Structure−Activity Relationship Studies on 1-[2-(4-Phenylphenoxy)ethyl]pyrrolidine (SC-22716), a Potent Inhibitor of Leukotriene A4 (LTA4) Hydrolase
Leukotriene B4 (LTB4) 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 LTA4 hydrolase is the rate-limiting step for LTB4 production, this enzyme represents an attractive p...
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Veröffentlicht in: | Journal of medicinal chemistry 2000-02, Vol.43 (4), p.721-735 |
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Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Leukotriene B4 (LTB4) 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 LTA4 hydrolase is the rate-limiting step for LTB4 production, this enzyme represents an attractive pharmacological target for the suppression of LTB4 production. From an in-house screening program, SC-22716 (1, 1-[2-(4-phenylphenoxy)ethyl]pyrrolidine) was identified as a potent inhibitor of LTA4 hydrolase. Structure−activity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA4 hydrolase, several of which demonstrated good oral activity in a mouse ex vivo whole blood assay. |
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ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm990496z |