Fatty acids as anti-inflammatory agents
View Patent ↗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 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.
1. A method of detecting a metabolite of a fatty acid according to Formula (I), the method comprising:
contacting a biological sample, or a cellular lysate thereof, with (i) at least one fatty acid according to Formula (I):
wherein:
R 1 is a heterocycle;
W is selected from —H, —OH, —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 , —NO 2 , ═O, NR P , ═CF 2 , and ═CHF;
V is —CH— when W is selected from the group consisting of —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 and NO 2 ; or V is —C— when W is selected from ═O, ═NR P , ═CF 2 , and ═CHF;
a is an integer between 5 and 15;
c is an integer between 1 and 15;
f is an integer between 5 and 15;
—R P and —R q are each independently selected from H, (C 1 -C 8 )alkyl, aryl, and (C 1 -C 8 )halo alkyl;
R t is independently selected from (C 1 -C 8 )alkyl, aryl, and (C 1 -C 8 )haloalkyl;
—R b , and —R b′ are each independently selected from —H, —OH, —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 , and —NO 2 ; and
—R b , and —R b′ do no simultaneously represent non-hydrogen groups; and
(ii) β-mercaptoethanol
resulting in forming one or more β-mercaptoethanol-fatty acid adducts;
and
(b) subjecting the one or more β-mercaptoethanol-fatty acid adducts from step (a) to analysis by mass spectrometry to identify one or more fatty acid metabolites of Formula (I).
2. The method of claim 1 , wherein W is H, ═O, or NR P .
3. The method of claim 1 , wherein V is —CH— and W is —H.
4. The method of claim 1 , wherein V is —C— and W is ═O.
5. The method of claim 1 , wherein c is 1, V is —C—, and W is ═O.
6. The method of claim 1 , wherein R b and R b′ are each —H, —OH, —CN, or —NO 2 .
7. The method of claim 1 , wherein R b and R b′ are each —H.
8. The method of claim 1 , wherein a is 3.
9. The method of claim 1 , wherein R a is a heteroaryl or a heterocycloalkyl.