Oxo-bridged isomers of aza-trishomocubane sigma (sigma) receptor ligands: Synthesis, in vitro binding, and molecular modeling.

Isomeric oxo-bridged analogs of aza-trishomocubane sigma (sigma) receptor ligands were synthesized and shown to display a reduced affinity for the sigma receptor. In the case of phenethyl derivative 4, there was a concomitant introduction of high-affinity for the alpha(2C) adrenergic receptor, and moderate affinity for the dopamine transporter. Molecular modeling was undertaken to rationalize these results. Copyright 2009 Elsevier Ltd. All rights reserved.