Collect. Czech. Chem. Commun. 1984, 49, 1800-1809

11-(4-Piperidylidene)-6,11-dihydrodibenzo[b,e]thiepins as potential antipsychotic agents; Synthesis and pharmacology

Václav Bártl, Antonín Dlabač, Martin Valchář and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


The secondary amine VIIIb, prepared by demethylation of 2-chloro-11-(1-methyl-4-piperidylidene)-6,11-dihydrodibenzo[b,e]thiepin (IVb), afforded by alkylation with 2-bromoethanol the amino alcohol Vb which was esterified to the decanoate VIb. A reaction of 5-fluorophthalide with the sodium salt of 4-chlorothiophenol in boiling 1-butanol gave the acid X which afforded by cyclization 2-chloro-8-fluorodibenzo[b,e]thiepin-11(6H)-one (XII). Treatment with 1-methyl-4-piperidylmagnesium chloride resulted in the tertiary alcohol IXc which was transformed by an acid catalyzed dehydration to the desired unsaturated amine IVc. While compounds Vb and IVc showed properties of mild tranquillizers, the ester VIb, surprisingly, brought about a mild dopaminomimetic activity (it potentiates the action of apomorphine, has anticataleptic activity and lowers the homovanillic acid level in the striatum of rat brain.