Potential antidepressants: 3-Aryl-3-(arylthio)propylamines as selective inhibitors of 5-hydroxytryptamine re-uptake in the brain

4-(Trifluoromethyl)thiophenol, 2-methylthiophenol, 2-methoxythiophenol, and 1-naphthalenethiol were transformed by reactions with N,N-dimethyl-3-chloro-3-phenylpropylamine to N,N-dimethyl-3-aryl-3-(arylthio)propylamines IVa-VIIa. These afforded the secondary amines IVb-VIIb by treatment with ethyl chloroformate and by the following hydrolysis and decarboxylation of the primarily formed N-(methyl)-N-(ethoxycarbonyl) analogues. Reaction of 1-naphthalenethiol with the 4-toluenesulfonic ester X in situ gave the thiophene analogue VIIIa which was similarly demethylated to VIIIb. Some of the prepared compounds (IVa, IVb, Va, VIIIa)were found to be selective inhibitors of 5-hydroxytryptamine re-uptake in the rat brain synaptosomes which indicates their potential antidepressant activity.