Patent ID: 6706723
Filing Date: 2004-03-16
Classification: A61P,C07D

Abstract:
A compound of the formula wherein A is optionally substituted (C6-C10)aryl or (C1-C10)heteroaryl;B is optionally substituted (C6-C10)aryl, (C3-C8)cycloalkyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C6-C10)aryl-(C1-C4)alkyl, (C3-C8)cycloalkyl-(C1-C4)alkyl, C1-C10)heteroaryl-(C1-C4)alkyl or (C1-C10)heterocyclic-(C1-C4)alkyl; wherein each of the aforesaid (C3-C8)cycloalkyl or (C1-C10)heterocyclic may optionally contain one or two double bonds; wherein A and B may be independently optionally substituted on any of the ring carbon atoms capable of forming an additional bond by one or two substituents independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, and (C3-C8)cycloalkyloxy; X is selected from the group consisting of oxygen, >C&boxH;O, sulfur, >SO2, >S&boxH;O, >NR10, â€”CH2Oâ€”, â€”OCH2â€”, â€”CH2Sâ€”, â€”CH2(S&boxH;O)â€”, â€”CH2SO2â€”, â€”SCH2â€”, â€”SOCH2â€”, â€”SO2CH2â€”, â€”[N(R10)]CH2â€”, â€”CH2[N(R10)]â€”, â€”[N(R10)]SO2â€” and â€”SO2[N(R10)]â€”; Y is selected from the group consisting of a bond, oxygen, sulfur, >C&boxH;O, >S&boxH;O, NR12, â€”CH2â€”, â€”CH2Oâ€”, â€”OCH2â€”, â€”CH2Sâ€”, â€”CH2(S&boxH;O)â€”, â€”CH2SO2â€”, â€”(S&boxH;O)CH2â€”, SO2CH2â€”, â€”[N(R12)]CH2â€”, â€”CH2[N(R12)]â€”, â€”CH2CH2â€”, â€”CH&boxH;CHâ€”, â€”[N(R12)]â€”SO2â€” and â€”SO2[N(R12)]â€”; R1 is hydrogen, (R2)2n+1â€”(C)nâ€” or (C3-C8)cycloalkyl wherein said (C3-C8)cycloalkyl may also optionally be substituted by one to two substituents independently selected from halo, (C1-C4)alkyl, (C1-C4)alkenyl, (C1-C4)alkynyl, R3â€”, R3â€”Oâ€”, perfluoro(C1-C4)alkoxy, R3â€”(C1-C4)alkyl-Oâ€”, R3â€”(C&boxH;O)â€”Oâ€”, (R3)2Nâ€”(C&boxH;O)â€”Oâ€”, â€”NO2, (R3)2Nâ€”, R3â€”(C&boxH;O)â€”(NR4)â€”, R3â€”(SO2)â€”(NR4)â€”, R3Oâ€”(C&boxH;O)â€”(NR4)â€”, (R3)2Nâ€”(C&boxH;O)â€”(NR4)â€”, R3â€”Sâ€”, R3â€”(S&boxH;O)â€”, R3â€”(SO2)â€”, (R3)2Nâ€”(SO2)â€”, â€”CN, R3â€”(C&boxH;O)â€”, R3â€”Oâ€”(C&boxH;O)â€” and (R3)2Nâ€”(C&boxH;O)â€”; n is an integer from one to ten; each R2 is independently selected from the group consisting of halo, (C1-C4)alkenyl, (C1-C4)alkynyl, R3â€”, R3â€”Oâ€”, perfluoro(C1-C4)alkoxy, R3â€”(C&boxH;O)â€”Oâ€”, (R3)2Nâ€”(C&boxH;O)â€”Oâ€”, â€”NO2, (R3)2Nâ€”, R3â€”(SO2)â€”(NR4)â€”, (R3)2â€”Nâ€”(C&boxH;O)â€”, R3â€”(C&boxH;O)â€”(NR4)â€”, R3Oâ€”(C&boxH;O)â€”(NR4)â€”, (R3)2â€”Nâ€”(C&boxH;O)â€”(NR4)â€”, R3â€”Sâ€”, R3â€”(S&boxH;O)â€”, R3â€”(SO2)â€”, (R3)2Nâ€”(SO2)â€”, â€”CN, R3â€”Oâ€”(C&boxH;O)â€” and R3â€”(C&boxH;O)â€”; wherein not more than three of said R2 substituents may be other than hydrogen and any one carbon atom of said â€”(C)nâ€” group can contain only one bond to a heteroatom; wherein a carbon atom of any two R2 groups may be taken together with the carbons to which they are attached to form a four to ten membered ring; each R3 is independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C6-C10)aryl, (C3-C8)cycloalkyl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl; wherein each R3 may be optionally substituted on any carbon atom able to support an additional substituent, by