Compositions and methods for treating respiratory injury or disease

Patent metadata

Field	Value
Publication number	US-9849098-B2
Application number	US-201415102827-A
Country	US
Kind code	B2
Filing date	Dec 9, 2014
Priority date	Dec 9, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

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 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; 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, 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 2 , wherein the composition is administered via intratracheal delivery.

4. The method of claim 2 , wherein the composition is administered via inhalation.

5. The method of claim 2 , wherein the composition is co-administered with a bronchodilator, a corticosteroid, or a combination thereof.

6. The method of claim 5 , wherein the bronchodilator is selected from a β2 agonist, an anticholinergic, a theophylline, or a combination thereof.

7. The method of claim 1 , wherein at least one of R 3 or R 8 is an N-heterocyclic.

8. The method of claim 1 , wherein R 3 is an N-heterocyclic and R 8 is an N-heterocycle.

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

10. The method of claim 9 , wherein X is an alkanediyl having a structure of —C n H 2n — wherein n is 2 to 5.

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

12. The method of claim 8 , wherein R 1 , R 2 , R 5 , R 6 , R 7 , and R 10 are each individually H, and R 4 and R 9 are each individually halogen.

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

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

14. The method of claim 13 , wherein the respiratory injury or disease is acute or chronic bronchitis.

15. The method of claim 13 , wherein the compound is administered via intratracheal delivery.

16. The method of claim 13 , wherein the compound is administered via inhalation.

17. The method of claim 13 , wherein the compound is co-administered with a bronchodilator, a corticosteroid, or a combination thereof.

18. The method of claim 17 , wherein the bronchodilator is selected from a β2 agonist, an anticholinergic, a theophylline, or a combination thereof.

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

20. The method of claim 13 , wherein R 3 is an N-heterocyclic and R 8 is an N-heterocyclic.

21. The method of claim 13 , wherein R 3 and R 8 are each a 6-membered N-heterocyclic.

22. The method of claim 21 , wherein X is an alkanediyl having a structure of —C n H 2n — wherein n is 2 to 5.

23. The method of claim 21 , wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 9 and R 10 are each individually H or halogen.

24. The method of claim 13 , wherein R 1 , R 2 , R 5 , R 6 , R 7 , and R 10 are each individually H, and R 4 and R 9 are each individually halogen.

25. A method comprising administering to a subject for muscle building in the subject a compound, or a pharmaceutically acceptable salt thereof, having a structure of formula V:

wherein X is a divalent 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.

26. A method for treating a patient in need of treatment for an injury, disease or condition, comprising administering to the patient in need thereof a compound, or a pharmaceutically acceptable salt thereof, having a structure of formula V:

wherein X is a divalent 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,
wherein the injury, disease or condition is selected from myopathy, steroid-induced myopathy, muscular dystrophy, amyotrophic lateral sclerosis (ALS), muscle weakness, critical illness myopathy, muscle atrophy, muscle wasting, rhabdomyolysis, dermatomyositis, myositis, mitochondrial myopathy, chronic obstructive lung disease, organ transplant rejection, psoriasis, myasthenia gravis, Addison's disease, celiac disease, Graves' disease, Hashimoto's thyroiditis, or pernicious anemia.

27. A compound, or a pharmaceutically acceptable salt thereof, having a structure of formula V:

wherein X is a divalent linking moiety; R 3 is an N-heterocyclic; R 8 is an N-heterocyclic; R 1 , R 2 , R 5 , R 6 , R 7 , and R 10 are each individually H; and R 4 and R 9 are each individually halogen.

28. A pharmaceutical composition comprising a compound of claim 27 , and a pharmaceutically acceptable carrier, excipient, or diluent.

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

• A61K31/341

  not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine · CPC title

• A61K31/381

  having five-membered rings · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title