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Bioorg Med Chem. 2015 Dec 15;23(24):7765-76. doi: 10.1016/j.bmc.2015.11.027. Epub 2015 Nov 22.

Synthesis and antitumor activity evaluation of PI3K inhibitors containing 3-substituted quinazolin-4(3H)-one moiety.

Author information

1
Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
2
Department of Genetics and Molecular Biology, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
3
Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: sqzhang@xjtu.edu.cn.

Abstract

In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl)phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3Kα. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents.

KEYWORDS:

Antitumor activity; PI3K inhibitor; Quinazolin-4(3H)-ones; Synthesis

PMID:
26652969
DOI:
10.1016/j.bmc.2015.11.027
[Indexed for MEDLINE]

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