1. From Quinoxaline, Pyrido[2,3-b]pyrazine and Pyrido[3,4-b]pyrazine to Pyrazino-Fused Carbazoles and Carbolines.
- Author
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Lassagne, Frédéric, Langlais, Timothy, Caytan, Elsa, Limanton, Emmanuelle, Paquin, Ludovic, Boullard, Manon, Courtel, Coline, Curbet, Idriss, Gédéon, Clément, Lebreton, Julien, Picot, Laurent, Thiéry, Valérie, Souab, Mohamed, Baratte, Blandine, Ruchaud, Sandrine, Bach, Stéphane, Roisnel, Thierry, Mongin, Florence, and Bunce, Richard A.
- Subjects
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QUINOXALINES , *HETEROCYCLIC compounds , *ANILINE , *AROMATIC amines , *HYDRAZONES - Abstract
2,3-Diphenylated quinoxaline, pyrido[2,3-b]pyrazine and 8-bromopyrido[3,4-b]pyrazine were halogenated in deprotometalation-trapping reactions using mixed 2,2,6,6-tetramethyl piperidino-based lithium-zinc combinations in tetrahydrofuran. The 2,3-diphenylated 5-iodo- quinoxaline, 8-iodopyrido[2,3-b]pyrazine and 8-bromo-7-iodopyrido[3,4-b]pyrazine thus obtained were subjected to palladium-catalyzed couplings with arylboronic acids or anilines, and possible subsequent cyclizations to afford the corresponding pyrazino[2,3-a]carbazole, pyrazino[2′,3′:5,6] pyrido[4,3-b]indole and pyrazino[2′,3′:4,5]pyrido[2,3-d]indole, respectively. 8-Iodopyrido[2,3-b] pyrazine was subjected either to a copper-catalyzed C-N bond formation with azoles, or to direct substitution to introduce alkylamino, benzylamino, hydrazine and aryloxy groups at the 8 position. The 8-hydrazino product was converted into aryl hydrazones. Most of the compounds were evaluated for their biological properties (antiproliferative activity in A2058 melanoma cells and disease-relevant kinase inhibition). [ABSTRACT FROM AUTHOR]
- Published
- 2018
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