TY - JOUR
T1 - Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists--structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC)
AU - Hansen, Camilla Petrycer
AU - Jensen, Anders Asbjørn
AU - Balle, Thomas
AU - Bitsch-Jensen, Klaus
AU - Hassan, Mohamud M
AU - Liljefors, Tommy
AU - Frølund, Bente
N1 - Keywords: Carbachol; Carbamoylcholine (CCh); Carbamates; Humans; Nicotinic Agonists; Protein Binding; Receptors, Nicotinic; Structure-Activity Relationship;
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.bmcl.2008.11.011
DO - 10.1016/j.bmcl.2008.11.011
M3 - Journal article
C2 - 19027295
SN - 0960-894X
VL - 19
SP - 87
EP - 91
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
IS - 1
ER -