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

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

Bingbing Zhao, Fei Lei, Caolin Wang, Binliang Zhang, Zunhua Yang, Wei Li, Wufu Zhu, Shan Xu

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.

2018

4-phenylaminoquinoline, phenylsulfonylurea, PI3K/mTOR, inhibitor

DOI: 10.3390/molecules23071553

Molecules

MDPI AG

Organic chemistry

EN