Synthesis, Antitumor Evaluation and Docking Study of Novel 4-Anilinoquinazoline Derivatives as Potential Epidermal Growth Factor Receptor (EGFR) Inhibitors

摘要

Protein kinases, in particular receptor tyrosine kinases, are considered to be the second largest class of therapeutic targets by Gray etal. The most extensively studied receptor tyrosine kinase is the epidermal growth factor receptor (EGFR). Aberrant expression or activation of EGFR homologues has been connected with multiple human carcinomas, and drugs targeting ErbB activity have been licensed for treatment of lung, colon, breast, and head-and-neck carcinomas. These drugs fall into two categories: monoclonal antibodies targeting ErbB extracellular regions, and small-molecule reversible tyrosine kinase inhibitors, such as erlotinib, gefitinib, and lapatinib. These drugs are all 4-anilinoquinazoline derivatives and are among the most potent known tyrosine kinase inhibitors. Numerous studies have aimed to identify novel compounds containing the 4-anilinoquinazoline core as small-molecule inhibitors of EGFR.