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Synthesis and Biological Evaluation of 5H-Indolo [3,2-b][1,5]Benzothiazepine Derivatives, Designed as Conformationally Constrained Analogues of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitor L-737,126:

Synthesis and Biological Evaluation of 5H-Indolo [3,2-b][1,5]Benzothiazepine Derivatives,... In the presence of sodium hydride, reaction of aryldisulphides with ethyl esters of indole-2-carboxylic acids furnished ethyl 3-arylthioindole-2-carboxy-lates, which were cyclized intramolecularly to afford 5H-indolo[3,2-b][1,5]benzothiazepin-6(7H)-ones or hydrolysed in alkaline medium to give 3-arylthioindole-2-carboxylic acids. These acids, also obtained by the action of aryldisulphides on indole-2-carboxylic acids, afforded tetracyclic 5H-indolo [3,2-b][1,5]benzothiazepin-6(7H)-ones upon treatment with EDCI–DMAP. Transformation of cyclic sulphides into the required sulphones was achieved by treatment with hydrogen peroxide or with m-chloroperbenzoic acid. The title derivatives are conformationally constrained analogues of the potent human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor 3-benzene-sulphonyl-5-chloroindole-2-carboxamide (L-737, 126). Although the indolobenzothiazepine derivatives, as well as the indolyl aryl sulphones used for their synthesis, were endowed with anti-HIV-1 activities in the submicromolar and micromolar range, none of them proved more potent than L-737,126. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Antiviral Chemistry and Chemotherapy SAGE

Synthesis and Biological Evaluation of 5H-Indolo [3,2-b][1,5]Benzothiazepine Derivatives, Designed as Conformationally Constrained Analogues of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitor L-737,126:

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Publisher
SAGE
Copyright
Copyright © 2019 by SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses
ISSN
2040-2066
eISSN
2040-2066
DOI
10.1177/095632029800900205
Publisher site
See Article on Publisher Site

Abstract

In the presence of sodium hydride, reaction of aryldisulphides with ethyl esters of indole-2-carboxylic acids furnished ethyl 3-arylthioindole-2-carboxy-lates, which were cyclized intramolecularly to afford 5H-indolo[3,2-b][1,5]benzothiazepin-6(7H)-ones or hydrolysed in alkaline medium to give 3-arylthioindole-2-carboxylic acids. These acids, also obtained by the action of aryldisulphides on indole-2-carboxylic acids, afforded tetracyclic 5H-indolo [3,2-b][1,5]benzothiazepin-6(7H)-ones upon treatment with EDCI–DMAP. Transformation of cyclic sulphides into the required sulphones was achieved by treatment with hydrogen peroxide or with m-chloroperbenzoic acid. The title derivatives are conformationally constrained analogues of the potent human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor 3-benzene-sulphonyl-5-chloroindole-2-carboxamide (L-737, 126). Although the indolobenzothiazepine derivatives, as well as the indolyl aryl sulphones used for their synthesis, were endowed with anti-HIV-1 activities in the submicromolar and micromolar range, none of them proved more potent than L-737,126.

Journal

Antiviral Chemistry and ChemotherapySAGE

Published: Nov 28, 2016

Keywords: Anti-HIV agents,NNRTIs,5H-indolo [3,2-b][1,5]benzothiazepine derivatives

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