Hepatitis B antiviral agents

Patent metadata

Field	Value
Publication number	US-12054493-B2
Application number	US-202117143326-A
Country	US
Kind code	B2
Filing date	Jan 7, 2021
Priority date	Mar 7, 2016
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:X-A-Y-L-R  (I)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.

First claim

What is claimed:

1. A compound represented by Formula (I):
X - A - Y - L - R   (I)

or a pharmaceutically acceptable salt thereof, wherein:
X is phenyl substituted with one or more substituents independently selected from fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, CN and cyclopropyl;
Y is

A is —NHC(O)—;
L is S(O) 2 ; and
R is selected from the group consisting of

each of which is optionally substituted.

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

3. The compound of claim 2 wherein X is

4. The compound of claim 1 wherein R is

each of which is optionally substituted.

5. The compound of claim 1 wherein X is

each of which is optionally substituted.

6. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or excipient.

7. A method of treating or preventing an HBV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to claim 1 .

8. The method of claim 7 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors, interferon, viral entry inhibitors, viral maturation inhibitors, capsid assembly, core protein inhibitors, core protein modulators, reverse transcriptase inhibitors, TLR-agonists, inducers of cellular viral RNA sensor, therapeutic vaccines, RNA interference (RNAi), small interfering RNA (siRNA) and combinations thereof.

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

10. The method of claim 8 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone.

Assignees

• Enanta Pharm Inc

Inventors

• Qiu Yao-Ling
• Gao Xuri
• Li Wei
• Cao Hui
• Jin Meizhong
• Kass Jorden
• Peng Xiaowen
• Or Yat Sun

Classifications

• C07D493/04

  Ortho-condensed systems · CPC title

• C07D451/04

  with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D327/10

  two oxygen atoms and one sulfur atom, e.g. cyclic sulfates · CPC title

• C07D317/72

  spiro-condensed with carbocyclic rings · CPC title