Referenced in: none

Automatically associated channels: Kir2.3

Title: Synthesis, chiral resolution, and enantiopharmacology of a potent 2,3-benzodiazepine derivative as noncompetitive AMPA receptor antagonist.

Authors: Maria Zappalà, Giovanna Postorino, Nicola Micale, Salvatore Caccamese, Nunziatina Parrinello, Giovanni Grazioso, Gabriella Roda, Frank S Menniti, Giovambattista De Sarro, Silvana Grasso

Journal, date & volume: J. Med. Chem., 2006 Jan 26 , 49, 575-81

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16420043

Abstract
This paper describes the synthesis of racemic 3,5-dihydro-5-methyl-7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one (+/-)-5, attempted stereoselective synthesis of its enantiomers, chiral HPLC resolution of the racemate, and assignment of the absolute configuration. Enantiomer (5S)-(-)-5 is provided with an in vivo anticonvulsant activity 8 times higher than its enantiomer (5R)-(+)-5. This result is confirmed in the in vitro test by the ability to inhibit the kainate-induced increase of the [Ca(2+)](i) in a primary culture of rat cerebellar granule cells which express alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. Binding affinity of compound (+/-)-5 at the AMPA and N-methyl-d-aspartic acid (NMDA) receptors was also evaluated.