Synthesis of 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)-substituted pyrazolo[3,4-d]pyrimidin-4-amines via click chemistry: potential inhibitors of the Plasmodium falciparum PfPK7 protein kinase

Org Biomol Chem. 2009 Sep 7;7(17):3421-9. doi: 10.1039/b906482f. Epub 2009 Jul 2.

Abstract

Efficient routes to 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)pyrazolo[3,4-d]pyrimidin-4-amines using a one-pot two-step reaction are presented. The two routes give easy access to two different isomers of 1,4-disubstituted triazoles and the target compounds are obtained from a variety of readily available aromatic and aliphatic halides without isolation of potentially unstable organic azide intermediates. Two compounds show activity towards the PfPK7 kinase (IC(50) 10-20 microM) of P. falciparum, the organism responsible for the most virulent form of malaria, and can be regarded as hits useful for further development into lead compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis*
  • Amines / pharmacology
  • Inhibitory Concentration 50
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Plasmodium falciparum / enzymology*
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinases / drug effects
  • Protozoan Proteins / antagonists & inhibitors*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology

Substances

  • Amines
  • Protein Kinase Inhibitors
  • Protozoan Proteins
  • Pyrimidines
  • Triazoles
  • Protein Kinases
  • PK7 protein, Plasmodium falciparum
  • Mitogen-Activated Protein Kinase Kinases