Fatty acid amide hydrolase inhibitors. 3: Tetra-substituted azetidine ureas with in vivo activity

…, K Benwell, T Brooks, J D'Alessandro, Z Daniels…

Index: Roughley, Stephen D.; Browne, Helen; MacIas, Alba T.; Benwell, Karen; Brooks, Teresa; D'Alessandro, Jalanie; Daniels, Zoe; Dugdale, Sarah; Francis, Geraint; Gibbons, Ben; Hart, Terance; Haymes, Timothy; Kennett, Guy; Lightowler, Sean; Matassova, Natalia; Mansell, Howard; Merrett, Angela; Misra, Anil; Padfield, Anthony; Parsons, Rachel; Pratt, Robert; Robertson, Alan; Simmonite, Heather; Tan, Kiri; Walls, Steven B.; Wong, Melanie Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 2 p. 901 - 906

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Citation Number: 8

Abstract

We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.