ZINClick: a database of 16 million novel, patentable, and readily synthesizable 1,4-disubstituted triazoles

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.