Claims for Patent: 9,586,978

Summary for Patent: 9,586,978

Title:	Anti-viral compounds
Abstract:	Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
Inventor(s):	Mary E. Bellizzi, David A. Betebenner, Jean C. Califano, William A. Carroll, Daniel D. Caspi, David A. Degoey, Pamela L. Donner, Charles A. Flentge, Yi Gao, Charles W. Hutchins, Douglas K. Hutchinson, Tammie K. Jinkerson, Warren M. Kati, Ryan G. Keddy, Allan C. Krueger, Wenke Li, Dachun Liu, Clarence J. Maring, Mark A. Matulenko, Christopher E. Motter, Lissa T. Nelson, Sachin V. Patel, John K. Pratt, John T. Randolph, Todd W. Rockway, Kathy Sarris, Michael D. Tufano, Seble H. Wagaw, Rolf Wagner, Kevin R. Woller
Assignee:	AbbVie Inc
Application Number:	US14/558,318
Patent Claims:	1. A method of treating HCV infection, comprising administering to an HCV patient a therapeutic effective amount of a compound of Formula IB or a pharmaceutically acceptable salt thereof, wherein: RC′ is each independently selected from RC; RD′ is each independently selected from RD; R2 and R5, taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more RA; R9 and R12, taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more RA; X is wherein X3 is N which is directly linked to -L3-D, and X is optionally substituted with one or more RA or RF; L1, L2, and L3 are bond; A is and is optionally substituted with one or more RA; B is and is optionally substituted with one or more RA; D is phenyl, and is substituted with J and optionally substituted with one or more RA; J is C3-C6carbocycle, 3- to 6-membered heterocycle, 6- to 12-membered bicycle, 10- to 15-membered tricycle, or 13- to 15-membered carbocycle or heterocycle, and J is optionally substituted with one or more RA; -T-RD′ is each independently selected from —C(O)-LY′-N(RB)C(O)—RD′ or —C(O)-LY′-N(RB)C(O)O—RD′, wherein LY′ is each independently C1-C6alkylene and optionally substituted with one or more substituents selected from RL; RD is each independently selected at each occurrence from hydrogen or RA; RA is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -LS-RE, wherein two adjacent RA, taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; RB is each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RB is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RC is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RC is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RE is independently selected at each occurrence from —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′), —N(RS)C(O)RS′, —N(RS)C(O)N(RS′RS″), —N(RS)SO2RS′, —SO2N(RSRS′), —N(RS)SO2N(RS′RS″), —N(RS)S(O)N(RS′RS″), —OS(O)—RS,—OS(O)2—RS, —S(O)2ORS, —S(O)ORS, —OC(O)ORS, —N(RS)C(O)ORS′, —OC(O)N(RSRS′), —N(RS)S(O)—RS′, —S(O)N(RSRS′), —P(O)(ORS)2, ═C(RSRS′), or —C(O)N(RS)C(O)—RS′; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C12carbocycle, 3- to 12-membered heterocycle or 7- to 12-membered carbocycle or heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from (1) halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, —C(O)ORS, or —N(RSRS′), or (2) trimethylsilyl, —O—RS, —S—RS or —C(O)RS; RF is independently selected at each occurrence from C1-C10alkyl, C2-C10alkenyl or C2-C10alkynyl, each of which contains 0, 1, 2, 3, 4 or 5 heteroatoms selected from O, S or N and is optionally substituted with one or more RL; or —(RX—RY)Q-(RX—RY′), wherein Q is 0, 1, 2, 3 or 4, and each RX is independently O, S or N(RB), wherein each RY is independently C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene each of which is independently optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano, and wherein each RY′ is independently C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl each of which is independently optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; RL is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′) or —N(RS)C(O)RS′; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; wherein two adjacent RL, taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; LS is each independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more RL; and RS, RS′ and RS″ are each independently selected at each occurrence from hydrogen; C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, —O-C1-C6alkyl, —O-C1-C6alkylene—O-C1-C6alkyl, or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RS , RS′ or RS′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 2. The method of claim 1, wherein J is 3- to 6-membered heterocycle, and is optionally substituted with one or more RA. 3. The method of claim 2, wherein: X is optionally substituted with one or more RA; J is C3-C6carbocycle or 3- to 6-membered heterocycle, and is optionally substituted with one or more RA; RL is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—RS, —S—RS, —C(O)RS, —OC(O )RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′) or —N(RS)C(O)RS′; or C3-C6carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; and RS, RS′ and RS″ are each independently selected at each occurrence