IP Library › Granted Patent US 8,003,659

Granted Patent B2

US 8,003,659 · App. 12/365,127 · Granted Aug 23, 2011

Macrocyclic serine protease inhibitors

Assignee: Indenix Pharmaceuticals, Inc.

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Quick Facts

Patent No.: US 8,003,659
App. No.: 12/365,127
Granted: Aug 23, 2011
Kind: B2

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Abstract

Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula I, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Claims (383)

1. A compound of Formula I:

or a single enantiomer, a racemic mixture, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt, thereof;

wherein:

R 5 is —OH, —NR 8 R 9 , —NHS(O) 2 R 8 , —NHS(O) 2 NR 8 R 9 , —NHC(O)R 8 , —NHC(O)NR 8 R 9 , —C(O)R 9 , or —C(O)NR 8 R 9 ; wherein:

each R 8 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, C 1-6 alkyl-C 3-7 cycloalkylene, —CH 2 NR 8a R 8b , —CH(R 8c )NR 8a R 8b , —CHR 8c CHR 8d NR 8a R 8b , or —CH 2 CR 8c R 8d NR 8a R 8b , wherein:

each R 8a , R 8c , and R 8d is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, or C 6-14 aryl-C 1-6 alkylene; and

each R 8b is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, —S(O) k R 11 , —S(O) k NR 11 R 12 , —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , or —C(NR 13 )NR 11 R 12 ; wherein each R 11 , R 12 , and R 13 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R 11 and R 12 together with the N atom to which they are attached form heterocyclyl; or

R 8a and R 8b together with the N atom to which they are attached form heterocyclyl; and

each R 9 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or

R 8 and R 9 together with the N atom to which they are attached form heterocyclyl;

R 6 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl;

L is a bond, C 1-6 alkylene, C 3-7 cycloalkylene, C 2-6 alkenylene, C 2-6 alkynylene, X, or —(CR 6a R 6b ) p X—; wherein p is an integer of 1, 2, or 3; R 6a and R 6b are each independently hydrogen, halo, cyano, hydroxyl, or alkoxy; and X is —O—, —C(O)—, —C(O)O—, —OC(O)O—, —C(O)NR 14 —, —NR 14 —, —NR 14 C(O)NR 15 —, —C(═NR 14 )NR 15 —, —NR 14 C(═NR 15 )NR 16 —, —S(O) k —, —S(O) k NR 14 —, —NR 14 S(O) k NR 15 —, —P(O)(OR 14 )—, or —OP(O)(OR 14 )—, where each R 14 , R 15 , and R 16 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and each k is independently an integer of 1 or 2;

Q 1 is —O—, —N(R 17 )—,—C(R 18 R 19 )—, or —CR 17 (NR 18 R 19 )—; wherein:

each R 17 and R 18 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and

each R 19 is independently —R 20 , —C(O)R 20 , —C(O)OR 20 , —C(O)NR 21 R 22 , —C(—NR 20 )NR 21 R 22 , or —S(O) k R 20 ; where each R 20 , R 21 , and R 22 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R 21 and R 22 together with the N atom to which they are attached form heterocyclyl; or

R 18 and R 19 together with the C or N atom to which they are attached form C 3-7 cycloalkyl or heterocyclyl; and

Q 2 is selected from the group consisting of:

where Z 1 is —O—, —S—, or —N(R Z )—, where R Z is hydrogen, C 1-6 alkyl, aryl, heteroaryl, heterocyclyl, —C(O)R Za , —C(O)OR Z0a , —C(O)NR Zb R Zc , —S(O) 2 NR Zb R Zc , or —S(O) 2 R Za ; and R Za , R Zb , and R Zc are each independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R Zb and R Zc together with the N atom to which they are attached form heterocyclyl or heteroaryl;

wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, aryl, cycloalkyl, cycloalkylene, heterocyclyl, and heteroaryl is optionally substituted with one or more groups, each independently selected from cyano, halo, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q;

wherein each Q is independently selected from the group consisting of cyano, halo, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R f , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , NR e S(O)R f , —NR e S(O) 2 R f , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —SR e , —S(O)R e , or —S(O) 2 R e ; wherein each R e , R f , R g , and R h is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R f and R g together with the N atom to which they are attached form heterocyclyl.

