Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity

作者：Qu, Menghua; Liu, Zhihao; Zhao, Dan; Wang, Changyuan; Zhang, Jianbin; Tang, Zeyao; Liu, Kexin; Shu, Xiaohong^*; Yuan, Hong^*; Ma, Xiaodong^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(15): 3989-3996.

DOI：10.1016/j.bmc.2017.05.044

• Cancer
• FAK
• Inhibitor
• Pyrimidine
• Sulfonamide

A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100 nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10 mu M, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10 mu M. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.

• 出版日期2017-8-1
• 单位大连医科大学