Toward orthopoxvirus countermeasures: A novel heteromorphic nucleoside of unusual structure

被引:40
作者
Fan, Xuesen
Zhang, Xinying
Zhou, Longhu
Keith, Kathy A.
Prichard, Mark N.
Kern, Earl R.
Torrence, Paul F. [1 ]
机构
[1] No Arizona Univ, Dept Chem & Biochem, Flagstaff, AZ 86011 USA
[2] Univ Alabama Birmingham, Sch Med, Dept Pediat, Birmingham, AL 35233 USA
关键词
D O I
10.1021/jm060404n
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Two privileged drug scaffolds have been hybridized to create the novel heteromorphic nucleoside 5-(2-amino-3-cyano-5-oxo-5,6,7,8-tetrahydro-4H-chromen-4-yl)-1-(2-deoxypentofuranosyl)pyrimidine-2,4(1H,3H)-dione (2). Compound 2 inhibited the replication of two orthopoxviruses, vaccinia virus (VV) (EC50 = 4.6 +/- 2.0 mu M), and cowpox virus (CV) (EC50 = 2.0 +/- 0.3 mu M). Compound 2 exhibited reduced activity against a thymidine kinase (TK) negative strain of CV, implying a requirement for 5 '-monophosphorylation for antior-thopoxvirus activity. Compound 2 was efficiently phosphorylated by VV TK, establishing that VV TK is more promiscuous than previously believed.
引用
收藏
页码:4052 / 4054
页数:3
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