Patil Pravin, Khoury Kareem, Herdtweck Eberhardt, Dömling Alexander
Department of Drug Design, University of Groningen, A. Deusinglaan 1, Groningen 9700 AD, The Netherlands.
Carmolex Inc., Pittsburgh, USA.
Bioorg Med Chem. 2015 Jun 1;23(11):2699-715. doi: 10.1016/j.bmc.2014.12.021. Epub 2014 Dec 20.
Scaffold diversity is key in the ongoing exercise of discovery of novel bioactive compounds using high throughput screening (HTS). Based on the Ugi tetrazole synthesis we have designed novel bi- and tri-cyclic scaffolds featuring interesting pharmacophore properties. The compounds of the scaffold (B) are synthesizable in large diversity and numbers in two steps using (hetero)phenylethylamines, HN3, oxo components and iscyanoacetaldehyde(dimethylacetale). The chemistry is amenable to parallel synthesis and is used to enhance and fill the screening decks of the European Lead factory (ELF). Here, we are reporting full experimental details, scope and limitations of the reaction, cheminformatic analysis and the 3D structures of selected compounds.
在利用高通量筛选（HTS）进行新型生物活性化合物发现的持续工作中，支架多样性是关键。基于乌吉四唑合成，我们设计了具有有趣药效团特性的新型双环和三环支架。支架（B）的化合物可通过两步反应，使用（杂）苯乙胺、叠氮化氢、羰基化合物和异氰基乙醛（二甲基缩醛）大量多样地合成。该化学方法适用于平行合成，并用于扩充和充实欧洲先导化合物工厂（ELF）的筛选库。在此，我们报告了完整的实验细节、反应的范围和局限性、化学信息学分析以及所选化合物的三维结构。
