808134-96-5Relevant academic research and scientific papers
Delineation of a fundamental α-ketoheterocycle substituent effect for use in the design of enzyme inhibitors
Romero, F. Anthony,Hwang, Inkyu,Boger, Dale L.
, p. 14004 - 14005 (2007/10/03)
The synthesis and examination of a systematic series of 5-substituted 2-keto oxazoles as inhibitors of fatty acid amide hydrolase (FAAH) defined a fundamental substituent effect that led to the discovery of inhibitors with Ki's as low as 400 pM. The intrinsic basis of the relationship (-log Ki vs σp), which relates Ki with the Hammett σp constant of the substituent, the magnitude of the effect (ρ = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH. Copyright
Discovery of a potent, selective, and efficacious class of reversible α-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics
Boger, Dale L.,Miyauchi, Hiroshi,Du, Wu,Hardouin, Christophe,Fecik, Robert A.,Cheng, Heng,Hwang, Inkyu,Hedrick, Michael P.,Leung, Donmienne,Acevedo, Orlando,Guimar?es, Cristiano R. W.,Jorgensen, William L.,Cravatt, Benjamin F.
, p. 1849 - 1856 (2007/10/03)
Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routine implementation of a proteomics-wide selectivity screen against the serine hydrolase superfamily ensuring selectivity for FAAH coupled with systematic in vivo examinations of candidate inhibitors.
