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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety
Author
Tănase, Constantin I 1   VIAFID ORCID Logo  ; Drăghici, Constantin 2 ; Hanganu, Anamaria 2   VIAFID ORCID Logo  ; Pintilie, Lucia 1   VIAFID ORCID Logo  ; Maganu, Maria 2 ; Volobueva, Alexandrina 3 ; Sinegubova, Ekaterina 3 ; Zarubaev, Vladimir V 3   VIAFID ORCID Logo  ; Neyts, Johan 4 ; Jochmans, Dirk 4 ; Slita, Alexander V 4 

 National Institute for Chemical-Pharmaceutical Research and Development, Department of Bioactive Substances and Pharmaceutical Technologies, 112 Vitan Av., 031299 Bucharest-3, Romania 
 Organic Chemistry Center “C.D.Nenitescu”, Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, Romania 
 Department of Virology, Pasteur Institute of Epidemiology and Microbiology, 197101 St. Petersburg, Russia 
 KU Leuven Department of Micobiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, BE-3000 Leuven, Belgium 
First page
2446
Publication year
2019
Publication date
2019
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2549035146
Copyright
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.