Compositions and methods for treating respiratory injury or disease

Patent metadata

Field	Value
Publication number	US-10092526-B2
Application number	US-201715816963-A
Country	US
Kind code	B2
Filing date	Nov 17, 2017
Priority date	Dec 9, 2013
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

A method for treating a respiratory injury or disease comprising: administering to a patient in need of treatment a pharmaceutical composition comprising a compound of general Formula I:

or salt, ester, solvate, hydrate, or prodrug thereof;
wherein:
x is an integer from 1 to 10;
A and B are each, independently, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-6 alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl-C 1-6 alkyl, C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl, C 3-9 heteroaryl, or C 3-9 heteroaryl-C 1-6 alkyl; and
n and p are each, independently, integers from 1 to 10; and
a pharmaceutically acceptable carrier, excipient, or diluent.

First claim

What is claimed is:

1. A method for treating a respiratory injury or disease comprising:
administering to a patient in need of treatment a pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, having a structure of formula V:

wherein X is —CH 2 CH 2 —; and
R 1 -R 10 are each individually H, optionally-substituted alkyl, optionally-substituted alkoxy, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted heterocyclic, halogen, amino, or hydroxy; and
a pharmaceutically acceptable carrier, excipient, or diluent,
wherein the respiratory injury or disease is selected from the group consisting of acute and chronic bronchitis, emphysema, respiratory infections, flu, post-lung transplant rejection including acute and chronic rejection and bronchiolitis obliterans, acute lung injury or the acute respiratory distress syndrome, and bronchiectasis.

2. The method of claim 1 , wherein the respiratory injury or disease is acute or chronic bronchitis.

3. The method of claim 1 , wherein the composition is administered via intratracheal delivery.

4. The method of claim 1 , wherein the composition is administered via inhalation.

5. The method of claim 1 , wherein the composition is co-administered with a bronchodilator, a corticosteroid, or a combination thereof.

6. The method of claim 1 , wherein R 3 and R 8 are each a 6-membered N-heterocycle.

7. The method of claim 6 , wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 9 and R 10 are each individually H or halogen.

8. A method for treating a respiratory infection comprising:
administering to a patient in need of treatment a pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, having a structure of formula V:

wherein X is a divalent or tetravalent linking moiety; and
R 1 -R 10 are each individually H, optionally-substituted alkyl, optionally-substituted alkoxy, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted heterocyclic, halogen, amino, or hydroxy, provided at least one of R 3 or R 8 is an optionally-substituted heterocyclic; and
a pharmaceutically acceptable carrier, excipient, or diluent.

9. The method of claim 8 , wherein the respiratory injury or disease is acute or chronic bronchitis.

10. The method of claim 8 , wherein the composition is administered via intratracheal delivery.

11. The method of claim 8 , wherein the composition is administered via inhalation.

12. The method of claim 8 , wherein the composition is co-administered with a bronchodilator, a corticosteroid, or a combination thereof.

13. The method of claim 8 , wherein at least one of R 3 or R 8 is an N-heterocyclic.

14. The method of claim 8 , wherein R 3 is an N-heterocyclic and R 8 is an N-heterocycle.

15. The method of claim 8 , wherein R 3 and R 8 are each a 6-membered N-heterocycle.

16. The method of claim 15 , wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 9 and R 10 are each individually H or halogen.

17. A method for treating a respiratory injury or disease comprising:
administering to a patient in need of treatment a pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, having a structure of

and a pharmaceutically acceptable carrier, excipient, or diluent,
wherein the respiratory injury or disease is selected from the group consisting of acute and chronic bronchitis, emphysema, respiratory infections, flu, post-lung transplant rejection including acute and chronic rejection and bronchiolitis obliterans, acute lung injury or the acute respiratory distress syndrome, and bronchiectasis.

18. The method of claim 17 , wherein the respiratory injury or disease is acute or chronic bronchitis.

19. The method of claim 17 , wherein the composition is administered via intratracheal delivery.

20. The method of claim 17 , wherein the composition is administered via inhalation.

21. The method of claim 17 , wherein the composition is co-administered with a bronchodilator, a corticosteroid, or a combination thereof.

Assignees

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

Inventors

• Chen Beibei
• Mallampalli Rama

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• C07D295/135

  with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title