8-AZA DERIVATIVES OF 3-DEAZAPURINE NUCLEOSIDES - SYNTHESIS AND IN-VITRO EVALUATION OF ANTIVIRAL AND ANTITUMOR-ACTIVITY

The syntheses of 4-amino-1-(beta-D-ribofuranosyl)-1H-1,2,3-triazolo[4,5-c]pyridine (8-aza-3-deazaadenosine, 1), 4-amino-1-(2-deoxy-beta-D-erythro-pentofura-nosyl)-1H-1,2,3-triazolo[4,5-c]pyridine (2'-deoxy-8-aza-3-deazaadenosine, 2), and their N8 and N7 glycosylated analogues (I 2, 13, 21, 22) and 4-amino-1-(2,3-dideoxy-beta-D-erythro-pentofuranosyl)-1H-1,2,3-triazolo [4,5-c]pyridine (2',3'-dideoxy-8-aza-3-deazaadenosine, 3) were carried out by glycosylation of the 4-chloro-3H-1,2,3-triazolo[4,5-c]pyridine anion. The anomeric configuration as well as the position of glycosylation were determined by H-1-, C-13-NMR, UV and N.O.E. difference spectroscopy. Nucleoside (2) and its parent compound 2'-deoxy-3-deazaadenosine were found active against ASFV and VSV. The 4-chloro-2-(beta-D-ribofuranosyl)-2H-1,2,3-triazolo[4,5-c] pyridine (9) was active against Coxsackie B1, whereas none of the 8-aza-3-deaza purine nucleosides, compound (3) included, was active against HIV-1. The 6-chloro derivatives of 8-aza-3-deazapurine ribo- and 2'-deoxyribonucleosides (11) and (20) showed some activity against LoVo human colon adenocarcinoma.