Since Professors Sharpless, Finn, and Kolb first introduced the concept of 鈥渃lick reactions鈥?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鈥搑eceptor 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.