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

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Penning TD, Chandrakumar NS, Chen BB, Chen HY, Desai BN, Djuric SW, Docter SH, Gasiecki AF, Haack RA, Miyashiro JM, Russell MA, Yu SS, Corley DG, Durley RC, Kilpatrick BF, Parnas BL, Askonas LJ, Gierse JK, Harding EI, Highkin MK, Kachur JF, Kim SH, Krivi GG, Villani-Price D, Pyla EY, Smith WG

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.

PubMed ID
10691697 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
KelatorphanLeukotriene A-4 hydrolaseIC 50 (nM)5N/AN/ADetails
KelatorphanLeukotriene A-4 hydrolaseIC 50 (nM)>50000N/AN/ADetails