Synthesis, Characterization and Biological Activity of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as the Epidermal Growth Factor Recepter Inhibitors

The epidermal growth factor receptor has become one of the targets of anticancer drug research and development because of its widely distribution in several human tumor cells including non-small cell lung cancer. Based on molecular docking, a novel series of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives have been synthesized and their biological evaluation for anti-proliferative activities on the human pulmonary carcinoma cell line A549 and EGFR inhibitory activities in vitro has been finished. According to the screening result, the target compound 7-(4-ethoxyphenyl)-4-(4-methoxylbenzylamino)-5,6,7,8-tetrahydrobenzo [4,5] thieno [2,3-d] pyrimidine (6d) and 7-(4-hydroxyphenyl)-4-(4-methoxylbenzylamino)-5,6,7,8-tetrahydrobenzo[4,5]thieno [2,3-d]pyrimidine (8d) demonstrated significant anti-tumor activity, and the preliminary structure-activity relationships of the target compounds were summarized. They were worthy of further modification to obtain more potent anticancer candidate drugs.