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

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.

SUBMITTER: Johnson DS

PROVIDER: S-EPMC3150822 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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

Johnson Douglas S DS Ahn Kay K Kesten Suzanne S Lazerwith Scott E SE Song Yuntao Y Morris Mark M Fay Lorraine L Gregory Tracy T Stiff Cory C Dunbar James B JB Liimatta Marya M Beidler David D Smith Sarah S Nomanbhoy Tyzoon K TK Cravatt Benjamin F BF

Bioorganic & medicinal chemistry letters 20090324 10

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 inf ...[more]

PMID: 19386497

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