Synthesis and pp60c-Src tyrosine kinase inhibitory activities of novel indole-3-imine and amine derivatives substituted at N1 and C5

Arch Pharm (Weinheim). 2009 Jun;342(6):333-43. doi: 10.1002/ardp.200800216.


A series of novel 1,3,5-trisubstituted indole derivatives, namely, N-benzyl 5-phenyl indole-3-imine, N-benzyl-5-(p-fluorophenyl)indole-3-imine and their corresponding amine congeners, were designed and synthesized as pp60(c-Src) tyrosine kinase inhibitors, and their inhibitory activities toward pp60(c-Src) tyrosine kinase were evaluated by in-vitro kinase assay. Pre-screening at two doses of compounds against kinase target revealed that, except for the N-benzyl-5-phenyl indole imine derivatives 7a-7d, all indole derivatives show the target inhibition at varying levels. Consequently, the compounds, 8c, 8f, 8g, and 8h, were selected for prescreening tests. The dose-response curves for up to six concentrations (250 to 7.8 muM) of the active compounds were obtained by tyrosine kinase assay and the four-parameter logistic analysis of these data resulted in the IC(50)s of 4.69, 74.79, 75.06, and 84.23 muM for compounds 8c, 8f, 8g, and 8h, respectively. Therefore, compound 8c, 1-(1-benzyl-5-phenyl-1H-indole-3-yl)-N-(4-fluorobenzyl)methanamine.HCl, was the promising inhibitor for pp60(c-Src), followed by compounds 8g and 8h. Under the same conditions, compound 8f did not provide any reasonable inhibition pattern to be considered as active compound. Therefore, among all four active compounds, compound 8f was not found suitable for further analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / administration & dosage
  • Amines / chemical synthesis
  • Amines / pharmacology
  • Dose-Response Relationship, Drug
  • Indoles / administration & dosage
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Logistic Models
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Amines
  • Indoles
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins pp60(c-src)