Potential hypnotics and anxiolytics: 8-Chloro-6-(2-chlorophenyl)-1-[4-(2-methoxyethyl)piperazino]-methyl-4H-s-triazolo[4,3-a]-1,4-benzodiazepine and related compounds

Abstract

Ethyl esters of 4-substituted piperazinoacetic acids IIIa-f were prepared by alkylation of 1-(ethoxycarbonylmethyl)piperazine with 2-methoxyethyl bromide, 2-ethoxyethyl bromide, 2-methylthioethyl chloride, 2-phenoxyethyl bromide and 2-phenylthioethyl bromide or by reactions of 1-(3-methoxypropyl)piperazine and 1-(2-methylthioethyl)piperazine with ethyl chloroacetate. Reactions of the esters with hydrazine hydrate gave the hydrazides IVa-f. Their treatment with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-thione resulted in the title compound Ia and analogues Ib-f. 1-(4-Methylpiperazinomethyl) derivatives Ig and IIg were similarly prepared from 4-methylpiperazinoacetic acid hydrazide (IVg). Compound Ig showed significant central depressant and anticonvulsant (electroshock) activity in mice. The enlargement of the substituent in position 4 of the piperazine residue results in an important decrease of these activities.