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

Authors :
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
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 May 15; Vol. 19 (10), pp. 2865-9. Date of Electronic Publication: 2009 Mar 24.
Publication Year :
2009

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.

Details

Language :
English
ISSN :
1464-3405
Volume :
19
Issue :
10
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
19386497
Full Text :
https://doi.org/10.1016/j.bmcl.2009.03.080