Design, synthesis and biological evaluation of 2-methyl-(1,1'-biphenyl)-pyrimidine conjugates

  • Bioorg Med Chem Lett. 2020 Aug 15;30(16):127328. doi: 10.1016/j.bmcl.2020.127328.
An Chen  1 ,  Dong-Liang Wu  1 ,  Jia Shi  2 ,  Suresh Narva  1 ,  Xiao-Yin Zhao  1 ,  Yan-Ling Wu  3 ,  Wen Zhang  4
Affiliations
  • 1. Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, China.
  • 2. Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
  • 3. Lab of Molecular Immunology, Virus Inspection Department, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China. Electronic address: [email protected].
  • 4. Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: [email protected].
PMID: 32631533 DOI: 10.1016/j.bmcl.2020.127328
Abstract

Small molecule inhibitors of biphenyl structure as core backbone have shown a significant effect on PD-1/PD-L1 axis, and 2-amino-pyrimidine structure is a promising privileged scaffold in medicinal chemistry and drug discovery. We designed by combination principles and synthesized 27 novel compounds with N-((2-methyl-[1,1'-biphenyl]-3-yl)methyl)pyrimidin-2-amine as a basic skeletal structure, and their anti-cancer activity was evaluated. Among compounds, 15a-d and 16b displayed strong anti-cancer effects on 9 tested Cancer cell lines, in particular, the 16b did the highest inhibitive activity, but against HepG2 cells, and possessed the lowest IC50 value of 2.08 μΜ towards HT-29 cells.

Keywords
2-Amino-pyrimidine; Anti-cancer activity; Biphenyl.