HCV NS3 protease inhibitors

A method of manufacturing a medicament for preventing or treating infection by HCV in a subject in need thereof, said method comprising providing a compound of formula (I):

• or a pharmaceutically acceptable salt and/or hydrate thereof, wherein:
• n is 1 or 2;
• R1 is —CONHP(O)R11R12, or —P(O)R11R12;
• R2 is C1-C6 alkyl, C2-C6 alkenyl or C3-C8 cycloalkyl, wherein said alkyl, alkenyl or cycloalkyl is optionally substituted with 1 to 3 halo;
• R3 is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C8)alkyl, aryl(C1-C8)alkyl, or Het wherein a 1 is phenyl or naphthyl and said alkyl cycloalkyl or aryl is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), —NO2, —CN, —CF3, —SO21-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO7R6—SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• Het is a 5- to 6-membered saturated cyclic ring having 1, 2 or 3 heteroatoms selected from N, O and S, wherein said ring is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6—SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and)-CON(R10)2;
• R4 is H, C1-C8 alkyl, C3-C8 cycloalkyl(C1-C8)alkyl, or aryl(C1-C8)alkyl;
• wherein aryl is phenyl or naphthyl and said alkyl, cycloalkyl, or aryl is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), —NO2—CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6 —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• R5 is H, halo, —OH, C1-C6 alkoxy, C1-C6 alkyl, —CN, —CF3, —SR10, —SO2(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R7)7, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein said aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkoxy, alkyl or alkoxy is optionally substituted with 1 to 4 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R7)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), C3-C6 cycloalkyl, C2-C6 cycloalkoxy, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —NR10SO2R6—SO2N(R6)2, —S(O)(C1-C6 alkyl), —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• R6 is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C5)alkyl, aryl, aryl(C1-C4)alkyl, heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl, or heterocyclyl(C1-C8 alkyl), wherein said alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with 1 to 2 W′ substituents or aryl is substituted by —P(O)R11R12;
• and wherein each aryl is independently phenyl or naphthyl, each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• Y is —C(═O)—, —SO2—, or —C(═N—CN)—;
• Z is)-C(R10)2—, —O—, or —N(R4)—;
• M is C1-C12 alkylene or C2-C12 alkenylene or C2-C12 alkynylene, wherein said alkylene or alkenylene is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of C1-C8 alkyl, C3-C8 cycloalkyl(C1-C8 alkyl), and aryl(C1-C8 alkyl);
• wherein 2 substituents on adjacent carbon atoms of M are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S, or 2 substituents on the same carbon atom of M are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• A is —C(R16)— or —N—;
• when R5 is other than H, R16 is H, C1-C6 alkyl, halo, —OR10, —SR10, or —N(R10)2;
• when R5 is H, R16 is H, C1-C6 alkyl, halo, —OH, C1-C6 alkoxy, —CN, —CF3, —SR10, —SO2(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R7)2, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein said aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkoxy, alkyl or alkoxy is optionally substituted with 1 to 4 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R7)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), C3-C6 cycloalkyl, C1-C6 cycloalkoxy, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —NR10SO2R6—SO2N(R6)2, —S(O)(C1-C6 alkyl), —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• or R5 and R16 are optionally taken together to form a 5- to 6-membered saturated, unsaturated non-aromatic, or aromatic cyclic ring having 0 to 2 heteroatoms selected from N, O and S;
• each R7 is independently H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C5)alkyl, aryl, aryl(C1-C4)alkyl, heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl, or heterocyclyl(C1-C8 alkyl), wherein said alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with 1 to 2 W′ substituents;
• and wherein each aryl is independently phenyl or naphthyl, each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• each W is independently H, halo, —OR7, C1-C6 alkyl, —CN, —CF3 —SR7, —CO2R7, —CON(R7)2, —C(O)R7, —N(R10)C(O)R7, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R7)7, —N(C1-C6 alkyl)O(C1-C6 alkyl), halo(C1-C6 alkoxy), —NR10SO2R7, —SO2N(R7)2, —NHCOOR7, —NHCONHR7, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein 2 adjacent W moieties are optionally taken together with the atoms to which they are attached to form a 5- to 6-membered saturated, unsaturated non-aromatic, or aromatic cyclic ring having 0 to 2 heteroatoms selected from N, O and S;
