Design And Synthesis Of 4 - Aniline Quinazoline EGFR Inhibitors

In this thesis, the pathobiology and molecular biology of cancer were introduced briefly, the relationship between epidermal growth factor and cancer was reviewed, and the progress of epidermal growth factor receptor inhibitors was described in detail.The design and synthesis of 4-anilino-quinazoline derivatives were emphasized in this paper. Based on the analysis of structure-activity relationship of quinazoline derivatives, taking Iressa as the lead compound, modification was made at 4 position and 7 position on quinazoline nucleu. As a result we designed a series of 4-anilino-quinazoline derivatives. A synthetic scheme was developed, and the target compounds were synthesized from 3-hydroxy-4-methoxybenzoic acid, followed by esterification, etherification, nitrification, reduction, cyclizition, chlorination, substitution, Mannich reaction and oxidation. The structures of fifteen new compounds were confirmed by MS and ~1H-NMR.