Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale , "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy.
J Chem Inf Model. 2014 Feb 24;54(2):396-406. doi: 10.1021/ci400529h. Epub 2014 Jan 31.
Since Professors Sharpless, Finn, and Kolb first introduced the concept of "click reactions" in 2001 as powerful tools in drug discovery, 1,4-disubstituted-1,2,3-triazoles have become important in medicinal chemistry due to the simultaneous discovery by Sharpless, Fokin, and Meldal of a perfect click 1,3-dipolar cycloaddition reaction between azides and alkynes catalyzed by copper salts. Because of their chemical features, these triazoles are proposed to be aggressive pharmacophores that participate in drug-receptor interactions while maintaining an excellent chemical and metabolic profile. Surprisingly, no virtual libraries of 1,4-disubstituted-1,2,3-triazoles have been generated for the systematic investigation of the click-chemical space. In this manuscript, a database of triazoles called ZINClick is generated from literature-reported alkynes and azides that can be synthesized within three steps from commercially available products. This combinatorial database contains over 16 million 1,4-disubstituted-1,2,3-triazoles that are easily synthesizable, new, and patentable! The structural diversity of ZINClick ( http://www.symech.it/ZINClick ) will be explored. ZINClick will also be compared to other available databases, and its application during the design of novel bioactive molecules containing triazole nuclei will be discussed.
自 2001 年 Sharpless 教授、Finn 教授和 Kolb 教授首次提出“点击反应”概念，将其作为药物发现的有力工具以来，由于 Sharpless 教授、Fokin 教授和 Meldal 教授同时发现了叠氮化物和炔烃在铜盐催化下的完美点击 1,3-偶极环加成反应，1,4-二取代-1,2,3-三唑在药物化学中变得非常重要。由于其化学特性，这些三唑被认为是具有侵略性的药效团，在保持良好的化学和代谢特性的同时，参与药物受体相互作用。令人惊讶的是，目前还没有为系统研究点击化学空间生成 1,4-二取代-1,2,3-三唑的虚拟库。在本文中，从文献报道的可通过三步反应从商业产品中合成的炔烃和叠氮化物中生成了一个名为 ZINClick 的三唑数据库。该组合数据库包含超过 1600 万个易于合成、新颖且可申请专利的 1,4-二取代-1,2,3-三唑！将对 ZINClick 的结构多样性（http://www.symech.it/ZINClick）进行探索。还将对 ZINClick 与其他可用数据库进行比较，并讨论其在设计含有三唑核的新型生物活性分子中的应用。
