Toward Orthopoxvirus Countermeasures: A Novel Heteromorphic Nucleoside of Unusual Structure
- 17 June 2006
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (14) , 4052-4054
- https://doi.org/10.1021/jm060404n
Abstract
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 μM), and cowpox virus (CV) (EC50 = 2.0 ± 0.3 μM). Compound 2 exhibited reduced activity against a thymidine kinase (TK) negative strain of CV, implying a requirement for 5‘-monophosphorylation for antiorthopoxvirus activity. Compound 2 was efficiently phosphorylated by VV TK, establishing that VV TK is more promiscuous than previously believed.Keywords
This publication has 43 references indexed in Scilit:
- A pyrimidine–pyrazolone nucleoside chimera with potent in vitro anti-orthopoxvirus activityBioorganic & Medicinal Chemistry Letters, 2006
- 5-(Dimethoxymethyl)-2‘-Deoxyuridine: A Novel Gem Diether Nucleoside with Anti-Orthopoxvirus ActivityJournal of Medicinal Chemistry, 2006
- An Orally Bioavailable Antipoxvirus Compound (ST-246) Inhibits Extracellular Virus Formation and Protects Mice from Lethal Orthopoxvirus ChallengeJournal of Virology, 2005
- The 4′,4′-difluoro analog of 5′-noraristeromycin: A new structural prototype for possible antiviral drug development toward orthopoxvirus and cytomegalovirusBioorganic & Medicinal Chemistry, 2005
- Combinatorial Optimization of Isatin-β-Thiosemicarbazones as Anti-poxvirus AgentsJournal of Medicinal Chemistry, 2005
- New Class of Orthopoxvirus Antiviral Drugs That Block Viral MaturationJournal of Virology, 2004
- Inhibitory Activity of Alkoxyalkyl and Alkyl Esters of Cidofovir and Cyclic Cidofovir against Orthopoxvirus Replication In VitroAntimicrobial Agents and Chemotherapy, 2004
- 4′,6-Dichloroflavan (BW683C), a new anti-rhinovirus compoundNature, 1981
- Oxime and dithiolane derivatives of 5-formyl-2'-deoxyuridine and their 5'-phosphates: antivirial effects and thymidylate synthetase inhibitionJournal of Medicinal Chemistry, 1980
- Synthesis of 5-substituted 2'-deoxyuridinesJournal of Medicinal Chemistry, 1976