Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists

Patent metadata

Field	Value
Publication number	US-10577330-B2
Application number	US-201816049679-A
Country	US
Kind code	B2
Filing date	Jul 30, 2018
Priority date	Dec 30, 2015
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

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 pharmaceutical composition comprising:
a) a compound of the formula:

wherein:
A is C—OH or N;
R′ is hydrogen, alkyl (C≤8) , or 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; and
b) an excipient,
wherein the carbon atom labeled β is in the S configuration.

2. The pharmaceutical composition of claim 1 , wherein:
R′ is hydrogen, or alkyl (C≤8) ; and
X and Y are each independently halo, fluoroalkoxy (C1-2) , alkyl (C1-2) , or fluoroalkyl (C1-2 .

3. The pharmaceutical composition of claim 1 , wherein A is N.

4. The pharmaceutical composition of claim 1 , wherein A is C—OH.

5. The pharmaceutical composition of claim 1 , wherein R′ is hydrogen.

6. The pharmaceutical composition of claim 1 , wherein X is halo.

7. The pharmaceutical composition of claim 6 , wherein X is —F, —Cl, or —Br.

8. The pharmaceutical composition of claim 7 , wherein X is —Br or —Cl.

9. The pharmaceutical composition claim 1 , wherein Y is fluoroalkoxy (C1-2) .

10. The pharmaceutical composition of claim 9 , wherein Y is —OCF 3 .

11. The pharmaceutical composition of claim 1 , wherein Y is fluoroalkyl (C1-2) .

12. The pharmaceutical composition of claim 8 , wherein Y is —CHF 2 or —CF 3 .

13. The pharmaceutical composition of claim 8 , wherein Y is fluoroalkoxy (C1-2) .

14. The pharmaceutical composition of claim 13 , wherein Y is —OCF 3 .

15. The pharmaceutical composition of claim 1 , wherein Y is alkyl (C1-2) .

16. The pharmaceutical composition of claim 15 , wherein Y is —CH 3 .

17. The pharmaceutical composition of claim 1 , wherein the compound is further defined as:

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

18. The pharmaceutical composition of claim 1 , wherein the compound is further defined as:

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

19. A method of treating and/or preventing a disease or a disorder in a patient in need thereof, comprising administering to the patient a composition 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

• A61P43/00

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

• A61P37/02

  Immunomodulators · 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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title