Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors

Bioorg Med Chem Lett. 2010 Jul 1;20(13):3925-9. doi: 10.1016/j.bmcl.2010.05.013. Epub 2010 May 12.

Abstract

During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Dose-Response Relationship, Drug
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Heterocyclic Compounds
  • Protein Kinase Inhibitors
  • Receptor, Macrophage Colony-Stimulating Factor