Synthesis of bridged analogues of the antidepressant drug tianeptine. Representatives of a new ring system

In continuation of our efforts to synthesize new analogues of antidepressant drug tianeptine, we have incorporated a two-carbon bridge between the two nitrogen atoms of the 11-amino-dibenzo[c,f][1,2] thiazepine core structure of the tricyclic parent compound, resulting in a new tetracyclic ring system closely related to tianeptine. The synthetic route leading to the tetracyclic ring system is suitable for the introduction of various substituents to the amine-type nitrogen. The pharmacophore moiety charac-teristic of tianeptine has been introduced into the new tetracyclic molecule with two different methods. Altogether 32 new compounds are described in the present manuscript, 3 of them are also characterized by single-crystal X-ray diffraction.(c) 2023 Elsevier Ltd. All rights reserved.