Development of new fluorescent xanthines as kinase inhibitors

Org Lett. 2010 Mar 19;12(6):1212-5. doi: 10.1021/ol100011n.

Abstract

An efficient and versatile synthetic approach for the preparation of highly substituted xanthine derivatives has been developed by a combination of direct N7- and C8-arylation. With this method, diverse xanthine analogues were prepared and potent kinase inhibitors could be identified. For example, compound 8a inhibits PI3Ks and proliferation in T47D tumor cells. In addition, these xanthine-based kinase inhibitors exhibited significant fluorescence emission in a concentration-dependent response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology*
  • Humans
  • Molecular Conformation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Xanthines / chemical synthesis
  • Xanthines / chemistry
  • Xanthines / pharmacology*

Substances

  • Antineoplastic Agents
  • Fluorescent Dyes
  • Protein Kinase Inhibitors
  • Xanthines
  • Protein Kinases