2. Academic Validation
  3. Design, synthesis and evaluation of 2'-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents

Design, synthesis and evaluation of 2'-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents

  • Eur J Med Chem. 2021 Dec 15:226:113852. doi: 10.1016/j.ejmech.2021.113852.
Linjie Yan 1,  Ruiyuan Cao 1,  Hongjie Zhang 1,  Yuexiang Li 1,  Wei Li 1,  Xiaoyuan Li 1,  Shiyong Fan 1,  Song Li 2,  Wu Zhong 3
Affiliations

Affiliations

  • 1 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
  • 2 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China. Electronic address: lis.lisong@gmail.com.
  • 3 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China. Electronic address: zhongwu@bmi.ac.cn.
PMID: 34560428 DOI: 10.1016/j.ejmech.2021.113852
Abstract

A series of phosphoamidate derivatives of nucleoside 2'-acetylene-7-deaza-adenosine (NITD008) were synthesized and evaluated for their in vitro Antiviral activities against the enteroviruses EV71 and EV-D68. The phosphoamidate (15f) containing a hexyl ester of l-alanine exhibited the most promising activity against EV71 (IC50 = 0.13 ± 0.08 μM) and was 4-times more potent than NITD008. Meanwhile, the derivative containing a cyclohexyl ester of l-alanine (15l) exhibited the most potent activity with high selectivity index against both EV71 (IC50 = 0.19 ± 0.27 μM, SI = 117.00) and EV-D68 (IC50 = 0.17 ± 0.16 μM, SI = 130.76), which were both higher than that of NITD008. The results indicated that the phosphoamidate 15l was the most promising candidate for further development as Antiviral agents for the treatment of both EV71 and EV-D68 Infection.

Keywords

Antiviral; Enterovirus; NITD008; Nucleoside/nucleotide inhibitor.

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