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

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

  • J Med Chem. 2000 Feb 24;43(4):721-35. doi: 10.1021/jm990496z.
T D Penning 1,  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
Affiliations

Affiliation

  • 1 Departments of Medicinal Chemistry, Structure-Activity Screening Program, Inflammatory Diseases Research, and Molecular Pharmacology, Searle Research and Development, Monsanto Company, Skokie, Illinois 60077, USA. [email protected]
PMID: 10691697 DOI: 10.1021/jm990496z
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.

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