Inhibitors of the farnesoid X receptor and uses in medicine

Patent metadata

Field	Value
Publication number	US-9540415-B2
Application number	US-201414909263-A
Country	US
Kind code	B2
Filing date	Aug 1, 2014
Priority date	Aug 1, 2013
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

Disclosed are inhibitors of the farnesoid X receptor, for example of formula (I), wherein R 1 , R 2 , R 4 , X, Y, Z, m, and n are as defined herein, which are useful in treating or preventing obesity, type 2 diabetes/insulin resistance and non alcoholic fatty liver disease in a mammal in need thereof. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least Cone compound of the invention, a method of method of inhibiting a farnesoid X receptor in a mammal, and a method of treating or preventing obesity in a mammal.

First claim

The invention claimed is:

1. A method of treating a disease or disorder selected from obesity, type 2 diabetes, insulin resistance, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and alcoholic liver disease in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula (I):

wherein R 1 and R 2 are independently selected from hydrogen, alkyl, and C(═O)R 3 ,
R 4 is selected from hydrogen, alkyl, and C(═O)R 3 ,
X is selected from C═O and CH 2 ,
Y is selected from CH 2 , NR 5 , O, S, SO, SO 2 , and Se,
or X and Y taken together form C═C,
Z is selected from COOR 6 , SO 3 R 7 , P(═O)(OR 8 ) 2 and NR 9 R 10 ,
R 3 , R 5 , R 6 , R 7 , R 8 R 9 , and R 10 are independently selected from hydrogen, alkyl, and aryl,
in is an integer of 1 to 6, and
n is an integer of 1 to 6,
or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound has formula (I), X is C═O, m is 1, Y is NH, and n is an integer of 1 to 6.

3. The method of claim 2 , wherein the compound is selected from:

4. The method of claim 2 , wherein the compound is selected from:

5. The method of claim 1 , wherein X is CH 2 , Y is selected from NH, O, S, and Se, m is 1, n is 2, and Z is SO 3 H.

6. The method of claim 5 , wherein the compound is selected from:

7. The method of claim 1 , wherein the compound is selected from:

8. The method of claim 1 , wherein the disease or disorder is selected from type 2 diabetes, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis.

9. The method of claim 1 , wherein the compound or salt thereof is administered orally.

Assignees

• Us Health
• Penn State Res Found

Inventors

• Gonzalez Frank J
• Jiang Changtao
• Xie cen
• Patterson Andrew D
• Li Fei
• Mitchell James B

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P5/50

  for increasing or potentiating the activity of insulin · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title