Patent ID: 6337335
Filing Date: 2002-01-08
Classification: A61P,C07D

Abstract:
A compound of formula (1) wherein: R1 is an â€”XR8, â€”NO2, â€”CN, â€”SO2N(R8)2, â€”CON(R8)2, â€”CSN(R8)2, â€”NH2, â€”NR9R10, â€”N(R10)COR9, â€”N(R10)CSR9, â€”N(R10)SOR9, â€”N(R10)SO2R9, â€”N(R10)CONH2, â€”N(R10)CONR9R10, â€”N(R10)C(O)OR9, â€”N(R10)C(NH)NH2, â€”N(R10)C(NH)NR9R10, â€”N(R10)CSNH2, â€”N(R10)CSNR9R10, â€”N(R10)SONH2, â€”N(R10)SONR9R10, â€”N(R10)SO2NH2, â€”N(R10)SO2NR9R10 or â€”N(R10)Cyc1 group; R2 and R3, which may be the same or different, is each a hydrogen or halogen atom or a group selected from an optionally substituted C1-10aliphatic group optionally interrupted with one to four X2 heteroatoms or groups, an optionally substituted C3-10cycloaliphatic group optionally containing one to four heteroatoms or groups X2 groups, â€”OR10, â€”OR10a, â€”NO2, â€”CN, â€”SR8, â€”COR8, â€”S(O)R8, â€”SO2R8, â€”SO2N(R8)2, â€”CO2R8, â€”CON(R8)2, â€”CSN(R8)2, â€”NH2, â€”NR9R10, â€”N(R10)COR9, â€”N(R10)CSR9, â€”N(R10)SOR9, â€”N(R10)SO2R9, â€”N(R10)CONH2, â€”N(R10)CONR9R10, â€”N(R10)C(O)OR9, â€”N(R10)C(NH)NH2, â€”N(R10)C(NH)NR9R10, â€”N(R10)CSNH2, â€”N(R10)CSNR9R10, â€”N(R10)SONH2, â€”N(R10)SONR9R10, â€”N(R10)SO2NH2, â€”N(R10)SO2NR9R10 or â€”N(R10)Cyc1 group; R4 is a hydrogen atom or a straight or branched chain C1-6alkyl group; R5 is a hydrogen atom or an optionally substituted straight or branched chain C1-6alkyl, C2-6alkenyl or C2-6alkynyl group; R6 is a hydrogen or halogen atom or an â€”NO2, â€”CO2R8, â€”NH2, â€”NR9R10, â€”N(R10)COR9, â€”N(R10)CSR9, â€”N(R10)SOR9, â€”N(R10)SO2R9, â€”N(R10)CONH2, â€”N(R10)CONR9R10, â€”N(R10)C(O)OR9, â€”N(R10)C(NH(NH)NH2, â€”N(R10)C)NR9R10, â€”N(R10)CSNH2, â€”N(R10)CSNR9R10, â€”N(R10)SONH2, â€”N(R10)SONR9R10, â€”N(R10)SO2NH2, â€”N(R10)SO2NR9R10, â€”N(R10)Cyc1 or â€”X1R6a group; R6a is an optionally substituted straight or branched chain C1-6alkyl, C2-6alkenyl or C2-6alkynyl group; R7 is an optionally substituted C1-10aliphatic group optionally interrupted with one to four heteroatoms or groups X2, an optionally substituted C3-10cycloaliphatic group optionally containing one to four heteroatoms or groups X2, an optionally substituted monocyclic or bicyclic C6-12aryl group or an optionally substituted monocyclic or bicyclic C1-9heteroaryl group containing one to four heteroatoms selected from oxygen, sulfur or nitrogen atoms; each R8 is independently a hydrogen atom or an optionally substituted C1-10aliphatic group optionally interrupted with one to four heteroatoms or groups X2, an optionally substituted C3-10cycloaliphatic group optionally containing one to four heteroatoms or groups X2, an optionally substituted monocyclic or bicyclic C6-12aryl group or an optionally substituted monocyclic or bicyclic C1-9heteroaryl group containing one to four heteroatoms selected from oxygen, sulfur or nitrogen atoms; R9 is an optionally substituted straight