title: Synthesis and biological profiling of 6- or 7-(het)aryl-7-deazapurine 4'-C-methylribonucleosides.
abstract: The synthesis and biological activity profiling of a large series of diverse pyrrolo[2,3-d]pyrimidine 4'-C-methylribonucleosides bearing an (het)aryl group at position 4 or 5 is reported as well as the synthesis of several phosphoramidate prodrugs. These compounds are 4'-C-methyl derivatives of previously reported cytostatic hetaryl-7-deazapurine ribonucleosides. The synthesis is based on glycosylation of halogenated 7-deazapurine bases with 1,2-di-O-acetyl-3,5-di-O-benzyl-4-C-methyl-β-d-ribofuranose followed by cross-coupling and nucleophilic substitution reactions. The final compounds showed low cytotoxicity and several derivatives exerted antiviral activity against HCV or Dengue viruses at micromolar concentrations.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Nauš
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Caletková
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Perlíková
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Poštová Slavětínská
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Tloušťová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hodek
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Weber
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 77515 Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Džubák
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 77515 Olomouc, Czech Republic.
authors.forename: Marián
authors.initials: M
authors.lastname: Hajdúch
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic; Department of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, CZ-12843 Prague 2, Czech Republic. Electronic address: hocek@uochb.cas.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Hocek
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003716:Dengue Virus / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology*; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D011685:Purine Nucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011355:Prodrugs; D011684:Purine Nucleosides; D011685:Purine Nucleotides
keywords: 4′-C-Methyl-ribonucleosides; Branched nucleosides; Nucleoside antivirals; Nucleosides; Prodrugs