Collect. Czech. Chem. Commun. 1985, 50, 1070-1077

Cataleptic and noncataleptic neuroleptic agents: Synthesis and pharmacology of 4-(2-chloro and 8-chloro substituted 10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine-1-ylalkyl ethers and sulfides

Vladimír Valenta, Zdeněk Prošek, Jiřina Metyšová, Martin Valchář, Antonín Dlabač and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


The title compounds Iab-Viab were prepared by substitution reactions of 2,11-dichloro- and 2,10-dichloro-10,11-dihydrodibenzo[b,f]thiepin with 1-(2-methoxyethyl)piperazine, 1-(3-methoxypropyl)piperazine, 1-(2-ethoxyethyl)piperazine, 1-(2-phenoxyethyl)piperazine, 1-(2-methylthioethyl)piperazine and 1-(2-phenylthioethyl)piperazine; they were transformed to hydrochlorides, maleates or methanesulfonates. Compounds of series a (8-chloro derivatives) are neuroleptics, with relatively strong cataleptic, antiapomorphine and central depressant activities (Ia, IIa, IIIa,Va) unless the volume and lipophilicity of the N-substituent exceeds certain limits (IVa and VIa are almost nontoxic and little active). Compounds of series b (2-chloro derivatives) are noncataleptic and devoid of the antiapomorphine potency; only two of them (IIb, Vb), however, showed a more pronounced effect in the test of influencing the turnover and metabolism of dopamine in the rat brain striatum.