New potent and selective polyfluoroalkyl ketone inhibitors of GVIA calcium-independent phospholipase A2

Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA(2) inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA(2) inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA(2) inhibitor ever reported with a X-1(50) value of 0.0001, and with no significant inhibition against GIVA cPLA(2) or GV sPLA(2). We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA(2), GIVA cPLA(2), and CV sPLA(2). (C) 2013 Elsevier Ltd. All rights reserved.