Treatment of pulmonary and other conditions

Patent metadata

Field	Value
Publication number	US-9862690-B2
Application number	US-201414890147-A
Country	US
Kind code	B2
Filing date	May 9, 2014
Priority date	May 10, 2013
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

Disclosed is a compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:

X 1 -L-X 2
wherein L is a linking moiety comprising an enone; and X 1 and X 2 are each independently an optionally-substituted N-heterocycle.

Also disclosed are method for treating pulmonary conditions and other organ or system conditions with the compounds.

First claim

What is claimed is:

1. A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:

wherein represents a single bond;
A is CH(S—R 5 ), wherein R 5 is an acylamino-substituted carboxylalkyl, a sulfonate-substituted alkyl, or an acylamino-substituted amido; and
X 1 and X 2 are each independently an optionally substituted 6-membered N-heterocycle.

2. The compound of claim 1 , wherein X 1 has a structure of:

and X 2 has a structure of:

wherein Z 1 , Z 2 , and Z 3 are each independently C or N, provided that at least one of Z 1 , Z 2 , or Z 3 is N; and
Y 1 , Y 2 , Y 3 , Y 4 and Y 5 are each independently H, optionally-substituted alkyl, amino, hydroxyl, optionally-substituted alkoxy, optionally-substituted thiol, acyl, or halogen.

3. The compound of claim 1 , wherein the compound has a structure of:

4. The compound of 3 , wherein the compound has a structure of:

wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H, optionally-substituted alkyl, amino, hydroxyl, optionally-substituted alkoxy, optionally-substituted thiol, acyl, or halogen.

5. The compound of claim 3 , wherein X 1 and X 2 are each optionally-substituted pyrazinyl or optionally-substituted pyrimidinyl.

6. The compound of claim 5 , wherein X 1 and X 2 are each the same.

7. The compound of claim 5 , wherein X 1 and X 2 are each different.

8. The compound of claim 3 , wherein R 5 is an acylamino-substituted carboxylalkyl, a sulfonate-substituted alkyl, or an acylamino-substituted amido.

9. The compound of claim 3 , wherein —S—R 5 is a N-acetylcysteine moiety, a 2-mercaptoethane sulfonate moiety, or a glutathione moiety.

10. A pharmaceutical composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable excipient.

11. The pharmaceutical composition of claim 10 , wherein the composition is in the form of an aerosol.

12. The pharmaceutical composition of claim 10 , wherein the composition is in the form of a dry powder.

13. The compound of claim 4 , wherein R 5 is an acylamino-substituted carboxylalkyl, a sulfonate-substituted alkyl, or an acylamino-substituted amido.

14. The compound of claim 4 , wherein —S—R 5 is a N-acetylcysteine moiety, a 2-mercaptoethane sulfonate moiety, or a glutathione moiety.

15. The compound of claim 1 , wherein the compound has a structure of:

16. The compound of claim 1 , wherein the compound has a structure of:

17. The compound of claim 4 , wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H.

18. The compound of claim 13 , wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H.

19. The compound of claim 14 , wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education
• Us Veterans Affairs

Inventors

• Reddy Raju

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · 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