l,3-oxazol-2-yl)thiophene-2-sulfonamide; Mass (m/z): 474.0; m. pt.: 48-50;
Compound No. 140: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]
thiophene-2-carboxamide; Mass (m/z): 343.2; m. pt.: Gummy;
Compound No. 141: N-(4-acetylphenyl)-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyl]urea; Mass (m/z): 408.1; m. pt.: 150-151 °C;
Compound No. 142: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l-benzothiophene-2-sulfonamide; Mass (m/z): 429.2; m. pt.: Gummy;
Compound No. 143: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-pyridin-4-ylthiophene-2-sulfonamide; Mass (m/z): 470.0; m. pt.: 84-86 °C
Compound No. 144: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-pyridin-3-ylthiophene-2-sulfonamide; Mass (m/z): 456.0; m. pt.: 78-80 °C
Compound No. 145: 2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl (4-acetylphenyl)carbamate; Mass (m/z): 409.1; m. pt.: 63-65 °C
Compound No. 146: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-l,2,4-triazol-l-yl)benzenesulfonamide; Mass (m/z): 440.0; m. pt.: 174-175 °C
Compound No. 147: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-l,2,4-triazol-l-yl)benzenesulfonamide; Mass (m/z): 468.1; m. pt.: 177-178 °C
Compound No. 148: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-ylpiperazin-l-yl)acetamide; Mass (m/z): 437.2; m. pt.: Gummy;
Compound No. 149: 6-({[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)-N-(4-methoxyphenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide; Mass (m/z): 578.1; m. pt.: 96-98 °C
Compound No. 150: 6-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl] amino}sulfonyl)-N-isopropyl-3,4-dihydroisoquinoline-2(1H)-carboxamide; Mass (m/z): 513.1; m. pt.: 94-95 °C
Compound No. 151: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-(1H-imidazol-l-ylcarbonyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide; Mass (m/z): 522.1; m. pt.: 79-81 °C
Compound No. 152: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-({[(4-methoxyphenyl)amino]carbonyl}amino)benzenesulfonamide; Mass (m/z): 551.1; m. pt.: 97-98
°C
Compound No. 153: 4-( {[(4-acetylphenyl)amino] carbonyl} amino)-N- [2-( {[(1 S)-2-cyclohexy 1-1 -methylethyl]amino}methyl)phenyl]benzenesulfonamide; Mass (m/z): 563.1; m. pt.: 155-156 °C
Compound No. 154: N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-2-sulfonamide; Mass (m/z): 548.0; m. pt.: 82-83 °C
Compound No. 155: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]aminolmethyl)phenyl]-!-pyrimidin-2-yl-1H-imidazole-4-sulfonamide; Mass (m/z): 455.1; m. pt.: 90-92 °C
Compound No. 156: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l-benzofuran-2-carboxamide; Mass (m/z): 391.0; m. pt.: 122-124 °C
Compound No. 157: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-!-benzofuran-2-carboxamide; Mass (m/z): 377.1; m. pt.: 150-152 °C
Compound No. 158: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]aminolmethyl)phenyl]-!-benzofuran-2-carboxamide; Mass (m/z): 405.2; m. pt.: 133-134 °C
Compound No. 159: N-{3-[5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl) phenyl]amino}sulfonyl)-2-thienyl]phenyl}acetamide; Mass (m/z): 526.1; m. pt.: 95-98 °C
Compound No. 160: N-{3-[5-({[2-({[(l,S)-2-cyclopentyl-l-methylethyl]amino} methyl) phenyl]amino}sulfonyl)-2-thienyl]phenyl}acetamide; Mass (m/z): 512.0; m. pt.: 84-87 °C
Compound No. 161: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl)thiophene-2-sulfonamide; Mass (m/z): 559.1; m. pt.: Gummy;
Compound No. 162: N-[2-({[(l1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl)thiophene-2-sulfonamide; Mass (m/z): 545.1; m. pt.: Gummy;
Compound No. 163: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide; Mass (m/z): 355.2; m. pt.: 103-105 °C
Compound No. 164: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide; Mass (m/z): 369.1; m. pt.: 118-120 °C
Compound No. 165: 4-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl) phenyljbenzamide; Mass (m/z): 366.2; m. pt.: 116-118 °C
Compound No. 166: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-isopropylurea; Mass (m/z): 332.2; m. pt.: 61-62 °C
Compound No. 167: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-isopropylthiourea; Mass (m/z): m. pt.: 167-169 °C
Compound No. 168: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(4-methoxyphenyl)urea; Mass (m/z): 396.1; m. pt.: 52-54 C
Compound No. 169: N-(4-acetylphenyl)-6-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino} methyl)phenyl]amino}sulfonyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide; Mass (m/z): 589.2 m.pt.: 92-97 °C
Compound No. 170: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-,1,2,3,4 -tetranydroisoquinoline-6-sulfonamide; Mass (m/z): 456.1; m. pt.: 88-90 °C
Compound No. 171: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-N-isopropylurea; Mass (m/z): 346.2; m. pt.: Gummy;
