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J Med Chem. 2017 Mar 23;60(6):2411-2424. doi: 10.1021/acs.jmedchem.6b01766. Epub 2017 Mar 3.

Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides.

Author information

1
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Gilead Sciences & IOCB Research Center , Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
2
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.
3
Department of Organic Chemistry, Faculty of Science, Charles University in Prague , Hlavova 8, CZ-12843 Prague 2, Czech Republic.

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.

PMID:
28221790
DOI:
10.1021/acs.jmedchem.6b01766
[Indexed for MEDLINE]
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