NUCLEOSIDES & NUCL20TIDES, 11(5), 1059-1076 (1992) 8-AZA ANALOGUES OF DEAZA PURINE NUCLEOSIDES. SYNTHESIS AND BIOLOGICAL EVALUATION OF 8-AZA-l- DEAZAADENOSINE AND 2 , -DEOXY-8-AZA-l-DEAZAADENOSI- NE. Palmarisa Franchetti,*"*- Loredana Cappellacci, 4" Mario Grifantini,"1" Giulio Lupidi, 0 Giuseppe Nocentini § and Anna Barzi§ + Dipartimento di Scienze Chimiche, Università di Camerino, 62032 Camerino, °Dipartimento di Biologia Cellulare, Università di Camerino, §Istituto di Farmacologia Medica, Università di Perugia, 06100 Perugia, Italy. Abstract -.The syntheses of 7-amino-3-(p-D-ribofuranosyl)-3//-1,2,3- triazolo[4,5-b]pyridine (8-aza-l-deazaadenosine) (2) and 7-amino-3-(2-deoxy- p-D-eryr/iro-pentofuranosyl)-3//-l,2,3-triazolo[4,5-b]pyridine (2'-deoxy-8-aza- 1-deazaadenosine) (3) by glycosylation of the anion of 7-chloro-3//-1,2,3-tri- azolo[4,5-b]pyridine are described. The anomeric configuration as well as the position of glycosylation were determined by *H, 1 3 C N M R , U V and N.O.E. difference spectroscopy. The cytotoxicity of these nucleosides against several murine and human tumor celi lines is discussed. Compounds 2 and 3 proved to be good inhibitors of aden%sine deaminase. The 3//-l,2,3-triazolo[4,5-d]pyrimidine (8-azapurine) nucleosides exhibit extraordinary biochemical and pharmacological activities.* In many bio- logical systems, they act as nucleoside antimetabolites. As they are isosteric to purine nucleosides, their incorporation into D N A or R N A fragment is of interest. The observance of in vivo activity for 8-azaadenosine, 8-azainosine and 8-azaguanine has served as the basis for the synthesis of a variety of congeners.l Ali three of these compounds are thought to be activated by conversion to the nucleotides of 8-azaadenosine or 8-azaguanosine, followed by incorporation into RNA. Furthermore it was observed that 8-aza-2'- deoxyadenosine has an antitumor activity slightly lower than that of 8- azaadenosine. * 1059 Copyright© 1992 by Marcel Dekker, Inc.