Compound No. 172: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] isoxazole-5-carboxamide; Mass (m/z): 342.1; m. pt.: not done
Compound No. 173: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-5-ylthiophene-2-carboxamide; Mass (m/z): 460.0; m. pt.: 65-67 °C
Compound No. 174: N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-4 -fluorobenzamide; Mass (m/z): 383.2; m. pt.: 73-74 °C
Compound No. 175: tert-butyl 4-(2-{[2-(2-furoylamino)benzyl]amino}propyl)piperidine-l-carboxylate; Mass (m/z): 442.2; m. pt.: 65-67 °C
Compound No. 176:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-nitrobenzamide; Mass (m/z): 396.1; m. pt.: 76-77 °C
Compound No. 177: tert-butyl 4-[2-({2-[(4-fluorobenzoyl)amino]benzyl}amino)propyl] piperidine-1-carboxylate; Mass (m/z): 470.1; m. pt.: 40-42 °C
Compound No. 178: tert-butyl 4-[2-({2-[(2-thienylcarbonyl)amino]benzyl}amino)propyl] piperidine-1-carboxylate; Mass (m/z): 458.1; m. pt.: 48-49 °C
Compound No. 179: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]ammolmethyl)phenyl]-!-pyrazin-2-yl-1H-imidazole-4-sulfonamide; Mass (m/z): 455.1; m. pt.: 90-92 °C
Compound No. 180: N-[2-({[(15',2^ )-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]thiophene-2-sulfonamide; Mass (m/z): 409.0; m. pt.: 74-76 °C
Compound No. 181: N-[2-({[( 15l,2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-l-benzofuran-2-carboxamide; Mass (m/z): 407.1; m. pt.: 146-147 C
Compound No. 182: tert-butyl 4-{2-[(2-{[(5-isoxazol-5-yl-2-thienyl)carbonyl]amino}benzyl) amino]propyl}piperidine-l-carboxylate; Mass (m/z): 561.1; m. pt.: 75-80 °C
Compound No. 183: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-5-ylthiophene-2-sulfonamide; Mass (m/z): 446.1; m. pt.: 51-55 °C
Compound No. 183a: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-Nl-[4-(l,3-oxazol-5-yl)phenyl]urea; Mass (m/z) 433.2; m. pt.: 72-74 C;
Compound No. 183b: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-[(methylsulfonyl)amino]benzenesulfonamide
The following compounds can be prepared following the above general procedures
Compound No. 184: N-(4-chlorophenyl)-N-(2-{[(2-cyclohexyl-l-methylethyl)amino] methyl}phenyl)urea;
Compound No. 185: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-phenylurea;
Compound No. 186: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N'-(3,4-dichlorophenyl)urea;
Compound No. 187: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(3,4,5-trichlorophenyl)urea;
Compound No. 188: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(2,4-dichlorophenyl)urea;
Compound No. 189: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(4-fluorophenyl)urea;
Compound No. 190: N-(2-{[(2-cyclohexyl-1 -methylethyl)amino]methyl}phenyl)-N-1 -naphthylurea;
Compound No. 191: N-(2-{[(2-cyclohexyl-1 -methylethyl)amino]methyl}phenyl)-N-isopropyl urea;
Compound No. 192: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-isopropylthiourea;
Compound No. 193: N-(2-{[(2-cydohexyl-l-methylethyl)ammo]methyl}phenyl)-N'-1-naphthylthiourea;
Compound No. 194: N-(2-{ [(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N-(trichloromethyl)thiourea;
Compound No. 195: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-phenylpiperazine-1 -carboxamide;
Compound No. 196: 4-benzyl-N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl) piperazine-1 -carboxamide;
Compound No. 197: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)piperazine-l-carboxamide;
Compound No. 198: 4-(4-chlorophenyl)-N-(2-{[(2-cyclohexyl-1-methylethyl)amino]methyl} phenyl)piperazine-1 -carboxamide;
Compound No. 199: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-methyl piperazine-1 -carboxamide;
Compound No. 200: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)morpholine-4-carboxamide;
Compound No. 201: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-pyrimidin-4-ylpiperazine-1 -carboxamide;
Compound No. 202: 4-chloro-N-{[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)
amino]carbonyl}benzenesulfonamide;
Compound No. 203: N-{[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)amino]
carbonyl} -4-methylbenzenesulfonamide;
Compound No. 204: N-{[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)amino] carbonyl} benzamide;
Compound No. 205: N-{[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)amino] carbonyl}benzenecarbothioamide;
Compound No. 206: 4-[(4-chlorophenyl)sulfonyl]-N-(2-{[(2-cyclohexyl-l-methylethyl) amino]methyl}phenyl)piperazine-l-carboxamide;
Compound No. 207: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-(phenylsulfonyl)piperazine-1 -carboxamide;
Compound No. 208: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-[(4-methylphenyl)sulfonyl]piperazine-1 -carboxamide;
Compound No. 209: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-4-(2-thienylsulfonyl)piperazine-1 -carboxamide;
