Hepatitis C inhibitors and uses thereof

A method of treating HCV infection, comprising administering a therapeutically effective amount of a compound having formula (I), or a pharmaceutically acceptable salt thereof,

• wherein:
• R1 is formula (i) or (iii);
• R1a, at each occurrence, is each independently hydrogen, halogen, C1-C3alkyl, or C1-C3haloalkyl;
• R1b, at each occurrence, is each independently hydrogen, halogen, C1-C3alkyl, or C1-C3haloalkyl, wherein, optionally, two geminal R1b taken together are oxo;
• R2 is C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, C2-C10haloalkenyl, C2-C10haloalkynyl, or L2A-G2a;
• L2A is a bond, C2alkenylene, or C2alkynylene;
• G2a is C6-C10aryl or 5- to 10-membered heteroaryl, wherein the aryl or heteroaryl is optionally substituted with 1, 2, or 3 substituents selected from the group consisting of R20, L2B-R21, G2b and L2B-G2b;
• L2B and L2C, at each occurrence, are each independently C1-C6alkylene, C2-C6alkenylene, or C2-C6alkynylene;
• R20 is hydrogen, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, C2-C10haloalkenyl, C2-C10haloalkynyl, halogen, —N(R2a)C(O)R2b, —C(O)N(R2a)(R2b), —O—R2b, —C(O)R2b, —OC(O)R2b, —CO2H, —CO2R2b, —N(R2a)C(O)N(R2a)(R2b), —S—R2b, —S(O)2R2b, —S(O)R2b, —SO2N(R2a)(R2b), —N(R2a)(R2b), —N(R2a)S(O)2R2b, N(R2a)C(O)O(R2b), or —C(═CH2)R2b;
• R21 is —N(R2a)C(O)R2b, —C(O)N(R2a)(R2b), —O—R2b, —C(O)R2b, —OC(O)R2b, —CO2H, —CO2R2b, —N(R2a)C(O)N(R2a)(R2b), —S—R2b, —S(O)2R2b, —S(O)R2b, —SO2N(R2a)(R2b), —N(R2a)(R2b), —N(R2a)S(O)2R2b, N(R2a)C(O)O(R2b), or —C(═CH2)R2b;
• R2a, at each occurrence, is each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C3-C8cycloalkyl, wherein the C3-C8cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, and C1-C3haloalkyl;
• R2b, at each occurrence, is each independently hydrogen, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, C2-C10haloalkenyl, C2-C10haloalkynyl, -L2C-R2c, G2b or -L2C-G2b;
• R2c is —N(R2d)C(O)R2d, —C(O)N(R2d)(R2d), —O—R2d, —C(O)R2d, —OC(O)R2d, —CO2H, —CO2R2d, —N(R2d)C(O)N(R2d)(R2d), —S—R2d, —S(O)2R2d, —S(O)R2d, —SO2N(R2d)(R2d), —N(R2d)(R2d), —N(R2d)S(O)2R2d, or N(R2d)C(O)O(R2d);
• R2d, at each occurrence, is each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylene-OH, or C3-C8cycloalkyl, wherein the C3-C8cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, and C1-C3haloalkyl;
• G2b is C3-C10cycloalkyl, C5-C10cycloalkenyl, C6-C10aryl, 3- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein G2b is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, C2-C10haloalkenyl, C2-C10haloalkynyl, halogen, oxo, cyano, hydroxy, —O—C1-C6alkyl, —O—C1-C6haloalkyl, —C1-C3alkylene-O—H, —C1-C3alkylene-O—C1-C6alkyl, C(O)H, —C1-C3alkylene-NH2, —NH2, —NO2, —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, and G2c;
