2-Oxoesters: A Novel Class of Potent and Selective Inhibitors of Cytosolic Group IVA Phospholipase A.

Cytosolic phospholipase A (GIVA cPLA) is the only PLA that exhibits a marked preference for hydrolysis of arachidonic acid containing phospholipid substrates releasing free arachidonic acid and lysophospholipids and giving rise to the generation of diverse lipid mediators involved in inflammatory conditions. Thus, the development of potent and selective GIVA cPLA inhibitors is of great importance. We have developed a novel class of such inhibitors based on the 2-oxoester functionality.