Hepatitis B antiviral agents

Patent metadata

Field	Value
Publication number	US-10738035-B2
Application number	US-201615152647-A
Country	US
Kind code	B2
Filing date	May 12, 2016
Priority date	May 13, 2015
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

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

X-A-Y—Z-L-R 1   (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 is:

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

or a pharmaceutically acceptable salt thereof, wherein:
X is an optionally substituted phenyl;
A is —NHCO—;
Y is selected from the groups set forth below,

wherein each group is optionally substituted and the amino group is connected to Z;
or Y is selected from the groups below,

wherein each group is optionally substituted; the second connection point of Y is any carbon atom; and the amino group is connected to Z;
Z is —C(O)—;
L is —NR 2 —; and
R 1 and R 2 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 1 and R 2 are taken together with the atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic.

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

wherein each of the above shown groups is optionally substituted.

3. The compound of claim 1 , wherein Y is selected from the following:

wherein each of the above shown groups is optionally substituted and the second connection point of Y is at any carbon atom.

4. The compound of claim 1 , represented by Formula (IIb-5-B), or a pharmaceutically acceptable salt thereof:

wherein each R 15 is independently selected from the group consisting of hydroxy, halogen, cyano, —CO 2 CH 3 , —CO 2 H, optionally substituted aryl, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted —C 1 -C 3 alkoxy; R 16 is independently selected from optionally substituted —C 1 -C 6 alkyl and optionally substituted —C 3 -C 8 cycloalkyl; and m is 1, 2, 3, 4 or 5.

5. The compound of claim 1 selected from the compounds set forth below or a pharmaceutically acceptable salt thereof:

Compound
Structure

 3

 6

 9

10

11

13

16

17

18

19

20

21

22

23

24

25

26

Assignees

• Enanta Pharm Inc

Inventors

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

Classifications

• A61K31/4155

  non condensed and containing further heterocyclic rings · CPC title

• A61K31/4545

  containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D211/46

  having a hydrogen atom as the second substituent in position 4 · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title