2. The compound of claim 1 , having the structure of Formula II:

wherein:

R 30 is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, or C 1-6 alkyl-C 3-7 cycloalkylene, each optionally substituted with one or more substituents Q; or —CH 2 NR 30a R 30b , —CHR 30c NR 30a R 30b , —CHR 30c CHR 30d NR 30a R 30b , or —CH 2 CR 30v R 30d NR 30a R 30b , wherein:

each R 30a , R 30c , and R 30d is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, or C 6-14 aryl-C 1-6 alkylene, each optionally substituted with one or more substituents Q; and

each R 30b is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —S(O) k R 11 , —S(O) k NR 11 R 12 , —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , or —C(═NR 13 )NR 11 R 12 ; wherein R 11 , R 12 , and R 13 are each independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R 11 and R 12 together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q; or

R 30a and R 30b together with the N atom to which they are attached form heterocyclyl or heteroaryl, each optionally substituted with one or more substituents Q.

3. The compound of claim 1 , having the structure of Formula III:

wherein:

Z is CR 3′ or N; and

R 2′ , R 3′ , R 5′ , R 6′ , R 7′ , and R 8′ are each independently:

hydrogen, halo, cyano, trifluoromethyl, or nitro;

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or

—C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q.

4. The compound of claim 2 , having the structure of Formula IV:

wherein:

Z is CR 3′ or N; and

R 2′ , R 3′ , R 5′ , R 6′ , R 7′ , and R 8′ are each independently:

hydrogen, halo, cyano, trifluoromethyl, or nitro;

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or

—C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q.

5. A compound of Formula V:

or a single enantiomer, a racemic mixture, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt, thereof;

wherein:

R 5 is —OH, —NR 8 R 9 , —NHS(O) 2 R 8 , —NHS(O) 2 NR 8 R 9 , —NHC(O)R 8 , —NHC(O)NR 8 R 9 , —C(O)R 9 , or —C(O)NR 8 R 9 ; wherein:

each R 8a , R 8c , and R 8d is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, or C 6-14 aryl-C 1-6 alkylene; and

each R 8b is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, —S(O) k R 11 , —S(O) k NR 11 R 12 , —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , or —C(═NR 13 )NR 11 R 12 ; wherein each R 11 , R 12 , and R 13 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R 11 and R 12 together with the N atom to which they are attached form heterocyclyl; or

R 8a and R 8b together with the N atom to which they are attached form heterocyclyl; and

each R 9 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or

R 8 and R 9 together with the N atom to which they are attached form heterocyclyl;

R 6 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl;

Q 1 is —O—, —N(R 17 )—, —C(R 18 R 19 )—, or —CR 17 (NR 18 NR 19 )—; wherein:

each R 17 and R 18 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and

each R 19 is independently —R 20 , —C(O)R 20 —C(O)OR 20 , —C(O)NR 21 R 22 , —C(═NR 20 )NR 21 R 22 , or —S(O) k R 20 ; where each R 20 , R 21 , and R 22 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R 21 and R 22 together with the N atom to which they are attached form heterocyclyl; or

