title: Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors.
abstract: Monoglyceride lipase (MGL) inhibition may offer an approach in treating diseases in which higher 2-arachidonoyglycerol activity would be beneficial. We report here the synthesis and pharmacological evaluation of bis(dialkylaminethiocarbonyl)disulfide derivatives as irreversible MGL inhibitors. Inhibition occurs through interactions with MGL C208 and C242 residues, and these derivatives exhibit high inhibition selectivity over fatty acid amide hydrolase, another endocannabinoid-hydrolyzing enzyme.
authors.affiliation: Universite Catholique de Louvain, Louvain Drug Research Institute, Endocannabinoid and Cannabinoid Research Group, Drug Design and Discovery Center, Unite de Chimie Pharmaceutique et de Radiopharmacie, 73-40 Avenue E. Mounier UCL-CMFA (7340), B-1200 Bruxelles, Belgium.
authors.forename: Coco N
authors.initials: CN
authors.lastname: Kapanda
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Geoffray
authors.initials: G
authors.lastname: Labar
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Poupaert
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009584:Nitrogen / Q000737:chemistry; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D004220:Disulfides; D004791:Enzyme Inhibitors; D008994:Monoacylglycerol Lipases; D009584:Nitrogen; D000099252:Fatty Acid Amide Hydrolases