Patent ID: 6608104
Filing Date: 2003-08-19
Classification: A61P,C07D

Abstract:
A compound of the formula or a pharmaceutically acceptable salt thereof, whereinX is oxygen; Z is â€”OR11, â€”NR12R13 or (C1-C6)alkyl optionally substituted with one to three substituents independently selected from the group consisting of halo, hydroxy, â€”CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, mercapto, (C1-C6)alkylthio, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl, perfluoro(C1-C6)alkoxy, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C9)heterocyclic, (C3-C9)cycloalkyl, (C6-C10)arylamino, (C6-C10)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino, (C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-Sâ€”, (C3-C9)heterocyclic-Oâ€”, (C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-Sâ€”, (C3-C9)cycloalkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”Sâ€”, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkoxy-(C&boxH;O)â€”, â€”CO2H, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€” and [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”; R1, R2, R5 and R6 are each independently selected from the group consisting of hydrogen, â€”CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl(C&boxH;O)â€”, (C1-C6)alkoxy-(C&boxH;O)â€”, â€”CO2H, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€” and [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”; wherein said R1, R2, R5 and R6 (C1-C6)alkyl groups are each independently optionally substituted by one to three groups selected from halo, trifluoromethyl, hydroxy, amino, â€”CN, (C1-C6)alkylthio, (C1-C6)alkoxy, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C6-C10)arylamino, (C6-C10)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino,(C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-Sâ€”,(C3-C9)heterocyclic-Oâ€”, (C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-Sâ€”, (C3-C9)cycloalkyl-Oâ€”,(C6-C10)aryl(C1-C2)alkoxy, (C1-C9)heteroaryl(C1-C2)alkoxy, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”Sâ€”, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkylsulfinyl, (C6-C10)arylsulfinyl, (C1-C6)alkylsulfonyl, (C6-C10)arylsulfonyl, (C1-C6)alkylamino, or ((C1-C6)alkyl)2amino; R3 is hydrogen; (C1-C6)alkyl optionally substituted by one or more of â€”CN, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C3-C6)cycloalkyl, (C1-C6)alkyl(C&boxH;O)â€”, (C1-C6)alkoxy-(C&boxH;O)â€”, â€”CO2H, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, and [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”; (C6-C10)arylsulfonyl; (C1-C6)alkylsulfonyl; (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”; [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”; or (R10R9N)â€”(C&boxH;O)â€” wherein R9 and R10 are taken together with the nitrogen to which they are attached to form a ring selected from azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl and thiomorphonyl; R4 is hydrogen or (C1-C4)alkyl; R7 and R8 are each independently selected from the group consisting of hydrogen, hydroxy, halo, â€”CN, (C1-C9)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, (C1-C6)alkylthio, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl, perfluoro(C1-C6)alkoxy, (C3-C6)cycloalkyl, (C6-C10)aryl, (C3-C9)heterocyclic, (C1-C9)heteroaryl, (C6-C10)arylamino, (C6-C10)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino, (C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-Sâ€”, C3-C9)heterocyclic-Oâ€”,(C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-Sâ€”, (C3-C9)cycloalkyl-Oâ€”, (C1-C9)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, (C1-C6)alkyl(C&boxH;O)â€”, (C1-C6)alkyl(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl(C&boxH;O)â€”Sâ€”, (C1-C6)alkyl(C&boxH;O)â€”Oâ€”, (C1-C6)alkoxy-(C&boxH;O)â€”, â€”CO2H, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€” and [(C1-C9)alkyl]2-Nâ€”(C&boxH;O)â€”; wherein each