Synthesis, receptor affinity and effect on pentylenetetrazole-induced seizure threshold of novel benzodiazepine analogues: 3-Substituted 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles and 2-amino-5-(phenoxybenzyl)-1,3,4-oxadiazoles

The new series of 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles, possessing C-3 thio, alkylthio and ethoxy substituents, and 2-amino-5-(2-phenoxybenzyl)-1,3,4-oxadiazoles were designed and synthesized as novel benzodiazepine analogues. Most of them revealed similar to superior binding affinity to the GABAA/benzodiazepine receptor complex, relative to diazepam as the reference drug. Among them, 5-(4-chloro-2-(2-fluorophenoxy)benzyl)-3-benzylthio-4H-1,2,4-triazole (8l) showed the highest affinity (IC50 = 0.892 nM) relative to diazepam (IC50 = 2.857 nM) and also showed the most increase in pentylenetetrazole-induced seizure threshold relative to diazepam as the reference drug.

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