Synthesis and antiviral evaluation of certain novel pyrazinoic acid C-nucleosides

Journal of Medicinal Chemistry
J A WalkerLeroy B Townsend

Abstract

Pyrazine (1,4-diazine) C-nucleosides constitute a rare class of nucleic acid analogues that has only recently been reported in the literature. As part of our ongoing investigation into the synthesis and reactivity of these compounds, we have developed an electrophilic esterification of a lithiated pyrazine C-nucleoside (1) to give, following deprotection, the versatile intermediate ethyl 3,5-dichloro-6-(beta-d-ribofuranosyl)pyrazine-2-carboxylate (4). This intermediate was subjected to a variety of reaction conditions to generate a series of pyrazinoic acid C-nucleosides. These compounds, along with 3, 5-dichloro-2-(beta-d-ribofuranosyl)pyrazine (2) and 4, were evaluated for antiviral activity and cytotoxicity. No significant activity was observed for compounds 2 and 5-9, but 4 was active against two herpes viruses and cytotoxic in the micromolar range.

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Citations

Apr 13, 2001·Medicinal Research Reviews·A MartinezC Perez
Oct 30, 2015·Journal of Medicinal Chemistry·Erik De Clercq
Apr 19, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohsine DriowyaKhalid Bougrin
Sep 4, 2013·Organic & Biomolecular Chemistry·Zhengwang ChenLiangxian Liu
Sep 19, 2009·Chemical Reviews·Jan StambaskýPavel Kocovský
Oct 17, 2013·The Journal of Organic Chemistry·Lionel NicolasJanine Cossy
Jan 11, 2011·The Journal of Organic Chemistry·Sachin G ModhaErik V Van der Eycken
Aug 5, 2003·The Journal of Organic Chemistry·Vassilios N KourafalosLeroy B Townsend

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