A series of 6-(hetero)aryl- or 6-methyl-7-deazapurine ribonucleosides bearing a substituent at position 2 (Cl, F, NH2, or CH3) were prepared by cross-coupling reactions at position 6 and functional group transformations at position 2. Cytostatic, antiviral, and antimicrobial activity assays were performed. The title compounds were observed to be potent and selective inhibitors of Mycobacterium tuberculosis adenosine kinase (ADK), but not human ADK; moreover, they were found to be non-cytotoxic. The antimycobacterial activities against M. tuberculosis, however, were only moderate. The reason for this could be due to either poor uptake through the cell wall or to parallel biosynthesis of adenosine monophosphate by the salvage pathway.

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

Institute of Molecular and Translational Medicine Palacky University and University Hospital in Olomouc Faculty of Medicine and Dentistry Hněvotínská 5 77515 Olomouc

Institute of Organic Chemistry and Biochemistry Academy of Science Czech Republic Gilead Sciences and IOCB Research Center Flemingovo nám 2 16610 Prague 6 http www uochb cas cz hocekgroup

Laboratory for Mycobacterial Diagnostics and Tuberculosis Regional Institute of Public Health in Ostrava Partyzánské nám 7 70200 Ostrava

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