R 18 and R 19 together with the C or N atom to which they are attached form C 3-7 cycloalkyl or heterocyclyl; and

n is an integer of 0, 1, or 2;

wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, aryl, cycloalkyl, cycloalkylene, heterocyclyl, and heteroaryl is optionally substituted with one or more groups, each independently selected from cyano, halo, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR a C(O)R b , —NR a C(O)NR b R c , NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R 6 , —NR a S(O)NR b R c , NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q;

wherein each Q is independently selected from the group consisting of cyano, halo, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or —C(O)R e , —C(O)OR e , —C(O)NR f R g , —C(NR e )NR f R g , —OR e , —OC(O)R e , —OC(O)OR e , —OC(O)NR f R g , —OC(═NR e )NR f R g , —OS(O)R e , —OS(O) 2 R e , —OS(O)NR f R g , —OS(O) 2 NR f R g , —NR f R g , —NR e C(O)R f , —NR e C(O)OR f , —NR e C(O)NR f R g , —NR e C(═NR h )NR f R g , NR e S(O)R f , —NR e S(O) 2 R f , —NR e S(O)NR f R g , —NR e S(O) 2 NR f R g , —S(O)R e , or —S(O) 2 R e ; wherein each R e , R f , R g , and R h is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; or R f and R g together with the N atom to which they are attached form heterocyclyl.

6. The compound of claim 5 , having the structure of Formula VI:

wherein:

R 30 is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, or C 1-6 alkyl-C 3-7 cycloalkylene, each optionally substituted with one or more substituents Q; or —CH 2 NR 30a R 30b , CHR 30c NR 30a R 30b , —CHR 30c CHR 30d NR 30a R 30b , or —CH 2 CR 30c R 30d NR 30a R 30b , wherein:

R 30a and R 30b together with the N atom to which they are attached form heterocyclyl or heteroaryl, each optionally substituted with one or more substituents Q; and

n is an integer of 0, 1, or 2.

7. The compound of claim 5 , having the structure of Formula VII:

wherein:

Z is CR 3 or N;

R 2′ , R 3′ , R 5′ , R 6′ , R 7′ , and R 8′ are each independently:

hydrogen, halo, cyano, trifluoromethyl, or nitro;

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or

wherein each R a , R b , R c , and R d is independently hydrogen; or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q; and

n is an integer of 0, 1, or 2.

8. The compound of claim 6 , having the structure of Formula VIII:

wherein:

Z is CR 3′ or N;

R 2′ , R 3′ , R 5′ , R 6 , R 7′ , and R 8′ are each independently:

hydrogen, halo, cyano, trifluoromethyl, or nitro;

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or

—C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q; and

n is an integer of 0, 1, or 2.

9. The compound of claim 1 , wherein R 6 is C 1-6 alkyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

10. The compound of claim 9 , wherein R 6 is C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

11. The compound of claim 9 , wherein R 6 is selected from the group consisting of:

wherein:

each R 1′ , R 2′ , R 3′ , R 5′ , R 6′ , R 7′ , and R 8′ is independently:

hydrogen, halo, cyano, trifluoromethyl, or nitro;

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q.

12. The compound of claim 1 , wherein Q 1 is —O—.

13. The compound of claim 1 , wherein Q 1 is —C(R 18 R 19 )—.

14. The compound of claim 13 , wherein R 18 and R 19 are each independently hydrogen; C 1-6 alkyl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q.

15. The compound of claim 13 , wherein R 18 and R 19 are hydrogen.

16. The compound of claim 1 , wherein Q 1 is —N(R 17 )—.

17. The compound of claim 8 , having the structure of Formula IX:

18. The compound of claim 17 , wherein R 17 is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

19. The compound of claim 18 , wherein R 17 is hydrogen; C 1-6 alkyl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q.

20. The compound of claim 18 , wherein R 17 is hydrogen or methyl.

21. The compound of claim 18 , wherein R 17 is methyl.

22. The compound of claim 1 , wherein Q 1 is —CR 17 (NR 18 R 19 )—.

23. The compound of claim 22 , wherein R 17 and R 18 are each independently hydrogen; C 1-6 alkyl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q.

