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

  • Bioorg Med Chem. 2015 Dec 15;23(24):7765-76. doi: 10.1016/j.bmc.2015.11.027.
Hao Zhang  1 ,  Min-Hang Xin  1 ,  Xiao-Xiao Xie  1 ,  Shuai Mao  1 ,  Sai-Jie Zuo  1 ,  She-Min Lu  2 ,  San-Qi Zhang  3
Affiliations
  • 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: [email protected].
PMID: 26652969 DOI: 10.1016/j.bmc.2015.11.027
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.