Fatty acids as anti-inflammatory agents

Patent metadata

Field	Value
Publication number	US-10213417-B2
Application number	US-201715662024-A
Country	US
Kind code	B2
Filing date	Jul 27, 2017
Priority date	Jul 31, 2009
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

Abstract

Compounds of formula I and their metabolites are potent mediators of an inflammatory response:

where a, b, c, d, e, f, V, W, X, Y, R a , R a′ , R b , R b′ , R c , and R c′ are defined herein. In particular, the compounds of the invention are candidate therapeutics for treating inflammatory conditions.

First claim

What is claimed is:

1. A method of treating an inflammatory condition comprising administering to the subject in need thereof a formulation comprising a therapeutically effective amount of a compound having the formula:

wherein:
R 1 is a heterocyclyl;
is an optional double bond;
W is —OH, —C(O)H, —C(O), —C(O)R p , —COOH, —COOR p , —Cl, —Br, —I, —CF 3 , —CN, —SO 3 , —SO 2 R p , —SO 3 H, —NH 3 +, —NH 2 R p+ , —NR p R q R t , —NO 2 , ═O, ═NR p , ═CF 2 , or —CHF;
each V is, independently —CH or —C—, wherein:
V is —CH— when W is —OH, —H, —C(O)H, —C(O), —C(O)R p , —COOH, —COOR p , —Cl, —Br, —I, —F, —CF 3 , —CN, —SO 3 , —SO 2 R p , —SO 3 H, —NH 3+ , —NH 2 R p+ , —NR p R q R t or —NO 2 ; or
V is —C— when W is ═O, ═NR p , ═CF 2 or ═CHF;
R p and R q are each, independently, H, (C 1 -C 8 ) alkyl, aryl, or (C 1 -C 8 ) haloalkyl;
R t is (C 1 -C 8 ) alkyl, aryl, or (C 1 -C 8 ) haloalkyl;
R b and R b′ are each independently, —H, —OH, —C(O)H, —C(O), —C(O)R p , —COOH, —COOR p , —Cl, —Br, —I, —F, —CF 3 , —CHF 2 , —CH 2 F, —CN, —SO 3 , —SO 2 R p , SO 3 H, —NH 3 + , —NH 2 R p+ , —NR p R q R t or —NO 2 , wherein:
R b and R b′ are not simultaneously non-hydrogen groups;
a is an integer between 5 and 15 inclusive, c is an integer from 1 and 15 inclusive, and f is an integer between 5 and 15 inclusive; and

a pharmaceutically acceptable carrier.

2. The method according to claim 1 , wherein W is —H, ═O or ═NR p .

3. The method according to claim 1 , wherein V is —CH— and W is —H.

4. The method according to claim 1 , wherein V is —C— and W is ═O.

5. The method according to claim 1 , wherein c is 1, V is —C—, and W is ═O.

6. The method according to claim 1 , wherein R b and R b′ , are each, independently, —H, —OH, —CN, or —NO 2 .

7. The method according to claim 1 , wherein R b and R b′ are each —H.

8. The method according to claim 1 , wherein a is 3.

9. The method to claim 1 , wherein R 1 is a heteroaryl or a heterocycloalkyl.

10. The method according to claim 1 , wherein the pharmaceutically acceptable carrier comprises a solid, solution, powder, fluid emulsion, fluid suspension, semi-solid, or dry powder.

11. The method according to claim 1 , further comprising at least one pharmaceutically acceptable diluent, filler, disintegrant, binder, lubricant, surfactant, hydrophobic vehicle, water soluble vehicle, emulsifier, buffer, humectant, moisturizer, solubilizer, antioxidant, or preservative, or a combination thereof.

12. The method according to claim 1 , wherein the inflammatory condition being treated is selected from the group consisting of pulmonary fibrosis, pulmonary inflammation, asthma, acquired respiratory distress syndrome, tobacco induced lung disease and chronic obstructive pulmonary disease.

13. A method of treating pulmonary inflammation in a subject comprising administering to a subject in need thereof a compound having a formula of:

wherein:
R 1 is a heterocyclyl;
is an optional double bond;
W is —OH, —C(O)H, —C(O), —C(O)R p , —COOH, —COOR p , —Cl, —Br, —I, —CF 3 , —CN, —SO 3 , —SO 2 R p , —SO 3 H, —NH 3 + , —NH 2 R p+ , —NR p R q R t , —NO 2 , ═O, ═NR p , ═CF 2 , or —CHF;
each V is, independently —CH or —C—, wherein:
V is —CH— when W is —OH, —H, —C(O)H, —C(O), —C(O)R p , —COOH, —COOR p , —Cl, —Br, —I, —F, —CF 3 , —CN, —SO 3 , —SO 2 R p , —SO 3 H, —NH 3 + , —NH 2 R p+ , —NR p R q R t or —NO 2 ; or
V is —C— when W is ═O, ═NR p , ═CF 2 or ═CHF;
R p and R q are each, independently, H, (C 1 -C 8 ) alkyl, aryl, or (C 1 -C 8 ) haloalkyl;
R t is (C 1 -C 8 ) alkyl, aryl, or (C 1 -C 8 ) haloalkyl;
R b and R b′ are each independently, —H, —OH, —C(O)H, —C(O), —C(O)R p , —COOH, —COOR p , —Cl, —Br, —I, —F, —CF 3 , —CHF 2 , —CH 2 F, —CN, —SO 3 , —SO 2 R p , SO 3 H, —NH 3 + , —NH 2 R p+ , —NR p R q R t or —NO 2 , wherein:
R b and R b′ are not simultaneously non-hydrogen groups;
a is an integer between 5 and 15 inclusive, c is an integer from 1 and 15 inclusive, and f is an integer between 5 and 15 inclusive.

14. The method according to claim 13 , wherein W is ═O or ═NR p .

15. The method according to claim 14 , wherein R 1 is a heteroaryl or a heterocycloalkyl.

16. The method according to claim 14 , wherein V is —C— and W is ═O.

17. The method according to claim 14 , wherein c is 1.

18. The method according to claim 13 , wherein the pulmonary inflammation is further selected from the group consisting of pulmonary fibrosis, asthma, acquired respiratory distress syndrome, tobacco induced lung disease and chronic obstructive pulmonary disease.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Freeman Bruce A
• Schopfer Francisco J

Classifications

• A61P43/00

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

• A61P37/08

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

• A61P37/06

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

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title