2. Academic Validation
  3. Design, synthesis and bioevaluation of N-trisubstituted pyrimidine derivatives as potent aurora A kinase inhibitors

Design, synthesis and bioevaluation of N-trisubstituted pyrimidine derivatives as potent aurora A kinase inhibitors

  • Eur J Med Chem. 2014 May 6:78:65-71. doi: 10.1016/j.ejmech.2014.03.027.
Yu Luo 1,  Yan-Qiu Deng 1,  Jing Wang 2,  Zi-Jie Long 2,  Zheng-Chao Tu 3,  Wei Peng 1,  Ji-Quan Zhang 1,  Quentin Liu 4,  Gui Lu 5
Affiliations

Affiliations

  • 1 Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
  • 2 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.
  • 3 Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, PR China.
  • 4 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China. Electronic address: liuq9@mail.sysu.edu.cn.
  • 5 Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China; Institute of Human Virology, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: lugui@mail.sysu.edu.cn.
PMID: 24681066 DOI: 10.1016/j.ejmech.2014.03.027
Abstract

The design and synthesis of a new series of N-trisubstituted (at C2, C4 and C6 respectively) pyrimidine derivatives were reported, their in vitro structure-activity relationships vs. Aurora A kinase were also discussed. Our results demonstrated that the introduction of characteristic N-substituted side chain at C2 of pyrimidines possessed a potent Aurora A inhibitory activity, the position and the nature of the substituents on the phenyl ring of aniline side chain played key roles in cellular kinase inhibitory potency. Most tested compounds exhibited good inhibitory activities against Aurora A kinase and various human tumor cell lines. Compounds 7j, 7m-n and 7p showed strong growth-inhibitory activities in the solid CNE-2 tumor cell and selectively blocked cell-cycle progression at the G2/M phase.

Keywords

Antitumor; Aurora A kinase; Pyrimidine derivative; Small molecule inhibitor; Synthesis.

Figures