@article {9778, title = {Potent and Selective Fluoroketone Inhibitors of Group VIA Calcium-Independent Phospholipase A2}, journal = {Journal of Medicinal Chemistry}, volume = {53}, number = {9}, year = {2010}, month = {2010/05/13}, pages = {3602-3610}, publisher = {American Chemical Society}, abstract = {Group VIA calcium-independent phospholipase A2\ (GVIA iPLA2) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA2\ inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one (FKGK18) is the most potent inhibitor of GVIA iPLA2\ (XI(50) = 0.0002) ever reported. Being 195 and \>455 times more potent for GVIA iPLA2\ than for GIVA cPLA2\ and GV sPLA2, respectively, makes it a valuable tool to explore the role of GVIA iPLA2\ in cells and in vivo models. 1,1,1,2,2,3,3-Heptafluoro-8-(naphthalene-2-yl)octan-4-one inhibited GVIA iPLA2\ with a\ XI(50) value of 0.001 while inhibiting the other intracellular GIVA cPLA2\ and GV sPLA2\ at least 90 times less potently. Hexa- and octafluoro ketones were also found to be potent inhibitors of GVIA iPLA2; however, they are not selective.}, isbn = {0022-2623}, author = {Kokotos, George and Hsu, Yuan-Hao and Burke, John E. and Baskakis, Constantinos and Kokotos, Christoforos G. and Magrioti, Victoria and Dennis, Edward A.} }