Hepatitis C virus inhibitors

Patent metadata

Field	Value
Publication number	US-10617675-B2
Application number	US-201615749557-A
Country	US
Kind code	B2
Filing date	Jul 27, 2016
Priority date	Aug 6, 2015
Publication date	Apr 14, 2020
Grant date	Apr 14, 2020

Abstract

The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

First claim

What is claimed is:

1. A combination comprising an NS5A-targeting compound and an NS5A synergist, which, when administered, provides synergistic anti-HCV activity against variants that contain mutation(s) conferring resistance to the NS5A-targeting compound alone, wherein the NS5A-targeting compound is BMS-790052, or a pharmaceutically acceptable salt thereof, and wherein the NS5A synergist is a compound selected from:

or a pharmaceutically acceptable salt thereof.

2. A composition comprising the combination of claim 1 and one or more pharmaceutically acceptable carriers.

3. A method of treating an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a combination of claim 1 .

4. The method of claim 3 further comprising administering one or two additional compounds having anti-HCV activity prior to, after or simultaneously with the combination.

5. The method of claim 4 wherein at least one of the additional compounds is an interferon or a ribavirin.

6. The method of claim 5 wherein interferon is selected from interferon alpha 2B, pegylated interferon alpha, pegylated interferon lambda, consensus interferon, interferon alpha 2A, and lymphoblastoid interferon tau.

7. The method of claim 4 wherein at least one of the additional compounds is effective to inhibit the function of a target selected from HCV protease, HCV polymerase, HCV helicase, HCV NS4B protein, HCV entry, HCV assembly, HCV egress, HCV NS5A protein, and IMPDH for the treatment of an HCV infection.

8. A method of treating an HCV infection in a patient, comprising administering to the patient a pharmaceutical composition comprising an NS5A-targeting compound and a pharmaceutical composition comprising an NS5A synergist, which, when administered, provides synergistic anti-HCV activity against variants that contain mutation(s) conferring resistance to the NS5A-targeting compound alone, wherein the NS5A-targeting compound is BMS-790052, or a pharmaceutically acceptable salt thereof, and wherein the NS5A synergist is a compound selected from:

or a pharmaceutically acceptable salt thereof.

9. The method of claim 8 , wherein the pharmaceutical composition comprising the NS5A-targeting compound and the pharmaceutical composition comprising the NS5A synergist are administered sequentially.

Assignees

• Bristol Myers Squibb Co

Inventors

• Frennesson David B
• Hewawasam Piyasena
• Lopez Omar D
• Nguyen Van N
• Saulnier Mark G
• Tu Yong
• Wang Alan Xiangdong
• Wang Gan
• Xu Ningning
• Nimje Roshan Yadavrao
• Rahaman Hasibur
• Gupta Samayamunthula Venkata Satya Arun Kumar
• Meanwell Nicholas A
• Belema Makonen

Classifications

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/497

  containing further heterocyclic rings · CPC title

• A61K31/7056

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K45/06

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

• A61K31/417

  Imidazole-alkylamines, e.g. histamine, phentolamine · CPC title