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.

1 . A compounds having Formula I, or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 X is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A  or R F ; 
 L 1  and L 2  are each independently selected from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; 
 L 3  is bond or -L S -K-L S ′-, wherein K is selected from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O)—, —N(R B )C(O)N(R B ′), —N(R B )SO 2 N(R B ′)—, or —N(R B )S(O)N(R B ′); 
 A and B are each independently C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and are each independently optionally substituted with one or more R A ; 
 D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A ; or D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle which is substituted with J and optionally substituted with one or more R A , where J is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more R A , or J is —SF 5 ; or D is hydrogen or R A ; 
 Y is selected from -T′-C(R 1 R 2 )N(R 5 )-T-R D , -T′-C(R 3 R 4 )C(R 6 R 7 )-T-R D , -L K -T-R D , or -L K -E; 
 R 1  and R 2  are each independently R C , and R 5  is R B ; or R 1  is R C , and R 2  and R 5 , 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 R A ; 
 R 3 , R 4 , R 6 , and R 7  are each independently R C ; or R 3  and R 6  are each independently R C , and R 4  and R 7 , 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 R A ; 
 Z is selected from -T′-C(R 8 R 9 )N(R 12 )-T-R D , -T′-C(R 10 R 11 )C(R 13 R 14 )-T-R D , -L K -T-R D , or -L K -E; 
 R 8  and R 9  are each independently R C , and R 12  is R B ; or R 8  is R C , and R 9  and R 12 , 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 R A ; 
 R 10 , R 11 , R 13 , and R 14  are each independently R C ; or R 10  and R 13  are each independently R C , and R 11  and R 14 , 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 R A ; 
 T and T′ are each independently selected at each occurrence from bond, -L S -, -L S -M-L S ′-, or -L S -M-L S ′-M′-L S ″-, wherein M and M′ are each independently selected at each occurrence from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O) —, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, —N(R B )S(O)N(R B ′)—, C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and wherein said C 3 -C 12 carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more R A ; 
 L K  is independently selected at each occurrence from bond, -L S -N(R B )C(O)-L S ′- or -L S -C(O)N(R B )-L S ′-; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; or C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more R A ; 
 E is independently selected at each occurrence from C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is independently optionally substituted at each occurrence with one or more R A ; 
 R D  is each independently selected at each occurrence from hydrogen or R A ; 
 R A  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E , wherein two adjacent R A , 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; 
 R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 R B  or R B ′ 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R C  is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 R C  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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S ′, —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′), —P(O)(OR S ) 2 , or —C(O)N(R S )C(O)—R S ′; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 C 3 -C 6 carbocycle 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C(O)OR S , or —N(R S R S ′); 
 R F  is independently selected at each occurrence from C 1 -C 10 alkyl, C 2 -C 10 alkenyl or C 2 -C 10 alkynyl, 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 R L ; or —(R X —R Y ) Q —(R X —R Y ′), wherein Q is 0, 1, 2, 3 or 4, and each R X  is independently O, S or N(R B ), wherein each R Y  is independently C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene 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 R Y ′ is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl 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; 
 R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , N(R S R S ′), —S(O)R S , —SO 2 R S , C(O)N(R S R S ′) or —N(R S )C(O)R S ′; or C 3 -C 6 carbocycle 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; wherein two adjacent R L , 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; 
 L S , L S ′ and L S ″ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; and 
 R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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—C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, 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 R S , R S ′ or R S ′ 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl. 
 
     
     
         2 . A compounds having Formula I E , or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 X is 4- to 8-membered heterocycle, and is optionally substituted with one or more R A ; 
 L 1  and L 2  are each independently selected from bond or C 1 -C 6 alkylene which is independently optionally substituted at each occurrence with one or more halo, hydroxy, —O—C 1 -C 6 alkyl, or —O—C 1 -C 6 haloalkyl; 
 L 3  is bond or C 1 -C 6 alkylene; 
 A and B are each independently phenyl, pyridinyl, thiazolyl, or 
 
       
         
           
           
               
               
