Anti-viral compounds

Patent metadata

Field	Value
Publication number	US-10039754-B2
Application number	US-201715431069-A
Country	US
Kind code	B2
Filing date	Feb 13, 2017
Priority date	Jun 11, 2009
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

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 method of treating hepatitis C virus (HCV) infection, comprising administering an effective amount of a compound having Formula I or a pharmaceutically acceptable salt thereof, and another anti-HCV agent, to an HCV patient in need thereof,

wherein:
X is 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)—, —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 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 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

Assignees

• Abbvie Inc

Inventors

• Bellizzi Mary E
• Betebenner David A
• Califano Jean-Christophe C
• Carroll William A
• Caspi Daniel D
• Degoey David A
• Donner Pamela L
• Flentge Charles A
• Gao Yi
• Hutchins Charles W
• Hutchinson Douglas K
• Jinkerson Tammie K
• Kati Warren M
• Keddy Ryan G
• Krueger Allan C
• Li Wenke
• Liu Dachun
• Maring Clarence J
• Matulenko Mark A
• Motter Christopher E
• Nelson Lissa T
• Patel Sachin V
• Pratt John K
• Randolph John T
• Rockway Todd W
• Sarris Kathy
• Tufano Michael D
• Wagaw Seble H
• Wagner Rolf
• Woller Kevin R

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61K31/695

  Silicon compounds · CPC title