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), 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.
2,3-benzodiazepin-4-one; Absolute configuration; Ampar; Binding assays; Chiral HPLC
Settore CHIM/08 - Chimica Farmaceutica
Article (author)
File in questo prodotto:
File Dimensione Formato  
Calabr-_et_al-2009-ChemMedChem.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 358.54 kB
Formato Adobe PDF
358.54 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/145815
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 56
social impact