           
         
          where Z 1  is independently selected at each occurrence from O, S, NH or CH 2 , Z 3  is independently selected at each occurrence from N or CH, and W 1 , W 2 , and W 3  are each independently selected at each occurrence from CH or N; A and B are each independently optionally substituted with one or more R A . 
         D is C 6 -C 10 carbocycle or 5- to 12-membered heterocycle, each of which is optionally substituted with one or more R M ; 
         Y is -T′-C(R 1 R 2 )N(R 5 )-T-R D ; 
         Z is -T′-C(R 8 R 9 )N(R 12 )-T-R D ; 
         R 1  is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or 3- to 6-membered carbocycle or heterocycle, wherein each said 3- to 6-membered carbocycle or heterocycle is independently optionally substituted at each occurrence with one or more substituents selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —O—C 1 -C 6 alkyl or —O—C 1 -C 6 haloalkyl; 
         R 2  and R 5  are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or 3- to 6-membered carbocycle or heterocycle, wherein each said 3- to 6-membered carbocycle or heterocycle is independently optionally substituted at each occurrence with one or more substituents selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —O—C 1 -C 6 alkyl or —O—C 1 -C 6 haloalkyl; or R 2  and R 5 , 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 R A ; 
         R 8  is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or 3- to 6-membered carbocycle or heterocycle, wherein each said 3- to 6-membered carbocycle or heterocycle is independently optionally substituted at each occurrence with one or more substituents selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —O—C 1 -C 6 alkyl or —O—C 1 -C 6 haloalkyl; 
         R 9  and R 12  are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or 3- to 6-membered carbocycle or heterocycle, wherein each said 3- to 6-membered carbocycle or heterocycle is independently optionally substituted at each occurrence with one or more substituents selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —O—C 1 -C 6 alkyl or —O—C 1 -C 6 haloalkyl; or R 9  and R 12 , 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 R A ; 
         T is independently selected at each occurrence from bond or —C(O)-L S ′-; 
         T′ is independently selected at each occurrence from bond, —C(O)N(R B )—, —N(R B )C(O)—, or 3- to 12-membered heterocycle, wherein said 3- to 12-membered heterocycle is independently optionally substituted at each occurrence with one or more R A ; 
         R D  is each independently selected at each occurrence from hydrogen or R A ; 
         R A  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E ; 
         R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl which is independently optionally substituted at each occurrence with one or more substituents selected from halogen 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 R B  or R B ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —O—C 1 -C 6 alkyl, or —O—C 1 -C 6 haloalkyl; 
         R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S  ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S ′, —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′), —C(O)N(R S )C(O)—R S ′, or ═C(R S R S ′); or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 C 3 -C 12 carbocycle 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
         R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , N(R S R S ′), —S(O)R S , —SO 2 R S , C(O)N(R S R S ′), or —N(R S )C(O)R S ′; or C 3 -C 12 carbocycle 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
         L S  is independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each independently optionally substituted with halogen; 
         L S ′ is independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; 
         R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, 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 R S , R S ′ or R S ″ 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
         R M  is independently selected at each occurrence from:
 halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, SF 5 , —N(R S R S ′), —O—R S , —OC(O)R S , —OC(O)OR S , —OC(O)N(R S R S ′), —C(O)R S , —C(O)OR S , C(O)N(R S R S ′), N(R S )C(O)R S ′, N(R S )C(O)OR S ′, —N(R S )SO 2 R S ′, —S(O)R S , —SO 2 R S , —S(O)N(R S R S ′), —SR S , —Si(R S ) 3 , or —P(O)(OR S ) 2 ; 
 C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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, —N(R S R S ′), —O—R S , —OC(O)R S , —OC(O)OR S , —OC(O)N(R S R S ′), —C(O)R S , —C(O)OR S , C(O)N(R S R S ′), —N(R S )C(O)R S ′ N(R S )C(O)OR S ′, —N(R S )SO 2 R S ′, —S(O)R S , —SO 2 R S , —S(O)N(R S R S ′), —SR S , or —P(O)(OR S ) 2 ; or 
 G 2 , wherein G 2  is a C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more R G2 , and each R G2  is independently selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—R S , —C(O)OR S , —C(O)R S , —N(R S R S ′), or -L 4 -G 3 ; 
 
         L 4  is a bond, C 1 -C 6 alkylene, C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, or —N(R B )S(O)N(R B ′)—; 
         G 3  is a C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R G3 ; and 
         R G3  is each independently, at each occurrence, halogen, —C 1 -C 6 alkyl, —C(O)C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —O—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, C 3 -C 6 carbocycle, or 3- to 6-membered heterocycle. 
       
     
     
         3 . The compound or salt according to  claim 2 , wherein A is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and B is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and D is C 6 -C 10 aryl or 5- to 10-membered heteroaryl and is substituted with one or more R M . 
     