or branched chain C1-6alkyl, C2-6alkenyl or C2-6alkynyl group, each of which is optionally interrupted with one or two heteroatoms or groups X3; R10 is a hydrogen atom or an optionally substituted straight or branched chain C1-6alkyl, C2-6alkenyl or C2-6alkynyl group, each of which is optionally interrupted with one to four heteroatoms or groups X3; R10a is an optionally substituted C1-10aliphatic group optionally interrupted with one to four heteroatoms or groups X2, an optionally substituted C3-10cycloaliphatic group optionally containing one to four heteroatoms or groups X2, an optionally substituted monocyclic or bicyclic C6-12aryl group or an optionally substituted monocyclic or bicyclic C1-9heteroaryl group containing one to four heteroatoms selected from oxygen, sulfur or nitrogen atoms; X is a direct bond or a linker atom or group selected from â€”Oâ€”, â€”Sâ€”, â€”C(O)â€”, â€”C(S)â€”, â€”C(O)Oâ€”, â€”S(O)â€”, â€”S(O)2â€”, â€”CH2â€” or â€”N(R9a)â€”, where R9a is a hydrogen atom or a straight or branched chain C1-6alkyl group; X1 is a direct bond or a linker atom or group selected from â€”Oâ€”, â€”Sâ€”, â€”C(O)â€”, â€”C(S)â€”, â€”S(O)â€”, â€”S(O)2â€”, â€”N(R11)â€”, â€”CON(R11)â€”, â€”OC(O)N(R11)â€”, â€”CSN(R11)â€”, â€”N(R11)COâ€”, â€”N(R11)C(O)Oâ€”, â€”N(R11)CSâ€”, â€”SON(R11)â€”, â€”SO2N(R11)â€”, â€”N(R11)SO2â€”, â€”N(R11)CON(R11)â€”, â€”N(R11)CSN(R11)â€”, â€”N(R11)SON(R11)â€” and â€”N(R11)SO2N(R11)â€”; R11 is a hydrogen atom or a C1-6 alkyl group; X2 and X3, which may be the same or different, is each a linker atom or group selected from â€”Oâ€”, â€”Sâ€”, â€”C(O)â€”, â€”C(S)â€”, â€”S(O), â€”S(O)2â€”, â€”N(R11)â€”, â€”CON(R11)â€”, â€”OC(O)N(R11)â€”, â€”CSN(R11)â€”, â€”N(R11)COâ€”, â€”N(R11)C(O)Oâ€”, â€”N(R11)CSâ€”, â€”SON(R11)â€”, â€”SO2N(R11)â€”, â€”N(R11)SO2â€”, â€”N(R11)CON(R11)â€”, â€”N(R11)CSN(R11)â€”, â€”N(R11)SON(R11)â€” and â€”N(R11)SO2N(R11)â€”; wherein said optional substituents on said alkyl, alkenyl, alkynyl, aliphatic, heteroaliphatic, cycloaliphatic and heterocycloaliphatic groups in R2, R3, R5, R6a, R7, R8, R9, R10 and R10a are one or more groups selected from halogen, hydroxyl, C1-6alkoxy, thiol, C1-6alkylthio, â€”SC(NH)NH2, â€”CH2SC(NH)NH2, NH2, â€”NR9R10, and C3-7cyclic amino which is optionally substituted with one to three halogen atoms or C1-4alkyl, hydroxyl or C1-4alkoxy groups and which optionally contains one or more other heteroatoms or heteroatom containing groups selected from â€”Oâ€”, â€”Sâ€”, â€”C(O)â€”, â€”C(S)â€”, â€”S(O)â€” or â€”S(O)2â€”; wherein said optional substituents on said aryl and heteroaryl groups in R7, R8 and R10a are one or more R12 groups, where R12 is R13 or â€”Alk(R13)m; R13 is a halogen