Design, Synthesis and Biological Evaluation of Novel Phenylsulfonylurea Derivatives as PI3K/mTOR Dual Inhibitors

作者：Zhao, Bingbing; Lei, Fei; Wang, Caolin; Zhang, Binliang; Yang, Zunhua; Li, Wei; Zhu, Wufu^*; Xu, Shan^*

来源：Molecules, 2018, 23(7): 1553.

DOI：10.3390/molecules23071553

• 4-phenylaminoquinoline
• phenylsulfonylurea
• PI3K/mTOR
• inhibitor

Five series of novel phenylsulfonylurea derivatives, 19a-d, 20a-d, 21a-d, 22a-d and 23a-d, bearing 4-phenylaminoquinoline scaffold were designed, synthesized and their IC50 values against four cancer cell lines (HepG-2, A549, PC-3 and MCF-7) were evaluated. Most compounds showed moderate cytotoxicity activity against the cancer cell lines. Structure-activity relationships (SARs) and pharmacological results indicated that introduction of 4-aminoquinoline scaffold and phenylsulfonylurea scaffold were beneficial for anti-tumor activity. Moreover, para-methoxyl substitution of 4-anilino moiety and para-halogen substitution of phenylsulfonylurea have different impacts on different series of compounds. Furthermore, the micromolecule group substitution in the 6-position of the quinoline ring have a slight impact on the cellular activity of the target compounds.

• 出版日期2018-7
• 单位江西中医药大学; 江西科技师范大学; 宜春学院