Molecular design, synthesis, and structure-Activity relationships leading to the potent and selective p56(lck) inhibitor BMS-243117

Bioorg Med Chem Lett. 2003 Jul 7;13(13):2145-9. doi: 10.1016/s0960-894x(03)00380-9.

Abstract

A series of structurally novel benzothiazole based small molecule inhibitors of p56(lck) were prepared to elucidate their structure-activity relationships (SARs), selectivity and cell activity in the T-cell proliferation assay. BMS-243117 (compound 2) is identified as a potent, and selective Lck inhibitor with good cellular activity (IC(50)=1.1 microM) against T-cell proliferation.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Binding Sites / drug effects
  • Cell Division / drug effects
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship
  • Substrate Specificity
  • T-Lymphocytes / drug effects
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology*
  • Urea / chemistry

Substances

  • BMS-243117
  • Enzyme Inhibitors
  • Thiazoles
  • Adenosine Triphosphate
  • Urea
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)