Inhibitors of protein tyrosine phosphatases

Patent metadata

Field	Value
Publication number	US-9340574-B2
Application number	US-201314432511-A
Country	US
Kind code	B2
Filing date	Oct 3, 2013
Priority date	Oct 4, 2012
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Novel protein tyrosine phosphatase (PTP) inhibitor compounds synthesized from phosphonodifluoromethyl phenylalanine (F2Pmp) are provided. Use of these compounds for inhibiting a PTP enzyme (such as PTP-MEG2), as well as treating a disease, disorder, or condition associated with inappropriate activity of a PTP (such as type 2 diabetes), is also provided.

First claim

What is claimed is:

1. A compound of Formula A:

or a therapeutically suitable prodrug thereof or a therapeutically suitable salt thereof, wherein R 1 , R 2 , and R 3 are the same or different and each individually is an acyl group of a carboxylic acid.

2. The compound according to claim 1 , wherein R 1 and R 2 are the same or different and each individually is an acyl group of a benzoic acid, the benzoic acid being optionally substituted with one or more moieties selected from the group consisting of halogen, hydroxyl, C 1 -C 5 alkyl, and C 1 -C 5 alkoxy, and wherein R 3 is an acyl group of a phenylacetic acid, the phenylacetic acid being optionally substituted with one or more moieties selected from the group consisting of halogen, hydroxyl, C 1 -C 5 alkyl, and C 1 -C 5 alkoxy.

3. The compound according to claim 1 , having the structure of Compound 7:

or a therapeutically suitable prodrug thereof or a therapeutically suitable salt thereof.

4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4 , wherein the compound is Compound 7, a therapeutically suitable prodrug thereof, or a therapeutically suitable salt thereof.

6. The pharmaceutical composition of claim 5 , wherein the composition is a formulation selected from the group consisting of capsule, cachet, tablet, lozenge, powder, granule, solution, suspension, emulsion, bolus, electuary, and paste.

7. The pharmaceutical composition of claim 5 , wherein the composition further comprises an agent selected from the group consisting of antioxidant, buffer, bacteriostat, suspending agent, and thickening agent.

8. A method for treating a disease, disorder, or condition associated with inappropriate activity of a protein tyrosine phosphatase in an individual, the method comprising administering to the individual the compound of claim 1 .

9. The method according to claim 8 , wherein the compound is Compound 7, a therapeutically suitable prodrug thereof, or a therapeutically suitable salt thereof.

10. The method according to claim 9 , wherein the disease, disorder, or condition is type 2 diabetes.

11. A method of manufacturing a medicament for the treatment of a disease, disorder, or condition associated with inappropriate activity of a protein tyrosine phosphatase, the method comprising mixing the compound of claim 1 with a pharmaceutically acceptable carrier.

12. The method according to claim 11 , wherein the compound is Compound 7, a therapeutically suitable prodrug thereof, or a therapeutically suitable salt thereof.

13. The method according to claim 12 , wherein the disease, disorder, or condition is type 2 diabetes.

14. A method for inhibiting a protein tyrosine phosphatase enzyme in an individual, the method comprising administering the compound of claim 1 to the individual.

15. The method according to claim 14 , wherein R 1 , R 2 , and R 3 are the same or different and each individually is an acyl group of a benzoic acid, wherein the benzoic acid may be substituted with one or more moieties selected from the group consisting of halogen, hydroxyl, C 1 -C 5 alkyl, and C 1 -C 5 alkoxy.

16. The method according to claim 14 , wherein the compound is Compound 7, a therapeutically suitable prodrug thereof, or a therapeutically suitable salt thereof.

17. The method according to claim 14 , wherein the protein tyrosine phosphatase enzyme is protein tyrosine phosphatase, non-receptor type 9 (PTP-MEG2).

18. The method according to claim 14 , wherein the protein tyrosine phosphatase enzyme is located in a human cell or an animal cell.

Assignees

• Univ Indiana Res & Tech Corp

Inventors

• Zhang Zhong-Yin
• Zhang Sheng

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07K5/06078

  and aromatic or cycloaliphatic · CPC title

• C07F9/3882

  Arylalkanephosphonic acids (C07F9/3839 takes precedence) · CPC title

• C07F9/65586

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• C07F9/65522 Primary

  condensed with carbocyclic rings or carbocyclic ring systems · CPC title