one to three substituents per alkyl moiety or by one to three substituents per ring, independently selected from the group consisting of halo, hydroxy, amino, â€”CN, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkyl-NHâ€”, [(C1-C4)alkyl]2â€”Nâ€”, (C6-C10)aryl, (C3-C8)cycloalkyl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl; wherein said (C3-C8)cycloalkyl and (C1-C10)heterocyclyl may also optionally be substituted by oxo; wherein said (C1-C10)heteroaryl and (C1-C10)heterocyclyl may optionally be substituted on any ring nitrogen atom able to support an additional substituent by one to two substituents per ring independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkyl-(C&boxH;O)â€”, (C6-C10)aryl, (C3-C8)cycloalkyl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl; wherein said R3 group may optionally be taken together with an R4 group to form a three to eight membered ring; wherein two of said R4 groups may be taken together to form a three to eight membered ring; R4 wherever it occurs is independently selected from hydrogen and (C1-C4)alkyl; G is R5â€” or R6â€”(CHR13)pâ€”; wherein G is a substituent on any ring carbon atom of B capable of forming an additional bond and is oriented at a position other than alpha to the point of attachment of the B ring to Y; p is an integer from one to six; wherein R5 is selected from the group consisting of R7â€”, R11â€”Oâ€”, R7â€”(C1-C4)alkyl-Oâ€”, R8â€”(C&boxH;O)â€”Oâ€”, H2N(C&boxH;O)â€”Oâ€”, H2N(C&boxH;O)â€”Oâ€”, R8â€”NH(C&boxH;O)â€”Oâ€”, (R8)2N(C&boxH;O)â€”Oâ€”, R8â€”Sâ€”, R8â€”(S&boxH;O)â€”, R8â€”(SO2)â€”, H2Nâ€”(SO2)â€”, R8â€”NHâ€”(SO2)â€”, (R8)2Nâ€”(SO2)â€”, formyl, R8â€”(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, R8â€”Oâ€”(C&boxH;)â€”, H2Nâ€”(C&boxH;O)â€”, R8NHâ€”(C&boxH;O)â€”, (R8)2Nâ€”(C&boxH;O)â€”, â€”NO2, NH2, R8â€”NHâ€”, (R8)2Nâ€”, H(C&boxH;O)â€”(NR9)â€”, R8â€”(C&boxH;O)â€”(NR9)â€”, H2Nâ€”(C&boxH;O)â€”(NR9)â€”, R8NHâ€”(C&boxH;O)â€”(NR9)â€”, (R8)2Nâ€”(C&boxH;O)â€”(NR9)â€”, R8Oâ€”(C&boxH;O)â€”(NR9)â€”, R8â€”(SO2)â€”NHâ€” and R8â€”(SO2)â€”(NR9)â€”; R6 is selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkenyl, (C1-C4)alkynyl, R7, OH, R8â€”Oâ€”, R8â€”(C1-C4)alkyl-Oâ€”, perfluoro(C1-C4)alkoxy, R8â€”(C&boxH;O)â€”Oâ€”, H2N(C&boxH;O)â€”Oâ€”, R8â€”NH(C&boxH;O)â€”Oâ€”, (R8)2N(C&boxH;O)â€”Oâ€”, R8â€”(S&boxH;O)â€”, R8â€”(SO2)â€”, H2Nâ€”(SO2)â€”, R8â€”NH(C&boxH;O)â€”(R8)2N(C&boxH;O)â€”Oâ€”,R8â€”Sâ€”, R8â€”(SO2)â€”, (R8)2Nâ€”(SO2)â€”, formyl, â€”CN, R8â€”(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, R8â€”Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, R8NHâ€”(C&boxH;O)â€”, (R8)2Nâ€”(C&boxH;O)â€”, â€”NO2, NH2, R8â€”NHâ€”, (R8)2Nâ€”, H(C&boxH;O)â€”(NR9)â€”, R8â€”(C&boxH;O)â€”(NR9)â€”, (R8)2Nâ€”(C&boxH;O)â€”(NR9)â€”, R8Oâ€”(C&boxH;O)â€”NR9)â€”, R8NHâ€”(C&boxH;O)â€”(NR9)â€”,(NR9)â€”, R8NHâ€”(C&boxH;O)â€”(NR9)â€”, R8â€”(SO2)â€”NHâ€” and R8â€”(SO2)â€”(NR9)â€”; R7 is selected from the group consisting of (C6-C10)aryl. (C3-C8)cycloalkyl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl; wherein said (C6-C10)aryl, (C3-C8)cycloalkyl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl