Synthesis and in vitro evaluation of imidazopyridazines as novel inhibitors of the malarial kinase PfPK7

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5294-8. doi: 10.1016/j.bmcl.2008.08.043. Epub 2008 Aug 19.

Abstract

A high-throughput screening campaign identified a number of imidazopyridazines as novel inhibitors of the malarial kinase PfPK7. Further synthetic chemistry efforts enabled the preparation of a number of analogues with promising in vitro potencies. Although these compounds show likely broad spectrum inhibitory activity, they represent a useful starting point for further chemical optimisation.

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Inhibitory Concentration 50
  • KB Cells
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Molecular Structure
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / enzymology*
  • Protozoan Proteins / antagonists & inhibitors*
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Pyridazines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Imidazoles
  • Protozoan Proteins
  • Pyridazines
  • PK7 protein, Plasmodium falciparum
  • Mitogen-Activated Protein Kinase Kinases