HPLC resolution of C5 chiral 4,5-dihydro-1,4-benzodiazepines: stereochemical characterization and enantioselective GABAA receptor binding.
HPLC resolution on chiral stationary phases has been successfully employed to obtain single enantiomers of C5 chiral 4,5-dihydro-1,4-benzodiazepines and to determine the enantiomeric composition of the collected stereoisomeric fractions. The absolute configuration of the prevailing enantiomer has been assigned on the basis of the circular dichroism spectra, as compared with that of the structural analogue (5R)- and (5S)-dihydrodiazepam. The single enantiomers, assayed for their binding to the central nervous system receptor, showed relatively low affinity but significant differences in displacing radioactively labelled flunitrazepam from specific benzodiazepine site. GABA shift experiments allowed the classification of these benzodiazepines as partial agonist or antagonist.
Bertucci
C
C
Centro Studio CNR Macromolecole Stereordinate Otticamente Attive, Dipartimento di Chimica e Chimica Industriale, Pisa, Italy.
Demuro
A
A
Giannaccini
G
G
D001569:Benzodiazepines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D008968:Molecular Conformation; D011963:Receptors, GABA-A / Q000737:chemistry*; D013237:Stereoisomerism
D011963:Receptors, GABA-A; D001569:Benzodiazepines