Synthesis and antitumor activity evaluation of 4,6-disubstituted quinazoline derivatives as novel PI3K inhibitors

  • Bioorg Med Chem Lett. 2016 Sep 15;26(18):4408-4413. doi: 10.1016/j.bmcl.2016.08.015.
Yuan-Yuan Hei  1 ,  Minhang Xin  2 ,  Hao Zhang  1 ,  Xiao-Xiao Xie  1 ,  Shuai Mao  1 ,  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 Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: [email protected].
  • 3. Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: [email protected].
PMID: 27544401 DOI: 10.1016/j.bmcl.2016.08.015
Abstract

A series of 4,6-disubstituted quinazoline derivatives as potential PI3K inhibitors were designed and synthesized. All compounds exhibited significant anti-proliferative activities against HCT-116 and MCF-7 cell lines, and compounds A7, A9, and A11 displayed the most potent anti-proliferative activity against the HCT-116. Further PI3K inhibitory activity evaluation showed that compound A7 displayed high potency against PI3K Enzymes. The in vivo anti-tumor study showed compound A7 can efficaciously inhibit tumor growth in a mice S-180 model. These results suggest that our designed compounds can serve as potent PI3K inhibitors and effective antitumor agents.

Keywords
Anti-proliferative; Antitumor; PI3K inhibitor; Quinazoline derivatives; Synthesis.