Chiral 1,4-benzodiazepin-2-ones: relationship between stereochemistry and pharmacological activity.
Pure enantiomers of 3-substituted-1,4-benzodiazepin-2-ones, obtained by HPLC resolution on chiral stationary phases, show significant differences in their pharmacological activity. The occurrence of biotransformation during the pharmacological test is monitored using a new chromatographic method. The reliability of the pharmacological activity data is discussed.
Salvadori
P
P
Centro di Studio del CNR per le Macromolecole Stereordinate Otticamente Attive, Dipartimento di Chimica e Chimica Industriale, Pisa, Italy.
Bertucci
C
C
Domenici
E
E
Giannaccini
G
G
D000818:Animals; D001570:Benzodiazepinones / Q000737:chemistry* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002942:Circular Dichroism; D005445:Flunitrazepam / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D008968:Molecular Conformation; D011963:Receptors, GABA-A / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D005445:Flunitrazepam