Collect. Czech. Chem. Commun. 1989, 54, 1995-2008

Potential antidepressants: 2-(Phenylthio)aralkylamines

Jiří Jílek, Jiří Urban, Petr Taufmann, Jiří Holubek, Antonín Dlabač, Martin Valchář and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Reactions of 2-(phenylthio)benzyl chloride with dimethylamine, diethylamine, pyrrolidine, piperidine, morpholine, and 1-methylpiperazine afforded the title compounds VI-XI. Reaction of 2-(phenylthio)benzaldehyde with nitromethane gave the nitrostyrene XIV which was reduced with lithium aluminium hydride to 2-(2-(phenylthio)phenyl)ethylamine (XVI). This was transformed to the N-methyl and N,N-dimethyl derivatives XVIII and XIX. The Claisen reaction of (2-(phenylthio)phenyl)acetonitrile with ethyl acetate afforded compound XXI which was cleaved by phosphoric acid to (2-(phenylthio)phenyl)acetone (XX). The Leuckart-Wallach reaction afforded the formamide XXIII which was used as starting material for preparing the amines XXIV-XXVI. The alternative approach to these compounds starting by reaction of the aldehyde XII with nitroethane was complicated by the fact that in addition to the nitropropene XV 2-(phenylthio)benzonitrile was also formed. The synthetic use of the inhomogeneous XV resulted then in mixtures of amines XXIV-XXVI with IV-VI which was followed by means of mass and 1H NMR spectra. The amines XXIV-XXVI were oxidized to the sulfoxides XXVII-XXIX. The oily bases were transformed to crystalline salts and spectra of all homogeneous bases were recorded. Pharmacological testing showed the amine VI (VÚFB-15 370) to be a promising potential antidepressant. The amines XI and XXV showed also pharmacological profile of potential antidepressants.