24. The compound of claim 22 , wherein R 17 is hydrogen.

25. The compound of claim 8 , having the structure of Formula X:

26. The compound of claim 25 , wherein R 18 is hydrogen or methyl.

27. The compound of claim 25 , wherein R 19 is hydrogen, —C(O)R 20 , —C(O)OR 20 , —C(O)NR 21 R 22 , or —C(═NR 20 )NR 21 R 22 .

28. The compound of claim 27 , wherein R 19 is —C(O)OR 20 .

29. The compound of claim 27 , wherein R 20 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

30. The compound of claim 29 , wherein R 20 is C 1-6 alkyl.

31. The compound of claim 29 , wherein R 20 is t-butyl.

32. The compound of claim 29 , wherein R 20 is C 6-14 aryl.

33. The compound of claim 29 , wherein R 20 is benzyl.

34. The compound of claim 3 , wherein R 2′ is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

35. The compound of claim 34 , wherein R 2′ is C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

36. The compound of claim 34 , wherein R 2′ is selected from the group consisting of:

wherein

each A is independently hydrogen, halo, cyano, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q; and

each E is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q.

37. The compound of claim 36 , wherein A is hydrogen, halo, cyano, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

38. The compound of claim 36 , wherein A is hydrogen or C 1-6 alkyl, optionally substituted with one or more substituents Q.

39. The compound of claim 36 , wherein A is hydrogen, methyl, trifluoromethyl, ethyl, n-propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, ethenyl, or ethynyl.

40. The compound of claim 36 , wherein A is isopropyl.

41. The compound of claim 36 , wherein A is trifluoromethyl.

42. The compound of claim 36 , wherein A is —NR b R c .

43. The compound of claim 36 , wherein A is isopropylamino.

44. The compound of claim 36 , wherein E is hydrogen or cyano; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

45. The compound of claim 44 , wherein E is hydrogen or methyl.

46. The compound of claim 44 , wherein E is hydrogen.

47. The compound of claim 3 , wherein R 7′ is hydrogen, cyano, or halo; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —OR a , wherein R a is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

48. The compound of claim 47 , wherein R 7′ is hydrogen, halo, or —OR a .

49. The compound of claim 47 , wherein R 7′ is —OR a .

50. The compound of claim 48 , wherein R a is C 1-6 alkyl, C 3-7 cycloalkyl, or C 6-14 aryl, each optionally substituted with one or more substituents Q.

51. The compound of claim 50 , wherein R a is C 1-6 alkyl, optionally substituted with one or more substituents Q.

52. The compound of claim 50 , wherein R 7′ is methoxy, difluoromethoxy, or trifluoromethoxy.

53. The compound of claim 3 , wherein R 7′ is methanesulfonamido.

54. The compound of claim 3 , wherein R 8′ is hydrogen, hydroxyl, cyano, or halo; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —OR a , wherein R a is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

55. The compound of claim 54 , wherein R 8′ is hydrogen, halo, or C 1-6 alkyl, optionally substituted with one or more substituents Q.

56. The compound of claim 54 , wherein R 8′ is methyl.

57. The compound of claim 3 , wherein R 6′ is hydrogen, cyano, or halo; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —OR a , wherein R a is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

58. The compound of claim 57 , wherein R 6′ is hydrogen, halo, or —OR a .

59. The compound of claim 58 , wherein R a is C 1-6 alkyl, C 3-7 cycloalkyl, or C 6-14 aryl.

60. The compound of claim 58 , wherein R 6′ is methoxy.

61. The compound of claim 58 , wherein R 6′ is chloro.

62. The compound of claim 3 , wherein R 5′ is hydrogen or —OR a .

63. The compound of claim 62 , wherein R 5′ is methoxy.

64. The compound of claim 3 , wherein R 3′ is hydrogen.

65. The compound of claim 3 , wherein R 2′ is selected from the group consisting of:

66. The compound of claim 1 , wherein L is a bond; C 1-6 alkylene, or C 3-7 cycloalkylene, each optionally substituted with one or more substituents Q; or —O—, —(CH 2 ) p —, —C(O)—, —(CH 2 ) p C(O)—, —C(O)O—, —C(O)NR 14 —, —C(═NR 14 )NR 15 —, —NR 14 —, —S(O) k —, or —S(O) k NR 15 —; wherein p is an integer of 1, 2, or 3.