     
         4 . The compound or salt according to  claim 2 , wherein A is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and B is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and D is phenyl or pyridyl and is substituted by one or more R M , wherein at least one R M  is G 2  which is substituted with L 4 -G 3  and optionally substituted with one or more R G2 . 
     
     
         5 . The compound or salt according to  claim 2 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , A is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and B is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and D is phenyl or pyridyl and is substituted by one or more R M , and wherein at least one R M  is 
       
         
           
           
               
               
           
         
       
       which is a monocyclic 4-8 membered nitrogen-containing heterocycle optionally substituted with one or more R G2 . 
     
     
         6 . The compound or salt according to  claim 2 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , A is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and B is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and D is phenyl or pyridyl and is substituted by one or more R M , and at least one R M  is 
       
         
           
           
               
               
           
         
       
       wherein 
       
         
           
           
               
               
           
         
       
       is a monocyclic 4-8 membered nitrogen-containing heterocycle optionally substituted with one or more R G2 . 
     
     
         7 . The compound or salt according to  claim 2 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , A is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and B is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and D is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted by one or more additional R M . 
     
     
         8 . The compound or salt according to  claim 7 , wherein R 1  is hydrogen, and R 2  and R 5  taken together with the atoms to which they are attached form 
       
         
           
           
               
               
           
         
       
       which is substituted with 0, 1, 2, 3, or 4 R A , wherein R 8  is hydrogen, and R 9  and R 12  taken together with the atoms to which they are attached form 
       
         
           
           
               
               
           
         
       
       which is substituted with 0, 1, 2, 3, or 4 R A , and wherein each T′ is bond. 
     
     
         9 . The compound or salt according to  claim 2 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , A is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and B is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A , and D is 
       
         
           
           
               
               
           
         
       
       wherein G 3  is phenyl optionally substituted with one or two R G3 ; g is 0, 1, or 2; R M  is each independently fluoro, chloro, methyl, methoxy, trifluoromethyl, or trifluoromethoxy; and 
       
         
           
           
               
               
           
         
       
       is a monocyclic 4-8 membered nitrogen-containing heterocycle optionally substituted with one or more R G2 . 
     
     
         10 . The compound or salt according to  claim 9 , wherein R 1  is hydrogen, and R 2  and R 5  taken together with the atoms to which they are attached form 
       
         
           
           
               
               
           
         
       
       which is substituted with 0, 1, 2, 3, or 4 R A , wherein R 8  is hydrogen, and R 9  and R 12  taken together with the atoms to which they are attached form 
       
         
           
           
               
               
           
         
       
       which is substituted with 0, 1, 2, 3, or 4 R A , and wherein each T′ is bond. 
     
     
         11 . A compounds having Formula I B , or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 R C ′ is each independently selected from R C ; 
 R D ′ is each independently selected from R D ; 
 R 2  and R 5 , 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 R A ; 
 R 9  and R 12 , 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 R A ; 
 X is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A  or R F ; 
 L 1  and L 2  are each independently selected from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; 
 L 3  is bond or -L S -K-L S ′-, wherein K is selected from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O)—, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, or —N(R B )S(O)N(R B ′)—; 
 A is 
 
       
         
           
           
               
               
           
         
          and is optionally substituted with one or more R A ; 
         B is 
       
       
         
           
           
               
               
           
         
          and is optionally substituted with one or more R A ; 
         D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle which is substituted with J and optionally substituted with one or more R A , where J is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more R A ; 
         T is each independently selected at each occurrence from bond, -L S -, -L S -M-L S ′-, or -L S -M-L S ′-M′-L S ″-, wherein M and M′ are each independently selected at each occurrence from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—,—N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O)—, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, —N(R B )S(O)N(R B ′)—, C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and wherein said C 3 -C 12 carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more R A ; 
         R D  is each independently selected at each occurrence from hydrogen or R A ; 
         R A  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E , wherein two adjacent R A , 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; 
         R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 R B  or R B ′ 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
         R C  is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 R C  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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
         R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S , —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S ′, —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′), —P(O)(OR S ) 2 , or —C(O)N(R S )C(O)—R S ′; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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 C 3 -C 6 carbocycle 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C(O)OR S , or —N(R S R S ′); 
         R F  is independently selected at each occurrence from C 1 -C 10 alkyl, C 2 -C 10 alkenyl or C 2 -C 10 alkynyl, 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 R L ; or —(R X —R Y ) Q —(R X —R Y ′), wherein Q is 0, 1, 2, 3 or 4, and each R X  is independently O, S or N(R B ), wherein each R Y  is independently C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene 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 R Y ′ is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl 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; 
         R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′) or —N(R S )C(O)R S ′; or C 3 -C 6 carbocycle 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; wherein two adjacent R L , 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; 
         L S , L S ′ and L S ″ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; and 
         R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, 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—C 1 -C 6 alkyl, —O—C 1 -C 6 alkylene-O—C 1 -C 6 allyl, 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 R S , R S ′ or R S ′ 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, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl. 
       
