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

An Chen; Dong-Liang Wu; Jia Shi; Suresh Narva; Xiao-Yin Zhao; Yan-Ling Wu; Wen Zhang

doi:10.1016/j.bmcl.2020.127328

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. Epub 2020 Jun 10.

Authors

An Chen¹, Dong-Liang Wu¹, Jia Shi², Suresh Narva¹, Xiao-Yin Zhao¹, Yan-Ling Wu³, Wen Zhang⁴

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: ylwu@cdc.zj.cn.
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: wzhang63@zjut.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents