Studies on specific inhibition of benzodiazepine receptor binding by some C-benzoyl-1,2,3-triazole derivatives.
Certain new (1-15) or previously described (16-25) 1,2,3-triazole derivatives, characterized by a C-benzoyl substituent, were synthesized and tested for their ability to displace [3H]flunitrazepam from bovine brain membrane. Compounds 11a and 9a, bearing neutral and lipophilic substituents (phenethyl and cyclohexyl, respectively) showed the higher activity. The 5-benzoyl isomer 11b presented a lower activity, equivalent to that of the triazole acetic derivative 23, which is 4-benzyl substituted. Generally, the carboxymethyl radical in the 1-position of the triazole ring decreased the activity, probably because of intramolecular hydrogen bonding with the carbonyl function of the benzoyl substituent. The N-1 unsubstituted triazole derivatives 24 and 25 were ineffective; this result is in disagreement with our previous observations. Probably these molecules interact with the receptor site by a hydrogen bonding acceptor group and by a bulky and lipophilic portion or a hydrogen bonding donor function that is appropriately arranged.
Biagi
G
G
Istituto di Chimica Farmaceutica e Tossicologica, Facoltà di Farmacia, Università di Pisa, Italy.
Giorgi
I
I
Livi
O
O
Lucacchini
A
A
Martini
C
C
Scartoni
V
V
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005445:Flunitrazepam / Q000493:pharmacokinetics; D058787:GABA-A Receptor Antagonists; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D011963:Receptors, GABA-A / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D014230:Triazoles; D005445:Flunitrazepam