Compound No. 210: N-{(1E)-amino[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl} phenyl)amino]methylene}-4-chlorobenzenesulfonamide;
Compound No. 211: N-{(1E)-amino[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl} phenyl)amino]methylene} -4-methylbenzenesulfonamide;
Compound No. 212: N-{(1E)-amino[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl} phenyl)amino]methylene} methanesulfonamide;
(Compound No. 213): N-{(1E)-amino[(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl} phenyl)amino]methylene}thiophene-2-sulfonamide;
(Compound No. 214): N-(2-{[(l-methyl-2-piperazin-l-ylethyl)amino]methyl}phenyl) benzenesulfonamide;
(Compound No. 215): 4-methyl-N-(2-{[(l-methyl-2-piperazin-l-ylethyl)amino]methyl} phenyl)benzenesulfonamide;
(Compound No. 216): 4-chloro-N-(2-{[(l-methyl-2-piperazin-l-ylethyl)amino]methyl} pheny l)benzenesulfonam ide;
Compound No. 217: N-(2-{[(l-methyl-2-piperazin-l-ylethyl)amino]methyl}phenyl) thiophene-2-sulfonamide;
Compound No. 218: 5-bromo-N-(2-{[(l-methyl-2-piperazin-l-ylethyl)amino]methyl}phenyl) thiophene-2-sulfonamide;
Compound No. 219: 4-methyl-N-[2-({[l-methyl-2-(4-phenylpiperazin-l-yl)ethyl]amino} methyl)phenyl]benzenesulfonamide;
Compound No. 220: N-[2-({[l-methyl-2-(4-phenylpiperazin-l-yl)ethyl]amino}methyl) phenyl]benzenesulfonamide; Mass (m/z): m. pt.:
Compound No. 221: N-[2-({[l-methyl-2-(4-phenylpiperazin-l-yl)ethyl]amino}methyl) phenyl]thiophene-2-sulfonamide;
Compound No. 222: 5-bromo-N-[2-({[l-methyl-2-(4-phenylpiperazin-l-yl)ethyl]amino} methyl)phenyl]thiophene-2-sulfonamide;
Compound No. 223: 4-methyl-N-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl]amino} methyl)phenyl]benzenesulfonamide;
Compound No. 224: 4-chloro-N-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl]amino} methyl)phenyl]benzenesulfonamide;
Compound No. 225: N-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl]amino}methyl) phenyl]thiophene-2-sulfonamide;
Compound No. 226: N-(4-chlorophenyl)-N'-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl] amino} methy l)pheny 1] urea;
Compound No. 227: N-(4-chlorophenyl)-N-[2-({[l-methyl-2-(4-phenylpiperazin-l-yl)ethyl] amino} methyl)phenyl]urea;
Compound No. 228: N-{2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino) methyl]phenyl}methanesulfonamide;
Compound No. 229: N-{2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino)methyl] phenyl}benzenesulfonamide;
Compound No. 230: {2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino)methyl] phenyl}-4-methylbenzenesulfonamide;
Compound No. 231: N-{2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino)methyl] phenyl} thiophene-2-sulfonamide;
Compound No. 232: 5-bromo-N-{2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino) methyl]phenyl} thiophene-2-sulfonamide;
Compound No. 233: 4-chloro-N-{2-[({[(2-cyclohexyl-l-methylethyl)amino]carbonyl}amino) methyl] phenyl} benzenesulfonamide;
Compound No. 234: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-3-methoxy-4-piperazin-1 -ylbenzenesulfonamide;
Compound No. 235: N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)-5-(phenylsulfonyl)thiophene-2-sulfonamide;
Compound No. 236: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-l-benzofuran-2-carboxamide;
Compound No. 237: N-(2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl)-2-(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)acetamide;
Compound No. 238: 2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl (4-methoxypheny l)carbamate;
Compound No. 239: N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)-6-(1H-imidazol-1 -yl)nicotinamide;
Compound No. 240: N-(4-{[(2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl)amino] sulfonyl}phenyl)thiophene-2-sulfonamide;
Compound No. 241: N-(2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl)-2-(1H-l,2,4-triazol-1 -yl)acetamide;
Compound No. 242: N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)-2-(4-pyrim idin-2-ylpiperazin-1 -yl)acetamide;
Compound No. 243: 2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl (4-acetylphenyl)carbamate;
Compound No. 244: N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl) isonicotinamide;
Compound No. 245: N-(2-{[(2-cycloheptyl-l-methylethyl)amino]methyl}phenyl)-4-fluorobenzenesulfonamide;
Compound No. 246: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-6-(3-furyl) nicotinamide;
Compound No. 247: N-(2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl)-4-(1H-l,2,3-triazol-1 -yl)benzenesulfonamide;
Compound No. 248: N-(3-{[(2-cycloheptyl-l-methylethyl)amino]methyl}pyridin-2-yl)-2-furamide;
Compound No. 249: N-(2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl)
isonicotinamide;
Compound No. 250: N-(2-{[(2-cyclohex-l-en-l-yl-l-methylethyl)amino]methyl}phenyl)-5-(l,3-
oxazol-5-yl)furan-2-sulfonamide;
Compound No. 251: N-(2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl)-N'-(3-methylisoxazol-5-yl)urea;
