Identification of potent, noncovalent fatty acid amide hydrolase (FAAH) inhibitors

…, M Lindstrom, D Lester-Zeiner, G Xu, TJ Carlson…

Index: Gustin, Darin J.; Ma, Zhihua; Min, Xiaoshan; Li, Yihong; Hedberg, Christine; Guimaraes, Cris; Porter, Amy C.; Lindstrom, Michelle; Lester-Zeiner, Dianna; Xu, Guifen; Carlson, Timothy J.; Xiao, Shouhua; Meleza, Cesar; Connors, Richard; Wang, Zhulun; Kayser, Frank Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 8 p. 2492 - 2496

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Citation Number: 30

Abstract

Starting from a series of ureas that were determined to be mechanism-based inhibitors of FAAH, several spirocyclic ureas and lactams were designed and synthesized. These efforts identified a series of novel, noncovalent FAAH inhibitors with in vitro potency comparable to known covalent FAAH inhibitors. The mechanism of action for these compounds was determined through a combination of SAR and co-crystallography with rat FAAH.