Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2

Eur J Med Chem. 2011 Mar;46(3):870-6. doi: 10.1016/j.ejmech.2010.12.025. Epub 2011 Jan 9.

Abstract

A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC(50) values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / metabolism*
  • Humans
  • Models, Molecular
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Carboxylic Acids
  • Protein Kinase Inhibitors
  • Pyrimidines
  • thienopyrimidine
  • Casein Kinase II