Compound No. 252: 2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl [4-(1H-imidazol-l-y l)pheny 1] carbamate;
Compound No. 253: N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-5-(3-furyl)nicotinamide;
Compound No. 254: l-benzofuran-2-ylmethyl (2-{[(2-cyclohexyl-l-methylethyl)amino] methyl} phenyl)carbamate;
Compound No. 255: N-[2-({[l-methyl-2-(4-methylpiperazin-l-yl)ethyl]amino}methyl) phenyl]thiophene-2-sulfonamide;
Compound No. 256: N-l-benzothien-2-yl-N-[2-({[l-methyl-2-(tetrahydro-2H-pyran-4-yl)ethyl]amino}methyl)phenyl]urea;
Compound No. 257: 2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl [4-(1H-pyrazol-l-yl)pheny 1] carbamate;
Compound No. 258: 2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl [4-(2-furyl)phenyl] carbamate;
Compound No. 259: 3,3'-bipyridin-6-yl (2-{[(2-cyclohexyl-l-methylethyl)amino]methyl} phenyl)carbamate;
Compound No. 260: Pyridin-4-yl (2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl) carbamate;
Compound No. 261: N-l-benzothien-2-yl-N-(4-{[(2-cyclohexyl-l-methylethyl)amino] methyl}pyridin-3-yl)urea;
Compound No. 262: N-l-benzothien-2-yl-N'-(2-{[(2-cyclohexyl-l-methylethyl)amino] methyl} pyridin-3 -yl)urea;
Compound No. 263: 3-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-4-yl 1-benzothien-2-ylcarbamate;
Compound No. 264: 3-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-2-yl 1-benzothien-2-ylcarbamate;
Compound No. 265: N-l-benzothien-2-yl-N'-(3-{[(2-cyclohexyl-l-methylethyl)amino] methyl}pyridin-2-yl)urea;
Compound No. 266: N-l-benzothien-2-yl-N-(3-{[(2-cyclohexyl-l-methylethyl)amino] methyl} pyridin-4-yl)urea;
Compound No. 267: 2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-3-yl 1-benzothien-2-ylcarbamate;
Compound No. 268: 4-{[(2-cyclohexyl-l-methylethyl)amino]methyl}pyridin-3-yl 1-benzothien-2-ylcarbamate;
Compound No. 269: l-benzothien-2-yl (3-{[(2-cyclohexyl-l-methylethyl)amino]methyl} pyridin-2-yl)carbamate;
Compound No. 270: l-benzothien-2-yl (4-{[(2-cyclohexyl-l-methylethyl)amino]methyl} pyridin-3-yl)carbamate;
Compound No. 271: l-benzothien-2-yl (2-{[(2-cyclohexyl-l-methylethyl)amino]methyl} pyridin-3 -yl)carbamate;
Compound No. 272: 2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl [4-(2-furyl) phenyl] carbamate;
Compound No. 273: 2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl 1 -benzothien-2-ylcarbamate;
Compound No. 274: l-benzothien-2-yl [2-({[l-methyl-2-(tetrahydro-2H-pyran-4-yl)ethyl] amino} methyl)phenyl] carbamate;
Compound No. 275: l-benzothien-2-yl (3-{[(2-cyclohexyl-l-methylethyl)amino]methyl} pyridin-4-yl)carbamate;
Compound No. 276: l-benzothien-2-yl (2-{[(2-cyclopropyl-l-methylethyl)amino]methyl} phenyl)carbamate;
Compound No. 277: N-(2-{[(2-cyclopropyl-l-methylethyl)amino]methyl}phenyl)-2-(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)acetamide;
Compound No. 278: l-benzothien-2-yl [2-({[l-methyl-2-(tetrahydro-2H-pyran-4yl)ethyl] amino} methyl)pyridin-3 -yl] carbamate;
Compound No. 279: N-(2-{[(2-cyclopentyl-l-methylethyl)amino]methyl}phenyl)-2-(1H-l,2,4-triazol-1 -yl)acetamide;
Compound No. 280: l-benzothien-2-yl (2-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl} phenyl)carbamate;
Compound No. 281: 3-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl}pyridin-4-yl 1-benzothien-2-ylcarbamate;
Compound No. 282: N-l-benzothien-2-yl-N'-(2-{[(l-methyl-2-piperidin-4-ylethyl)amino] methyl} phenyl)urea;
Compound No. 283: N-(2-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl} phenyl) thiophene-2-sulfonamide;
Compound No. 284: N-(2-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl}phenyl)-2-(1H-pyrazol-1 -yl)acetamide;
Compound No. 285:N-(2-{[(l-methyl-2-piperidin-4-ylethyl)amino]methyl}phenyl) isonicotinamide.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Microbiological activity
Microbroth minimum inhibitory concentration (MIC) was performed using NCCLS method in Cation adjusted Mueller Hinton broth for facultative cultures (S.aureus, Enterococcus) and Cation adjusted Mueller Hinton broth +2.5% lysed horse blood for S.pneumoniae. MIC against H.influenzae strains was performed by NCCLS broth dilution method using HTM broth. Overnight grown cultures were adjusted to 0.5 Mcfarland using normal saline and diluted 100 times. 1 mg/ml concentration of stock solution of drug in DMSO/distilled water/solvent given in NCCLS manual were prepared. NCCLS double dilutions were done to get the required concentration range of the drugs in the 96 well microtiter plates using the respective media. 100 µl of culture broth was added in wells already containing 100 µl
of broth containing antibiotic to get approximately 3-7x105 CFU/ml. The plates were incubated at 37°C for about 18- 24 hours. The concentration of drug at which there was complete disappearance of growth was considered as MIC.
