通过片段生长研究设计的 8-烷基噻唑并[5,4-]喹唑啉-9-酮的金属催化 C⁻H 芳基化来开发激酶抑制剂。
Development of Kinase Inhibitors via Metal-Catalyzed C⁻H Arylation of 8-Alkyl-thiazolo[5,4-]-quinazolin-9-ones Designed by Fragment-Growing Studies.
机构信息
Normandie University, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, 76000 Rouen, France.
Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans, UMR CNRS, 7311 BP 6759, 45067 Orléans CEDEX 2, France.
出版信息
Molecules. 2018 Aug 29;23(9):2181. doi: 10.3390/molecules23092181.
Efficient metal catalyzed C⁻H arylation of 8-alkyl-thiazolo[5,4-]-quinazolin-9-ones was explored for SAR studies. Application of this powerful chemical tool at the last stage of the synthesis of kinase inhibitors allowed the synthesis of arrays of molecules inspired by fragment-growing studies generated by molecular modeling calculations. Among the potentially active compounds designed through this strategy, () exhibits nanomolar IC values against some kinases, and is the best candidate for the development as a DYRK kinase inhibitor.
探索了高效的金属催化 C⁻H 芳基化 8-烷基噻唑并[5,4-]喹唑啉-9-酮，以进行 SAR 研究。该强大化学工具在激酶抑制剂合成的最后阶段的应用，允许通过分子建模计算生成的片段生长研究的灵感分子进行阵列合成。在所设计的潜在活性化合物中，()对一些激酶表现出纳摩尔的 IC 值，是作为 DYRK 激酶抑制剂开发的最佳候选物。
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