Potential antidepressants: 2-(fluoro-, chloro-, bromo- and cyanophenylthio)benzylamines as inhibitors of 5-hydroxytryptamine and noradrenaline re-uptake in brain

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Title:Potential antidepressants: 2-(fluoro-, chloro-, bromo- and cyanophenylthio)benzylamines as inhibitors of 5-hydroxytryptamine and noradrenaline re-uptake in brain
Creators:
Kmoníček, Vojtěch
Pomykáček, Josef
Holoubek, Jiří
Svátek, Emil
Valchář, Martin
Metyšová, Jiřina
Polívka, Zdeněk
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 56, 11, pp. 2468-2481

Abstract

2-, 3- and 4-Fluorothiophenol, 2-, 3- and 4-chlorothiophenol, and 2-bromothiophenol were converted in two steps into the corresponding 2-(halogenphenylthio)benzoyl chlorides <i>IV</i> which afforded amides <i>V</i> and <i>VI</i> by reaction with dimethylamine and N,N,N’-trimethylethylenediamine. The amides were reduced either by lithium aluminium hydride or by diborane to benzylamines <i>Ia-Ig</i> and <i>IIa-IIc</i>. The reaction of 2-chlorobenzaldehyde with 3-bromothiophenol or 4-bromothiophenol afforded aldehydes <i>VIIh</i> and <i>VIIi</i> yielding subsequently benzylamines <i>Ih</i> and <i>Ii</i> by subsequent reducing amination. Cyano analogs <i>Ij</i> and <i>Il</i> were obtained from the bromo derivatives <i>Ig</i> and <i>Ii</i> by their reaction with cuprous cyanide in hexamethylphosphoric triamide. The synthesis of compound <i>Ik</i> was effected via aldehyde acid <i>VIIm</i> affording amino acid <i>Im</i> on reducing amination. The conversion of the latter to amide <i>In</i> and its dehydration yielded nitrile <i>Ik</i>. Some of the compounds synthesized, especially <i>Ic, Id, Ie</i> and <i>If</i>, are efficient and selective inhibitors of re-uptake of 5-hydroxytryptamine in brain structures. The most interesting from this aspect is compound <i>If</i>(hydrochloride VUFB-17649) of this series which was chosen for detailed pharmacological testing.

Title:Potential antidepressants: 2-(fluoro-, chloro-, bromo- and cyanophenylthio)benzylamines as inhibitors of 5-hydroxytryptamine and noradrenaline re-uptake in brain
Creators:
Kmoníček, Vojtěch
Pomykáček, Josef
Holoubek, Jiří
Svátek, Emil
Valchář, Martin
Metyšová, Jiřina
Polívka, Zdeněk
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:56
Number:11
Page Range:pp. 2468-2481
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19912468UNSPECIFIED
ID Code:5178
Item Type:Article
Deposited On:22 Feb 2010 11:32
Last Modified:22 Feb 2010 10:32

Citation

Kmoníček, Vojtěch; Pomykáček, Josef; Holoubek, Jiří; Svátek, Emil; Valchář, Martin; Metyšová, Jiřina; Polívka, Zdeněk (1991) Potential antidepressants: 2-(fluoro-, chloro-, bromo- and cyanophenylthio)benzylamines as inhibitors of 5-hydroxytryptamine and noradrenaline re-uptake in brain. Collection of Czechoslovak Chemical Communications, 56 (11). pp. 2468-2481. ISSN 0010-0765

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