title: Synthesis, cytostatic, antimicrobial, and anti-HCV activity of 6-substituted 7-(het)aryl-7-deazapurine ribonucleosides.
abstract: A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)aryl-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.
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.forename: Olga
authors.initials: O
authors.lastname: Caletková
authors.forename: Petr
authors.initials: P
authors.lastname: Konečný
authors.forename: Petr
authors.initials: P
authors.lastname: Džubák
authors.forename: Kateřina
authors.initials: K
authors.lastname: Bogdanová
authors.forename: Milan
authors.initials: M
authors.lastname: Kolář
authors.forename: Jana
authors.initials: J
authors.lastname: Vrbková
authors.forename: Lenka
authors.initials: L
authors.lastname: Slavětínská
authors.forename: Eva
authors.initials: E
authors.lastname: Tloušt'ová
authors.forename: Pavla
authors.initials: P
authors.lastname: Perlíková
authors.forename: Marián
authors.initials: M
authors.lastname: Hajdúch
authors.forename: Michal
authors.initials: M
authors.lastname: Hocek
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009163:Mycobacterium bovis / Q000187:drug effects; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D000998:Antiviral Agents; D054697:Cytostatic Agents; D003603:Cytotoxins; D011684:Purine Nucleosides; D012263:Ribonucleosides