67. The compound of claim 66 , wherein L is a bond.

68. The compound of claim 66 , wherein L is —O— or —NR 14 —.

69. The compound of claim 66 , wherein L is C 1-6 alkylene, optionally substituted with one or more substituents Q.

70. The compound of claim 66 , wherein L is methylene.

71. The compound of claim 66 , wherein L is ethylene.

72. The compound of claim 66 , wherein L is —(CH 2 ) p —.

73. The compound of claim 66 , wherein L is —(CH 2 ) p CF 2 —.

74. The compound of claim 66 , wherein L is —CF 2 —.

75. The compound of claim 66 , wherein L is —C(O)—.

76. The compound of claim 66 , wherein L is —C(O)O—.

77. The compound of claim 66 , wherein L is —C(O)NR 14 —.

78. The compound of claim 68 , wherein R 14 is hydrogen or C 1-6 alkyl.

79. The compound of claim 66 , wherein L is —C(O)NH—.

80. The compound of claim 5 , wherein n is 1, 2, or 3.

81. The compound of claim 1 , wherein R 5 is —OH.

82. The compound of claim 1 , wherein R 5 is —NR 7 S(O) k R 8 .

83. The compound of claim 52 , wherein R 8 is C 1-6 alkyl, C 6-14 aryl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q; or —CH 2 NR 8a R 8 b, —CHR 8c CHR 8d NR 8a R 8b , or —CH 2 CR 8c R 8d NR 8a R 8b .

84. The compound of claim 82 , wherein R 8 is C 3-7 cycloalkyl, optionally substituted with one or more substituents Q.

85. The compound of claim 82 , wherein R 8 is methyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

86. The compound of claim 2 , wherein R 30 is C 1-6 alkyl, C 6-14 aryl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q; or —CH 2 NR 30a R 30b , —CHR 30c CHR 30d NR 30a R 30b , or —CH 2 CR 30c R 30d NR 30a R 30b .

87. The compound of claim 86 , wherein R 30 is C 3-7 cycloalkyl, optionally substituted with one or more substituents Q.

88. The compound of claim 86 , wherein R 30 is cyclopropyl, 1-methylcyclopropyl, 1-ethynylcyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

89. The compound of claim 3 , wherein Z is CH.

90. The compound of claim 3 , wherein Z is N.

91. The compound of claim 4 selected from the group consisting of

and pharmaceutically acceptable salts thereof.

92. The compound of claim 5 selected from the group consisting of

and pharmaceutically acceptable salts thereof.

93. The compound of claim 4 selected from the group consisting of

and pharmaceutically acceptable salts thereof.

94. The compound of claim 4 selected from the group consisting of

and pharmaceutically acceptable salts thereof;

Cmpd #

R 6

62a

62b

62c

62d

62e

62f

62g

62h

69a

69b

69c

69d

69e

69f

69g

69h

91e

91f

91g

G 1

G 3

O 1

O 3

T 1

AC 1

AC 2

wherein the symbol * indicates the point of attachment.

95. The compound of claim 4 selected from the group consisting of

and pharmaceutically acceptable salts thereof;

Cmpd #

R 6

56a

56b

56c

56d

56e

56f

56g

56h

68a

68b

68c

68d

68e

68f

68g

68h

91a

91b

91c

91d

96a

96b

96c

96d

96e

96f

96g

96h

101a

101b

101c

101d

101e

101f

101g

101h

110a

110b

110c

110d

110e

110f

110g

110h

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

G 2

G 4

O 2

O 4

T 2

AC 3

wherein the symbol * indicates the point of attachment.