• G2c is C6-C10aryl or 5- to 10-membered heteroaryl, wherein G2c is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, C2-C10haloalkenyl, C2-C10haloalkynyl, halogen, oxo, cyano, hydroxy, —O—C1-C6alkyl, —O—C1-C6haloalkyl, —C1-C3alkylene-O—H, —C1-C3alkylene-O—C1-C6alkyl, C(O)H, —C1-C3alkylene-NH2, —NH2, —NO2, —C(O)C1-C6alkyl, and —C(O)OC1-C6alkyl;
• A and B together are a bicyclic heteroaryl, wherein A is formula (vi) or formula (vii):
• wherein,
• V1 and V2 are each C, or one of V1 and V2 is N and the other is C, wherein, when V3 is N, O or S or when A is (vii), V2 is C;
• when A is (vi), V3 is CR7, NR7, N, O, or S;
• or, when A is (vii), V3 is N;
• R7 is hydrogen, C1-C3alkyl, C1-C3haloalkyl, or C3-C6cycloalkyl;
• is a single or double bond;
• W1 is N or CR6, W2 is N or CR5, W3 is N or CR4, and W4 is N or CR3, wherein none, one or two of W1, W2, W3 and W4 is N;
• W5 is N or CR6, and W6 is N or CR5, wherein none or one of W5 and W6 is N;
• W7 is N, O, or S;
• R3 and R6 are each independently hydrogen, C1-C3alkyl, C1-C3haloalkyl, halogen, —OC1-C3alkyl, or —OC1-C3haloalkyl;
• R4 is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, —O—C1-C6haloalkyl, cyano, —NH2, L4A-OH, 5-membered heteroaryl optionally substituted with 1 or 2 alkyl or halogen, 5-membered heterocycle or —N(R40)(SO2R4a);
• R40 is hydrogen, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, C2-C10haloalkenyl, C2-C10haloalkynyl, C3-C8cycloalkyl, 3- to 8-membered heterocyclyl, -L4A-G4a, -L4A-C(O)-L4B-G4a, -L4A-O-L4B-G4a, -L4A-S(O)2-L4B-G4a, -L4A-N(R4b)(L4B-G4a), -L4A-N(R4b)C(O)-L4B-G4a, -L4A-N(R4b)S(O)2-L4B-G4a, or -L4A-R4c, wherein the C1-C10alkyl, C2-C10alkenyl, and C2-C10alkynyl are each optionally substituted with 2, 3, or 4 hydroxy substituents;
• and wherein the C3-C8cycloalkyl or 3- to 8-membered heterocyclyl is each optionally substituted with L4B-G4b and optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, C1-C3haloalkyl, —O—C1-C3alkyl, and —O—C1-C3haloalkyl;
• L4A is C1-C10alkylene, C2-C10alkenylene, or C2-C10alkynylene, wherein L4A is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, C1-C6alkyl, and C1-C6haloalkyl;
• G4a is C3-C12cycloalkyl, C6-C12aryl, 3- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl, wherein G4a is optionally substituted with L4C-G4b and optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, C1-C3haloalkyl, —OH, —O—C1-C3alkyl, —O—C1-C3haloalkyl, thioxo, —NH2, —NH(C1-C3alkyl), and —N(C1-C3alkyl)2;
• L4B and L4C, at each occurrence, are each independently a bond, C1-C6alkylene, C2-C6alkenylene, or C2-C6alkynylene, wherein L4B and L4C are each optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, C1-C6alkyl, and C1-C6haloalkyl;
• G4b is C3-C12cycloalkyl, 3- to 12-membered heterocyclyl, C6-C12aryl, or 5- to 12-membered heteroaryl, wherein G4b is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, oxo, C1-C6alkyl, C1-C6haloalkyl, hydroxy, —O—C1-C6alkyl, —O—C1-C6haloalkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, —C(O)—C1-C6alkyl, C1-C3alkylene-OH, C1-C3alkylene-O—C1-C3alkyl, C1-C3alkylene-N(C1-C3alkyl)2, and C1-C3alkylene-(N-heterocyclyl);
