Hepatitis B antiviral agents

• US 10,640,511 B2
• Filed: 12/14/2018
• Issued: 05/05/2020
• Est. Priority Date: 06/10/2016
• Status: Active Grant

• Current Assignee: Enanta Pharmaceuticals Incorporated
• Original Assignee: Enanta Pharmaceuticals Incorporated
• Inventors: Qiu, Yao-Ling, Cao, Hui, Peng, Xiaowen, Li, Wei, Kass, Jorden, Gao, Xuri, Jin, Meizhong, Or, Yat Sun
• Primary Examiner(s): Murray, Jeffrey H
• Application Number:
  US16/220,267
• Publication Number:
  US 20190119288A1
• Time in Patent Office: 508 Days
• Field of Search: 514284
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, thereof:

which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Claims

1. A method of treating an HBV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound represented by Formula (IIIa), or a pharmaceutically acceptable salt thereof,

2. The method of claim 1, wherein Y is selected from the following:

3. The method of claim 1 wherein Y is selected from the groups below:

4. The method of claim 1 wherein R₅ is selected from the groups set forth below:

5. The method of claim 1, wherein the compound of Formula (IIIa) is represented by Formula (IIIa-5) or Formula (IIIa-6),

6. The method of claim 5, wherein each X₁ is halo.

7. The method of claim 1, wherein the compound is selected from the compounds set forth below or a pharmaceutically acceptable salt thereof:

8. The method of claim 1, further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, literature-described capsid assembly modulator, reverse transcriptase inhibitor, TLR-agonist, inducer of cellular viral RNA sensor, and therapeutic vaccine.

9. The method of claim 8, wherein the compound of Formula (I) and the at least one additional therapeutic agent are co-formulated.

10. The method of claim 8, wherein the compound of Formula (I) and the at least one additional therapeutic agent are co-administered.

11. The method of claim 8, wherein the subject is refractory to at least one compound selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, distinct capsid assembly modulator, inducer of cellular viral RNA sensor, therapeutic vaccine, antiviral compounds of distinct or unknown mechanism, and combination thereof.