Compounds of this invention have shown good activity againsts microbial strains. Some of the compounds disclosed herein have shown very good activity against microbial strains, for example, Streptococcus pneumoniae, Haemophilius influenzas, Streptococcus pyogenes or Staphylococcus aureus.

We Claim:
1. A compound having the structure of Formula I,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy is cycloalkyl or heterocyclyl; X and Z are alkylene; Y is NRi (wherein Riis hydrogen, alkyl or OCOalkyl); X1-X4 is CH or N; R is OR2, OCONHR2, OCONHSO2R2, CONHR6, SR3, S(O)o-2NHR3 (wherein R2 is aryl or heteroaryl and R3 is hydrogen, alkyl, cycloalkyl, heterocyclyl, heteroaryl or aryl) or MR4R5 {wherein R4 and R are independently hydrogen, S02R6, COR6, CSR6, or COOR6 [wherein R6 is alkyl, aryl, heteroaryl, heterocyclyl, aralkyl, heteroarylalkyl, heterocycloalkyl, OR7, NHR7, NHSO2R7, NHCOR7, NHCSR7, or NH2C=NHSO2R7 (wherein R7 is hydrogen, alkyl, aryl, heteroaryl or heterocyclyl)]}, or R4 and R5, together with the nitrogen to which they are attached, can form a heterocyclic ring.
2. A compound, which is:
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2,3,4,5,6-pentafluorobenzenesulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-methoxyphenyl)thiophene-2-sulfonamide;
5-( 1 -benzothien-2-yl)-N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl) phenyl]thiophene-2-sulfonamide;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5 -(3,4-dimethoxyphenyl)thiophene-2-sulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl)thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl)thiophene-2-sulfonamide;
5-(3-acetylphenyl)-N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] thiophene-2-sulfonamide;
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(l- hydroxyethyl) phenyl]thiophene-2-sulfonamide;
5 -(3 -acetylphenyl)-N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] thiophene-2-sulfonamide;
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(2,5-dimethoxyphenyl)thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-1 -m ethyl ethyl]amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide;
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl]-1 -benzothiophene-2-sulfonamide;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] -5-(3,4-dimethoxyphenyl)thiophene-2-sulfonamide;
6-chloro-N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl) phenyl]imidazo [2,1 -b] [ 1,3]thiazole-5-sulfonamide;
•N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(trifluoromethyl)phenyl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfonamide;
N- [2-( {[(1S)2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -5 - [ 1 -methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(trifluoromethoxy)phenyl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfbnamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[5-(trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfonamide;
N- [2-( {[(1 S)-2-cycloheptyl-1 -methylethy 1] amino} methyl)phenyl] -5- [ 1 -methyl-3 -(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-[l-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide;
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5-[ 1 -methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(trifluoromethoxy)phenyl]thiophene-2-sulfonamide;
5-chloro-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3-methyl-1 -benzothiophene-2-sulfonamide;
methyl 5-({[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)-4-methylthiophene-2-carboxylate;
methyl 4-( {[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] amino} sulfonyl)-2,5-dimethyl-3-furoate;
5 -chloro-N-[2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1,3-dimethyl-1H-pyrazole-4-sulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2,2'-bithiophene-5-sulfonamide;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -5-(3 -fury 1) thiophene-2-sulfonamide;
N-[2-({ [(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-5-phenylthiophene-2-sulfonamide;
N- [2-( {[(1R)-2-cyclohexyl-1 -(hydroxymethyl)ethyl] amino} methyl)phenyl]thiophene-2-sulfonamide;
methyl 5 -({[2-( {[(1 S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-4-methylthiophene-2-carboxylate;
5-chloro-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-3-methyl-1 -benzothiophene-2-sulfonamide;
5-chloro-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2,2'-bithiophene-5-sulfonamide;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino } methyl)phenyl] -5-(3 -fury 1) thiophene-2-sulfonamide;
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -5-(3 -fury 1) thiophene-2-sulfonamide;
N-[2-({[(l S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5-phenylthiophene-
2-sulfonamide;
5-bromo-N- [2-( {[(1S)2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] thiophene-
2-sulfonamide;
N- [2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]thiophene-2-sulfonamide;
N- [2-( {[(1S)2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl]thiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl]isonicotinamide; N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]nicotinamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,2'-bithiophene-5-sulfonamide;
N- [2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -3,5-bis(trifluoromethyl)benzenesulfonamide;