• R4a and R4b, at each occurrence, are each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C3-C8cycloalkyl, wherein the C3-C8cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, and C1-C3haloalkyl;
• R4c is —O—R4b, —OC(O)R4b, —O—Si(C1-C6alkyl)3, —CN, —C(O)R4b, —CO2R4b, —C(O)N(R4b)2, —C(O)N(R4b)S(O)2R4b, —S—R4b, —S(O)2R4b, —S(O)R4b, —SO2N(R4b)2, —N(R4b)2, —N(R4b)C(O)R4b, —N(R4b)S(O)2R4b, —C(NOH)N(R4b)2, —C(O)C(OH)(R4b)2, or —P(O)(OR4b)2;
• R5 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, —O—C1-C6alkyl, —O—C1-C6haloalkyl, —O—C3-C6cycloalkyl, or G5a, wherein the C3-C6cycloalkyl groups are optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, C1-C3alkyl, C1-C3haloalkyl, and oxo;
• G5a is phenyl, wherein G5a is substituted with —C(O)N(R5a)-L5B-G5b, —C(O)-G5f, or —C(O)N(R5a)(R5e), and optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, halogen, —O—R5b, CN, —N(R5b)C(O)R5b, —C(O)N(R5a)(R5b), —C(O)R5b, —OC(O)R5b, —CO2H, —CO2R5b, —N(R5b)C(O)N(R5a)(R5b), —S—R5b, —S(O)2R5b, —S(O)R5b, —SO2N(R5a)(R5b), —N(R5a)(R5b), —N(R5b)S(O)2R5b, N(R5b)C(O)O(R5b), -L5A-O—R5b, -L5A-CN, -L5A-N(R5b)C(O)R5b, -L5A-C(O)N(R5a)(R5b), -L5A-C(O)R5b, -L5A-OC(O)R5b, -L5A-CO2H, -L5A-CO2R5b, -L5A-N(R5b)C(O)N(R5a)(R5b), -L5A-S—R5b, -L5A-S(O)2R5b, -L5A-S(O)R5b, -L5A-SO2N(R5a)(R5b), -L5A-N(R5a)(R5b), -L5A-N(R5b)S(O)2R5b, -L5A-N(R5b)C(O)O(R5b), -G5d, and -L5A-G5d;
• G5b is C3-C12cycloalkyl, C6-C12aryl, 3- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl, wherein each G5b is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of oxo, halogen, C1-C6alkyl, C1-C6haloalkyl, —O—R5d, —CN, —N(R5d)C(O)R5d, —CON(R5a)(R5d), —C(O)R5d, —OC(O)R5d, —CO2H, —CO2R5d, —N(R5d)C(O)N(R5d)2, —S—R5d, —S(O)2R5d, —S(O)R5d, —SO2N(R5a)(R5d), —N(R5a)(R5d), —N(R5d)S(O)2R5d, N(R5d)C(O)O(R5d), -L5C-O—R5d, -L5C-CN, -L5C-N(R5d)C(O)R5d, -L5C-CON(R5a)(R5d), -L5C-C(O)R5d, -L5C-OC(O)R5d, -L5C-CO2H, -L5C-CO2R5d, -L5C-N(R5d)C(O)N(R5d)2, -L5C-S—R5d, -L5C-S(O)2R5d, -L5C-S(O)R5d, -L5C-SO2N(R5a)(R5d), -L5C-N(R5a)(R5d), -L5C-N(R5d)S(O)2R5d, -L5C-N(R5d)C(O)O(R5d), G5c, and -L5C-G5c;
• G5c, at each occurrence, is each independently C3-C8cycloalkyl, C6-C10aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein G5c is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, oxo, C1-C6alkyl, C1-C6haloalkyl, —O—C1-C6alkyl, and —O—C1-C6haloalkyl;
• G5d, is at each occurrence, is each independently C3-C8cycloalkyl, C6-C10aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein G5d is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of oxo, halogen, C1-C6alkyl, C1-C6haloalkyl, —O—R5d, —CN, —N(R5d)C(O)R5d, —CON(R5a)(R5d), —C(O)R5d, —OC(O)R5d, —CO2H, —CO2R5d, —N(R5d)C(O)N(R5d)2, —S—R5d, —S(O)2R5d, —S(O)R5d, —SO2N(R5a)(R5d), —N(R5a)(R5d), —N(R5d)S(O)2R5d, N(R5d)C(O)O(R5d), -L5C-O—R5d, -L5C-CN, -L5C-N(R5d)C(O)R5d, -L5C-CON(R5a)(R5d), -L5C-C(O)R5d, -L5C-OC(O)R5d, -L5C-CO2H, -L5C-CO2R5d, -L5C-N(R5d)C(O)N(R5d)2, -L5C-S—R5d, -L5C-S(O)2R5d, -L5C-S(O)R5d, -L5C-SO2N(R5a)(R5d), -L5C-N(R5a)(R5d), -L5C-N(R5d)S(O)2R5d, -L5C-N(R5d)C(O)O(R5d), G5c, and -L5C-G5c;
