Methods for treating hepatitis C

A compound of Formula (I):

• wherein:
• X is:
• -cyano;
• Y is:
• Z is:
• -hydrogen;
• —C1 to C6 alkyl optionally substituted with:
• —C1 to C6 alkoxy,
• -one or more halogen substituents, or
• -aryl;
• —C2 to C6 alkenyl;
• -aryl optionally substituted with C1 to C6 alkoxy or one or more C1 to C6 alkyl substituents;
• —COORx, where Rx is as defined above;
• -cyclopropyl;
• -cyclobutyl;
• -cyclopentyl;
• -cyclohexyl;
• -cyclopropylmethyl;
• -cyclobutylmethyl;
• or
• -cyclopentylmethyl;
• R is hydrogen, halogen or C1 to C6 alkoxy;
• R1 is:
• -hydrogen;
• -hydroxy;
• -halogen;
• —C1 to C6 haloalkyl;
• -nitro;
• -5 or 6 membered heteroaryl;
• -5 or 6 membered heterocycle;
• —C1 to C6 alkoxy optionally substituted with:
• -one or more halogen substituents,
• -aryl, or
• -5 or 6 membered heterocycle;
• -aryl optionally substituted with C1 to C6 alkoxy;
• —CORx, where Rx is as defined above;
• —C1 to C6 alkyl optionally substituted with di-C1 to C6 alkyl-amino or 5 or 6 membered heterocycle;
• -cyclopropyl;
• -cyclobutyl;
• -cyclopentyl;
• or
• -cyclohexyl;
• R2 is:
• -nitro;
• -hydrogen;
• -halogen;
• -hydroxy;
• —C1 to C6 alkyl, optionally substituted with one or more halogen substituents;
• -cyclopropyl;
• -cyclobutyl;
• -cyclopentyl;
• -cyclohexyl;
• -amino;
• —C1 to C6 alkoxy optionally substituted with:
• -one or more halogen substituents,
• —OCORX, where Rx is as defined above,
• -di-C1 to C6 alkyl-amino optionally substituted with C1 to C6 alkoxy,
• -5 or 6 membered heterocycle optionally substituted with C1 to C6 alkyl,
• -5 or 6 membered heteroaryl, or
• -aryl;
• —COORx, where Rx is as defined above;
• —C1 to C6 haloalkyl;
• -amide optionally substituted with:
• -hydroxy, or
• -aryl;
• -5 or 6 membered heteroaryl;
• —OCORx, where Rx is as defined above;
• —NHCORjj, where Rjj is:
• —C1 to C6 alkoxy, or
• -amino optionally substituted with one or more C1 to C6 alkyl substituents;
• —ORkk, where Rkk is 5 to 6 membered heteroaryl;
• —NHSO2Rx, where Rx is as defined above;
• —NHSO2cyclopropyl;
• —NHSO2cyclobutyl;
• —NHSO2cyclopentyl;
• or
• —NHSO2cyclohexyl;
• and
• R3 is:
• -hydrogen;
• or
• —CH2OCORx, where Rx is as defined above;
• or a pharmaceutically acceptable salt thereof.

