4-(1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one analogs as potent CDC7 inhibitors

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4482-5. doi: 10.1016/j.bmcl.2008.07.061. Epub 2008 Jul 17.

Abstract

A series of 4-(4-hydroxyphenyl)-6-phenylpyrimidin-2(1H)-ones were identified by HTS as inhibitors of CDC7. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus on removing potential metabolic liabilities and improving cellular potency.

MeSH terms

  • Binding Sites
  • Caco-2 Cells
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / chemistry*
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indazoles / chemistry
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Conformation
  • Molecular Structure
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / chemistry*
  • Pyrimidinones / chemistry
  • Structure-Activity Relationship

Substances

  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Indazoles
  • Pyrimidinones
  • CDC7 protein, human
  • Protein Serine-Threonine Kinases