Fatty acids as anti-inflammatory agents
View Patent ↗Compounds of formula I and their metabolites are potent mediators of an inflammatory response: (I) 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.
1. A pharmaceutical formulation comprising: an effective amount of 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 , —COON, —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 formulation according to claim 1 , wherein W is —H, ═O or ═NR p .
3. The formulation according to claim 1 , wherein V is —CH— and W is —H.
4. The formulation according to claim 1 , wherein V is —C— and W is ═O.
5. The formulation according to claim 1 , wherein c is 1, V is —C—, and W is ═O.
6. The formulation according to claim 1 , wherein R b and R b′ , are each, independently, —H, —OH, —CN, or —NO 2 .
7. The formulation according to claim 1 , wherein R b and R b′ are each —H.
8. The formulation according to claim 1 , wherein a is 3.
9. The formulation according to claim 1 , wherein the pharmaceutically acceptable carrier comprises a solid, solution, powder, fluid emulsion, fluid suspension, semi-solid, or dry powder.
10. The formulation 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 combinations thereof.
11. 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, ═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)RP, —COOH, —COORP, —Cl, —Br, —I, —F, —CF 3 , —CN, —SO 3 , —SO 2 RP, —SO 3 H, —NH 3+ , —NH 2 RP + , —NR p R q R t or —NO 2 ; or
V is —C— when W is ═O, ═NRP, ═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.
12. The compound according to claim 11 , wherein W is ═O or ═NRP.
13. The formulation of claim 1 , wherein R 1 is a heteroaryl or a heterocycloalkyl.
14. The compound of claim 11 , wherein R 1 is a heteroaryl or a heterocycloalkyl.
15. The compound according to claim 11 , wherein V is —C— and W is ═O.
16. The compound according to claim 15 , wherein c is 1.