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

Patent metadata

Field	Value
Publication number	US-11718641-B2
Application number	US-202117186447-A
Country	US
Kind code	B2
Filing date	Feb 26, 2021
Priority date	Nov 26, 2014
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

The present invention provides compounds of Formula I,

pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.

First claim

What is claimed is:

1. A compound represented by Formula (VI-A) or (VI-B), or a pharmaceutically acceptable salt thereof:

wherein:
m is 0, 1, 2 or 3; and
R 10 is selected from hydrogen, substituted or unsubstituted —C 1 -C 8 alkyl, substituted or unsubstituted —C 2 -C 8 alkenyl, substituted or unsubstituted —C 2 -C 8 alkynyl, and substituted or unsubstituted —C 3 -C 8 cycloalkyl.

2. The compound of claim 1 , wherein m is 1 and R 10 is selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, butyl, t-butyl, propyl, benzyl, vinyl, allyl, CF 3 ,

3. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

4. A method for ameliorating a disease or condition selected from the group consisting of primary biliary cirrhosis, cerebrotendinous xanthomatosis, primary sclerosing cholangitis, alcoholic liver disease, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, atherosclerosis, hypercholesterolemia, hypertriglyceridemia, Type II diabetes, and hepatocellular carcinoma in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .

5. The method according to claim 4 , wherein the disease or condition is selected from the group consisting of primary biliary cirrhosis (PBC), nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH).

Assignees

• Enanta Pharm Inc

Inventors

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

Classifications

• C07J41/0066 Primary

  the 17-beta position being substituted by a carbon atom forming part of an amide group · CPC title

• C07J41/0055 Primary

  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

• C07J43/003

  not condensed · CPC title

• C07J43/006

  spiro-condensed · CPC title