Thiazolo[5,4- f ]quinoxalines, Oxazolo[5,4- f ]quinoxalines and Pyrazino[ b,e ]isatins: Synthesis from 6-Aminoquinoxalines and Properties

Frédéric Lassagne (1) , Joshua M. Sims (2) , William Erb (1) , Olivier Mongin (1) , Nicolas Richy (1) , Nour El Osmani (3) , Ziad Fajloun (3) , Laurent Picot (4) , Valérie Thiéry (4) , Thomas Robert (5, 6, 7) , Stéphane Bach (8, 6, 7) , Vincent Dorcet (1) , Thierry Roisnel (1) , Florence Mongin (1)

1 ISCR - Institut des Sciences Chimiques de Rennes
2 LC - Laboratoire de Chimie - UMR5182
3 Université Libanaise
4 LIENSs - LIttoral ENvironnement et Sociétés
5 APHM - Assistance Publique - Hôpitaux de Marseille
6 FR2424 - Fédération de recherche de Roscoff
7 SBR - Station biologique de Roscoff
8 LBI2M - Laboratoire de Biologie Intégrative des Modèles Marins

The regioselective iodination of different 2-mono-, 3-mono- and 2,3-disubstituted 6-aminoquinoxalines, which takes place at their 5-position, was rationalized on the basis of Hückel theory calculations. Oxazolo- and thiazolo[5,4-f]quinoxaline analogues of reported disease-related protein kinases inhibitors were synthesized from the obtained 6-amino-5-iodoquinoxalines by using as key step copper-catalyzed azole ring formation. Pyrazino[b,e]isatins were obtained, for the first time, from the same substrates by recourse to Sonogashira coupling, alkyne hydration, and oxidative cyclization. The absorption and emission properties of the most promising compounds were recorded. In addition, most of the synthesized polycycles were evaluated as protein kinase inhibitors and for their antiproliferative activity towards cancer cells.

Keywords: Iodination; Kinase inhibitor; Oxazole; Quinoxaline; Regioselectivity

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry

Frédéric Lassagne, Joshua M. Sims, William Erb, Olivier Mongin, Nicolas Richy, et al.. Thiazolo[5,4- f ]quinoxalines, Oxazolo[5,4- f ]quinoxalines and Pyrazino[ b,e ]isatins: Synthesis from 6-Aminoquinoxalines and Properties. European Journal of Organic Chemistry, 2021, 2021 (19), pp.2756-2763. ⟨10.1002/ejoc.202100362⟩. ⟨hal-03269555⟩