Expression And Synthesis Of 5 - Pyrimidino [5,4-b] Indole Derivatives Of EGFR Tyrosine Kinase Inhibitors

It was well known that cancer was the second leading cause of death in the world. In recent years, a large number of compounds with novel structures and targeted strategies were developed and evaluated as potential anticancer drugs. Small-molecular epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors are among the hottest races in pharmaceutical development. In this paper the structure, the function of EGFR tyrosine kinases and the development of their inhibitors were reviewed.Based on the analysis of structure-activity relationships of 4-anilinoquinazoline-like EGFR inhibitors and the binding model of inhibitor with EGFR, pharmacophore of quinazoline-like inhibitors was summarized. According to the pharmacophore model a series of 4-anilino-5H-pyrimido[5,4-b]indole derivatives were synthesized as inhibitors of EGFR tyrosine kinases. Different substituted furyl were introduced into 8-position, and various anilines were introduced into 4-position in order to investigatetheir influence on anti-tumor activity.18 novel 4-anilino-5H-pyrimido [5,4-b]indole derivatives were synthesized and their structures were confirmed by MS and 1H NMR.