Antiviral compounds

Patent metadata

Field	Value
Publication number	US-9693997-B2
Application number	US-201414768915-A
Country	US
Kind code	B2
Filing date	Mar 3, 2014
Priority date	Mar 6, 2013
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

The present invention discloses compounds of Formula I: wherein the variables in Formula I are defined as described herein. Also disclosed are pharmaceutical compositions containing such compounds and methods for using the compounds of Formula I in the prevention or treatment of HCV infection.

First claim

The invention claimed is:

1. A compound of formula I:

wherein:
A is phenyl, naphthyl, or bicyclic unsaturated or partially saturated heteroaryl, substituted with one or more A;
each A is independently lower alkyl, halo, lower alkoxy, S(═O) 2 (CH 2 ) m A″, C(═O)NHA″, NHC(O)A″, —O(CH 2 ) m A″, (CHA 1 ) m NHS(═O) 2 A 1 ; or S(═O) 2 NHA″;
each A″ is independently, heterocycloalkyl or heteroaryl, optionally substituted with one or more A′″;
each A′″ is independently hydroxy, lower alkyl, oxo, C(═O)OA 1 , halo loweralkyl,
each A 1 is independently H, lower alkyl, halo loweralkyl, amino, lower alkoxy,
each m is independently 0, 1, 2, or 3;
R 1 is H, halo, lower alkyl, halo loweralkyl, SF 5 , and
R 2 is H, halo, lower alkyl, halo loweralkyl,
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein A is phenyl.

