Discovery of a novel class of 2-ureido thiophene carboxamide checkpoint kinase inhibitors

Bioorg Med Chem Lett. 2008 Jul 15;18(14):4242-8. doi: 10.1016/j.bmcl.2008.05.016. Epub 2008 May 6.

Abstract

Checkpoint kinase-1 (Chk1, CHEK1) is a Ser/Thr protein kinase that mediates the cellular response to DNA-damage. A novel class of 2-ureido thiophene carboxamide urea (TCU) Chk1 inhibitors is described. Inhibitors in this chemotype were optimized for cellular potency and selectivity over Cdk1.

MeSH terms

  • Amides / chemistry
  • Apoptosis
  • Carbon / chemistry
  • Cell Cycle
  • Checkpoint Kinase 1
  • Chemistry, Pharmaceutical / methods*
  • DNA Damage
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Phenyl Ethers / chemistry
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry*
  • Thiophenes / chemistry
  • Urea / chemistry

Substances

  • Amides
  • Phenyl Ethers
  • Protein Kinase Inhibitors
  • Thiophenes
  • Carbon
  • Urea
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1