Enantiomerically pure 1,3-dioxanes as highly selective NMDA and σ1 receptor ligands

Köhler J., Bergander K., Fabian J., Schepmann D., Wünsch B.

Abstract

We synthesized and investigated the NMDA and σ1 receptor affinity of enantiomerically pure 2-(2-phenyl-1,3-dioxan-4-yl)ethanamines 17-26. The primary amines (R,R)-18-20 with an axially oriented phenyl moiety in position 2 interacted with high enantioselectivity (eudismic ratios 70-130) and high affinity (Ki((R,R)-19) = 13 nM) with the PCP binding site of the NMDA receptor. Introduction of an N-benzyl moiety led to potent σ1 ligands including compound (S,R)-22 (Ki = 6 nM) with an equatorially oriented phenyl moiety in position 2. © 2012 American Chemical Society.