Synthesis and anti-CVB3 activity of 4-amino acid derivative substituted pyrimidine nucleoside analogues

Le Tao; Yujiang Li; Xiaohe Guo; Lihong Dong; Luping Liu; Qiang Wang; Xuejun Yu; Chuanjun Song; Junbiao Chang

doi:10.1016/j.bmcl.2019.126770

Synthesis and anti-CVB3 activity of 4-amino acid derivative substituted pyrimidine nucleoside analogues

Bioorg Med Chem Lett. 2020 Jan 1;30(1):126770. doi: 10.1016/j.bmcl.2019.126770. Epub 2019 Oct 28.

Authors

Le Tao¹, Yujiang Li¹, Xiaohe Guo², Lihong Dong¹, Luping Liu¹, Qiang Wang¹, Xuejun Yu¹, Chuanjun Song³, Junbiao Chang⁴

Affiliations

¹ High & New Technology Research Center of Henan Academy of Sciences, Zhengzhou, Henan Province 450002, PR China.
² High & New Technology Research Center of Henan Academy of Sciences, Zhengzhou, Henan Province 450002, PR China. Electronic address: zhangshengqian@ncwu.edu.cn.
³ College of Chemistry, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China.
⁴ Henan Key Laboratory of Organic Functional Molecules and Drug Innovation, Henan Normal University, Xinxiang 453007, PR China. Electronic address: cjb@htu.edu.cn.

PMID: 31735601
DOI: 10.1016/j.bmcl.2019.126770

Abstract

Seven novel 4-amino acid derivative substituted pyrimidine nucleoside analogues were designed, synthesized, and tested for their anti-CVB3 activity. Initial biological studies indicated that among these 4-amino acid derivative substituted pyrimidine nucleoside analogues, 4-N-(2'-amino-glutaric acid-1'-methylester)-1-(2'- deoxy-2'-β-fluoro-4'-azido)-furanosyl-cytosine 2 exhibited the most potent anti-CVB activity (IC₅₀ = 9.3 μM). The cytotoxicity of these compounds has also been assessed. The toxicity of compound 2 was similar to that of ribavirin.

Keywords: Amino acid; Anti-CVB3 activity; Pyrimidine nucleoside; Synthesis.

Publication types

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

MeSH terms

Humans
Pyrimidine Nucleosides / chemical synthesis*
Structure-Activity Relationship

Substances

Pyrimidine Nucleosides