A compound of Formula (I):

• wherein:
• X is:
• -cyano;
• Y is:
• -aryl substituted with one or more of the following:
• —C1 to C6 alkoxy, optionally substituted with:
• —C1 to C6 alkoxy,
• -hydroxy,
• -one or more halogen substituents,
• -5 or 6 membered heterocycle, optionally substituted with:
• —C1 to C6 alkyl, or
• -hydroxy,
• -amino optionally substituted with one or more C1 to C6 alkyl substituents,
• —NRiSO2Rx, where Rx is C1 to C6 alkyl and Ri is:
• -hydrogen,
• —C1 to C6 alkyl,
• —CORx, where Rx is as defined above,
• —C1 to C6 haloalkyl, or
• —C1 to C6 haloalkoxy,
• —NRjCORk, where Rk is:
• —C1 to C6 alkyl,
• -hydrogen, or
• -amino optionally substituted with one or more C1 to C6 alkyl substituents, and Rj is:
• -hydrogen,
• —C1 to C6 alkyl,
• —CORx, where Rx is as defined above,
• —C1 to C6 haloalkyl, or
• —C1 to C6 haloalkoxy,
• —N═N═+═N−, or
• —COR1, where R1 is 5 or 6 membered heterocycle optionally substituted with hydroxy,
• -amino optionally substituted with one or more C1 to C6 alkyl substituents,
• -nitro,
• —C1 to C6 alkyl, optionally substituted with:
• —NHSO2Rx, where Rx is as defined above, or
• —NRxSO2Rx, where Rx is as defined above,
• —C1 to C6 haloalkoxy,
• -halogen,
• -hydroxy,
• —COORx, where Rx is as defined above,
• —CORm, where Rm is:
• -amino optionally substituted with:
• (i) -cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or
• (ii) one or more C1 to C6 alkyl substituents, where the C1 to C6 alkyl substituents are optionally substituted with:
• -hydroxy
• -5 or 6 membered heterocycle,
• -amino optionally substituted with one or more C1 to C6 alkyl substituents,
• —C1 to C6 alkoxy,
• -3 to 7 membered heterocycle, optionally substituted with C1 to C6 alkyl, optionally substituted with di-C1 to C6 alkyl-amino,
• —NHRn, where Rn is:
• —CH2CONH2, or
• -aryl optionally substituted with:
• —C1 to C6 alkyl,
• -one or more halogen substituents,
• -nitro, or
• -one or more C 1 to C6 alkoxy substituents,
• —NRoCORp, where Rp is:
• —C1 to C6 alkyl optionally substituted with:
• -halogen,
• —C1 to C6 alkoxy, or
• -aryl,
• -cyclopropyl,
• -cyclobutyl,
• -cyclopentyl,
• -cyclohexyl,
• -5 or 6 membered heterocycle,
• -aryl, optionally substituted with halogen,
• -5 or 6 membered heteroaryl optionally substituted with one or more C1 to C6 alkyl substituents,
• -hydrogen,
• and where Ro is:
• -hydrogen,
• —C1 to C6 alkyl,
• —CORx, where Rx is as defined above,
• —C1 to C6 haloalkyl, or
• —C1 to C6 haloalkoxy,
• —NRqCONRqRr where Rq is:
• -hydrogen,
• —C1 to C6 alkyl,
• —C1 to C6 haloalkyl,
• —C1 to C6 haloalkoxy, or
• —CORx, where Rx is as defined above,
• and where Rr, is:
• -aryl optionally substituted with:
• —C1 to C6 alkyl,
• —C1 to C6 haloalkyl,
• —ORs, where Rs is aryl, or
• —COORx, where Rx is as defined above,
• —C1 to C6 alkyl optionally substituted with one or more of the following:
• -halogen,
• —C2 to C6 alkenyl,
• -aryl, or
• —COORx, where Rx is as defined above,
• —COORx, where Rx is as defined above,
• -cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl,
• —NRtCOORu, where Ru, is:
• —C1 to C12 alkyl, optionally substituted with:
• -aryl optionally substituted with C1 to C6 alkyl or C1 to C6 alkoxy,
• —C2 to C6 alkenyl,
• —C1 to C6 alkoxy,
• —C2 to C6 alkynyl,
• -halogen,
• -5 or 6 membered heterocycle,
• -cyclopropyl,
• -cyclobutyl,
• -cyclopentyl, or
• -cyclohexyl,
• -aryl, optionally substituted with:
• —C1 to C6 alkoxy,
• -halogen, or
• —C1 to C6 alkyl,
• -5 or 6 membered heterocycle,
• -cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl are optionally substituted with one or more C1 to C6 alkyl substituents,
• and Rt is:
• -hydrogen,
