Structure-activity relationship studies on 1-[2-(4-phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A(4) (LTA(4)) hydrolase

Leukotriene B-4 (LTB4) is a pro-inflammatory mediator that has been implica ted in the pathogenesis of a number of diseases including inflammatory bowe l disease (IBD) and psoriasis. Since the action of LTA(4) hydrolase is the rate-limiting step for LTB4 production, this enzyme represents an attractiv e pharmacological target for the suppression of LTB4 production. From an in -house screening program, SC-22716 (1, 1-[2-(4-phenylphenoxy)ethyl] pyrroli dine) was identified as a potent inhibitor of LTA(4) hydrolase. Structure-a ctivity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA(4) hydro lase, several of which demonstrated good oral activity in a mouse ex vivo w hole blood assay.