Collect. Czech. Chem. Commun. 1986, 51, 156-166

Potential noncataleptic neuroleptic agents; 2,6-Dichloro-, 2,7-dichloro- and 2,8-dichloro-10-piperazino-10,11-dihydrodibenzo[b,f]thiepins

Miroslav Protiva, Antonín Dlabač, Martin Valchář, Stanislav Wildt, Irena Červená and Zdeněk Šedivý

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Substitution reactions of 2,6,10-trichloro-, 2,7,10-trichloro- and 2,8,10-trichloro-10,11-dihydrodibenzo[b,f]thiepin (Vabc) with 1-(2-hydroxyethyl)piperazine, 1-methylpiperazine and 1-benzylpiperazine gave the title compounds IIabc, IIIab and IVab. The new chloro compounds Va and Vb were obtained in 6 steps starting from reactions of 2,5-dichloroacetophenone with 2-chlorothiophenol or 3-chlorothiophenol. Compounds IIabc are 6-chloro, 7-chloro and 8-chloro derivatives of the noncataleptic neuroleptic agent docloxythepin (I). They are almost devoid of cataleptic activity and do not inhibit the apomorphine stereotypies in rats. Compounds IIab have a clozapine-like affinity to dopaminergic receptors in the rat brain striatum; the affinity of IIc is much higher. On the other hand only compounds IIb and IIIa prove a significant antidopaminergic activity in vivo (increase significantly the homovanillic acid level in the rat brain striatum).