Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists--structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC).
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.
Hansen
Camilla P
CP
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Copenhagen University, Copenhagen Ø, Denmark.
Jensen
Anders A
AA
Balle
Thomas
T
Bitsch-Jensen
Klaus
K
Hassan
Mohamud M
MM
Liljefors
Tommy
T
Frølund
Bente
B
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
D002219:Carbamates; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D002217:Carbachol