PMID: 11606136Oct 19, 2001Paper

Design, synthesis, and biological evaluation of novel nucleoside and nucleotide analogues as agents against DNA viruses and/or retroviruses

Journal of Medicinal Chemistry
G H HakimelahiS Hakimelahi

Abstract

A novel strategy was developed for the synthesis of N(7)-purine acyclic nucleosides 9 and 14. The key step involved the reaction between [2-(p-methoxyphenyloxy)ethoxy]methyl chloride and N(9)-tritylated nucleobases 6 or 11 followed by concomitant self-detritylation. N(7)-Guanine acyclic nucleoside 9 exhibited antiviral activity, but was phosphorylated by both HSV and Vero cell thymidine kinases. Thus, it showed more potent cellular toxicity than acyclovir (2). N(7)-Adenine acyclic nucleoside 14 was found to be an excellent antiviral agent as well as a good inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows for a greater expression of antiviral activity of antiviral agents, such as N(9)-adenine acyclic nucleoside 1 and ara-A (3). Compound 14 was phosphorylated neither by herpes simplex virus (HSV) thymidine kinase nor by Vero cell thymidine kinase, yet it enhanced the rate constant for the monophosphorylation of acyclovir (2) by HSV thymidine kinase. Consequently, the combination of acyclovir (2) and 14 exhibited greater antiviral activity than acyclovir alone. 7-[2-(Phosphonomethoxy)ethyl]adenine (20) was also synthesized. The key step involved the reaction of 9-(2-cyanoethyl)adenine (15) with methyl...Continue Reading

References

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Citations

Apr 22, 2009·Journal of the American Chemical Society·Sarah K Jarchow-ChoyEric T Kool
Dec 17, 2015·Organic Letters·Shuai ChenAlessandro A Boezio
Dec 12, 2012·Cell Reports·Pablo De IoannesAneel K Aggarwal
Aug 12, 2004·Organic & Biomolecular Chemistry·M Alice CarvalhoBrian L Booth
Feb 12, 2010·Dalton Transactions : an International Journal of Inorganic Chemistry·Jin-Tao WangLiang-Nian Ji
Jul 31, 2019·Antioxidants·Andrijana Meščić MacanSilvana Raić-Malić
Apr 18, 2019·Beilstein Journal of Organic Chemistry·David J JonesTimothy P O'Sullivan
Feb 6, 2013·Organic & Biomolecular Chemistry·Honorine LebraudBernard T Golding
Feb 25, 2019·European Journal of Medicinal Chemistry·Rémi GuillonSuzanne Peyrottes

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