Thiazolo[5, 4‐f]quinoxalines, Oxazolo[5, 4‐f]quinoxalines and Pyrazino[b, e]isatins: Synthesis from 6‐Aminoquinoxalines and Properties. Issue 19 (18th May 2021)

• Record Type: Journal Article
• Authors: Lassagne, Frédéric; Sims, Joshua M.; Erb, William; Mongin, Olivier; Richy, Nicolas; El Osmani, Nour; Fajloun, Ziad; Picot, Laurent; Thiéry, Valérie; Robert, Thomas; Bach, Stéphane; Dorcet, Vincent; Roisnel, Thierry; Mongin, Florence
• Is Part Of: European journal of organic chemistry. Issue 19(2021)
• Page Start: 2756
• Page End: 2763
• Publication Date: 2021-05-18
• Subjects: Iodination -- Kinase inhibitor -- Oxazole -- Quinoxaline -- Regioselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202100362
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: 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. Abstract : Oxazolo[5, 4‐ f ]quinoxalines, thiazolo[5, 4‐ f ]quinoxalines and pyrazino[ b, e ]isatins were all obtained from 5‐iodo‐6‐aminoquinoxalines. While the first two families were synthesized by nitrogen functionalization and subsequent copper‐catalyzed cyclization, the latter was obtained by Sonogashira coupling, alkyne hydration, and oxidative cyclization. Most of the synthesized polycycles were evaluated in biological tests.