96. A pharmaceutical composition comprising the compound of claim 1 , and one or more pharmaceutically acceptable carriers.

97. The pharmaceutical composition of claim 96 , further comprising a second antiviral agent.

98. The pharmaceutical composition of claim 97 , wherein the second antiviral agent is selected from the group consisting of an interferon, ribavirin, an interleukin, an NS3 protease inhibitor, a cysteine protease inhibitor, a phenathrenequinone, a thiazolidine, a benzanilide, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, a liotoxin, acerulenin, an antisense phosphorothioate oligodeoxynucleotide, an inhibitor of IRES-dependent translation, and a ribozyme.

99. The pharmaceutical composition of claim 97 , wherein the second antiviral agent is an interferon.

100. The pharmaceutical composition of claim 99 , wherein the interferon is selected from the group consisting of pegylated interferon alpha 2a, interferon alfahcon-1, natural interferon, albuferon, interferon beta-1a, omega interferon, interferon alpha, interferon gamma, interferon tau, interferon delta, and interferon gamma-1b.

101. The pharmaceutical composition of claim 96 , wherein the composition is formulated for single dose administration.

102. The pharmaceutical composition of claim 96 , wherein the composition is formulated as oral, parenteral, or intravenous dosage form.

103. The pharmaceutical composition of claim 102 , wherein the oral dosage form is a tablet or capsule.

104. The pharmaceutical composition of claim 96 , wherein the compound is administered in a dose of about 0.5 milligram to about 1,000 milligram daily.

105. A method for treating an HCV infection, which comprises administering the compound of claim 1 .

106. A method of treating one or more symptoms of a liver disease or disorder associated with an HCV infection, comprising administering the compound of claim 1 .

107. The method of claim 105 , wherein the method comprises administering a second antiviral agent, in combination or alternation.

108. The method of claim 107 , wherein the second antiviral agent is selected from the group consisting of an interferon, ribavirin, amantadine, an interleukin, a NS3 protease inhibitor, a cysteine protease inhibitor, a phenathrenequinone, a thiazolidine, a benzanilide, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, a liotoxin, acerulenin, an antisense phosphorothioate oligodeoxynucleotide, an inhibitor of IRES-dependent translation, and a ribozyme.

109. The method of claim 107 , wherein the second antiviral agent is an interferon.

110. The method of claim 109 , wherein the interferon is selected from the group consisting of pegylated interferon alpha 2a, interferon alfacon-1, natural interferon, albuferon, interferon beta-1a, omega interferon, interferon alpha, interferon gamma, interferon tau, interferon delta, and interferon gamma-1b.

111. The compound of claim 5 , wherein R 6 is C 1-6 alkyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

112. The compound of claim 111 , wherein R 6 is C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

113. The compound of claim 111 , wherein R 6 is selected from the group consisting of:

wherein:

each R 1′ , R 2′ , R 3′ , R 5′ , R 6′ , R 7′ , and R 8′ is independently:

hydrogen, halo, cyano, trifluoromethyl, or nitro;

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or

—C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or —S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q.

114. The compound of claim 5 , wherein Q 1 is —O—.

115. The compound of claim 5 , wherein Q 1 is —C(R 18 R 19 )—.

116. The compound of claim 115 , wherein R 18 and R 19 are each independently hydrogen; C 1-6 alkyl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q.

117. The compound of claim 115 , wherein R 18 and R 19 are hydrogen.

118. The compound of claim 5 , wherein Q 1 is —N(R 17 )—.

119. The compound of claim 118 , wherein R 17 is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

120. The compound of claim 118 , wherein R 17 is hydrogen; C 1-6 alkyl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q.

121. The compound of claim 118 , wherein R 17 is hydrogen or methyl.

122. The compound of claim 118 , wherein R 17 is methyl.

123. The compound of claim 5 , wherein Q 1 is —CR 17 (NR 18 R 19 )—.

124. The compound of claim 123 , wherein R 17 and R 18 are each independently hydrogen; C 1-6 alkyl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q.