atom, â€”NH2, â€”NHR14, â€”N(R14)2, â€”NO2, â€”CN, â€”OH, â€”OR14, â€”CHO, â€”CO2H, â€”CO2Alk1, â€”SH, SR14, â€”COR14, â€”CSR14, â€”SO3H, â€”SO2R14, â€”SO2NH2, â€”SO2NHR14, â€”SO2N(R14)2, â€”CONH2, â€”CSNH2, â€”CONHR14, â€”CSNHR14, â€”CON(R14)2, â€”CSN(R14)2, â€”N(R11)SO2H, â€”N(R11)SO2R14, â€”N(SO2R14)2, â€”N(R11)SO2NH2, â€”N(R11)SO2NHR14, â€”N(R11)SO2N(R14)2, â€”N(R11)COR14, â€”N(R11)CONH2, â€”N(R11)CONHR14, â€”N(R11)CON(R14)2, â€”N(R11)CSR14, â€”N(R11)CSNH2, â€”N(R11)CSNHR14, â€”N(R11)CSN(R14)2, â€”N(R11)C(O)OR14, optionally substituted C5-7cycloalkyl, optionally substituted monocyclic or bicyclic C6-12aryl or optionally substituted monocyclic or bicyclic C5-13heteroaryl, wherein said cycloalkyl, aryl and heteroaryl substituents are one or two groups selected from C1-6alkyl, hydroxyl (â€”OH), hydroxyC1-6alkyl and C1-6alkyoxy groups; R14 is â€”Alk(R3)m, heteroC3-6cycloalkyl, â€”Alk-heteroC3-6cycloalkyl, monocyclic or bicyclic C6-12aryl or monocyclic or bicyclic C1-9heteroaryl; Alk is a straight or branched chain C1-6alkylene, C2-6alkenylene or C2-6alkynylene group optionally interrupted by one, two or three â€”Oâ€” or â€”Sâ€”atoms  or â€”SOâ€”, â€”S(O)2â€” or â€”N(R11)â€” groups; Alk1 is a straight or branched chain C1-8alkyl group which is optionally substituted with one or more R13 groups; Cyc1 is a optionally substituted C3-7monocyclic carbocyclic group optionally containing one or more â€”Oâ€” or â€”Sâ€” atoms or â€”C(O)â€”, â€”C(S)â€”, â€”SOâ€”, â€”S(O)2â€” or â€”N(R11)â€” groups, wherein said optional Cyc1 substituents are selected from one to three halogen atoms or C1-4alkyl, hydroxy or C1-4alkoxy groups; m is zero or an integer 1, 2 or 3; and the salts, solvates, hydrates and N-oxides thereof; with the provisos that: (1) when one or both of R2 and R3 is an â€”OR10 group, then R1 is an â€”OR8 group in which R8 is an optionally substituted C1-10aliphatic group substituted by a cyclic amino group, an optionally substituted C1-10aliphatic group interrupted with one to four atoms or groups X2, an optionally substituted C3-10cycloaliphatic group optionally containing one to four atoms or groups X2, an optionally substituted monocyclic or bicyclic C6-12aryl group or an optionally substituted monocyclic or bicyclic C1-9heteroaryl group containing one to four heteroatoms selected from oxygen, sulfur or nitrogen atoms; (2) when R5 is a C1-6alkyl or trifluoromethyl group and R7 is a C1-6alkyl group optionally substituted with cyano or alkoxy or a C2-6alkenyl, C2-6alkynyl or â€”CH2Ar group where Ar is phenyl, then at least one of R1, R2, R3, R4 and R6 is other than a hydrogen atom; (3) when one of R1, R2 and R3 is bromo, chloro, fluoro, trifluoromethyl, methyl, methoxy, isopropoxy, or trifluoromethoxy and the other of R1, R2 and R3 are hydrogen, chloro, fluoro, methyl or trifluoromethyl, R4 and R6 are hydrogen and R7 is methyl, ethyl, propyl or butyl, then R5 is other than trifluoromethyl; and (4) when R4 and R6 are hydrogen, R5 is hydrogen or methyl and R7 is ethyl, propyl, butyl or â€”CH2Ar where Ar is phenyl, then at least two of R1, R2 and R3 are other than nitro groups.