Hepatitis C inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-9567355-B2
Application number	US-201615240753-A
Country	US
Kind code	B2
Filing date	Aug 18, 2016
Priority date	Dec 22, 2010
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

This disclosure relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

First claim

What is claimed is:

1. A compound having formula (I), or a pharmaceutically acceptable salt thereof,

wherein:
R 1 is formula (v);

R 1a , at each occurrence, is each independently hydrogen, halogen, C 1 -C 3 alkyl, or C 1 -C 3 haloalkyl;
R 2 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 2 -C 10 haloalkenyl, C 2 -C 10 haloalkynyl, or L 2A -G 2a ;
L 2A is a bond, C 2 alkenylene, or C 2 alkynylene;
G 2a is C 6 -C 10 aryl or 5- to 10-membered heteroaryl, wherein the aryl or heteroaryl is optionally substituted with 1, 2, or 3 substituents selected from the group consisting of R 20 , L 2B -R 21 , G 2b and L 2B -G 2b ;
L 2B and L 2C , at each occurrence, are each independently C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene;
R 20 is hydrogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 2 -C 10 haloalkenyl, C 2 -C 10 haloalkynyl, halogen, —N(R 2a )C(O)R 2b , —C(O)N(R 2a )(R 2b ), —O—R 2b , —C(O)R 2b , —OC(O)R 2b , —CO 2 H, —CO 2 R 2b , —N(R 2a )C(O)N(R 2a )(R 2b ), —S—R 2b , —S(O) 2 R 2b , —S(O)R 2b , —SO 2 N(R 2a )(R 2b ), —N(R 2a )(R 2b ), —N(R 2a )S(O) 2 R 2b , N(R 2a )C(O)O(R 2b ), or —C(═CH 2 )R 2b ;
R 21 is —N(R 2a )C(O)R 2b , —C(O)N(R 2a )(R 2b ), —O—R 2b , —C(O)R 2b , —OC(O)R 2b , —CO 2 H, —CO 2 R 2b , —N(R 2a )C(O)N(R 2a )(R 2b ), —S—R 2b , —S(O) 2 R 2b , —S(O)R 2b , —SO 2 N(R 2a )(R 2b ), —N(R 2a )(R 2b ), —N(R 2a )S(O) 2 R 2b , N(R 2a )C(O)O(R 2b ), or —C(═CH 2 )R 2b ;
R 2a , at each occurrence, is each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 8 cycloalkyl, wherein the C 3 -C 8 cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl;
R 2b , at each occurrence, is each independently hydrogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 2 -C 10 haloalkenyl, C 2 -C 10 haloalkynyl, -L 2C -R 2c , G 2b or -L 2C -G 2b ;
R 2c is —N(R 2d )C(O)R 2d , —C(O)N(R 2d )(R 2d ), —O—R 2d , —C(O)R 2d , —OC(O)R 2d , —CO 2 H, —CO 2 R 2d , —N(R 2d )C(O)N(R 2d )(R 2d ), —S—R 2d , —S(O) 2 R 2d , —S(O)R 2d , —SO 2 N(R 2d )(R 2d ), —N(R 2d )(R 2d ), —N(R 2d )S(O) 2 R 2d , or N(R 2d )C(O)O(R 2d );
R 2d , at each occurrence, is each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkylene-OH, or C 3 -C 8 cycloalkyl, wherein the C 3 -C 8 cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl;
G 2b is C 3 -C 10 cycloalkyl, C 5 -C 10 cycloalkenyl, C 6 -C 10 aryl, 3- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein G 2b is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 2 -C 10 haloalkenyl, C 2 -C 10 haloalkynyl, halogen, oxo, cyano, hydroxy, —O—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, —C 1 -C 3 alkylene-O—H, —C 1 -C 3 alkylene-O—C 1 -C 6 alkyl, C(O)H, —C 1 -C 3 alkylene-NH 2 , —NH 2 , —NO 2 , —C(O)C 1 -C 6 alkyl, —C(O)OC 1 -C 6 alkyl, and G 2c ;
G 2c is C 6 -C 10 aryl or 5- to 10-membered heteroaryl, wherein G 2c is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 2 -C 10 haloalkenyl, C 2 -C 10 haloalkynyl, halogen, oxo, cyano, hydroxy, —O—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, —C 1 -C 3 alkylene-O—H, —C 1 -C 3 alkylene-O—C 1 -C 6 alkyl, C(O)H, —C 1 -C 3 alkylene-NH 2 , —NH 2 , —NO 2 , —C(O)C 1 -C 6 alkyl, and —C(O)OC 1-C 6 alkyl;

