Research progress in quinazoline derivatives as multi-target tyrosine kinase inhibitors

Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), are involved in multiple human tumors. Therefore, RTKs are attractive targets for various antitumor strategies. Two classes of tyrosine kinase antagonists were applied in the clinic for monoclonal antibodies and small-molecule tyrosine kinase inhibitors. A well-studied class of small-molecule inhibitors is represented by 4-anilinoquinazolines, exemplified by gefitinib and erlotinib as mono-targeted EGFR inhibitors, which were approved for the treatment of non-small-cell lung cancer. Mono-target drugs may result in drug resistance and the innovation of multi-target drugs has grown up to be an active field. Recent advances in research on antitumor bioactivity of 4-anilino(or phenoxy) quinazoline derivatives with multiple targets are reviewed in this paper. At the same time, synthetic methods of quinazo-lines were introduced from the point of building the ring skeleton and based on the types of reaction.