from hydrogen; C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RS , RS′ or RS′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 4. The method of claim 3, wherein D is and each RN is independently selected from RD. 5. The method of claim 4, wherein: R2 and R5, taken together with the atoms to which they are attached, form which is optionally substituted with one or more RA; and R9 and R12, taken together with the atoms to which they are attached, form which is optionally substituted with one or more RA. 6. The method of claim 5, wherein: RC′ is hydrogen; and RD′ is independently selected at each occurrence from C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 7. A method of treating HCV infection, comprising administering to an HCV patient a therapeutic effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein: X is wherein X3 is N which is directly linked to -L3-D, and X is optionally substituted with one or more RA; L1, L2 and L3 are bond; A is and is optionally substituted with one or more RA; B is and is optionally substituted with one or more RA; D is C3-C12carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more RA; Y is -LS-C(R1R2)N(R5)—C(O)-LY′-N(RB)C(O)O—RD, -LS-C(R1R2)N(R5)—C(O)-LY′-N(RB)C(O)—RD; Z is -LS-C(R8R9)N(R12)—C(O)-LY′-N(RB)C(O)O —RD or -LS-C(R8R9)N(R12)—C(O)-L Y′-N(RB)C(O)—RD; LY′ is each independently C1-C6alkylene which is optionally substituted with one or more RL; R1 is RC; R2 and R5, taken together with the atoms to which they are attached, form a 5- to 6-membered heterocycle or 6- to 12-membered bicycle which is optionally substituted with one or more RA; R8 is RC; R9 and R12, taken together with the atoms to which they are attached, form a 5- to 6-membered heterocycle or 6- to 12-membered bicycle which is optionally substituted with one or more RA; RD is each independently selected at each occurrence from hydrogen or RA; RA is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -LS-RE; RB is independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RB is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RC is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RC is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RE is independently selected at each occurrence from —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS,—SO2RS, —C(O)N(RSRS′), —N(RS)C(O)RS′, —N(RS)C(O)N(RS′RS″), —N(RS)SO2RS′, —SO2N(RSRS′), —N(RS)SO2N(RS′RS″), —N(RS)S(O)N(RS′RS″), —OS(O)—RS, —OS(O)2—RS, —S(O)2ORS, —S(O)ORS, —OC(O)ORS, —N(RS)C(O)ORS′, —OC(O)N(RSRS′), —N(RS)S(O)—RS′, —S(O)N(RSRS′) or —C(O)N(RS)C(O)—RS′; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RL is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′) or —N(RS)C(O)RS′; or C3-C6carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; LS is independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more RL; and RS, RS′ and RS″ are each independently selected at each occurrence from hydrogen; C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RS, RS′ or RS′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 8. The method of claim 7, wherein: R2 and R5, taken together with the atoms to which they are attached, form which is optionally substituted with one or more RA R9 and R12, taken together with the atoms to which they are attached, form which is optionally substituted with one or more RA. 9. A method of treating HCV infection, comprising administering to an HCV patient a therapeutic effective amount of a compound of Formula IF or a pharmaceutically acceptable salt thereof, wherein: X is and is optionally substituted with one or more RA A is and is optionally substituted with one or more RA; B is and is optionally substituted with one or more RA; D is wherein G3 is phenyl optionally substituted with one or two RG3; g is 0, 1, or 2; RM is each independently fluoro, chloro, methyl, methoxy, trifluoromethyl, or trifluoromethoxy; is a monocyclic 4-8 membered nitrogen-containing heterocycle and is optionally substituted with one or more RG2; Y is -T′-C(R1R2)N(R5)-T-RD; Z is -T′-C(R8R9)N(R12)-T-RD; R1 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or 3- to 6-membered carbocycle or heterocycle, wherein each said 3- to 6-membered carbocycle or heterocycle in R1 is independently optionally substituted at each occurrence with one or more substituents selected from halogen, C1-C6alkyl, C1-C6haloalkyl, —O —C1-C6alkyl or —O —C1-C6haloalkyl; R2 and R5, taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more RA; R8 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or 3- to 6-membered carbocycle or heterocycle, wherein each said 3- to 6-membered carbocycle or heterocycle in R8 is independently optionally substituted at each occurrence with one or more substituents selected from halogen, C1-C6alkyl, C1-C6haloalkyl, —O—C1-C6alkyl or —O—C1-C6haloalkyl; R9 and R12, taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more RA; T is independently selected at each occurrence —C(O)-LS′-; T′ is bond; RD is each independently