Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization

Bioorg Med Chem. 2009 Sep 15;17(18):6728-37. doi: 10.1016/j.bmc.2009.07.047. Epub 2009 Jul 25.

Abstract

Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Aurora Kinases
  • Benzothiazoles / chemistry*
  • Benzothiazoles / pharmacology*
  • Cell Line, Tumor
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phosphorylation / drug effects
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzothiazoles
  • Protein Kinase Inhibitors
  • Protein Kinases
  • ErbB Receptors
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • benzothiazole