The resolution of 1-(4-aminophenyl)-3,5-dihydro-3-N-ethylcarbamoyl-5- methyl-7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one (R,S)-(±)-5 by chiral HPLC and assignment of the absolute configuration of the two enantiomers was carried out. Compound (R,S)-(±)-5 and its enantiomers were tested in a binding assay to evaluate their affinity for AMPA receptors. Enantiomer (S)-(-)-5 appears to be more potent than its optical antipode (R)-(+)-5. In a primary culture of rat cerebellar granule cells, which express AMPA receptors, (R,S)-(±)-5 and (S)-(-)-5 inhibited kainate-induced [Ca 2+]i increase, thus confirming the antagonism at the AMPA receptor.
Synthesis, chiral resolution and pharmacological evaluation of a 2,3-benzodiazepine-derived noncompetitive AMPA receptor antagonist / M.L. Calabrò, D. Raneri, P. Ficarra, T. Mennini, S. Colleoni, G. Grazioso, N. Micale, M. Zappalà, S. Grasso. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 4:3(2009 Mar 16), pp. 415-420. [10.1002/cmdc.200800341]
Synthesis, chiral resolution and pharmacological evaluation of a 2,3-benzodiazepine-derived noncompetitive AMPA receptor antagonist
S. Colleoni;G. Grazioso;
2009
Abstract
The resolution of 1-(4-aminophenyl)-3,5-dihydro-3-N-ethylcarbamoyl-5- methyl-7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one (R,S)-(±)-5 by chiral HPLC and assignment of the absolute configuration of the two enantiomers was carried out. Compound (R,S)-(±)-5 and its enantiomers were tested in a binding assay to evaluate their affinity for AMPA receptors. Enantiomer (S)-(-)-5 appears to be more potent than its optical antipode (R)-(+)-5. In a primary culture of rat cerebellar granule cells, which express AMPA receptors, (R,S)-(±)-5 and (S)-(-)-5 inhibited kainate-induced [Ca 2+]i increase, thus confirming the antagonism at the AMPA receptor.File | Dimensione | Formato | |
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