2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl [(2-methylphenyl) sulfonyl]carbamate hydrochloride salt;
N~ [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -6-phenoxypyridine-3-sulfonamide;
5-bromo-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-furamide;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2-furamide;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -1 -benzothiophene-3 -sulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] thiophene-2-carboxamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]thiophene-2-carboxamide hydrochloride salt;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-fiiramide hydrochloride salt;
5-bromo-N-[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-ruramide hydrochloride salt;
5-(3-acetylphenyl)-N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl) phenyl] thiophene-2-sulfonamide;
5-(l,3-benzodioxol-5-yl)-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)
phenyl]thiophene-2-sulfonamide;
N- [2-( {[(1 S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -3,3 '-bithiophene-5-
sulfonamide;
N- [2-( {[(1 S)-2-cycloheptyl-1 -methy lethy 1] amino} methy l)pheny 1] - 5 -(3 -methoxyphenyl)thiophene-2-sulfonamide;
methyl 3-({[2-( {[(1 S)-2-cyclohexy 1-1 -methylethy 1] amino} methyl)phenyl]amino} sulfonyl)-4-(isopropylsulfonyl)thiophene-2-carboxylate;
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(3-fluorophenyl) thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(hydroxymethyl)phenyl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-[4-(hydroxymethyl)phenyl]thiophene-2-sulfonamide;
methyl 5-({[2-({[(lS)-2-cyclopenty 1-1 -methylethy 1]amino}methyl)pheny 1]amino} sulfonyl)-4-metnylthiophene-2-carboxylate;
methyl 4-( {[2-( {[(1 S)-2-cycloheptyl-1 -methylethyl] amino} methy l)phenyl] amino} sulfonyl)-2,5 -dimethyl-3 -fiiroate;
N-[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-[3-(trifluoromethyl)phenyl]thiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5-(3 -fluorophenyl)thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(3-fluorophenyl)thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide;
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-methylthiophene-2-carboxamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-methylthiophene-2-carboxamide;
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]nicotinamide; N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]nicotinamide;
N-[3-({ [(lS)-2-cycloheptyl-1 -methylethyl]amino}methyl)pyridin-2-yl]thiophene-2-sulfonamide;
N- [3 -({[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)pyridin-2-yl]thiophene-2-sulfonamide;
N- [3-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)pyridin-2-yl] -4-fluorobenzenesulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyll-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
methyl 5-({[2-({[(1S)-2-cycloheptyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)-1 -methyl-1H-pyrrole-2-carboxylate;
methyl 5-( {[2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl]amino} sulfonyl)-1 -methyl-1H-pyrrole-2-carboxylate;
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] -1 -methyl-1H-imidazole-4-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide;
5-bromo-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2-furamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-3,5-bis(trifluoromethyl)benzenesulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-y lthiophene-2 -sulfonamide;
N-[2-({[(lS)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]isonicotinamide;
5-chloro-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide;
(l-benzothien-2-yl)-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]thiophene-2-sulfonamide;
5-( 1 -benzothien-2-yl)-N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl) phenyl]thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(3,4-dimethoxyphenyl)thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(4-methoxyphenyl)thiophene-2-sulfonamide:,
N- [2-( {[(1 S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl]-3,3 '-bithiophene-5-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-3,3'-bithiophene-5-sulfonamide;
-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
N-[2-({ [(1S)2-cyclopentyl-1 -methylethyl]amino}methyl)phenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
5-( 1,3-benzodioxol-5-yl)-N-[2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl) phenyl]thiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -2-[4-(4-methoxyphenyl)piperazin-1 -yl]acetamide;
5-chloro-N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-3-methyl-1 -benzothiophene-2-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-3-ylthiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2-methyl-l,3-thiazol-4-yl)thiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(2-methyl-l,3-thiazol-4-yl)thiophene-2-sulfonamide;
ethyl 3-[5-({ [2-({ [(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl) phenyl]amino} sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate;
ethyl 3-[5-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] amino} sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate;
ethyl 3-[5-({[2-({[(1S)-2-cycloheptyl-1 -methylethyl]amino}methyl) phenyl]amino} sulfonyl)-2-thienyl]-l,2,4-oxadiazole-5-carboxylate;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl]-2,4-dimethyl-1,3-thiazole-5-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide;