moieties may be optionally substituted on any of the ring carbon atoms capable of forming an additional bond by one to three substituents per ring independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, amino, (C1-C4)alkyl-NHâ€”, [(C1-C4)alkyl]2-Nâ€” and (C3-C8)cycloalkyloxy; wherein said (C3-C8)cycloalkyl and (C1-C10)heterocyclyl moieties may also optionally be substituted by oxo; wherein said (C1-C10)heteroaryl and (C1-C10)heterocyclyl moieties may optionally be substituted on any ring nitrogen atom able to support an additional substituent by one to two substituents per ring independently selected from the group consisting of (C1-C4)alkyl and (C1-C4)alkyl-(C=O)â€”; R8 is selected from the group consisting of (C1-C4)alkyl, (C6-C10)aryl, (C3-C8)cycloalkyl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl: wherein each R8 may be optionally substituted on any carbon atom able to support an additional substituent, by one to three substituents per alkyl moiety or by one to three substituents per ring, independently selected from the group consisting of F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, and (C3-C8)cycloalkyloxy; wherein said (C3-C8)cycloalkyl and (C1-C10)heterocyclyl may also optionally be substituted by oxo; wherein said (C1-C10)heteroaryl and (C1-C10)heterocyclyl may also optionally be substituted on any ring nitrogen atom able to support an additional substituent by one to two substituents per ring independently selected from the group consisting of (C1-C4)alkyl and (C1-C4)alkyl-(C&boxH;O)â€”; wherein two of said R8 may optionally be taken together with the heteroatom to which they are attached to form a three to eight membered ring; R9 wherever it occurs is independently selected from hydrogen and (C1-C4)alkyl; wherein said R8 and R9 may optionally be taken together with the heteroatoms to which they are attached to form a three to eight membered ring; R10 wherever it occurs is independently selected from hydrogen and (C1-C4)alkyl; R11 is selected from the group consisting of (C6-C10)aryl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl; wherein said (C6-C10)aryl, (C1-C10)heteroaryl and (C1-C10)heterocyclyl moieties may be optionally substituted on any of the ring carbon atoms capable of forming an additional bond by one to three substituents per ring independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, and (C3-C8)cycloalkyloxy; wherein said (C1-C10)heterocyclyl may also optionally be substituted by oxo; wherein said C1-C10)heteroaryl and (C1-C10)heterocyclyl may optionally be substituted on any ring nitrogen atom able to support an additional substituent by one to two substituents per ring independently selected from the group consisting of (C1-C4)alkyl and (C1-C4)alkyl-(C&boxH;O)â€”; R12 wherever it occurs is independently selected from hydrogen and (C1-C4)alkyl; R13 is independently selected from hydrogen and (C1-C4)alkyl: wherein R13 may optionally be taken together with R6 to form a four to 10 membered ring; or a pharmaceutically acceptable salt thereof.