Neuroleptics of the 8-methylthio-10-piperazino-10,11-dihydrodibenzo[b,f]thiepin series: New compounds and new procedures

Abstract

Heating of 8-methylthiodibenzo[b,f]thiepin-10(11H)-one with mono-p-toluenesulfonates of 1-methylpiperazine and piperazine in vacuo led in good yields to the enamines IX-XI, the first of which was reduced with zinc and acetic acid to the base I (methiothepin). The ester III(oxyprothepindecanoate) was obtained by reaction of the amino alcohol II (oxyprothepin) with decanoic acid in the presence of N,N'-carbonyldiimidazole and by substitution of 10-chloro-8-methylthio-10,11-dihydrobenzo[b,f]thiepin with 1-(3-decanoyloxypropyl)piperazine. The substitution reaction of the same chloro compound with piperazine gave two stereoisomeric 1,4-disubstituted piperazines V. Reaction of the amino alcohol II with octyl isocyanate afforded the carbamate VI, an isoster of oxyprothepin decanoate (III). This substance showed in the test of antiapomorphine activity in dogs the properties of a long-acting antiemetic. Two new potential metabolites (XII, XIII) of compounds I-III were synthesized and new pharmacological data are given for two further potential metabolites (XIV, XV) of oxyprothepin (II).