Collect. Czech. Chem. Commun.
1991, 56, 449-458
https://doi.org/10.1135/cccc19910449
Potential antidepressants and inhibitors of 5-hydroxytryptamine and noradrenaline re-uptake in the brain: N,N-Dimethyl-(arylthio)thenylamines and N,N-dimethyl-2-(thienylthio)benzylamines
Karel Šindelář, Josef Pomykáček, Martin Valchář, Karel Dobrovský, Jiřina Metyšová and Zdeněk Polívka
Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3
Abstract
3-(3-Methoxyphenylthio)thiophene-2-carboxylic acid (IV) and 2-(3-methoxyphenylthio)thiophene-3-carboxylic acid (VII) were transformed via acid chlorides and dimethylamides to the amines V and VIII which were demethylated to the phenolic amines VI and IX. N,N-Dimethyl-4-bromothiophene-3-carboxamide (XI) was reacted with 3-methoxythiophenol and the amide XII was reduced and demethylated to the amine XIV. 2-(2-Thienylthio)benzoic acid (XVa) and 2-(5-bromo-2-thienylthio)benzoic acid (XVb) were transformed via the isolated acid chlorides and N,N-dimethylamides to the amines XVIIIa and XVIIIb. The amines VI, IX, and XIV are thiophene isosters of moxifetin, the potent inhibitor of 5-hydroxytryptamine re-uptake in the brain structures. Out of the compounds prepared, only the methoxy amine VIII (VUFB-17697) showed a similar type of activity. The intermediate V, the phenolic amine VI, and the hydroxyl group lacking amine XVIIIa are selective inhibitors of noradrenaline re-uptake in the brain.
