Article ID | Journal | Published Year | Pages | File Type |
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1392666 | European Journal of Medicinal Chemistry | 2013 | 11 Pages |
•The synthesis of new acyclonucleoside phosphonates is proposed.•Challenging olefin acyclic cross metathesis is the key synthetic step.•CuAAC reaction under microwave activation led to substituted-1,2,3-triazoles.•Compounds exhibited pronounced anti-HCV activity.•Compounds were also evaluated on a wide panel of other viral strains.
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 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.
Graphical abstractSeventeen ANP bearing the (E)-but-2-enyl side chain with cytosine, 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide and 4-substituted-1,2,3-triazoles were prepared through challenging olefin acyclic cross metathesis. Some pronounced anti-HCV activity were found.Figure optionsDownload full-size imageDownload as PowerPoint slide