6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as selective inhibitors of PI3Kα

  • Bioorg Med Chem. 2015 Mar 15;23(6):1231-40. doi: 10.1016/j.bmc.2015.01.052.
Yong Yin  1 ,  Yan-Qing Zhang  1 ,  Biao Jin  1 ,  Shao Sha  1 ,  Xun Wu  1 ,  Chetan B Sangani  1 ,  She-Feng Wang  1 ,  Fang Qiao  1 ,  Ai-Min Lu  2 ,  Peng-Cheng Lv  1 ,  Hai-Liang Zhu  3
Affiliations
  • 1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
  • 2. College of Science, Nanjing Agriculture University, Nanjing 210095, People's Republic of China.
  • 3. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: [email protected].
PMID: 25693787 DOI: 10.1016/j.bmc.2015.01.052
Abstract

Twenty eight 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives were synthesized and evaluated their biological activities as PI3K inhibitors. Biological evaluation against four human tumor cell lines revealed that most target compounds showed impressively better antiproliferative activities than that of LY294002. Among these compounds, compound 25 exhibited the most potent and selective activity for PI3Kα, with the IC50 value of 0.016μM, an approximately 30-fold increase in comparison with LY294002, it also has an increased potency of approximately 11-fold for PI3Kβ. It indicated the potential of developing 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as the new PI3Kα selective inhibitors for tumor treatment.

Keywords
6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives; Antitumor; PI3Kα.