Specific inhibition of binding to benzodiazepine receptors by 1,2,3-triazole derivatives.
Certain 1,2,3-triazole derivatives were prepared and tested for their ability to displace [3H]diazepam that was bound to bovine brain membrane protein. All the tested compounds are essentially lacking in this ability, except for B.1, which inhibited binding of [3H]diazepam in 50% of the trials at 2.5 microM. The structure of B.1, with a 1,2,3-triazole ring with acidic properties, supports the hypothesis proposed for binding to the benzodiazepine receptor site. Comparison of B.1 with 1,2,3-triazole derivatives bearing a bicyclic substituent in position 1 of the heterocyclic ring suggests that a high steric hindrance increases the affinity of a compound for the benzodiazepine receptor.
Biagi
G
G
Istituto di Chimica Farmaceutica e Tossicologica, Facoltà di Farmacia, Università di Pisa, Italy.
Livi
O
O
Lucacchini
A
A
Martini
C
C
Scartoni
V
V
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D066298:In Vitro Techniques; D011485:Protein Binding / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D014230:Triazoles; C028513:4'-chlorodiazepam; D003975:Diazepam