Hepatitis B antiviral agents

Patent metadata

Field	Value
Publication number	US-10640511-B2
Application number	US-201816220267-A
Country	US
Kind code	B2
Filing date	Dec 14, 2018
Priority date	Jun 10, 2016
Publication date	May 5, 2020
Grant date	May 5, 2020

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.

First claim

What is claimed:

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,

wherein A 1 is thiazolyl;
B is hydrogen or methyl;
X is optionally substituted phenyl;
Y is optionally substituted phenyl or optionally substituted monocyclic heteroaryl; and

 is selected from the groups below,

wherein each of the above shown groups is optionally substituted;
R 5 is selected from the group consisting of hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, optionally substituted heteroaryl, —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , —S(O) 2 R 11 , —S(O) 2 NR 11 R 12 ; and
R 11 and R 12 at each occurrence are independently selected from the group consisting of hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl and optionally substituted heteroaryl; alternatively, R 5 and R 11 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic.

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

wherein each of the above shown groups is optionally substituted.

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

wherein R 20 is hydrogen, optionally substituted C 1 -C 4 -alkyl or optionally substituted C 3 -C 6 -cycloalkyl.

4. The method of claim 1 wherein R 5 is selected from the groups set forth below:

wherein each of the above shown groups is optionally substituted when possible.

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

or a pharmaceutically acceptable salt thereof,
wherein X 1 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; and
m is 0, 1, 2, 3, 4 or 5.

6. The method of claim 5 , wherein each X 1 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:

Compound
Structure

1

2

3

4

5

6

7

8

9

10

11

12

Assignees

• Enanta Pharm Inc
• Enant Pharmaceuticals Inc

Inventors

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

Classifications

• A61P31/20

  for DNA viruses · CPC title

• A61K45/06

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

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title