A and B together are a bicyclic heteroaryl, wherein A is formula (vi) or formula (vii):

 or

wherein,
V 1 and V 2 are each C, or one of V 1 and V 2 is N and the other is C, and V 3 is CR 7 , NR 7 , N, O, or S; wherein, when A is (vii), V 2 is C and V 3 is N, O, or S;
R 7 is hydrogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, or C 3 -C 6 cycloalkyl;

is a single or double bond;
W 1 is N or CR 6 , W 2 is N or CR 5 , W 3 is N or CR 4 , and W 4 is N or CR 3 , wherein none, one or two of W 1 , W 2 , W 3 and W 4 is N;
W 5 is N or CR 6 , and W 6 is N or CR 5 , wherein none or one of W 5 and W 6 is N;
W 7 is N, O, or S;
R 3 and R 6 are each independently hydrogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, halogen, —OC 1 -C 3 alkyl, or —OC 1 -C 3 haloalkyl;
R 4 is hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —O—C 6 alkyl, —O—C 1 -C 6 haloalkyl, cyano, —NH 2 , L 4A -OH, 5-membered heteroaryl optionally substituted with 1 or 2 alkyl or halogen, 5-membered heterocycle or —N(R 40 )(SO 2 R 4a );
R 40 is hydrogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 haloalkyl, C 2 -C 10 haloalkenyl, C 2 -C 10 haloalkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, -L 4A -G 4a , -L 4A -C(O)-L 4B -G 4a , -L 4A -O-L 4B -G 4a , -L 4A -S(O) 2 -L 4B -G 4a , -L 4A -N(R 4b )(L 4B -G 4a ), -L 4A -N(R 4b )C(O)-L 4B -G 4a , -L 4A -N(R 4b )S(O) 2 -L 4B -G 4a , or -L 4A -R 4c , wherein the C 1 -C 10 alkyl, C 2 -C 10 alkenyl, and C 2 -C 10 alkynyl are each optionally substituted with 2, 3, or 4 hydroxy substituents; and wherein the C 3 -C 8 cycloalkyl or 3- to 8-membered heterocyclyl is each optionally substituted with L 4B -G 4b and optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —O—C 1 -C 3 alkyl, and —O—C 1 -C 3 haloalkyl;
L 4A is C 1 -C 10 alkylene, C 2 -C 10 alkenylene, or C 2 -C 10 alkynylene, wherein L 4A is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl;
G 4a is C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl, wherein G 4a is optionally substituted with L 4C -G 4b and optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, oxo, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OH, —O—C 1 -C 3 alkyl, —O—C 1 -C 3 haloalkyl, thioxo, —NH 2 , —NH(C 1 -C 3 alkyl), and —N(C 1 -C 3 alkyl) 2 ;
L 4B and L 4C , at each occurrence, are each independently a bond, C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene, wherein L 4B and L 4C are each optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl;
G 4b is C 3 -C 12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6 -C 12 aryl, or 5- to 12-membered heteroaryl, wherein G 4b is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy, —O—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, —S(O)—C 1 -C 6 alkyl, —S(O) 2 —C 1 -C 6 alkyl, —C(O)—C 1 -C 6 alkyl, C 1 -C 3 alkylene-OH, C 1 -C 3 alkylene-O—C 1 -C 3 alkyl, C 1 -C 3 alkylene-N(C 1 -C 3 alkyl) 2 , and C 1 -C 3 alkylene-(N-heterocyclyl);
R 4a and R 4b , at each occurrence, are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 8 cycloalkyl, wherein the C 3 -C 8 cycloalkyl

Assignees

• Abbvie Inc
• Abbott Products Gmbh

Inventors

• Maring Clarence J
• Pratt John K
• Carroll William A
• Liu Dachun
• Betebenner David A
• Hutchinson Douglas K
• Tufano Michael D
• Rockway Todd W
• Schoen Uwe
• Pahl Axel
• Witte Andreas

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K31/422

  not condensed and containing further heterocyclic rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title