Referenced in: none

Automatically associated channels: Kv11.1

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

Authors: Andreas Müller, Georg Höfner, Thejavathi Renukappa-Gutke, Chris G Parsons, Klaus T Wanner

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Oct 1 , 21, 5795-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21875803

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 [1S,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.