Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 2. Discovery of 7-azaspiro [3.5] nonane urea PF-04862853, an orally efficacious …

…, J McDonald, SE Smith, S Foltin, J Rumsey…

Index: Meyers, Marvin J.; Long, Scott A.; Pelc, Matthew J.; Wang, Jane L.; Bowen, Scott J.; Schweitzer, Barbara A.; Wilcox, Mark V.; McDonald, Joseph; Smith, Sarah E.; Foltin, Susan; Rumsey, Jeanne; Yang, Young-Sun; Walker, Mark C.; Kamtekar, Satwik; Beidler, David; Thorarensen, Atli Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 21 p. 6545 - 6553

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Citation Number: 18

Abstract

Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase responsible for the degradation of fatty acid amide signaling molecules such as endocannabinoid anandamide (AEA), which has been shown to possess cannabinoid-like analgesic properties. Herein we report the optimization of spirocyclic 7-azaspiro [3.5] nonane and 1- oxa-8-azaspiro [4.5] decane urea covalent inhibitors of FAAH. Using an iterative design ...