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Synthesis 2022; 54(17): 3874-3882
DOI: 10.1055/s-0040-1719885
special topic
Special Issue in memory of Prof. Ferenc Fülöp

Towards Tianeptine Analogues: Synthesis of New Ring Systems Containing a Dibenzo[c,f][1,2]thiazepine S,S-Dioxide Core

Gábor Berecz
a   Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, 1475 Budapest, Hungary
,
András Dancsó
a   Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, 1475 Budapest, Hungary
,
Dóra R. Németh
a   Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, 1475 Budapest, Hungary
,
Loránd Kiss 
b   Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary
,
Gyula Simig 
a   Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, 1475 Budapest, Hungary
,
Balázs Volk  ∗
a   Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, 1475 Budapest, Hungary
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Dedicated to the memory of the late Professor Ferenc Fülöp (1952–2021)

Abstract

In the course of the synthesis of fused-ring analogues of the antidepressant drug tianeptine, representatives of three new heterocyclic ring systems, indolo[1,7-bc][1,2]benzothiazepines (and their 4,5-dihydro analogues), 5,6-dihydroquino[1,8-bc][1,2]benzothiazepines, and [1,2]benzothiazepino[4,3,2-jk]carbazoles, as well as their intermediates, have been prepared. The tetracyclic and pentacyclic ring systems containing either an oxo or a hydroxy functional group are suitable for introducing various side chains, including potential pharmacophores. For this latter transformation, examples are demonstrated by conversion of the hydroxy group into a chloro moiety and subsequent reaction with amines or with primary alcohols bearing a tertiary amino side chain. Two fused-ring derivatives exhibiting the side-chain characteristics of tianeptine have also been synthesized. Altogether 40 compounds are described in the present manuscript, eight of them are also characterized by single-crystal X-ray diffraction.

Key words

sulfonamides - ester hydrolysis - ring closure - new ring systems - intramolecular Friedel–Crafts acylation - rearrangement

Supporting Information



Publication History

Received: 15 October 2021

Accepted: 17 December 2021

Article published online:
07 February 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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