Fluorinated tricyclic neuroleptics: Synthesis and pharmacology of 8-fluoro-4-(4-methylpiperazino)-4,5-dihydrothieno[2,3-b]-1-benzothiepin

Abstract

A reaction of (4-fluoro-2-iodophenyl)acetic acid with 2-thiophenethiol gave the acid V which was cyclized to 8-fluorothieno[2,3-b]-1-benzothiepin-4(5H)-one (VII); two further steps led to 4-chloro-8-fluoro-4,5-dihydrothieno[2,3-b]-1-benzothiepin (IX). A substitution reaction with 1-methylpiperazine resulted in the title compound which showed a very strong central depressant and cataleptic activity, being at the same time almost inactive in the test of inhibition of apomorphine stereotypies in rats. Ethyl 2-amino-5-ethylthiopene-3-carboxylate (X) was transformed by multi-step procedures to the acids XV, XIX and XXVI out of which only the first one could be cyclized to a tricyclic ketone, i.e. 2-ethyldithieno[2,3-b; 3',2'-e]thiopyran-4-one (XX).