Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists

Patent metadata

Field	Value
Publication number	US-2018072684-A1
Application number	US-201715812986-A
Country	US
Kind code	A1
Filing date	Nov 14, 2017
Priority date	Dec 30, 2015
Publication date	Mar 15, 2018
Grant date	—

Abstract

The present disclosure provides pharmaceutical agents of the formula:

wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods of using the pharmaceutical agents for the treatment of a variety of diseases and disorders are also provided.

First claim

What is claimed is:

1 . A compound of the formula:

wherein:
A is C—H, C—OH, or N;
R′ is hydrogen, alkyl (C≦8) , substituted alkyl (C≦8) ; and
X and Y are each independently cyano, halo, fluoroalkoxy (C1-2) , alkyl (C1-2) , or fluoroalkyl (C1-2) , with the proviso that X and Y are not both cyano or alkyl (C1-2) ;

or a pharmaceutically acceptable salt or tautomer of the above formula.

2 . The compound of claim 1 , wherein the carbon atom labeled β is in the S configuration.

3 . The compound of claim 2 further defined as:

wherein:
A is C—OH or N;
R′ is hydrogen, alkyl (C≦8) , substituted alkyl (C≦8) ; and
X and Y are each independently cyano, halo, fluoroalkoxy (C1-2) , alkyl (C1-2) , or fluoroalkyl (C1-2) , with the proviso that X and Y are not both cyano or alkyl (C1-2) ;

or a pharmaceutically acceptable salt or tautomer of the above formula.

4 . The compound of claim 2 , wherein A is N.

5 . The compound of claim 2 , wherein A is C—OH.

6 . The compound of claim 2 , wherein R′ is hydrogen.

7 . The compound of claim 2 , wherein X is halo.

8 . The compound of claim 7 , wherein X is —F, —Cl, or —Br.

9 . The compound of claim 8 , wherein X is —Br or —Cl.

10 . The compound claim 2 , wherein Y is fluoroalkoxy (C1-2) .

11 . The compound of claim 10 , wherein Y is —OCF 3 .

12 . The compound of claim 2 , wherein Y is fluoroalkyl (C1-2) .

13 . The compound of claim 9 , wherein Y is —CHF 2 or —CF 3 .

14 . The compound of claim 9 , wherein Y is is fluoroalkoxy (C1-2) .

15 . The compound of claim 14 , wherein Y is —OCF 3 .

16 . The compound of claim 2 , wherein Y is alkyl (C1-2) .

17 . The compound of claim 16 , wherein Y is —CH 3 .

18 . The compound of claim 1 , further defined as:

or a pharmaceutically acceptable salt or tautomer of any of the above formulas.

19 . A pharmaceutical composition comprising:
a) the compound of claim 1 ; and b) an excipient.

20 . A method of treating and/or preventing a disease or a disorder in a patient in need thereof, comprising administering to the patient a compound of claim 1 in an amount sufficient to treat and/or prevent the disease or disorder, wherein the disease or disorder is associated with angiogenesis or fibrosis.

Assignees

• Univ Saint Louis

Inventors

• Ruminski Peter G
• Griggs David W

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title