Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity

Bioorg Med Chem. 2017 Aug 1;25(15):3989-3996. doi: 10.1016/j.bmc.2017.05.044. Epub 2017 May 20.


A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10µM, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10µM. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.

Keywords: Cancer; FAK; Inhibitor; Pyrimidine; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Cell Line, Tumor
  • Drug Design
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Proton Magnetic Resonance Spectroscopy
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Sulfonamides / chemistry*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Focal Adhesion Protein-Tyrosine Kinases