N-[2-({[(l-S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] -5 -methylthiophene-
2-carboxamide;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] isonicotinamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-ylpiperazin-1-yl)acetamide;
methyl 3-({[2-({[(1S)-2-cyclopentyl-1 -methylethyl]amino}methyl) phenyl]amino} sulfonyl)thiophene-2-carboxylate;
methyl 3-({[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl] amino} sulfonyl)thiophene-2-carboxylate;
N-[2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-imidazol-1 -y l)benzenesulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-2-(2-thienylsulfonyl)- l,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
N-[2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -6-phenoxypyridine-3-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-6-phenoxypyridine-3-sulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-pyrrol-1 -yl)benzenesulfonamide;
N-[2-({[(\ iS)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-pyrrol-1 -yl) benzenesulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-1,2,4-triazol-1 -y l)benzenesulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-1H-imidazole-4-sulfonamide;
N-[2-( {[(1 S)-2-cycloheptyl-1 -methylethyl] amino }methyl)phenyl] -1H-imidazole-4-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-yl - piperazin-1 -yl)acetamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2-(4-pyrimidin-2-yl- piperazin-l-yl)acetamide;
N-[2-( {[(1 S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] hydroxyethanimidoyl]phenyl}thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -5 - {3- [(1 E)-N-methoxyethanimidoyl]phenyl} thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-2-furamide;
2-( {[(1 S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl (4-methoxyphenyl) carbamate;
N-[2-({[(l S)-2-cycloheptyl-1 -methylethyl]amino} methyl)phenyl] -5-(phenylsulfonyl) thiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5 -(phenylsulfonyl) thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(phenylsulfonyl) thiophene-2-sulfonamide;
N-[2-( {[(1 S)-2-cyclohexyl-1 -methylethyl] [(2,2-dimethylpropanoyl)oxy] amino} methyl)phenyl]-2-(2-thienylsulfonyl)-l,2,3,4-tetrahydroisoquinoline-6- sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl][(2,2-dimethylpropanoyl)oxy] amino} methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl][(2,2-dimethylpropanoyl)oxy] amino} methyl) phenyl]-! ,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
5-(l,3-benzodioxol-5-yl)-N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl) phenyl]thiophene-2-sulfonamide;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-(1H-imidazol-1 -yl)benzenesulfonamide;
N-[2-( {[(1 S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl] -4-(1H-imidazol-1 -yl)benzenesulfonamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-5-(l,3-oxazol-2-yl)thiophene-2-sulfonamide;
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]thiophene-2-carboxamide;
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -1 -benzothiophene-2-sulfonamide;
N~ [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -5-pyridin-4-yl-thiophene-2-sulfonamide;
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-pyridin-3-yl-thiophene-2-sulfonamide;
2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl (4-acetylphenyl) carbamate;
N-[2-({[(l-S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-l,2,4-triazol-1 -yl)benzenesulfonamide;
•N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-l,2,4-triazol-1 -yl)benzenesulfonamide;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-(4-pyrimidin-2-yl- piperazin-l-yl)acetamide;
6-( {[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-N-(4-methoxyphenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide;
6-( {[2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] amino} sulfonyl)-N-isopropyl-3,4-dihydroisoquinoline-2(1H)-carboxamide;
N-[2-( {[(1 S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -2-(1H-imidazol-1 -ylcarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] -4-( {[(4-methoxyphenyl)amino]carbonyl}amino)benzenesulfonamide;
4-( {[(4-acetylphenyl)amino] carbonyl} amino)-N- [2-( {[(1 S)-2-cyclohexy 1-1 -methylethyl]amino}methyl)phenyl]benzenesulfonamide;
N-[4-( {[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl] amino} sulfonyl) phenyl]thiophene-2-sulfonamide;
N- [2-( {[(1 iS)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -1 -pyrimidin-2-yl-IH- imidazole-4-sulfonamide;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-1 -benzofuran-2-carboxamide;
N-[2-({[(1S)-2-cyclopentyl-l -methylethyl] amino }methyl)phenyl]-1-benzofuran-2-carboxamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-l-benzofuran-2-carboxamide;
N-{3-[5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)-2-thienyl]phenyl}acetamide;
N- {3 -[5 -({[2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl) phenyl] amino} sulfonyl)-2-thienyl]phenyl} acetamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl)thiophene-2-sulfonamide;
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl)thiophene-2-sulfonamide;
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide;
-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide;
4-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]benzamide; N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-isopropylurea;
