Hepatitis C virus inhibitor and uses thereof

• US 10,640,515 B2
• Filed: 12/21/2018
• Issued: 05/05/2020
• Est. Priority Date: 06/21/2016
• Status: Active Grant

• Current Assignee: Zhejiang Palo Alto Pharmaceuticals, Inc.
• Original Assignee: Zhejiang Palo Alto Pharmaceuticals, Inc.
• Inventors: Xi, Zhijian, Xu, Huaqiang, Lu, Chunping
• Primary Examiner(s): Rodriguez-Garcia, Valerie
• Application Number:
  US16/231,265
• Publication Number:
  US 20190135828A1
• Time in Patent Office: 501 Days
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07D 498/04 Ortho-condensed systems

Abstract

Disclosed is a compound of formula (I-a) as an inhibitor of hepatitis C virus (HCV), or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, usable to treat HCV infections or hepatitis C diseases and also usable as an inhibitor of HCV non-structural protein 5A (NS5A)

In the formula (I-a), A and A′ are independently

each R₁, R₄ and R₆ are independently selected from the group consisting of fluorine, chlorine, bromine and iodine; R₂ and R₂′ are independently selected from substituted or unsubstituted C₁-C₆ alkyl; R₃ and R₃′ are independently selected from substituted or unsubstituted C₁-C₆ alkyl; R₅ is selected from the group consisting of hydrogen, fluorine, chlorine, bromine and iodine; n is 2, 3, 4 or 5; m is 0, 1, 2 or 3; and p is 0, 1, 2 or 3.

Claims

1. A compound of formula (I-a)

2. The compound of claim 1, wherein the compound is selected from the group consisting of

3. A pharmaceutical composition comprising the compound of claim 1 or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, and a pharmaceutically acceptable auxiliary, diluent or carrier.

4. The pharmaceutical composition of claim 3, further comprising at least one HCV inhibitor for inhibiting HCV replication process and/or function of HCV protein.

5. The pharmaceutical composition of claim 4, wherein the HCV replication process comprises HCV entry, HCV uncoating, HCV transcription, HCV replication, HCV assembly and/or HCV release.

6. The pharmaceutical composition of claim 4, wherein the HCV protein is selected from the group consisting of NS2, NS3, NS4A, NS4B, NS5A and NS5B.

7. A method of preparing the compound of claim 1, comprising:

(a) reacting compound 1 with diphenylmethanimine in an inert solvent to form compound 2