of said R7 and R8 (C1-C6)alkyl group are independently optionally substituted by one to three substituents independently selected from halo, hydroxy, â€”CN, (C1-C6)alkoxy, (C1-C6)alkylthio, trifluoromethyl, (C3-C6)cycloalkyl, (C6-C10)aryl, (C3-C9)heterocyclic,(C1-C9)heteroaryl, (C6-C10)arylamino, (C6-C1)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino,(C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-Sâ€”,(C3-C9)heterocyclic-Oâ€”, (C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-Sâ€”, (C3-C9)cycloalkyl-Oâ€”,(C6-C10)aryl(C1-C2)alkoxy, (C1-C9)heteroaryl(C1-C2)alkoxy, (C1-C6)alkyl(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl(C&boxH;O)â€”Sâ€”, (C1-C6)alkyl(C&boxH;O)â€”Oâ€”, (C1-C6)alkylsulfinyl, (C6-C10)arylsulfinyl, (C1-C6)alkylsulfonyl, (C6-C10)arylsulfonyl, amino, (C1-C6)alkylamino and ((C1-C6)alkyl)2amino; or R1 and R2, R5 and R6 or R7 and R8 may be taken together to form a carbonyl group or an optionally substituted (C3-C6)cycloalkyl ring optionally containing 1 or 2 heteroatoms; wherein said heteroatoms may be selected from the group consisting of â€”Sâ€”, â€”Oâ€” or >NH or >N(C1-C6)alkyl; and said optional substituents (i.e. 1-3 substituents per ring) may be selected from (C1-C4)alkyl, fluoro, chloro, hydroxy, (C1-C4)alkoxy and â€”NR14R15; or R5 and R7, R5 and R8, R6 and R7 or R6 and R8 may be taken together to form an optionally substituted (C4-C6)cycloalkyl ring optionally containing 1 or 2 heteroatoms; wherein said heteroatoms may be selected from the group consisting of â€”Sâ€”, â€”Oâ€” or >NH or >N(C1-C6)alkyl; and said optional substituents (i.e. 1-3 substituents) may be selected from (C1-C4)alkyl, fluoro, chloro, hydroxy, (C1-C4)alkoxy and â€”NR14R15; R11 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C2-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkoxy-(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€” and [(C1-C6) alkyl]2-Nâ€”(C&boxH;O)â€”; R12 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkoxy-(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€” and [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”; R13 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl or (C3-C9)heterocyclic; R14 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkoxy-(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€” and [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”; R15 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl or (C3-C9)heterocyclic; Q is (C1-C9)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl, (C1-C9)heteroaryl(C1-C6)alkyl, (C3-C9)heterocyclic(C1-C6)alkyl, (C6-C10)aryl(C6-C10)aryl, (C6-C10)aryl(C1-C9)heteroaryl, (C6-C10)aryl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C6-C10)aryl, (C1-C9)heteroaryl(C1-C9)heteroaryl, (C1-C9)heteroaryl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C10)aryl, (C3-C9)heterocyclic(C1-C9)heteroaryl, (C3-C9)heterocyclic(C3-C9)heterocyclic, (C6-C10)aryloxy(C1-C9)alkyl, (C6-C10)aryloxy(C6-C10)aryl, (C6-C10)aryloxy(C1-C9)heteroaryl, (C6-C10)aryloxy(C3-C9)heterocyclic, (C1-C9)heteroaryloxy(C1-C6)alkyl, (C1-C9)heteroaryloxy(C6-C10)aryl, (C1-C9)heteroaryloxy(C1-C9)heteroaryl, (C1-C9)heteroaryloxy(C3-C9)heterocyclic, (C3-C9)heterocyclic-Oâ€”(C1-C6)alkyl, (C3-C9)heterocyclic-Oâ€”(C6-C10)aryl, (C3-C9)heterocyclic-Oâ€”(C1-C9)heteroaryl, (C3-C9)heterocyclic-Oâ€”(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl(C6-C10)aryl,(C6-C10)aryl(C1-C6)alkyl(C1-C9)heteroaryl, (C6-C10)aryl(C1-C6)alkyl(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkoxy(C6-C10)aryl, (C6-C10)aryl(C1-C6)alkoxy(C1-C9)heteroaryl, (C6-C10)aryl(C1-C6)alkoxy(C3-C9)heterocyclic, (C6-C10)aryloxy(C1-C6)alkyl(C6-C10)aryl, (C6-C10)aryloxy(C1-C6)alkyl(C1-C9)heteroaryl, (C6-C10)aryloxy(C1-C6)alkyl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryl(C1-C6)alkyl(C1-C9)heteroaryl, (C1-C9)heteroaryl(C1-C6)alkyl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