Hepatitis C virus inhibitors

Patent metadata

Field	Value
Publication number	US-9561212-B2
Application number	US-201615227709-A
Country	US
Kind code	B2
Filing date	Aug 3, 2016
Priority date	Oct 24, 2012
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

First claim

What is claimed is:

1. A compound selected from:
dimethyl ((R,S,R,1S,1′S)-((2S,2′S,5S,5′S)-5,5′-(5,5′-([1,1′-biphenyl]-4,4′-diyl)bis(1H-imidazole-5,2-diyl))bis(2-methylpyrrolidine-5,1-diyl))bis(1-((2R,4R,6S)-2-cyclopropyl-6-methyltetrahydro-2H-pyran-4-yl)-2-oxoethane-2,1-diyl))dicarbamate;
dimethyl ((S,R,R,1S,1′S)-((2S,2′S,5S,5′S)-5,5′-(5,5′-([1,1′-biphenyl]-4,4′-diyl)bis(1H-imidazole-5,2-diyl))bis(2-methylpyrrolidine-5,1-diyl))bis(1-((2S,4R,6R)-2-cyclopropyl-6-methyltetrahydro-2H-pyran-4-yl)-2-oxoethane-2,1-diyl))dicarbamate;
dimethyl ((S,R,S,1S,1′S)-((2S,2′S,5S,5′S)-5,5′-(5,5′-([1,1′-biphenyl]-4,4′-diyl)bis(1H-imidazole-5,2-diyl))bis(2-methylpyrrolidine-5,1-diyl))bis(1-((2R,4S,6S)-2-cyclopropyl-6-methyltetrahydro-2H-pyran-4-yl)-2-oxoethane-2,1-diyl))dicarbamate;
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5S)-5-methyl-2,1-pyrrolidinediyl)(1-(3-cyano-3-methylcyclobutylidene)-2-oxo-2,1-ethanediyl)))biscarbamate; and
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5S)-5-methyl-2,1-pyrrolidinediyl)(1-(3-cyano-3-methylcyclobutylidene)-2-oxo-2,1-ethanediyl)))biscarbamate;

or a pharmaceutically acceptable salt thereof.

2. A compound selected from:
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-5,2-diyl((2S,5R)-5-ethynyl-2,1-pyrrolidinediyl)((1S)-1-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5S)-5-ethynyl-2,1-pyrrolidinediyl)((1S)-1-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5R)-5-(hydroxymethyl)-2,1-pyrrolidinediyl)((1S)-1-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5R)-5-(hydroxymethyl)-2,1-pyrrolidinediyl)((1S)-1-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl(3S)-2-azaspiro[4.4]nonane-3,2-diyl((1S)-1-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate; and
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,4R)-4-(cyclopropylmethyl)-2,1-pyrrolidinediyl)((1S)-1-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;

or a pharmaceutically acceptable salt thereof.

3. A compound selected from:
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-5,2-diyl((2S,5S)-5-methyl-2,1-pyrrolidinediyl)((1S)-1-(2-oxaspiro[3.3]hept-6-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5S)-5-methyl-2,1-pyrrolidinediyl)((1S)-1-((2R,4R,4aS,7aS)-2-methyloctahydrocyclopenta[b]pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate; and
dimethyl (4,4′-biphenyldiylbis(1H-imidazole-4,2-diyl((2S,5S)-5-methyl-2,1-pyrrolidinediyl)((1S)-1-((2R,4S,4aS,7aS)-2-methyloctahydrocyclopenta[b]pyran-4-yl)-2-oxo-2,1-ethanediyl)))biscarbamate;

or a pharmaceutically acceptable salt thereof.

4. A compound which is
dimethyl ((R,S,S,1S,1′S)-((2S,2′S,5S,5′S)-5,5′-(5,5′-([1,1′-biphenyl]-4,4′-diyl)bis(1H-imidazole-5,2-diyl))bis(2-methylpyrrolidine-5,1-diyl))bis(1-((2S,4S,6R)-2-cyclopropyl-6-methyltetrahydro-2H-pyran-4-yl)-2-oxoethane-2,1-diyl))dicarbamate;

or a pharmaceutically acceptable salt thereof.

5. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. The composition of claim 5 further comprising at least one additional compound having anti-HCV activity.

7. A composition comprising a compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. The composition of claim 7 further comprising at least one additional compound having anti-HCV activity.

9. A composition comprising a compound of claim 3 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

10. The composition of claim 9 further comprising at least one additional compound having anti-HCV activity.

11. A composition comprising a compound of claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

12. The composition of claim 11 further comprising at least one additional compound having anti-HCV activity.

13. A method of inhibiting or relieving an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

14. A method of inhibiting or relieving an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound of claim 2 , or a pharmaceutically acceptable salt thereof.

15. A method of inhibiting or relieving an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound of claim 3 , or a pharmaceutically acceptable salt thereof.

16. A method of inhibiting or relieving an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound of claim 4 , or a pharmaceutically acceptable salt thereof.

Assignees

• Bristol Myers Squibb Co

Inventors

• Romine Jeffrey Lee
• Yang Zhong
• Wang Gan
• Nguyen Van N
• Bender John A
• St Laurent Denis R
• Belema Makonen

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• C07D405/14 Primary

  containing three or more hetero rings · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• A61K31/4178 Primary

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title