Univ Rennes, CNRS, Institut des Sciences Chimiques de Rennes (ISCR)-UMR 6226, F-35000 Rennes, France.
Laboratoire Littoral Environnement et Sociétés, UMRi CNRS 7266, Université de La Rochelle, 17042 La Rochelle, France.
Molecules. 2018 Nov 13;23(11):2961. doi: 10.3390/molecules23112961.
2,3-Diphenylated quinoxaline, pyrido[2,3-]pyrazine and 8-bromopyrido[3,4-]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-]pyrazine and 8-bromo-7-iodopyrido[3,4-]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-]carbazole, pyrazino[2',3':5,6] pyrido[4,3-]indole and pyrazino[2',3':4,5]pyrido[2,3-]indole, respectively. 8-Iodopyrido[2,3-] 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).
2,3-二苯基喹喔啉、吡啶并[2,3-]吡嗪和 8-溴吡啶并[3,4-]吡嗪在四氢呋喃中用混合 2,2,6,6-四甲基哌啶基锂-锌组合进行脱质子化-捕获反应进行卤化。得到的 2,3-二苯基 5-碘喹喔啉、8-碘吡啶并[2,3-]吡嗪和 8-溴-7-碘吡啶并[3,4-]吡嗪被钯催化与芳基硼酸或苯胺偶联，并可能随后环化，得到相应的吡嗪并[2,3-]咔唑、吡嗪并[2',3':5,6]吡啶并[4,3-]吲哚和吡嗪并[2',3':4,5]吡啶并[2,3-]吲哚。8-碘吡啶并[2,3-]吡嗪要么与唑类进行铜催化的 C-N 键形成，要么直接取代在 8 位引入烷基氨基、苄氨基、肼基和芳氧基。8-肼基产物被转化为芳基腙。大多数化合物都评估了它们的生物特性（在 A2058 黑色素瘤细胞中的抗增殖活性和与疾病相关的激酶抑制）。
