1. Fatty acid amide hydrolase inhibitors. 3: tetra-substituted azetidine ureas with in vivo activity
- Author
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Hart Terance William, Rachel Parsons, Ben Gibbons, Helen Browne, Macias Alba, Heather Simmonite, Sarah Dugdale, Sean Lightowler, Howard Langh Am Mansell, Guy A. Kennett, Anthony Padfield, Geraint L. Francis, Robert M. Pratt, Teresa Brooks, Timothy Haymes, Jalanie D’Alessandro, Natalia Matassova, K Benwell, Melanie Wong, Steven B. Walls, Stephen D. Roughley, A Misra, Zoe Daniels, Angela Merrett, Alan D. Robertson, and Kiri Tan
- Subjects
Models, Molecular ,ERG1 Potassium Channel ,Stereochemistry ,Clinical Biochemistry ,Azetidine ,Pharmaceutical Science ,Stereoisomerism ,Biochemistry ,Amidohydrolases ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cytochrome P-450 Enzyme System ,Fatty acid amide hydrolase ,In vivo ,Drug Discovery ,Structure–activity relationship ,Animals ,Cytochrome P-450 Enzyme Inhibitors ,Humans ,Urea ,Enzyme Inhibitors ,Molecular Biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Anandamide ,Ether-A-Go-Go Potassium Channels ,Rats ,nervous system ,chemistry ,Molecular Medicine ,Azetidines ,lipids (amino acids, peptides, and proteins) ,psychological phenomena and processes - 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.
- Published
- 2011