• R5a, at each occurrence, is each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C3-C8cycloalkyl, wherein the C3-C8cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, and C1-C3haloalkyl;
• R5b, at each occurrence, is each independently hydrogen, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, -L5D-G5e, or -L5G-R5c;
• R5c, at each occurrence, is each independently —CON(R5a)(R5g), —O—R5g, —OC(O)R5g, —CN, —C(O)R5g, —CO2H, —CO2R5g, —N(R5g)C(O)N(R5g)2, —S—R5g, —S(O)2R5g, —S(O)R5g, —SO2N(R5a)(R5g), —N(R5a)(R5g), —N(R5g)C(O)R5g, or —N(R5g)S(O)2R5g;
• R5d, at each occurrence, is each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, or -L5F-G5c;
• R5e, at each occurrence, is each independently hydrogen, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C10haloalkyl, or -L5E-R5f;
• R5f is —CON(R5a)(R5d), —O—R5d, —OC(O)R5d, —CN, —C(O)R5d, —CO2H, —CO2R5d, —N(R5d)C(O)N(R5d)2, —S—R5d, —S(O)2R5d, —S(O)R5d, —SO2N(R5a)(R5d), —N(R5a)(R5d), —N(R5d)C(O)R5d, or —N(R5d)S(O)2R5d;
• R5g is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or -L5H-G5e;
• G5e, at each occurrence, is each independently C3-C8cycloalkyl, C6-C10aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein G5e is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C6alkyl, C1-C6haloalkyl, —OH, —O—C1-C6alkyl, and —O—C1-C6haloalkyl;
• G5f is 4- to 10-membered heterocyclyl, wherein G5f is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C6alkyl, C1-C6haloalkyl, —O—C1-C6alkyl, and —O—C1-C6haloalkyl;
• L5A, at each occurrence, is each independently C1-C6alkylene or C3-C8cycloalkyl, wherein L5A is each optionally substituted with 1, 2, 3, or 4 halogen;
• L5B is a bond, C1-C6alkylene, or C3-C8cycloalkyl, wherein L5B is optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy;
• L5C, at each occurrence, is each independently C1-C6alkylene or C3-C8cycloalkyl, wherein L5C is each optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy;
• L5D, at each occurrence, is each independently a bond, C1-C6alkylene, or C3-C8cycloalkyl, wherein L5D is each optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy;
• L5E, at each occurrence, is each independently C1-C6alkylene, wherein L5E is optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy;
• L5F, at each occurrence, is each independently bond or C1-C6alkylene, wherein L5F is optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy;
• L5G, at each occurrence, is each independently C1-C6alkylene, wherein L5G is optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy;
• and
• L5H, at each occurrence, is each independently a bond, C1-C6alkylene, or C3-C8cycloalkyl, wherein L5H is each optionally substituted with 1, 2, 3, or 4 halogen and 1 or 2 hydroxy,
• optionally in combination with one or more additional therapeutic agents.