125. The compound of claim 123 , wherein R 17 is hydrogen.

126. The compound of claim 123 , wherein R 18 is hydrogen or methyl.

127. The compound of claim 123 , wherein R 19 is hydrogen, —C(P)R 20 , —C(O)OR 20 , —C(O)NR 21 R 22 , or —C(═NR 20 )NR 21 R 22 .

128. The compound of claim 123 , wherein R 19 is —C(O)OR 20 .

129. The compound of claim 128 , wherein R 20 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

130. The compound of claim 128 , wherein R 20 is C 1-6 alkyl.

131. The compound of claim 128 , wherein R 20 is t-butyl.

132. The compound of claim 128 , wherein R 20 is C 6-14 aryl.

133. The compound of claim 128 , wherein R 20 is benzyl.

134. The compound of claim 7 , wherein R 2′ is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

135. The compound of claim 134 , wherein R 2′ is C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

136. The compound of claim 134 , wherein R 2′ is selected from the group consisting of:

wherein

each E is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R b , —NR a C(O)OR b , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , NR a S(O)R b , —NR a S(O) 2 R b , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , or −S(O) 2 R a ; wherein each R a , R b , R c , and R d is independently hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or R b and R c together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Q.

137. The compound of claim 136 , wherein A is hydrogen, halo, cyano, or nitro; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

138. The compound of claim 136 , wherein A is hydrogen or C 1-6 alkyl, optionally substituted with one or more substituents Q.

139. The compound of claim 136 , wherein A is hydrogen, methyl, trifluoromethyl, ethyl, n-propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, ethenyl, or ethynyl.

140. The compound of claim 136 , wherein A is isopropyl.

141. The compound of claim 136 , wherein A is trifluoromethyl.

142. The compound of claim 136 , wherein A is —NR b R c .

143. The compound of claim 136 , wherein A is isopropylamino.

144. The compound of claim 136 , wherein E is hydrogen or cyano; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heterocyclyl, or heteroaryl, each optionally substituted with one or more substituents Q.

145. The compound of claim 144 , wherein E is hydrogen or methyl.

146. The compound of claim 144 , wherein E is hydrogen.

147. The compound of claim 7 , wherein R 7′ is hydrogen, cyano, or halo; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —OR a , wherein R a is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

148. The compound of claim 147 , wherein R 7′ is hydrogen, halo, or —OR a .

149. The compound of claim 147 , wherein R 7′ is —OR a .

150. The compound of claim 149 , wherein R a is C 1-6 alkyl, C 3-7 cycloalkyl, or C 6-14 aryl, each optionally substituted with one or more substituents Q.

151. The compound of claim 149 , wherein R a is C 1-6 alkyl, optionally substituted with one or more substituents Q.

152. The compound of claim 149 , wherein R 7′ is methoxy, difluoromethoxy, or trifluoromethoxy.

153. The compound of claim 7 , wherein R 7′ is methanesulfonamido.

154. The compound of claim 7 , wherein R 8′ is hydrogen, hydroxyl, cyano, or halo; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —OR a , wherein R a is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

155. The compound of claim 154 , wherein R 8′ is hydrogen, halo, or C 1-6 alkyl, optionally substituted with one or more substituents Q.

156. The compound of claim 154 , wherein R 8′ is methyl.

157. The compound of claim 7 , wherein R 6′ is hydrogen, cyano, or halo; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or —OR a , wherein R a is hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q.

