8-AZA-1-DEAZAPURINE NUCLEOSIDES AS ANTIVIRAL AGENTS

2',3'-Dideoxy-8-aza-1-deazaadenosine (21) and its alpha-anomer (20) were synthesized via glycosylation of 7-chloro-3H-1,2,3-triazolo[4,5-b]pyridine with 2,3-dideoxy-5-0-[(1,1)-dimethylethyl)diphenylsilyl]-D-glycero-pentofuranosyl chloride. The reaction gave a mixture of alpha- and beta-anomers of N-3-, N-2- and N-1-glycosylated regioisomers (12-15). The alpha- and beta-anomers of the N-4-glycosylated isomer 26 and 27 were also synthesized through the glycosylation of 8-aza-1-deazaadenine with 1-acetoxy-2,3-dideoxy-5-0-[(1,1-dimethylethyl)dimethylsilyl]-D-glycero-pen. These dideoxynucleosides and a series of previously synthesized 8-aza-1-deazapurine nucleosides were tested for activity against several DNA and RNA viruses, HIV-1 included. The alpha- and beta-anomers of 7-chloro-3-(2-deoxy-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-b]pyridine (3a and 4) showed activities against Sb-1 and Coxs viruses. The alpha- and beta-anomers of 2',3'-dideoxy-8-aza-1-deazaadenosine (20 and 21) were found active as inhibitors of adenosine deaminase.