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Synthesis and cytostatic and antiviral activities of 2 '-deoxy-2 ',2 '-difluororibo- and 2 '-deoxy-2 '-fluororibonucleosides derived from 7-(het)aryl-7-deazaadenines
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SYSNO ASEP 0393973 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Synthesis and cytostatic and antiviral activities of 2 '-deoxy-2 ',2 '-difluororibo- and 2 '-deoxy-2 '-fluororibonucleosides derived from 7-(het)aryl-7-deazaadenines Author(s) Perlíková, Pavla (UOCHB-X) RID, ORCID
Eberlin, Ludovic (UOCHB-X)
Ménová, Petra (UOCHB-X) RID
Raindlová, Veronika (UOCHB-X) RID
Slavětínská, Lenka (UOCHB-X) RID
Tloušťová, Eva (UOCHB-X) RID, ORCID
Bahador, G. (US)
Lee, Y. J. (US)
Hocek, Michal (UOCHB-X) RID, ORCIDNumber of authors 9 Source Title ChemMedChem. - : Wiley - ISSN 1860-7179
Roč. 8, č. 5 (2013), s. 832-846Number of pages 15 s. Language eng - English Country DE - Germany Keywords 7-deazapurines ; antiviral agents ; cytostatics ; fluorinated derivatives ; nucleosides Subject RIV CC - Organic Chemistry R&D Projects GAP207/11/0344 GA ČR - Czech Science Foundation (CSF) Institutional support UOCHB-X - RVO:61388963 UT WOS 000318245300016 EID SCOPUS 84877056542 DOI 10.1002/cmdc.201300047 Annotation A series of sugar-modified derivatives of cytostatic 7-heteroaryl-7-deazaadenosines (2-deoxy-2-fluororibo- and 2-deoxy-2,2-difluororibonucleosides) bearing an aryl or heteroaryl group at position7 was prepared and screened for biological activity. The difluororibonucleosides were prepared by non- stereoselective glycosidation of 6-chloro-7-deazapurine with benzoyl-protected 2-deoxy-2,2-difluoro-D-erythro-pentofuranosyl-1-mesylate, followed by amination and aqueous Suzuki cross-couplings with (het)arylboronic acids. The fluororibo derivatives were prepared by aqueous palladium-catalyzed cross-coupling reactions of the corresponding 7-iodo-7-deazaadenine 2-deoxy-2-fluororibonucleoside 20 with (het)arylboronic acids. The key intermediate 20 was prepared by a six-step sequence from the corresponding arabinonucleoside by selective protection of 3- and 5-hydroxy groups with acid-labile groups, followed by stereoselective SN2 fluorination and deprotection. Some of the title nucleosides and 7-iodo-7-deazaadenine intermediates showed micromolar cytostatic or anti-HCV activity. The most active were 7-iodo and 7-ethynyl derivatives. The corresponding 2-deoxy-2,2-difluororibonucleoside 5-O-triphosphates were found to be good substrates for bacterial DNA polymerases, but are inhibitors of human polymerase. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2014
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