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.

Department of Organic Chemistry Faculty of Science Charles University Prague Hlavova 8 CZ 12843 Prague 2 Czech Republic

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

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Gilead Sciences and IOCB Research Center Flemingovo nam 2 CZ 16610 Prague 6 Czech Republic

References provided by Crossref.org

Synthesis and Biological Profiling of Quinolino-Fused 7-Deazapurine Nucleosides

Adamantane-Substituted Purine Nucleosides: Synthesis, Host-Guest Complexes with β-Cyclodextrin and Biological Activity

Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C-H Dibenzothiophenation and Negishi Coupling

Pyrido-Fused Deazapurine Bases: Synthesis and Glycosylation of 4-Substituted 9H-Pyrido[2',3':4,5]- and Pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidines

Pyrrolo[2,3-d]pyrimidine (7-deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Sugar modified pyrimido[4,5-b]indole nucleosides: synthesis and antiviral activity