Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: A probe of structural and conformational features contributing to inhibition

Authors
Boger, DL Sato, H Lerner, AE Austin, BJ Patterson, JE Patricelli, MP Cravatt, BF
Citation
Dl. Boger et al., Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: A probe of structural and conformational features contributing to inhibition, BIOORG MED, 9(2), 1999, pp. 265-270
Citations number
49
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
2
Year of publication
1999
Pages
265 - 270
Database
ISI
SICI code
0960-894X(19990118)9:2<265:TKIOFA>2.0.ZU;2-Q
Abstract
The examination of a series of trifluoromethyl ketone inhibitors of Fatty A cid Amide Hydrolase (FAAH, oleamide hydrolase, anandamide amidohydrolase) i s detailed in efforts that define structural and conformational properties that contribute to enzyme inhibition and substrate binding. The results imp ly an extended bound conformation, highlight a role for the presence, posit ion, and stereochemistry of a Delta(9,10) cis double bond, and suggest litt le apparent role for C11-C18/C22 of the fatty acid amide substrates. (C) 19 99 Elsevier Science Ltd. All rights reserved.