Design, Synthesis, and Biological Evaluation of Pyridoquinazoline Derivatives as Potent Epidermal Growth Factor Receptor Inhibitors

Abstract

Pyridoquinazolines have been synthesized, characterized, and tested for their in vitro epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. The compounds were prepared from alkylideno/arylideno-bis-ureas. Their structures were elucidated on the basis of elemental analyses and spectral studies (infrared, nuclear magnetic resonance [1H NMR], fourier transform infrared spectroscopy [FTIR], and electron ionization mass spectrometry [EI-MS]). Three of the new compounds had IC50 values in the range of 4.5-11.0 nM. The cellular EGFR internalization response of selected compounds was evaluated using HeLa cells. Three halogenated derivatives had a pronounced effect in inhibiting EGFR internalization.