C1-C6)alkoxy(C6-C10)aryl, (C1-C9)heteroaryl(C1-C9)alkoxy(C1-C9)heteroaryl, (C1-C9)heteroaryl(C1-C6)alkoxy(C3-C9)heterocyclic, (C1-C9)heteroaryloxy(C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryloxy(C1-C6)alkyl(C1-C9)heteroaryl, (C1-C9)heteroaryloxy(C1-C6)alkyl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C6)alkyl(C6-C10)aryl, (C3-C9)heterocyclic(C1-C6)alkyl(C1-C9)heteroaryl, (C3-C9)heterocyclic(C1-C6)alkyl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C6)alkoxy(C6-C1-C9)aryl, (C3-C9)heterocyclic(C1-C6)alkoxy(C1-C9)heteroaryl, (C3-C9)heterocyclic(C1-C6)alkoxy(C3-C9)heterocyclic, (C3-C9)heterocyclic-Oâ€”(C1-C6)alkyl(C1-C10)aryl, (C3-C9)heterocyclic-Oâ€”(C1-C6)alkyl(C1-C9)heteroaryl, (C3-C9)heterocyclic-Oâ€”(C1-C6)alkyl(C3-C9)heterocyclic, (C6-C10)aryl(C6-C10)aryl(C1-C6)alkyl, (C6-C10)aryl-NHâ€”(C1-C6)alkyl, (C6-C10)aryl-NHâ€”(C6-C10)aryl, (C6-C10)aryl-NHâ€”(C1-C9)heteroaryl, (C6-C10)aryl-NHâ€”(C3-C9)heterocyclic, (C1-C9)heteroaryl-NHâ€”(C1-C6)alkyl, (C1-C9)heteroaryl-NHâ€”(C6-C10)aryl, (C1-C9)heteroaryl-NHâ€”(C1-C9)heteroaryl, (C1-C9)heteroaryl-NHâ€”(C3-C9)heterocyclic, (C3-C9)heterocyclic-NHâ€”(C1-C6)alkyl, (C3-C9)heterocyclic-NHâ€”(C6-C10)aryl, (C3-C9)heterocyclic-NHâ€”(C1-C9)heteroaryl, (C3-C9)heterocyclic-NHâ€”(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl-NHâ€”(C6-C10)aryl, (C6-C10)aryl(C1-C6)alkyl-NHâ€”(C1-C9)heteroaryl, (C6-C10)aryl(C1-C6)alkyl-NHâ€”(C3-C9)heterocyclic, (C6-C10)aryl-NHâ€”(C1-C6)alkyl(C6-C10)aryl, (C6-C10)aryl-NHâ€”(C1-C6)alkyl(C1-C9)heteroaryl, (C6-C10)aryl-NHâ€”(C1-C6)alkyl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C1-C9)alkyl-NHâ€”(C6-C10)aryl, (C1-C9)heteroaryl(C1-C6)alkyl-NHâ€”(C1-C9)heteroaryl, (C1-C9)heteroaryl(C1-C6)alkyl-NHâ€”(C3-C9)heterocyclic, (C1-C9)heteroaryl-NHâ€”(C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryl-NHâ€”(C1-C6)alkyl(C1-C9)heteroaryl, (C1-C9)heteroaryl-NHâ€”(C1-C6)alkyl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C6)alkyl-NHâ€”(C6-C10)aryl, (C3-C9)heterocyclic(C1-C6)alkyl-NHâ€”(C1-C9)heteroaryl, (C3-C9)heterocyclic(C1-C6)alkyl-NHâ€”(C3-C9)heterocyclic, (C3-C9)heterocyclic-NHâ€”(C1-C6)alkyl(C6-C10)aryl, (C3-C9)heterocyclic-NHâ€”(C1-C6)alkyl(C1-C9)heteroaryl, (C3-C9)heterocyclic-NHâ€”(C1-C6)alkyl(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl-NHâ€”(C1-C6)alkyl or (C6-C10)aryl(C1-C6)alkoxy(C1-C6)alkyl, wherein each of said (C6-C10)aryl, (C1-C9)heteroaryl or (C3-C9)heterocyclic groups may optionally be substituted by one or more substituents, independently selected from the group consisting of halo, â€”CN, (C1-C6)alkyl optionally substituted with one or more fluorine atoms, hydroxy, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy optionally substituted with one or more fluorine atoms, (C1-C6)alkoxy(C1-C6)alkyl, HOâ€”(C&boxH;O)â€”,(C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”,(C1-C6)alkyl-(C&boxH;O)â€”Oâ€”(C1-C6)alkyl, H(O&boxH;C)â€”, H(O&boxH;C)â€”(C1-C6)alkyl, (C1-C6)alkyl(O&boxH;C)â€”, (C1-C9)alkyl(O&boxH;C)â€”(C1-C6)alkyl, NO2, amino, (C1-C6)alkylamino, [(C1-C9)alkyl]2amino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, [(C1-C6)alkyl]2amino(C1-C6)alkyl, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2Nâ€”(C&boxH;O)â€”, H2N(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-HN(C&boxH;O)â€”(C1-C6)alkyl, [(C1-C6)alkyl]2Nâ€”(C&boxH;O)â€”(C1-C9)alkyl, H(O&boxH;C)â€”NHâ€”, (C1-C6)alkyl(C&boxH;O)â€”NH, (C1-C6)alkyl(C&boxH;O)â€” [NH](C1-C6)alkyl, (C1-C6)alkyl(C&boxH;O)â€” [N(C1-C6)alkyl](C1-C6)alkyl, (C1-C6)alkyl-Sâ€”(C1-C6)alkyl-(S&boxH;O)â€”, (C1-C6)alkyl-SO2â€”, (C1-C6)alkyl-SO2â€”NHâ€”, (C1-C6)alkyl-SO2-[Nâ€”(C1-C6)alkyl]-, H2Nâ€”SO2â€”, H2Nâ€”SO2â€”(C1-C6)alkyl, (C1-C6)alkyl HNâ€”SO2â€”(C1-C6)alkyl, [(C1-C9)alkyl]2Nâ€”SO2â€”(C1-C9)alkyl, CF3SO2â€”, (C1-C6)alkyl-SO2â€”, phenyl, phenyl(C1-C9)alkyl, (C3-C10)cycloalkyl, (C1-C9)heterocycloalkyl, and (C1-C9)heteroaryl.