158. The compound of claim 157 , wherein R 6′ is hydrogen, halo, or —OR a .

159. The compound of claim 158 , wherein R a is C 1-6 alkyl, C 3-7 cycloalkyl, or C 6-14 aryl.

160. The compound of claim 158 , wherein R 6′ is methoxy.

161. The compound of claim 158 , wherein R 6′ is chloro.

162. The compound of claim 7 , wherein R 5′ is hydrogen or —OR a .

163. The compound of claim 162 , wherein R 5′ is methoxy.

164. The compound of claim 7 , wherein R 3′ is hydrogen.

165. The compound of claim 7 , wherein R 2′ is selected from the group consisting of:

166. The compound of claim 5 , wherein L is a bond; C 1-6 alkylene, or C 3-7 cycloalkylene, each optionally substituted with one or more substituents Q; or —O—, —(CH 2 ) p —, —C(O)—, —(CH 2 ) p C(O)—, —C(O)O—, —C(O)NR 14 , —C(═NR 14 )NR 15 —, —NR 14 —, —S(O) k —, or —S(O) k NR 15 —; wherein p is an integer of 1, 2, or 3.

167. The compound of claim 166 , wherein L is a bond.

168. The compound of claim 166 , wherein L is —O— or —NR 14 —.

169. The compound of claim 166 , wherein L is C 1-6 alkylene, optionally substituted with one or more substituents Q.

170. The compound of claim 166 , wherein L is methylene.

171. The compound of claim 166 , wherein L is ethylene.

172. The compound of claim 166 , wherein L is —(CH 2 ) p —.

173. The compound of claim 166 , wherein L is —(CH 2 ) p CF 2 —.

174. The compound of claim 166 , wherein L is —CF 2 —.

175. The compound of claim 166 , wherein L is —C(O)—.

176. The compound of claim 166 , wherein L is —C(O)O—.

177. The compound of claim 166 , wherein L is —C(O)NR 14 —.

178. The compound of claim 177 , wherein R 14 is hydrogen or C 1-6 alkyl.

179. The compound of claim 177 , wherein L is —C(O)NH—.

180. The compound of claim 5 , wherein R 5 is —OH.

181. The compound of claim 5 , wherein R 5 is —NR 7 S(O) k R 8 .

182. The compound of claim 181 , wherein R 8 is C 1-6 alkyl, C 6-14 aryl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q; or —CH 2 NR 8a R 8b , —CHR 8c NR 8d NR 8a R 8b , or —CH 2 CR 8c R 8d NR 8a R 8b .

183. The compound of claim 181 , wherein R 8 is C 3-7 cycloalkyl, optionally substituted with one or more substituents Q.

184. The compound of claim 181 , wherein R 8 is methyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

185. The compound of claim 6 , wherein R 30 is C 1-6 alkyl, C 6-14 aryl, or C 3-7 cycloalkyl, each optionally substituted with one or more substituents Q; or —CH 2 NR 30a R 30b , —CHR 30c CHR 30d NR 30a R 30b , or —CH 2 CR 30c R 30d NR 30a R 30b .

186. The compound of claim 185 , wherein R 30 is C 3-7 cycloalkyl, optionally substituted with one or more substituents Q.

187. The compound of claim 185 , wherein R 30 is cyclopropyl, 1-methylcyclopropyl, 1-ethynylcyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

188. The compound of claim 7 , wherein Z is CH.

189. The compound of claim 7 , wherein Z is N.

Assignments (2)

CHANGE OF NAME Recorded Jul 30, 2015

From: IDENIX PHARMACEUTICALS, INC.

To: IDENIX PHARMACEUTICALS LLC

Reel/Frame 036234/0070 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 17, 2009

From: DEROCK, MICHEL; LEROY, FREDERIC; PARSY, CHRISTOPHE CLAUDE; ALEXANDRE, FRANCOIS- RENE; SURLERAUX, DOMINQUE

To: IDENIX PHARMACEUTICALS, INC.

Reel/Frame 022409/0824 →

Continuity (3)

Provisional Application 61026086 · Feb 4, 2008

Provisional Application 61083867 · Jul 25, 2008

Related Publication 20090202480A1 · Aug 13, 2009