Library-to-Library Synthesis of Highly Substituted α-Aminomethyl Tetrazoles via Ugi Reaction.,ACS Combinatorial Science

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Library-to-Library Synthesis of Highly Substituted α-Aminomethyl Tetrazoles via Ugi Reaction.
ACS Combinatorial Science Pub Date : 2018-01-04 , DOI: 10.1021/acscombsci.7b00137
Pravin Patil ₁ , Bhupendra Mishra ₁ , Gitanjali Sheombarsing ₁ , Katarzyna Kurpiewska ₂ , Justyna Kalinowska-Tłuścik ₂ , Alexander Dömling ₁

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α-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent reaction (MCR), were shown to be excellent starting materials for a further Ugi MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5-yl)methyl)amino)acetamides having four points of diversity in a library-to-library approach. The scope and limitations of the two-step sequence was explored by conducting more than 50 reactions. Irrespective of electron-rich and electron-deficient oxo-components and the nature of the isocyanide component, the reactions give excellent yields. Sterically less hindered α-aminomethyl tetrazoles give better yields of in further Ugi MCR. The target scaffold has four points of diversity and is finding applications to fill screening decks for high-throughput screening (HTS) in the European Lead Factory and in structure-based drug design.

中文翻译：

通过 Ugi 反应进行高度取代的 α-氨基甲基四唑的文库合成。

最近通过 Ugi 多组分反应 (MCR) 获得的 α-氨基甲基四唑被证明是进一步 Ugi MCR 的优异起始材料，产生取代的 N-甲基-2-(((1-甲基-1H-四唑-5) -基)甲基)氨基)乙酰胺在文库间方法中具有四个多样性点。通过进行 50 多个反应，探索了两步序列的范围和局限性。无论富电子和缺电子含氧组分以及异氰化物组分的性质如何，该反应都具有优异的产率。空间位阻较小的 α-氨甲基四唑可进一步提高 Ugi MCR 的产率。目标支架具有四个多样性点，正在寻找填充欧洲先导工厂高通量筛选 (HTS) 筛选平台和基于结构的药物设计的应用。

更新日期：2018-01-04

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