Compositions and methods for inhibition of phospholipase A2 mediated inflammation
View Patent ↗Specific, highly potent 2-oxo-amide based inhibitors of phospholipase A 2 (PLA 2 ) activity are provided. A role for PLA 2 activity in spinally mediated inflammatory processes is established, and a method for treating hyperalgesia and other inflammatory conditions associated with PLA 2 activity is provided.
1. A compound of the formula (I):
wherein:
R 1 is an acidic moiety, selected from the group consisting of carboxyl, phosphate, phosphinate, sulfate, and sulfonate; each of R 2 and R 3 is a moiety independently selected from the group consisting of phenyl, benzyl, and a carbyl having between 1 and 13 carbons, the carbyl being selected from the group consisting of a linear or branched, saturated or unsaturated alkyl, alkenyl, and alkynyl;
n is an integer having a value of 3, m is an integer having a value of 0 to 3, and k is an integer having a value of 0 to 22;
and isomers, enantiomers, and pharmacologically or immunologically acceptable salts thereof.
2. A pharmaceutical composition, comprising (4S)-4-[(2-oxododecanoyl)amino]octanoic acid, and a pharmaceutically acceptable carrier.
3. A pharmaceutical composition, comprising 4-[(2-oxohexadecanoyl)amino]butanoic acid, and a pharmaceutically acceptable carrier.
4. A pharmaceutical composition, comprising 4-[(2-oxooctanoyl)amino]butanoic acid, and a pharmaceutically acceptable carrier.
5. A pharmaceutical composition, comprising (4R)-4-[(2-oxododecanoyl)amino]octanoic acid, and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition, comprising the compound of formula (II),
and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition, comprising the compound of formula (III),
and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition, comprising the compound of formula (IV),
and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition, comprising the compound of formula (V),
and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition, comprising the compound of formula (VI),
and a pharmaceutically acceptable carrier.
11. A pharmaceutical composition, comprising the compound of formula (VII),
and a pharmaceutically acceptable carrier.
12. A pharmaceutical composition, comprising the compound of formula (VIII),
and a pharmaceutically acceptable carrier.