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

ABSTRACT: 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.

SUBMITTER: Zhao B

PROVIDER: S-EPMC6099940 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Zhao Bingbing B Lei Fei F Wang Caolin C Zhang Binliang B Yang Zunhua Z Li Wei W Zhu Wufu W Xu Shan S

Molecules (Basel, Switzerland) 20180627 7

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 ...[more]

PMID: 29954109

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