Design, Synthesis, and Characterization of α-Ketoheterocycles That Additionally Target the Cytosolic Port Cys269 of Fatty Acid Amide Hydrolase

K Otrubova, BF Cravatt, DL Boger

Index: Otrubova, Katerina; Cravatt, Benjamin F.; Boger, Dale L. Journal of Medicinal Chemistry, 2014 , vol. 57, # 3 p. 1079 - 1089

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Citation Number: 9

Abstract

A series of α-ketooxazoles incorporating electrophiles at the C5 position of the pyridyl ring of 2 (OL-135) and related compounds were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH) that additionally target the cytosolic port Cys269. From this series, a subset of the candidate inhibitors exhibited time-dependent FAAH inhibition and noncompetitive irreversible inactivation of the enzyme, consistent with the targeted ...