Anti-viral compounds

Patent metadata

Field	Value
Publication number	US-9394279-B2
Application number	US-201113328848-A
Country	US
Kind code	B2
Filing date	Dec 16, 2011
Priority date	Jun 11, 2009
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

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.

First claim

What is claimed is:

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,

wherein:
X is cyclopropyl, and is optionally substituted with one or more R A ;
L 1 , L 2 and L 3 are each a bond;
A is selected from

 or

 B is selected from

 or

 Z 1 is independently selected at each occurrence from O, S, NH or CH 2 , Z 2 is independently selected at each occurrence from N or CH, and W 1 , W 2 , W 3 , W 4 , W 5 and W 6 are each independently selected at each occurrence from CH or N, wherein A and B 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, and is substituted with J and optionally substituted with one or more R A , wherein J is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more R A ;
Y is —C(R 1 R 2 )N(R 5 )-T-R D , or —C(R 3 R 4 )C(R 6 R 7 )-T-R D ;
Z is —C(R 8 R 9 )N(R 12 )-T-R D , or —C(R 10 R 11 )C(R 13 R 14 )-T-R D ;
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 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 ;
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 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 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 ;
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 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;
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; 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
—(R G —R H ) n —(R G —R H ′), wherein each n is independently 0, 1, 2, 3 o

Assignees

• Krueger Allan C
• Kati Warren M
• Carroll William A
• Pratt John K
• Hutchinson Douglas K
• Abbvie Inc

Inventors

• Krueger Allan C
• Kati Warren M
• Carroll William A
• Pratt John K
• Hutchinson Douglas K

Classifications

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61P31/12

  Antivirals · CPC title