• each W′ is independently H, halo, —OR10, C1-C6 alkyl, —CN, —NO2, —SR10, —CO2R10, —CON(R10)2, —C(O)R10, —N(R10)C(O)R10, —SO2(C1-C6 alkyl), —S(O)(C1-C1-6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R10)2 —N(C1-C6 alkyl)O(C1-C6 alkyl), halo(C1-C6 alkoxy), —NR10SO2R10, —SO2N(R10)2, —NHCOOR10, —NHCONHR10, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein 2 adjacent W′ moieties are optionally taken together with the atoms to which they are attached to form a 5- to 6-membered saturated, unsaturated non-aromatic, or aromatic cyclic ring having 0 to 2 heteroatoms selected from N, O and S;
• each R10 is independently H or C1-C6 alkyl;
• each R11 is independently C1-C6 alkyl, —OR13, —N(R10-V-CO2R10, —O-V-CO2R10, —S-V-CO2R10, —N(R10)(R13), R14, or —N(R10)SO2R6;
• each R12 is independently —OR13, —N(R10)-V-CO2R10, —O-V-CO2R10, —S-V-CO2R10, or —N(R10)(R13);
• or R11 and R12 are optionally taken together, with the phosphorus atom to which they are attached, to form a 5- to 7-membered monocyclic ring;
• each V is independently —CH(R15) or C1-C4 alkylene-CH(R15);
• each R13 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein said alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with 1 to 2 substituents selected from the group consisting of aryl, aryl(C1-C4 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl, heterocyclyl(C1-C4 alkyl), C1-C6 alkyl, halo, —OC(O)OR6, —OC(O)R6, —OR10, —SR10, —N(R10)2, C(O)R10, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, and —C(O)N(R10)2;
• wherein each aryl is independently phenyl or naphthyl;
• each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• R14 is C1-C6 alkyl, C2-C6 alkenyl, aryl or heteroaryl, wherein aryl is phenyl or naphthyl, and heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and wherein said aryl or heteroaryl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6 alkyl, halo, —OC(O)OR6, —OC(O)R6, —OR10, —SR10, —N(R10)2, —C(O)R10, —NO2—CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO7R6—SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, and —C(O)N(R10)2;
• and
• each R15 is independently C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein said alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6 alkyl, halo, —OC(O)OR6, —OC(O)R6, —OR10, —SR10, —N(R10)2, —C(O)R10, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, and —C(O)N(R10)2;
• wherein each aryl is independently phenyl or naphthyl;
• each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S.

A method of inhibiting HCV NS3 protease in a subject in need thereof, said method comprising administering to the subject an effective amount of a compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• n is 1 or 2;
• R1 is —CONHP(O)R11R12, or —P(O)R11R12;
• R2 is C1-C6 alkyl, C2-C6 alkenyl or C3-C8 cycloalkyl, wherein said alkyl, alkenyl or cycloalkyl is optionally substituted with 1 to 3 halo;
• R3 is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C8)alkyl, aryl(C1-C8)alkyl, or Het, wherein aryl is phenyl or naphthyl and said alkyl, cycloalkyl, or aryl is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• Het is a 5- to 6-membered saturated cyclic ring having 1, 2 or 3 heteroatoms selected from N, O and S, wherein said ring is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and)-CON(R10)2;
• R4 is H, C1-C8 alkyl, C3-C8 cycloalkyl(C1-C8)alkyl, or aryl(C1-C8)alkyl;
• wherein aryl is phenyl or naphthyl and said alkyl, cycloalkyl, or aryl is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• R5 is H, halo, —OH, C1-C6 alkoxy, C1-C6 alkyl, —CN, —CF3, —SR10, —SO2(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R7)2, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein said aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkoxy, alkyl or alkoxy is optionally substituted with 1 to 4 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R7)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), C3-C6 cycloalkyl, C3-C6 cycloalkoxy, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —S(O)(C1-C6 alkyl), —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• R6 is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C5)alkyl, aryl, aryl(C1-C4)alkyl, heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl, or heterocyclyl(C1-C8 alkyl), wherein said alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with 1 to 2 W′ substituents or aryl is substituted by —P(O)R11R12;
• and wherein each aryl is independently phenyl or naphthyl, each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• Y is —C(═O)—, —SO2—, or —C(═N—CN)—;
• Z is —C(R10)2—, —O—, or —N(R4)—;
• M is C1-C12 alkylene or C2-C12 alkenylene or C2-C12 alkynylene, wherein said alkylene or alkenylene is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of C1-C8 alkyl, C3-C8 cycloalkyl(C1-C8 alkyl), and aryl(C1-C8 alkyl);
• wherein 2 substituents on adjacent carbon atoms of M are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S, or 2 substituents on the same carbon atom of M are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• A is —C(R16)— or —N—;
• when R5 is other than H, R16 is H, C1-C6 alkyl, halo, —OR10, —SR10, or —N(R10)2;
