Bioorg Med Chem Lett. 2009 May 15;19(10):2865-9. Epub 2009 Mar 24.

Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH).

Johnson DS, Ahn K, Kesten S, Lazerwith SE, Song Y, Morris M, Fay L, Gregory T, Stiff C, Dunbar JB Jr, Liimatta M, Beidler D, Smith S, Nomanbhoy TK, Cravatt BF.

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Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. doug.johnson@pfizer.com

Abstract

The synthesis and structure-activity relationships (SAR) of a series of benzothiophene piperazine and piperidine urea FAAH inhibitors is described. These compounds inhibit FAAH by covalently modifying the enzyme's active site serine nucleophile. Activity-based protein profiling (ABPP) revealed that these urea inhibitors were completely selective for FAAH relative to other mammalian serine hydrolases. Several compounds showed in vivo activity in a rat complete Freund's adjuvant (CFA) model of inflammatory pain.

PMID:: 19386497; [PubMed - indexed for MEDLINE]
PMCID:: PMC3150822

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