Collect. Czech. Chem. Commun. 1986, 51, 2598-2616

Noncataleptic neuroleptic agents: 4-Substituted 1-(2-chloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazines and related compounds

Miroslav Protiva, Jiří Jílek, Irena Červená, Josef Pomykáček, Václav Bártl, Antonín Dlabač, Martin Valchář, Jiřina Metyšová, Jiří Holubek and Emil Svátek

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


1-(2-Chloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine (VI) was used to prepare a new group of potential noncataleptic neuroleptic agents. Addition of acrylonitrile and acrylamide gave the nitrile VII and the amide X. Further transformations of the nitrile VII led to the phenone VIII and the amidoxime IX. Alkylations of compound VI with 2-(2-chloroethyl)-1,3-dioxolane and 2-(2-chloroethyl)-1,3-dioxane resulted in the cyclic acetals XII and XIII. Several improvements of the synthesis of compound VI are reported. Out of the compounds prepared, the amide X (methanesulfonate VňFB-15 496) proved most interesting: it has low acute toxicity, is noncataleptic and has significantly higher antidopaminergic activity than clozapine.