Document Report Card

ID: ALA1132318

Journal: J Med Chem

Title: Hydroxylated decahydroquinolines as ligands for the vesicular acetylcholine transporter: synthesis and biological evaluation.

Authors: Efange SM, Khare AB, Mach RH, Parsons SM.

Abstract: Analogues of the potent anticholinergic 2-(4-phenylpiperidino)cyclohexanol (vesamicol, 1) in which the cyclohexyl fragment was replaced with an N-acyl or N-alkyl trans-decahydroquinolyl moiety were synthesized and evaluated as potential ligands for the vesicular acetylcholine transporter (VAChT). The binding of compounds, such as 18, 20, and 21, was both stereospecific and of comparable magnitude to that of the closely related vesamicol analogue 2,3-trans-4a, 8a-trans-3-hydroxy-2-(4-phenylpiperidino)-1,2,3,4,5,6,7, 8-decahydronaphthalene (6) which displays subnanomolar affinity for this transporter. However, these compounds also demonstrated high affinities for sigma(1) and sigma(2) receptors and thus failed to show significantly improved selectivity over previously reported vesamicol analogues.

CiteXplore: 10425095

DOI: 10.1021/jm980560x