| Literature DB >> 10691697 |
T D Penning1, N S Chandrakumar, B B Chen, H Y Chen, B N Desai, S W Djuric, S H Docter, A F Gasiecki, R A Haack, J M Miyashiro, M A Russell, S S Yu, D G Corley, R C Durley, B F Kilpatrick, B L Parnas, L J Askonas, J K Gierse, E I Harding, M K Highkin, J F Kachur, S H Kim, G G Krivi, D Villani-Price, E Y Pyla, W G Smith.
Abstract
Leukotriene B(4) (LTB(4)) is a pro-inflammatory mediator that has been implicated in the pathogenesis of a number of diseases including inflammatory bowel disease (IBD) and psoriasis. Since the action of LTA(4) hydrolase is the rate-limiting step for LTB(4) production, this enzyme represents an attractive pharmacological target for the suppression of LTB(4) production. From an in-house screening program, SC-22716 (1, 1-[2-(4-phenylphenoxy)ethyl]pyrrolidine) was identified as a potent inhibitor of LTA(4) hydrolase. Structure-activity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA(4) hydrolase, several of which demonstrated good oral activity in a mouse ex vivo whole blood assay.Entities:
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Year: 2000 PMID： 10691697 DOI： 10.1021/jm990496z
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446