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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.

A series of 80 7-(het)aryl-and 7-ethynyl-7-deazapurine ribonucleosidesbearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl,or oxo group at position 6, or 2,6-disubstituted derivatives bearinga methyl or amino group at position 2, were prepared, and the biologicalactivity of the compounds was studied and compared with that of theparent 7-(het)aryl-7-deazaadenosine series. Several of the compounds,in particular 6-substituted 7-deazapurine derivatives bearing a furylor ethynyl group at position 7, were significantly cytotoxic at lownanomolar 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 ina replicon assay. [ABSTRACT FROM AUTHOR]