Abstract

Background: Triazolobenzodiazepinones, i.e. 2,3-benzodiazepines condensed with a triazolone ring, exhibited significant anticonvulsant activity in vivo. In this paper, their new pyrrole bioisosteres, 2,11-dihydro-3H-pyrrolo[1,2-e][1,2,4] triazolo[4,3-b][1,2,5]triazepin-3-ones were synthesized.

Methods: Starting from the corresponding bicyclic hydrazino intermediates, final ring closure of the triazolone ring has been attempted with several reagents under various conditions. Among these, only triphosgene provided the tricyclic title compounds.

Results: Six representatives of the title new ring system were synthesized. The structure of the new scaffold was determined by single crystal X-ray measurement as well as 1H and 13C NMR spectra.

Conclusions: Starting from 1-aryl-4-hydrazino-5H-pyrrolo[2,1-d][1,2,5]triazepines (15), representatives of a new tricyclic compound family, 6-aryl-2,11-dihydro-3H-pyrrolo[1,2-e][1,2,4]triazolo[4,3-b][1,2,5] triazepin-3-ones (17) have been synthesised. These compounds are pyrrole bioisosteres of 6-aryl-2,11- dihydro-3H-[1,2,4]triazolo[4,3-c][2,3] benzodiazepine-3-ones (8), a family exhibiting an outstanding in vivo anticonvulsant activity in mice.

Keywords: Acylation, carbonylation, heterocycles, pyrrolotriazepines, triphosgene, X-ray structure.

Graphical Abstract