     
     
         12 . The compound or salt according to  claim 11 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A  or R F , wherein X 3  is N and is directly linked to -L 3 -D, wherein L 1 , L 2  and L 3  are bond, and D is C 5 -C 6 carbocycle, 5- to 6-membered heterocycle or 6- to 12-membered bicycle and is substituted with J and optionally substituted with one or more R A , and wherein J is C 3 -C 6 carbocycle, 3- to 6-membered heterocycle or 6- to 12-membered bicycle and is optionally substituted with one or more R A . 
     
     
         13 . The compound or salt according to  claim 12 , wherein J is substituted with a C 3 -C 6 carbocycle or 3- to 6-membered heterocycle which is optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C(O)OR S  or —N(R S R S ′), and J is optionally substituted with one or more R A . 
     
     
         14 . The compound or salt according to  claim 11 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A  or R F , and X 3  is N and is directly linked to -L 3 -D, wherein L 1 , L 2  and L 3  are bond, wherein D is 
       
         
           
           
               
               
           
         
       
       and each R N  is independently R D , wherein J is C 3 -C 6 carbocycle, 3- to 6-membered heterocycle or 6- to 12-membered bicycle and is optionally substituted with one or more R A , wherein R 2  and R 5 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A , wherein R 9  and R 12 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A , wherein -T-R D ′ is —C(O)-L Y ′-R D ′, —C(O)O-L Y ′-R D ′, —C(O)-L Y ′-N(R B )C(O)-L S ″-R D ′, —C(O)-L Y ′-N(R B )C(O)O-L S ″-R D ′, —N(R B )C(O)-L Y ′-N(R B )C(O)-L S ″- R D ′, —N(R B )C(O)-L Y ′-N(R B )C(O)O-L S ″-R D ′, or N(R B )C(O)-L Y ′-N(R B )-L S ″-R D ′, and wherein L Y ′ is each independently L S ′. 
     
     
         15 . The compound or salt according to  claim 11 , wherein X is 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A  or R F , and X 3  is N and is directly linked to -L 3 -D, wherein L 1 , L 2  and L 3  are bond, wherein D is 
       
         
           
           
               
               
           
         
       
       and each R N  is independently R D , wherein J is C 3 -C 6 carbocycle and 3- to 6-membered heterocycle and is substituted with a C 3 -C 6 carbocycle or 3- to 6-membered heterocycle which is independently optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C(O)OR S  or —N(R S R S ′), and J is optionally substituted with one or more R A , wherein R 2  and R 5 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A , wherein R 9  and R 12 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A , wherein -T-R D ′ is —C(O)-L Y ′-R D ′, —C(O)O-L Y ′-R D ′, —C(O)-L Y ′-N(R B )C(O)-L S ″-R D ′, —C(O)-L Y ′-N(R B )C(O)O-L S ″-R D ′, —N(R B )C(O)-L Y ′-N(R B )C(O)-L S ″-R D ′, —N(R B )C(O)-L Y ′-N(R B )C(O)O-L S ″-R D ′, or —N(R B )C(O)-L Y ′-N(R B )-L S ″-R D ′, and wherein L Y ′ is each independently L S ′. 
     
     
         16 . A pharmaceutical composition comprising a compound or salt according to  claim 1 . 
     
     
         17 . A pharmaceutical composition comprising a compound or salt according to  claim 1  and another anti-HCV agent. 
     
     
         18 . A method of treating HCV infection, comprising administering to an HCV patient a compound or salt according to  claim 1 . 
     
     
         19 . A process of making a compound according to  claim 1 , comprising a step described in one of the Schemes, General Procedures or Examples described herein. 
     
     
         20 . An intermediate described in one of Schemes, General Procedures or Examples described herein.