Synthesis, Chiral Resolution, and Enantiopharmacology of a Potent 2,3-Benzodiazepine Derivative as Noncompetitive AMPA Receptor Antagonist

阅读量：

作者：

Maria，Zappalà，Giovanna，Postorino，Nicola，Micale，Salvatore，Caccamese，Nunziatina，Parrinello

展开

摘要：

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 [Ca2+]i in a primary culture of rat cerebellar granule cells which express α-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.

展开

关键词：

density functional theory QSPRs polymers solubility parameter

DOI：

10.1021/jm050552y

被引量：

年份：

2006