Collect. Czech. Chem. Commun. 1988, 53, 340-360

Aminoalkylidene and aminoalkyl derivatives of 6,11-dihydrodibenzo[b,e]thiepin-2- and -9-carbonitrile and 4,10-dihydrothieno[2,3-c]-1-benzothiepin-6-carbonitrile; Antidepressants with a new activity profile

Karel Šindelář, Jiří Holubek, Oluše Matoušová, Emil Svátek, Martin Valchář, Antonín Dlabač, Nataša Dlohožková, Marta Hrubantová and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Starting from the bromo ketones VIIc, XIII, and XXIV and proceeding via the alcohols VIIIc, IXc, XIV, XVII, and XXVI, the olefinic compounds IIc (+ VI), Xc (+XI), XVc and XIXc(+XXc), and the saturated compound XVIc were prepared. The pairs of geometrical isomers were separated by crystallization of salts and the individual compounds Iic, Xc, XVc, XVIc, XIXc, and XXc were transformed by treatment with cuprous cyanide in hexamethylphosphoric triamide to the corresponding cyano compounds IIb, Xb, XVb, XVIb, XIXb, and XXb. Compound IIb was synthesized also from the ketone VIIc via the cyano ketone VIIb and the cyano carbinol VIIIb. The secondary amine IIIb was prepared from IIc by partial demethylation with ethyl chloroformate, the following hydrolysis to IIIc, protection of NH group with butyrolactone, the following treatment with cuprous cyanide, and deprotection by mild hydrolysis. The title compounds, which are the cyano analogues of antidepressants of the prothiadene series, showed in pharmacological and biochemical tests properties of potential antidepressants and more or less selective inhibitors of the 5-hydroxytryptamine uptake in the rat brain; at the same time they are rather strong central cholinolytics.