title: Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides.
abstract: Two isomeric series of new thieno-fused 7-deazapurine ribonucleosides (derived from 4-substituted thieno[2',3':4,5]pyrrolo[2,3-d]pyrimidines and thieno[3',2':4,5]pyrrolo[2,3-d]pyrimidines) were synthesized by a sequence involving Negishi coupling of 4,6-dichloropyrimidine with iodothiophenes, nucleophilic azidation, and cyclization of tetrazolopyrimidines, followed by glycosylation and cross-couplings or nucleophilic substitutions at position 4. Most nucleosides (from both isomeric series) exerted low micromolar or submicromolar in vitro cytostatic activities against a broad panel of cancer and leukemia cell lines and some antiviral activity against HCV. The most active were the 6-methoxy, 6-methylsulfanyl, and 6-methyl derivatives, which were highly active to cancer cells and less toxic or nontoxic to fibroblasts.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Gilead Sciences & IOCB Research Center , Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Michal
authors.identifier: 0000-0002-8460-7680
authors.initials: M
authors.lastname: Tichý
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Gilead Sciences & IOCB Research Center , Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Sabina
authors.initials: S
authors.lastname: Smoleń
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Gilead Sciences & IOCB Research Center , Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Tloušt'ová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Gilead Sciences & IOCB Research Center , Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry , Hněvotínská 5, CZ-775 15 Olomouc, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Oždian
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry , Hněvotínská 5, CZ-775 15 Olomouc, Czech Republic.
authors.forename: Klára
authors.initials: K
authors.lastname: Hejtmánková
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry , Hněvotínská 5, CZ-775 15 Olomouc, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Lišková
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry , Hněvotínská 5, CZ-775 15 Olomouc, Czech Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Gurská
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry , Hněvotínská 5, CZ-775 15 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, CZ-775 15 Olomouc, Czech Republic.
authors.forename: Marián
authors.initials: M
authors.lastname: Hajdúch
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Gilead Sciences & IOCB Research Center , Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.|Department of Organic Chemistry, Faculty of Science, Charles University in Prague , Hlavova 8, CZ-12843 Prague 2, Czech Republic.
authors.forename: Michal
authors.identifier: 0000-0002-1113-2047
authors.initials: M
authors.lastname: Hocek
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012263:Ribonucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C512929:7-deazapurine; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011687:Purines; D012263:Ribonucleosides