Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11958879-B2
Application number	US-202117324464-A
Country	US
Kind code	B2
Filing date	May 19, 2021
Priority date	Mar 31, 2015
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The present invention provides compounds represented by Formula I, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates or combination thereof,The invention also provides pharmaceutical compositions comprising these compounds and methods of using this compounds for treating FXR-mediated or TGR5-mediated diseases or conditions.

First claim

What is claimed is:

1. A compound represented by Formula (IV) or a pharmaceutically acceptable salt thereof:

wherein:
R a is selected from the group consisting of:
1) Hydrogen;
2) Substituted or unsubstituted —C 1 -C 6 alkoxy;
3) Substituted or unsubstituted —C 1 -C 8 alkyl;
4) Substituted or unsubstituted —C 2 -C 8 alkenyl;
5) Substituted or unsubstituted —C 2 -C 8 alkynyl;
6) Substituted or unsubstituted arylalkyl;
7) Substituted or unsubstituted aryl; and
8) Substituted or unsubstituted C 3 -C 6 -cycloalkyl;

R b is selected from the group consisting of:
1) Hydrogen;
2) Substituted or unsubstituted —C 1 -C 8 alkyl;
3) Substituted or unsubstituted —C 2 -C 8 alkenyl;
4) Substituted or unsubstituted —C 2 -C 8 alkynyl;
5) Substituted or unsubstituted arylalkyl; and
6) Substituted or unsubstituted aryl;

or R a and R b are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring; and
m is selected from 0, 1, 2 and 3.

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

Example #
Structure

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

Assignees

• Enanta Pharm Inc

Inventors

• Wang Guoqiang
• Or Yat Sun
• Shen Ruichao
• Xing Xuechao
• Long Jiang
• Dai Peng
• Granger Brett
• He Jing

Classifications

• C07J43/003 Primary

  not condensed · CPC title

• C07J41/005 Primary

  the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives · CPC title

• C07J41/0055

  the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives · CPC title

• C07J41/0088

  containing unsubstituted amino radicals · CPC title

• C07J9/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane · CPC title