N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -N-isopropylthiourea;
N-[2-({[(lS)-2-cyclohexyl-l -methylethyl] amino }methyl)phenyl]-N-(4-methoxyphenyl)urea;
N-(4-acetylphenyl)-6-( {[2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl) phenyl] amino} sulfonyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide;
N- [2-( {[(1 S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -1,2,3,4-tetrahydroisoquinoline-6-sulfonamide;
N- [2-( {[(1S)-2-cycloheptyl-1 -methylethyl] amino} methyl)phenyl] -N-isopropylurea;
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] isoxazole-5-carboxamide;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-5-ylthiophene-2-carboxamide;
N-[2-({[(1S)-2-cycloheptyl-l-methylethyl]amino}methyl)phenyl]-4-fluorobenzamide; tert-butyl4-(2-{[2-(2-furoylammo)benzyl]amino}propyl)piperidine-l-carboxylate; N- [2-( {[(1S)-2-cyclohexyl-1 -methylethyl] amino} methyl)phenyl] -4-nitrobenzamide;
tert-butyl4-[2-({2-[(4-fluorobenzoyl)amino]benzyl}amino)propyl]piperidine-l-carboxylate;
tert-buty\ 4-[2-({2-[(2-thienylcarbonyl)amino]benzyl}amino)propyl]piperidine-l-carboxylate;
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l-pyrazin-2-yl-1H-imidazole-4-sulfonamide;
N-[2-({[(1S',2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino}methyl) phenyl] thiophene-2-sulfonamide;
N- [2-( {[(1S',2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl] amino } methyl)phenyl] -1 -benzofuran-2-carboxamide;
tert-butyl4-{2-[(2-{[(5-isoxazol-5-yl-2-thienyl)carbonyl]amino}benzyl)amino] propyl}piperidine-1 -carboxylate;
N- [2-( {[(1S)-2-cyclopentyl-1 -methylethyl] amino} methyl)phenyl] -5 -isoxazol-5-ylthiophene-2-sulfonamid; or
N-(2-{[(2-cyclohexyl-l-methylethyl)amino]methyl}phenyl)-N'-[4-(l,3-oxazol-5-yl)phenyl]urea;
N-(2- {[(2-cyclohexyl-1 -methylethyl)amino]methyl }phenyl)-4-[(methylsulfonyl) amino]benzenesulfonamide; or
its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites or N-oxide.
3. A pharmaceutical composition comprising a therapeutically effective amount of a
compound of claim 1 or 2 together with pharmaceutically acceptable carrier, excipients,
or diluents.
4. A method for treating or preventing a subject suffering from a condition caused by or
contributed to by bacterial infection or fungal infection, comprising administering to the
subject a therapeutically effective amount of a compound of claim 1 or 2 or a
pharmaceutical composition of claim 3.
5. The method according to claim 4 wherein bacterium is selected from Staphylococci,
Enterococci, Streptococci, Haemophilus, Moraxalla, Escherichia, Chlamydia,
Rickettsiae, Mycoplasm, Legionella, Mycobacterium, Helicobacter, Clostridium,
Bacteroides, Corymbacterium, Bacillus or Enterobactericeae, and the fungal organism
is selected from Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus,
Epidermophyton, Hendersonula, Histoplasma, Microsporum, Paecilomyces,
Paracoccidiodes, Pneumocystis, Trichophyton, or Trichosporium.
6. The method according to claim 4 wherein the condition is selected from community
acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue
infections, hospital acquired lung infections or bone and joint infections, mastitis,
catheter infection, foreign body, prosthesis infections and peptic ulcer disease.
7. A method for the preparation of a compound of Formula 32,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1-X4 and R6 are the same as defined in claim 1, which method comprises:reacting a compound of Formula 5 with a compound of Formula 24
(Formula Removed)
to give a compound of Formula 32.
8. A method for the preparation of a compound of Formula 33,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1-X4 and R6 are the same as defined in claim 1, which method comprises: reacting a compound of Formula 14 with a compound of Formula 24
(Formula Removed)
to give a compound of Formula 33.
9. A method for the preparation of a compound of Formula 34,
(Formula Removed)
pharmaceutically acceptable salte pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1-X4 and R6 are the same as defined in claim 1, which method comprises: reacting a compound of Formula 18 with a compound of Formula 24
(Formula Removed)
to give a compound of Formula 34.
10. A method for the preparation of a compound of Formula 46,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy and X1-X4 are the same as defined in claim 1, which method comprises:
(a) deprotecting a compound of Formula 35 with thiophenol
(Formula Removed)
to give a compound of Formula 42
(Formula Removed)
(b) reacting a compound of Formula 42 with a compound of Formula R6NCO to give
a compound of Formula 45; and
(c) deprotecting a compound of Formula 45 to give a compound of Formula 46.
11. A method for the preparation of a compound of Formula 51,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1-X4 and R6 are the same as defined in claim 1, which method comprises: (a) reacting a compound of Formula 47 with a compound of Formula 24
(Formula Removed)
to give a compound of Formula 48;
(Formula Removed)
(b) protecting a compound of Formula 48 to give a compound of Formula 49;
(Formula Removed)
(c) reacting a compound of Formula 49 with a compound of Formula R6NCO
to give a compound of Formula 50; and
(Formula Removed)
(d) deprotecting a compound of Formula 50 to give a compound of Formula 51.