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

J Chem Inf Model. 2014 Feb 24;54(2):396-406. doi: 10.1021/ci400529h. Epub 2014 Jan 31.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes / chemistry
  • Azides / chemistry
  • Click Chemistry*
  • Databases, Pharmaceutical*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Models, Molecular
  • Molecular Conformation
  • NADP / analogs & derivatives
  • NADP / chemical synthesis
  • NADP / chemistry
  • NADP / pharmacology
  • Patents as Topic*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry*
  • Triazoles / pharmacology

Substances

  • Alkynes
  • Azides
  • Protein Kinase Inhibitors
  • Small Molecule Libraries
  • Triazoles
  • NADP
  • NAADP
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3