title: Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists--structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC).
abstract: Compounds based on the 3-(dimethylamino)butyl dimethylcarbamate (DMABC) scaffold were synthesized and pharmacologically characterized at the alpha(4)beta(2), alpha(3)beta(4,) alpha(4)beta(4) and alpha(7) neuronal nicotinic acetylcholine receptors (nAChRs). The carbamate functionality and a small hydrophobic substituent in the C-3 position were found to be vital for the binding affinity to the nAChRs, whereas the carbamate nitrogen substituents were important for nAChR subtype selectivity. Finally, the compounds were found to be agonists at the alpha(3)beta(4) nAChR.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Copenhagen University, Copenhagen Ø, Denmark.
authors.forename: Camilla P
authors.initials: CP
authors.lastname: Hansen
authors.forename: Anders A
authors.initials: AA
authors.lastname: Jensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Balle
authors.forename: Klaus
authors.initials: K
authors.lastname: Bitsch-Jensen
authors.forename: Mohamud M
authors.initials: MM
authors.lastname: Hassan
authors.forename: Tommy
authors.initials: T
authors.lastname: Liljefors
authors.forename: Bente
authors.initials: B
authors.lastname: Frølund
mesh_terms: D002217:Carbachol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry*; D006801:Humans; D018722:Nicotinic Agonists / Q000138:chemical synthesis*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D002217:Carbachol