Collect. Czech. Chem. Commun.
1979, 44, 2139-2155
https://doi.org/10.1135/cccc19792139
Fluorinated neuroleptics of the 10-piperazino-10,11-dihydrodibenzo[b,f]thiepin series; 6-Fluoro derivatives of perathiepin, octoclothepin, doclothepin and some related compounds
Irena Červená, Jiřina Metyšová, Václav Bártl and Miroslav Protiva
Research Institute for Pharmacy and Biochemistry, 130 00 Prague 3
Abstract
The synthesis of a series of 6-fluoro-10-piperazino-10,11-dihydrodibenzo[b,f]thiepins Ic-IIIc, Vc and VIc is described; these compounds are derivatives of the neuroleptic agents perathiepin (Ia), octoclothepin (IIIa), doclothepin (Va) and their hydroxyethyl analogues IIa and VIa in which the metabolic hydroxylation to position 6 was made impossible by blockade. The synthesis used common procedures via the intermediates VII-XVIII. Fluorination in position 6 does not influence much the pharmacological profile of the compounds indicating that hydroxylation in position 6 is only a minor metabolic pathway. The most interesting substance is the 6-fluoro derivative of octoclothepin (IIIc) which is a potent central depressant and neuroleptic agent with some protraction of the sedative effects.
