Synthesis and biological evaluation of thienopyrrolizines, a new family of CDK/GSK-3 inhibitors

J Enzyme Inhib Med Chem. 2004 Dec;19(6):585-93. doi: 10.1080/14756360400004565.

Abstract

Fifteen new thieno[2,3-b ]- and thieno[3,4-b]pyrrolizines were synthesized and tested against two protein kinases, CDK1/cyclin B and GSK-3. Among these compounds, 3-(3-hydroxy-4-methoxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one 4g was identified as a moderate inhibitor of these kinases. Its molecular modeling study brought to the fore the pivotal role of the 2-methoxyphenol grouping and the interest in replacing it by bioisosteric moieties in future pharmacomodulations.

MeSH terms

  • Binding Sites / drug effects
  • CDC2 Protein Kinase / antagonists & inhibitors*
  • Cell Cycle / drug effects
  • Crystallography, X-Ray
  • Cyclin B / antagonists & inhibitors
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Conformation
  • Protein Structure, Tertiary
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cyclin B
  • Enzyme Inhibitors
  • Pyrroles
  • CDC2 Protein Kinase
  • Glycogen Synthase Kinase 3