Claims for Patent: 10,039,754

Summary for Patent: 10,039,754

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-Christophe 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:	US15/431,069
Patent Claims:	1. A method of treating hepatitis C virus (HCV) infection, comprising administering an effective amount of a compound having Formula I or a pharmaceutically acceptable salt thereof, and another anti-HCV agent, to an HCV patient in need thereof, wherein: X is C3-C12carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more RA or RF; L1 and L2 are each independently selected 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; L3 is bond or -LS-K-LS′-, wherein K is selected from bond, —O—, —S—, —N(RB)—, —C(O)—, —S(O)2—, —S(O)—, —OS(O)—, —OS(O)2—, —S(O)2O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)—, —C(O)N(RB)—, —N(RB)C(O)—, —N(RB)C(O)O—, —OC(O)N(RB)—, —N(RB)S(O)—, —N(RB)S(O)2—, —S(O)N(RB)—, —S(O)2N(RB)—, —C(O)N(RB)C(O)—, —N(RB)C(O)N(RB′)—, —N(RB)SO2N(RB′)—, or —N(RB)S(O)N(RB′)—; A and B are each independently 3- to 12-membered heterocycle, and are each independently 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; or D is C3-C12carbocycle or 3- to 12-membered heterocycle which is substituted with J and optionally substituted with one or more RA, where J is C3-C12carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more RA, or J is —SF5; or D is hydrogen or RA; Y is selected from -T′-C(R1R2)N(R5)-T-RD, -T′-C(R3R4)C(R6R7)-T-RD, -LK-T-RD, or -LK-E; R1 and R2 are each independently RC, and R5 is RB; or R1 is RC, and 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; R3, R4, R6, and R7 are each independently RC; or R3 and R6 are each independently RC, and R4 and R7, taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more RA; Z is selected from -T′-C(R8R9)N(R12)-T-RD, -T′-C(R10R11)C(R13R14)-T-RD, -LK-T-RD, or -LK-E; R8 and R9 are each independently RC, and R12 is RB; or R8 is RC, and 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; R10, R11, R13, and R14 are each independently RC; or R10 and R13 are each independently RC, and R and R14, taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more RA; T and T′ are each independently selected at each occurrence from bond, -LS-, -LS-M-LS′-, or -LS-M-LS′-M′-LS″-, wherein M and M′ are each independently selected at each occurrence from bond, —O—, —S—, —N(RB)—, —C(O)—, —S(O)2—, —S(O)—, —OS(O)—, —OS(O)2—, —S(O)2O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(RB)—, —N(RB)C(O)—, —N(RB)C(O)O—, —OC(O)N(RB)—, —N(RB)S(O)—, —N(RB)S(O)2—, —S(O)N(RB)—, —S(O)2N(RB)—, —C(O)N(RB)C(O)—, —N(RB)C(O)N(RB′)—, —N(RB)SO2N(RB′)—, —N(RB)S(O)N(RB′)—, C3-C12carbocycle or 3- to 12-membered heterocycle, and wherein said C3-C12carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more RA; LK is independently selected at each occurrence from bond, -LS-N(RB)C(O)-LS′- or -LS-C(O)N(RB)-LS′-; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more RL; or C3-C12carbocycle or 3- to 12-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more RA; E is independently selected at each occurrence from C3-C12carbocycle or 3- to 12-membered heterocycle, and is independently optionally substituted at each occurrence 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, 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 and RB′ are 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 or 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, 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, C2-C6haloalkynyl, C(O)ORS, or —N(RSRS′); 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, LS′ and LS″ are 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. A method of treating HCV infection, comprising administering an effective amount of a compound of Formula IB or a pharmaceutically acceptable salt thereof, and another anti-HCV agent, to an HCV patient in need 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. 3. The method of claim 2, wherein J is 3- to 6-membered heterocycle, and is optionally substituted with one or more RA. 4. 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. 5. The method of claim 4, wherein D is and each RN is independently selected from RD. 6. The method of claim 5, 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. 7. The method of claim 6, 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. 8. A method of treating HCV infection, comprising administering an effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof, and another anti-HCV agent, to an HCV patient in need 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(RS)—C(O)-LY′-N(RB)C(O)O—RD, -LS-C(R1R2)N(RS)—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)-LY′-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. 9. The method of claim 8, 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. 10. A method of treating HCV infection, comprising administering an effective amount of a compound of Formula IF or a pharmaceutically acceptable salt thereof, and another anti-HCV agent, to an HCV patient in need 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; LS is 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. 11. The method of claim 10, 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 12. The method of claim 11, wherein T-RD is independently selected at each occurrence from 13. The method of claim 12, wherein D is and RM1 is each independently hydrogen, fluoro, chloro, or methyl. 14. A method of treating HCV infection, comprising administering an 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, and another anti-HCV agent, to an HCV patient in need thereof. 15. The method of claim 14, wherein said another anti-HCV agent is an HCV polymerase inhibitor. 16. A method of treating HCV infection, comprising: making a pharmaceutical composition comprising 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, and another anti-HCV agent; and administering said pharmaceutical composition to an HCV patient in need thereof. 17. The method of claim 16, wherein said another anti-HCV agent is an HCV polymerase inhibitor.