Oxime carbamate--discovery of a series of novel FAAH inhibitors.
A series of novel oxime carbamates have been identified as potent inhibitors of the key regulatory enzyme of the endocannabinoid signaling system, fatty acid amide hydrolase (FAAH). In this Letter, the rationale behind the discovery and the biological evaluations of this novel class of FAAH inhibitors are presented. Both in vitro and in vivo results of selected targets are discussed, along with inhibition kinetics and molecular modeling studies.(1).
Sit
S Y
SY
Department of Chemistry, Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, CT 06492-7660, USA. sits@bms.com
Conway
Charles M
CM
Xie
Kai
K
Bertekap
Robert
R
Bourin
Clotilde
C
Burris
Kevin D
KD
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D010091:Oximes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D010091:Oximes; D000099252:Fatty Acid Amide Hydrolases