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Open AccessArticle

New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

1
National Institute for Chemical-Pharmaceutical Research and Development, Department of Bioactive Substances and Pharmaceutical Technologies, 112 Vitan Av., 031299 Bucharest-3, Romania
2
Organic Chemistry Center “C.D.Nenitescu”, Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, Romania
3
Department of Virology, Pasteur Institute of Epidemiology and Microbiology, 197101 St. Petersburg, Russia
4
KU Leuven Department of Micobiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, BE-3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(13), 2446; https://doi.org/10.3390/molecules24132446
Received: 6 June 2019 / Revised: 28 June 2019 / Accepted: 30 June 2019 / Published: 3 July 2019
New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (5) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (6j and 6d) had lower IC50 (15 ± 2 and 21 ± 4 µM) and compound 6f had an identical value of IC50 (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides. View Full-Text
Keywords: 1′-homocarbonucleosides; bicyclo[2.2.1]heptane nucleosides; 6-chloropurine; 6-substituted adenine nucleosides; antiviral activity; herpesviruses; molecular docking 1′-homocarbonucleosides; bicyclo[2.2.1]heptane nucleosides; 6-chloropurine; 6-substituted adenine nucleosides; antiviral activity; herpesviruses; molecular docking
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Tănase, C.I.; Drăghici, C.; Hanganu, A.; Pintilie, L.; Maganu, M.; Volobueva, A.; Sinegubova, E.; Zarubaev, V.V.; Neyts, J.; Jochmans, D.; Slita, A.V. New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety. Molecules 2019, 24, 2446.

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