Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides
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- 作者：Manabu Hamada ; Vincent Roy ; Tamara R. McBrayer ; Tony Whitaker ; Cesar Urbina-Blanco ; Steven P. Nolan ; Jan Balzarini ; Robert Snoeck ; Graciela Andrei ; Raymond F. Schinazi ; Luigi A. Agrofoglio
- 关键词：Nucleosides ; Synthesis ; Olefin cross metathesis ; Antiviral properties ; Modified heterocycles
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：67
- 期：Complete
- 页码：398-408
- 全文大小：747 K
文摘
A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step.
All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ¡«10?¦ÌM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100?¦ÌM.