• —C1 to C6 alkyl,
• —CORx, where Rx is as defined above,
• —C1 to C6 haloalkyl, or
• —C1 to C6 haloalkoxy,
• —NRvSO2Rw, where Rv is:
• -hydrogen,
• —CORx, where Rx is as defined above, or
• —C1 to C6 alkyl, optionally substituted with:
• -halogen,
• —CORx, where Rx is as defined above,
• —OCORx, where Rx is as defined above,
• -hydroxyl, or
• —C1 to C6 alkoxy,
• and where Rw is:
• —C1 to C6 alkyl optionally substituted with:
• -halogen,
• —C1 to C6 haloalkyl,
• -aryl, or
• -5 or 6 membered heterocycle,
• -cyclopropyl,
• -cyclobutyl,
• -cyclopentyl,
• -cyclohexyl,
• —C2 to C6 alkenyl,
• —C1 to C6 alkyl- or di-C1 to C6 alkyl-amino optionally substituted with halogen,
• -5 or 6 membered heterocycle, or
• -5 or 6 membered heteroaryl optionally substituted with:
• —C1 to C6 alkyl,
• -5 or 6 membered heterocycle, or
• optionally substituted with C1 to C6 alkyl, where Ry is C1 to C6 alkyl or hydrogen,
• where Rz, is hydrogen or C1 to C6 alkyl, optionally substituted with aryl,
• —SRx, where Rx is as defined above,
• —SO2Raa, where Raa is:
• —C1 to C6 alkyl,
• -amino,
• —C1 to C6 alkyl- or di-C1 to C6 alkyl-amino optionally substituted with hydroxy or —COORx, where Rx is as defined above,
• -5 or 6 membered heteroaryl,
• -cyclopropylamino, cyclobutylamino, cyclopentylamino, or cyclohexylamino, -aryl, or
• —NHRbb, where Rbb is:
• —C(═S)NH2, or
• —PO(ORx)2, where Rx is as defined above;
• Z is:
• —C1 to C6 alkyl optionally substituted with:
• —C1 to C6 alkoxy,
• -one or more halogen substituents, or
• -aryl;
• —C2 to C6 alkenyl;
• -aryl optionally substituted with C1 to C6 alkoxy or one or more C1 to C6 alkyl substituents;
• —COORx, where Rx is as defined above;
• -cyclopropyl;
• -cyclobutyl;
• -cyclopentyl;
• -cyclohexyl;
• -cyclopropylmethyl;
• -cyclobutylmethyl;
• or -cyclopentylmethyl;
• R is hydrogen, halogen or C1 to C6 alkoxy;
• R1 is:
• -hydrogen;
• -hydroxy;
• -halogen;
• —C1 to C6 haloalkyl;
• -nitro;
• -5 or 6 membered heteroaryl;
• -5 or 6 membered heterocycle;
• —C1 to C6 alkoxy optionally substituted with:
• -one or more halogen substituents,
• -aryl, or
• -5 or 6 membered heterocycle;
• -aryl optionally substituted with C1 to C6 alkoxy;
• —COR, where Rx is as defined above;
• —C1 to C6 alkyl optionally substituted with di-C1 to C6 alkyl-amino or 5 or 6 membered heterocycle;
• -cyclopropyl;
• -cyclobutyl;
• -cyclopentyl;
• or
• -cyclohexyl;
• and wherein when R2 is unsubstituted methoxy, then R1 is hydrogen;
• R2 is:
• -nitro;
• -hydrogen;
• -halogen;
• -hydroxy;
• —C1 to C6 alkyl, optionally substituted with one or more halogen substituents;
• -cyclopropyl;
• -cyclobutyl;
• -cyclopentyl;
• -cyclohexyl;
• -amino;
• —C1 to C6 alkoxy optionally substituted with:
• -one or more halogen substituents,
• —OCORx, where Rx is as defined above,
• -di-C1 to C6 alkyl-amino optionally substituted with C1 to C6 alkoxy,
• -5 or 6 membered heterocycle optionally substituted with C1 to C6 alkyl,
• -5 or 6 membered heteroaryl, or
• -aryl;
• —COORx, where Rx is as defined above;
• —C1 to C6 haloalkyl;
• -amide optionally substituted with:
• -hydroxy, or
• -aryl;
• -5 or 6 membered heteroaryl;
• —OCORx, where Rx is as defined above;
• —NHCORjj, where Rjj is:
• —C1 to C6 alkoxy, or
• -amino optionally substituted with one or more C1 to C6 alkyl substituents;
• —ORkk, where Rkk is 5 to 6 membered heteroaryl;
• —NHSO2Rx, where Rx is as defined above;
• —NHSO2cyclopropyl;
• —NHSO2cyclobutyl;
• —NHSO2cyclopentyl;
• or —NHSO2cyclohexyl;
• and wherein when R1 is unsubstituted methoxy, then R2 is hydrogen;
• and
• R3 is:
• -hydrogen;
• or
• —CH2OCORx, where Rx is as defined above;
• or a pharmaceutically acceptable salt thereof.