selected at each occurrence from hydrogen or RA; RA is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -LS-RE; RE is independently selected at each occurrence from —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′), —N(RS)C(O)RS′, —N(RS)C(O)N(RS′RS″), —N(RS)SO2RS′, —SO2N(RSRS′), —N(RS)SO2N(RS′RS″), —N(RS)S(O)N(RS′RS″), —OS(O)—RS, —OS(O)2—RS, —S(O)2ORS, —S(O)ORS, —OC(O)ORS, —N(RS)C(O)ORS′, —OC(O)N(RSRS′), —N(RS)S(O)—RS′, —S(O)N(RSRS′), —C(O)N(RS)C(O)—RS′, or ═C(RSRS′); or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C12carbocycle or 3- to 12-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RL is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′), or —N(RS)C(O)RS′; or C3-C12carbocycle or 3- to 12-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; LSis independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene, each independently optionally substituted with halogen; LS′ is independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more RL; RS, RS′ and RS″ are each independently selected at each occurrence from hydrogen; C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, —O-C1-C6alkyl, —O —C1-C6haloalkyl, or 3- to 12-membered carbocycle or heterocycle; or 3- to 12-membered carbocycle or heterocycle; wherein each 3- to 12-membered carbocycle or heterocycle in Rs , RS′ or RS″ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RG2 is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, —O—RS, —C(O)ORS, —C(O)RS, or —N(RSRS′); and RG3 is independently selected at each occurrence from halogen, —C1-C6alkyl, —C(O)C1-C6alkyl, —C1-C6haloalkyl, —O—C1-C6alkyl, —O—C1-C6haloalkyl, C3-C6carbocycle, or 3- to 6-membered heterocycle. 10. The method of claim 9, wherein: R1 and R8 are hydrogen; R2 and R5, taken together with the atoms to which they are attached, form and R9 and R12, taken together with the atoms to which they are attached, form 11. The method of claim 10, wherein T-RD is independently selected at each occurrence from 12. The method of claim 11, wherein D is and RM1 is each independently hydrogen, fluoro, chloro, or methyl. 13. A method of treating HCV infection, comprising administering to an HCV patient a therapeutic effective amount of methyl {(2S,3R)-1-[(2S)-2- {5-[(2R,5R)-1-{3,5-difluoro-4-[4-(4-fluorophenyl)piperidin-1-yl]phenyl}-5-(6-fluoro-2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H-benzimidazol-5-yl)pyrrolidin-2-yl]-6-fluoro-1H-benzimidazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl}carbamate or a pharmaceutically acceptable salt thereof. 14. The method of claim 1, wherein: RC′ is hydrogen; R2 and R5, taken together with the atoms to which they are attached, form R9 and R12, taken together with the atoms to which they are attached, form X is wherein N is directly linked to -L3-D; A is which is optionally substituted with one or more halogen; B is which is optionally substituted with one or more halogen; D is wherein each RN is independently hydrogen or halogen; J is C3-C6carbocycle or 3- to 6-membered heterocycle and is optionally substituted with one or more RA; -T-RD′ is each independently selected from and RA is each independently halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 15. The method of claim 14, wherein -T-RD′ is each independently selected from 16. The method of claim 14, wherein J is C3-C6carbocycle or 3- to 6-membered heterocycle and is substituted with RA, and said RA is C3-C6carbocycle or 3- to 6-membered heterocycle and is optionally substituted with one or more halogen. 17. The method of claim 15, wherein J is C3-C6carbocycle or 3- to 6-membered heterocycle and is substituted with RA, and said RA is C3-C6carbocycle or 3- to 6-membered membered heterocycle and is optionally substituted with one or more halogen. 18. The method of claim 7, wherein: Y is -LS-C(R1R2)N(R5)-T-RD, wherein LS is bond, and R1 is hydrogen; R2 and R5, taken together with the atoms to which they are attached, form Z is -LS-C(R8R9)N(R12)-T-RD, wherein LS is bond, and R8 is hydrogen; R9 and R12, taken together with the atoms to which they are attached, form -T-RD is each independently selected from X is wherein N is directly linked to -L3-D; A is which is optionally substituted with one or more halogen; B is which is optionally substituted with one or more halogen; and RA is each independently halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano; or C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 19. The method of claim 18, wherein -T-RD is each independently selected from 20. The method of claim 18, wherein D is substituted with one or more RA; and wherein each RA is independently (i) halogen, or (ii) 3- to 6-membered heterocycle or C3-C6carbocycle, each of which is optionally substituted with one or more halogen. 21. The method of claim 19, wherein D is substituted with one or more RA; and wherein each RA is independently (i) halogen, or (ii) 3- to 6-membered heterocycle or C3-C6carbocycle, each of which is optionally substituted with one or more halogen.