Collect. Czech. Chem. Commun.
1989, 54, 3294-3338
https://doi.org/10.1135/cccc19893294
Potential antidepressants: 2-(Methoxy- and hydroxyphenylthio)benzylamines as selective inhibitors of 5-hydroxytryptamine re-uptake in the brain
Jiří Jílek, Karel Šindelář, Josef Pomykáček, Vojtěch Kmoníček, Zdeněk Šedivý, Marta Hrubantová, Jiří Holubek, Emil Svátek, Miroslav Ryska, Ivan Koruna, Martin Valchář, Antonín Dlabač, Jiřina Metyšová, Nataša Dlohožková and Miroslav Protiva
Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3
Abstract
2-, 3- and 4Methoxythiophenol, and 2,4-, 2,5- and 3,4-dimethoxythiophenol were transformed in two steps to the corresponding 2-(methoxyphenylthio)benzoyl chlorides XIII which were reacted with ammonia, methylamine, diethylamine, dipropylamine, and di(2-propyl)amine to give the amides XIV-XIX. These were reduced mostly with lithium aluminium hydride to the amines II-VII. These methoxylated amines were demethylated mostly either by heating with pyridine hydrochloride or by treatment with boron tribromide. Some of the 2-(methoxy- and hydroxy-phenylthio)benzylamines prepared, especially compounds II, III, XXI, and XXII, indicated properties of potential antidepressants being highly active and selective inhibitors of 5-hydroxytryptamine re-uptake in the brain structures and having the typical antireserpine activity. The most interesting compound of the series is XXIb (hydrogen maleate VUFB-15 468) which is undergoing preclinical studies. On the basis of its structure, some further compounds (XXVII–XXIX, XXXIX-XLI) were prepared by various methods.
