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 α4β2, α3β4, α4β4 and α7 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 α3β4 nAChR.

Graphical abstractDesign and synthesis of a new series of DMABC analogs are presented together with the pharmacological profiles at the α4β2, α4β4 and α3β4 nAChRs and the α7/5-HT3A receptor chimera.Figure optionsDownload full-size imageDownload as PowerPoint slide