Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A2 (GIVA cPLA2)

Cytosolic phospholipase A(2) (GrvA cPLA(2)) has attracted great interest as a medicinal target because it initiates the eicosanoid cascade and is involved in a number of inflammatory diseases. As consequence, the development of potent synthetic inhibitors is of great importance We have developed highly potent 2-oxoester inhibitors of GIVA cPLA(2) presenting X-I (50) values between 0 000019 and 0 000066 We demonstrate that the 2-oxoester functionality is essential for in vitro inhibitory activity, making these inhibitors useful research reagents. However, their high reactivity results in rapid degradation of the inhibitors in human plasma, limiting their pharmaceutical utility without further modification.