• when R5 is H, R16 is H, C1-C6 alkyl, halo, —OH, C1-C6 alkoxy, —CN, —CF3, —SR10, —SO2(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R7)2, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein said aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkoxy, alkyl or alkoxy is optionally substituted with 1 to 4 substituents selected from the group consisting of halo, —OR10, —SR10, —N(R7)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), C1-C6 alkyl, C1-C6 haloalkyl, halo(C1-C6 alkoxy), C3-C6 cycloalkyl, C3-C6 cycloalkoxy, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —S(O)(C1-C6 alkyl), —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, —C(O)R10, and —CON(R10)2;
• wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• or R5 and R16 are optionally taken together to form a 5- to 6-membered saturated, unsaturated non-aromatic, or aromatic cyclic ring having 0 to 2 heteroatoms selected from N, O and S;
• each R7 is independently H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C5)alkyl, aryl, aryl(C1-C4)alkyl, heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl, or heterocyclyl(C1-C8 alkyl), wherein said alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with 1 to 2 W′ substituents;
• and wherein each aryl is independently phenyl or naphthyl, each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• each W is independently H, halo, —OR7, C1-C6 alkyl, —CN, —CF3, —NO2, —SR7, —CO2R7, —CON(R7)2, —C(O)R7, —N(R10)C(O)R7, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R7)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), halo(C1-C6 alkoxy), —NR10SO2R7, —SO2N(R7)2, —NHCOOR7, —NHCONHR7, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein 2 adjacent W moieties are optionally taken together with the atoms to which they are attached to form a 5- to 6-membered saturated, unsaturated non-aromatic, or aromatic cyclic ring having 0 to 2 heteroatoms selected from N, O and S;
• each W′ is independently H, halo, —OR10, C1-C6 alkyl, —CN, —CF3, —NO2, —SR10, —CO2R10, —CON(R10)2, —C(O)R10, —N(R10)C(O)R10, —SO2 (C1-C6 alkyl), —S(O)(C1-C6 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C1-C6 haloalkyl, —N(R10)2, —N(C1-C6 alkyl)O(C1-C6 alkyl), halo(C1-C6 alkoxy), —NR10SO2R10, —SO2N(R10)2, —NHCOOR10, —NHCONHR10, aryl, heteroaryl or heterocyclyl;
• wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and heterocyclyl is a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein 2 adjacent W′ moieties are optionally taken together with the atoms to which they are attached to form a 5- to 6-membered saturated, unsaturated non-aromatic, or aromatic cyclic ring having 0 to 2 heteroatoms selected from N, O and S;
• each R10 is independently H or C1-C6 alkyl;
• each R11 is independently C1-C6 alkyl, —OR13, —N(R10-V-CO2R10, —O-V-CO2R10, —S-V-CO2R10, —N(R10)(R13), —N(R10)SO2R6;
• each R12 is independently —OR13, —N(R10)-V-CO2R10, —O-V-CO2R10, —S-V-CO2R10, or —N(R10)(R13);
• or R11 and R12 are optionally taken together, with the phosphorus atom to which they are attached, to form a 5- to 7-membered monocyclic ring;
• each V is independently —CH(R15) or C1-C4 alkylene-CH(R15);
• each R13 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein said alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with 1 to 2 substituents selected from the group consisting of aryl, aryl(C1-C4 alkyl), C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl, heterocyclyl(C1-C4 alkyl), C1-C6 alkyl, halo, —OC(O)OR6, —OC(O)R6, —OR10, —SR10, —N(R10)2, —C(O)R10, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, and —C(O)N(R10)2;
• wherein each aryl is independently phenyl or naphthyl;
• each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S;
• R14 is C1-C6 alkyl, C2-C6 alkenyl, aryl or heteroaryl, wherein aryl is phenyl or naphthyl, and heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen, and wherein said aryl or heteroaryl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6 alkyl, halo, —OC(O)OR6, —OC(O)R6, —OR10, —SR10, —N(R10)2, —C(O)R10, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, and —C(O)N(R10)2;
• and
• each R15 is independently C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein said alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6 alkyl, halo, —OC(O)OR6, —OC(O)R6, —OR10, —SR10, —N(R10)2, —C(O)R10, —NO2, —CN, —CF3, —SO2(C1-C6 alkyl), —S(O)(C1-C6 alkyl), —NR10SO2R6, —SO2N(R6)2, —NHCOOR6, —NHCOR6, —NHCONHR6, —CO2R10, and —C(O)N(R10)2;
• wherein each aryl is independently phenyl or naphthyl;
• each heteroaryl is independently a 5- or 6-membered aromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and each heterocyclyl is independently a 5- to 7-membered saturated or unsaturated non-aromatic ring having 1, 2, 3 or 4 heteroatoms selected from N, O and S, attached through a ring carbon or nitrogen;
• and wherein the 2 adjacent substituents of said cycloalkyl, cycloalkoxy, aryl, heteroaryl or heterocyclyl are optionally taken together to form a 3- to 6-membered cyclic ring containing 0 to 3 heteroatoms selected from N, O and S.