Synthesis and antiviral evaluation of C5-substituted-(1,3-diyne)-2'-deoxyuridines

European Journal of Medicinal Chemistry
Ozkan SariLuigi A Agrofoglio

Abstract

Starting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown C5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl and disubstituted-phenyl substituents) have been synthesized via a nickel-copper catalyzed C-H activation between two terminal alkynes, in yields ranging from 19% to 67%. Their antiviral activities were measured against a large number of DNA and RNA viruses including herpes simplex virus type 1 and type 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. The 5-[4-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine (26) is the most potent inhibitor of this series against VZV with an EC(50) of ~1 μM and a CC(50) of 55 μM. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including influenza virus A (H1N1 and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovirus-1, Sindbis virus and Punta Toro virus in Vero cell cultures and vesicular stomatitis, coxsackie B4 and respiratory syncytial virus in HeLa cell cultures and against human immunodeficiency virus type 1 and 2...Continue Reading

References

Aug 31, 2001·Antiviral Chemistry & Chemotherapy·C McGuiganJ Balzarini
Sep 18, 2003·Journal of the American Chemical Society·Noriaki MinakawaAkira Matsuda
Oct 14, 2003·Bioorganic & Medicinal Chemistry Letters·Masayasu KuwaharaHiroaki Sawai
Mar 6, 2007·Bioorganic & Medicinal Chemistry·Srinivasarao MeneniRoman Dembinski

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Citations

Dec 1, 2015·ACS Medicinal Chemistry Letters·Andrijana MeščićSilvana Raić-Malić
Jun 6, 2014·Physical Chemistry Chemical Physics : PCCP·Avik Kumar PatiAshok K Mishra
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Graciela Andrei, Robert Snoeck

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