Synthesis and evaluation of phenylcarbamate derivatives as ligands for nicotinic acetylcholine receptors.
Phenylcarbamate derivatives were synthesized and evaluated in radioligand binding assays for different nicotinic acetylcholine receptor (nAChR) subtypes. Carbamate derivatives bearing a pyrrolidine or piperidine moiety 8-20 exhibited much lower affinity for alpha7* nAChR than the analogues in the quinuclidine series 21-25, although the same structural elements are present. Furthermore, in contrast to the quinuclidine analogues 21-25, all (S)-pyrrolidine derivatives 8-12 and the piperidine analogues 15 and 16 exhibited higher affinities for alpha4beta2* nAChR.
Gündisch
Daniela
D
Department of Pharmaceutical Chemistry, Rhein. Friedr.-Wilhelm-University, Kreuzbergweg 26, D-53115 Bonn, Germany. d.guendisch@uni-bonn.de
Andrä
Matthias
M
Munoz
Lenka
L
Cristina Tilotta
Maria
M
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008024:Ligands; D048448:Phenylcarbamates / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013552:Swine; D014101:Torpedo
D008024:Ligands; D048448:Phenylcarbamates; D011978:Receptors, Nicotinic