Synthesis of a series of γ-amino alcohols comprising an N-methyl isoindoline moiety and their evaluation as NMDA receptor antagonists.

Abstract We report a series of new stereoisomeric γ- amino alcohols comprising an N -methyl isoindoline moiety as ligands for the ifenprodil binding site of the NMDA receptor. Among the four series of stereoisomers, 8a – c , 9a – c , 10a – c , and 11a – c , synthesised, the highest potencies and NMDA-NR2B subtype selectivity was found for the methyl derivative 11a and the chloro derivative 11c , both possessing the [1 S ,1′ S ] configuration. However, additional moderate potency of 11a and 11c at the hERG channel with values of 2.6 ± 2.4% and 1.6 ± 2.0%, respectively, rendered them unsuitable for medical use.