Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6042-6. doi: 10.1016/j.bmcl.2009.09.057. Epub 2009 Sep 18.

Abstract

A series of analogs of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione, a putative substrate-specific ERK1/2 inhibitor, were synthesized and biologically characterized in human leukemia U937 cells to define its pharmacophore. It was discovered that shift of ethoxy substitution from the 4- to the 2-position on the phenyl ring significantly improved functional activities of inhibiting cell proliferation and inducing apoptosis. This may provide access to a new lead for developing ERK1/2 substrate-specific inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation
  • Computer Simulation
  • Humans
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thiazolidinediones / chemical synthesis
  • Thiazolidinediones / chemistry*
  • Thiazolidinediones / pharmacology

Substances

  • 3-(2-aminoethyl)-5-(4-ethoxybenzylidene)thiazolidine-2,4-dione
  • Protein Kinase Inhibitors
  • Thiazolidinediones
  • Mitogen-Activated Protein Kinase 3