Pyrrolidine inhibitors of human cytosolic phospholipase A2.: part 2:: Synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'

We synthesized a potent and crystallized human cytosolic phospholipase A(2)alpha inhibitor, pyrrophenone (6) which inhibits the isolated enzyme with an IC50 value of 4.2 nM. Pyrrophenone shows potent inhibition of arachidonic acid release, prostaglandin E-2, thromboxane B-2, and leukotriene B-4 formation in human whole blood. The magnitudes of prostaglandin E-2 and thromboxane B-2 inhibition are the same as those of indomethacin. (C) 2001 Elsevier Science Ltd. All rights reserved.