3. The compound of claim 2 , wherein R 1 is halo loweralkyl.

4. The compound of claim 3 , wherein R 2 is halo.

5. The compound of claim 2 , wherein R 1 is halo.

6. The compound of claim 5 , wherein R 2 is halo.

7. The compound of claim 1 , wherein A′ is S(═O) 2 (CH 2 ) m A″ or (CH 2 ) m S(═O) 2 A″.

8. The compound of claim 1 , wherein A′ is lower alkyl, halo, or lower alkoxy.

9. The compound of claim 1 , wherein A′ is C(═O)NHA″ or NHC(═O)A″.

10. The compound of claim 1 , wherein A′ is (CHA 1 ) m NHS(═O) 2 A 1 or S(═O) 2 NHA″.

11. The compound of claim 1 , wherein A′ is O(CH 2 ) m A″.

12. A compound selected from the group consisting of:
4-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonyl]-piperidine-1-carboxylic acid tert-butyl ester;
3-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonylmethyl]-piperidine-1-carboxylic acid tert-butyl ester;
(S)-1-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluormethyl-biphenyl-4-sulfonyl]-pyrrolidine-2-carboxylic acid tert-butyl ester;
N 3 -{6-Chloro-2-trifluoromethyl-4′-[1-(3,3,3-trifluoro-propyl)-piperidine-4-sulfonyl]-biphenyl-4-yl}-1H-[1,2,4]triazole-3,5-diamine;
N 3 -{6-Chloro-4′-[1-(3,3-dimethyl-butyl)-piperidine-4-sulfonyl]-2-trifluoromethyl-biphenyl-4-yl}-H-[1,2,4]triazole-3,5-diamine;
3-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonyl]-piperidine-1-carboxylic acid tert-butyl ester;
4-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonylmethyl]-piperidine-1-carboxylic acid tert-butyl ester;
4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-biphenyl-4-carboxylic acid tert-butylamide;
Pentanoic acid [4′-(5-amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-biphenyl-4-yl]-amide;
N 3 -[4-(2-tert-Butyl-1,1-dioxo-2,3-dihydro-1H-1λ 6 -benzo[d]isothiazol-6-yl)-3-chloro-5-trifluoromethyl-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -{6-Chloro-2-trifluoromethyl-4′-[1-(3,3,3-trifluoro-propyl)-piperidine-3-sulfonyl]-biphenyl-4-yl}-1H-[1,2,4]triazole-3,5-diamine;
N-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-biphenyl-4-ylmethyl]-methanesulfonamide;
N—{(S)-1-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-yl]-ethyl}-methanesulfonamide;
N 3 -(2,6-Dichloro-4′-methanesulfonyl-3′-trifluoromethyl-biphenyl-4-yl)-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[3,5-Dichloro-4-(1-methanesulfonyl-1H-indol-4-yl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
4-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonyl]-piperazine-1-carboxylic acid tert-butyl ester;
N 3 -{6-Chloro-4′-[1-(3,3-dimethyl-butyl)-piperidine-3-sulfonyl]-2-trifluoromethyl-biphenyl-4-yl}-1H-[1,2,4]triazole-3,5-diamine;
4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-4-methyl-6′-trifluoromethyl-biphenyl-3-sulfonic acid tert-butylamide;
N 3 -[2-Chloro-4′-methoxy-3′-(propane-2-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[2-Chloro-4′-(piperidine-4-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
4-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;
N 3 -[2-Chloro-4′-(4-methyl-piperazine-1-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[2-Chloro-6-fluoro-4′-(propane-2-sulfonyl)-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N—{(R)-1-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-yl]-ethyl}-methanesulfonamide;
N 3 -[2-Chloro-4′-(piperidin-3-ylmethanesulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
4-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-biphenyl-4-yloxy]-butyronitrile;
4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonic acid ((S)-1-pyrolidin-2-ylmethyl)-amide;
N-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-2-fluoro-biphenyl-4-yl]-methanesulfonamide;
N 3 -[2-Chloro-4′-(piperidine-3-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -(2-Chloro-6-fluoro-4′-methanesulfonyl-biphenyl-4-yl)-1H-[1,2,4]triazole-3,5-diamine;
N 3 -(2,6-Dichloro-4′-methanesufonylmethyl-biphenyl-4-yl)-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[4′-(Azetidin-3-ylmethoxy)-2,6-dichloro-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[2-Chloro-4′-(piperazine-1-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
4′(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-fluoro-biphenyl-4-sulfonic acid dimethylamide;
N 3 -[2-Chloro-4′-((S)-1-pyrrolidin-2-ylmethanesulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[2-Chloro-4′-(morpholine-4-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[4′-(Azetidin-3-ylmethoxy)-2-chloro-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N-{2-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-yl]-ethyl}-methanesulfonamide;
5-((3aR,6S,6aS)-2-Oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoic acid [4′-(5-amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-biphenyl-4-yl]-amide;
N 3 -[2-Chloro-4′-(piperidin-4-ylmethanesulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[2-Chloro-3′-(piperidin-4-yloxy)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[3,5-Dichloro-4-(1-methanesulfonyl-1H-indol-5-yl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
1-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-biphenyl-4-yl]-pyrrolidin-2-one;
N 3 -[3-Chloro-4-(4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-5-trifluoromethyl-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[2-Chloro-4′-(1,1-dioxo-1λ 6 -thiomorpholine-4-sulfonyl)-6-trifluoromethyl-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
N-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′,6′-dichloro-3-fluoro-biphenyl-4-yl]-methanesulfonamide;
6-[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-6-trifluoromethyl-phenyl]-4H-benzo[1,4]oxazin-3-one;
N 3 -(2,6-Dichloro-biphenyl-4-yl)-1H-[1,2,4]triazole-3,5-diamine;
N 3 -[4′-(4-Amino-butoxy)-2,6-dichloro-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine;
compound with trifluoro-acetic acid;
N 3 -(4′-Amino-2,6-dichloro-biphenyl-4-yl)-1H-[1,2,4]triazole-3,5-diamine;
(S)-1-[4′-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2′-chloro-6′-trifluoromethyl-biphenyl-4-sulfonyl]-pyrrolidine-2-carboxylic acid;
N 3 -[3,5-Dichloro-4-(2,2-dimethyl-4,4-dioxo-3,4-dihydro-2H-4λ 6 -benzo[1,4]oxathiin-6-yl

Assignees

• Hoffmann La Roche

Inventors

• Bilotta Joseph Anthony
• Chen Zhi
• Chi Feng
• Chin Elbert
• Ding Qingjie
• Erickson Shawn David
• Gabriel Stephen Deems
• Jiang Nan
• Kocer Buelent
• Mertz Eric
• Plancher Jean-Marc
• Weikert Robert J
• Zhang Jing
• Zhang Qiang

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

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title