Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases

Patent metadata

Field	Value
Publication number	US-9549917-B2
Application number	US-201214343448-A
Country	US
Kind code	B2
Filing date	Aug 16, 2012
Priority date	Sep 8, 2011
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

First claim

The invention claimed is:

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein:
the group

is selected from:

R 4 is H, —N(R 6 )SO 2 R 7 or

R 6 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and
R 7 is independently C 1 -C 6 alkyl.

2. The compound of claim 1 , wherein R 4 is —N(CH 3 )SO 2 CH 3 .

3. The compound of claim 1 , wherein the group

is selected from:

4. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

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

6. The pharmaceutical composition of claim 5 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents, immunomodulators, and anti-infective agents.

7. The pharmaceutical composition of claim 6 , wherein the second therapeutic agent is selected from the group consisting of HCV protease inhibitors, HCV NS5A inhibitors and HCV NS5B polymerase inhibitors.

8. A method of treating a patient infected with HCV, the method comprising administering to the patient the compound of claim 1 , or a pharmaceutically acceptable salt thereof, in an amount effective to treat infection by HCV in the patient.

9. The method of claim 8 , further comprising the step of administering pegylated-interferon alpha and ribovirin to the patient.

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

11. The pharmaceutical composition of claim 10 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents, immunomodulators, and anti-infective agents.

12. The pharmaceutical composition of claim 11 , wherein the second therapeutic agent is selected from the group consisting of HCV protease inhibitors, HCV NS5A inhibitors and HCV NS5B polymerase inhibitors.

13. A method of treating a patient infected with HCV, the method comprising administering to the patient the compound of claim 4 , or a pharmaceutically acceptable salt thereof, in an amount effective to treat infection by HCV in the patient.

14. The method of claim 13 , further comprising the step of administering pegylated-interferon alpha and ribovirin to the patient.

Assignees

• Mccomas Casey C
• Liverton Nigel J
• Habermann Joerg
• Koch Uwe
• Narjes Frank
• Li Peng
• Peng Xuanjia
• Soll Richard
• Wu Hao
• Palani Anandan
• Dai Xing
• Liu Hong
• He Shuwen
• Lai Zhong
• Dang Qun
• Zorn Nicolas
• Merck Sharp & Dohme

Inventors

• Mccomas Casey C
• Liverton Nigel J
• Habermann Joerg
• Koch Uwe
• Narjes Frank
• Li Peng
• Peng Xuanjia
• Soll Richard
• Wu Hao
• Palani Anandan
• Dai Xing
• Liu Hong
• He Shuwen
• Lai Zhong
• Dang Qun
• Zorn Nicolas

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K31/5383

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K31/497

  containing further heterocyclic rings · CPC title

• A61K31/695

  Silicon compounds · CPC title