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

doi:10.1016/j.bmcl.2020.127328

Bioorganic & Medicinal Chemistry Letters

Volume 30, Issue 16, 15 August 2020, 127328

https://doi.org/10.1016/j.bmcl.2020.127328 Get rights and content

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.

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Nos. 21572207, 21877101), the Zhejiang Leading Innovation and Entrepreneurship Team (2018R01015) and the Zhejiang Provincial Key Discipline of Chemical Biology.

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¹: Present affiliation/address: Department of Biochemistry, Hoshi University School of Pharmacy, 2-4-41, Ebara, Shinagawa-ku, Tokyo 144-8501, Japan.

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

Abstract

Graphical abstract

Section snippets

Declaration of Competing Interest

Acknowledgements

Int J Radiat Oncol Biol Phys

Eur J Cancer

Cancer Treat Rev

Biochem Biophys Res Commun

Eur J Med Chem

Eur J Med Chem

Cancer Lett

CA Cancer J Clin

Lung Cancer

CA Cancer J Clin

N Engl J Med

N Engl J Med

Nature