Hepatitis B antiviral agents

Patent metadata

Field	Value
Publication number	US-10934306-B2
Application number	US-201916715602-A
Country	US
Kind code	B2
Filing date	Dec 16, 2019
Priority date	Mar 7, 2016
Publication date	Mar 2, 2021
Grant date	Mar 2, 2021

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 (VIId-2),

or a pharmaceutically acceptable salt thereof, wherein:
each n is 0, 1, 2 or 3;
m4 is 0, 1 or 2;
E is —C(R 10 ) 2 —;
Each R 10 is independently selected from hydrogen, halo, hydroxy, protected hydroxy, —CN, —NO 2 , amino, protected amino, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 1 -C 6 alkoxy, optionally substituted aryl, and optionally substituted heteroaryl;
each R 21 is independently selected from the group consisting of halogen, CN, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 1 -C 6 alkoxy, and optionally substituted C 3 -C 8 cycloalkyl;
R 22 is selected from the group consisting of halogen, CN, optionally substituted —C 1 -C 6 alkyl, and optionally substituted —C 1 -C 6 alkoxy;
R 23 is selected from the group consisting of hydrogen, halogen, CN, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 1 -C 6 alkoxy, and optionally substituted C 3 -C 8 cycloalkyl; and
R 30 is hydrogen, optionally substituted —C 1 -C 6 alkyl or a hydroxy protecting group.

2. The compound of claim 1 , wherein:
n at each occurrence is independently 0, 1, or 2;
R 21 at each occurrence is independently halogen, CN, methyl, methoxy, or cyclopropyl;
R 22 is halogen, CN, methyl, or methoxy;
R 23 is hydrogen or halogen;
Each R 10 is independently hydrogen, halogen, hydroxyl, or optionally substituted C 1 -C 3 alkyl; and
R 30 is hydrogen or an acyl group derived from an amino acid.

3. The compound of claim 1 , wherein:
Each R 21 is fluorine;
R 22 is chlorine;
R 23 is hydrogen or fluorine; and
Each R 10 is independently hydrogen, halogen, hydroxyl, hydroxymethyl, fluoromethyl, trifluoromethyl, or methoxymethyl.

4. The compound of claim 1 , wherein R 30 is an acyl group derived from alanine or valine.

5. The compound of claim 1 , wherein R 23 is fluorine.

6. A compound selected from the compounds set forth below, or a pharmaceutically acceptable salt thereof,

Compound
Structure

 60

106

120

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

Assignees

• Enanta Pharm Inc

Inventors

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

Classifications

• C07D493/08 Primary

  Bridged systems · CPC title

• 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