Collect. Czech. Chem. Commun.
1989, 54, 235-247
https://doi.org/10.1135/cccc19890235
Potential antidepressants: Saturated side chain amines derived from 6,11-dihydrodibenzo[b,e]thiepin and 4,9-dihydrothieno[2,3-c]-2-benzothiepin
Zdeněk Polívkaa, Vladimír Valentaa, Karel Šindelářa, Jiří Holubeka, Miloš Buděšínskýb, Miroslav Ryskaa, Ivan Korunaa, Jitka Kohoutováb, Jan Metyša, Jiřina Metyšováa, Martin Valchářa and Miroslav Protivaa
a Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3
b Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6
Abstract
Reduction of IV with hydroiodic acid afforded almost quantitatively the spirocyclic amino sulfide VII, evidently via V and VI. The carbamate II was chlorinated with N-chlorosuccinimide, the product (XII) was reacted with phenylmagnesium bromide and then reduced with LiAlH4 to give the 6-phenyl derivative X of the antidepressant agent hydrothiadene (I). Treatment of 11-methyl-6,11-dihydrodibenzo[b,e]thiepin (XIII) with butyllithium followed by alkylation with 3-dimethylaminopropyl chloride resulted in 6-(3-dimethylaminopropyl) derivative XIV. Reaction of XIV with ethyl chloroformate and the following alkaline hydrolysis gave the 6-(3-methylaminopropyl) derivative XV (mixture of stereoisomers). Reduction of the corresponding olefinic amine and the tertiary alcohol with hydroiodic acid gave the saturated side chain amines derived from 4,9-dihydrothieno[2,3-c]-2-benzothiepin XVIII and XIX. The dihydro derivative of dithiadene XVIII (VÚFB-17 031) proved very effective in a series of tests predictive of antidepressant activity.
