'ANKAR NUCLEOSIDES & NUCLEOTIDES, 13(8), 1739-1755 (1994) zyxwvutsrqponmlkjihgfedcbaZYXWVU 8-AZA-l-DEAZAPURINE NUCLEOSIDES AS ANTIVIRAL AGENTS P. Franchetti, + * L. Messini, 4 * L. Cappellacci, 4 " G. Abu Sheikha 4 ", M . Grifantini, 4 * P. Guarracino, 0 A. De Montis, 0 A. G. Loi,° M . E . Marongiu, 0 and P. La Colla 0 zyxwvutsrqponmlkjihgfed +Dipartimento di Scienze Chimiche, Università di Camerino, 62032 Camerino, °Dipartimento di Biologia Sperimentale, Università di Cagliari, 09124 Cagliari, Italy. Abstract- 2',3'-Dideoxy-8-aza-l-deazaadenosine (21) and its oc-anomer (20) were synthesized via glycosylation of 7-chloro-3#-1,2,3-triazolo[4,5-&]pyridi- ne with 2,3-dideoxy-5-0-[(l ,l)-dimethylethyl)diphenylsilyl]-D zyxwvutsrqponmlkjihgfedcbaZYX -^/ycer6 >-pen- tofuranosyl chloride. The reaction gave a mixture of a- andzyxwvutsrqponmlkjihgfedcbaZYX P-anomers of N 3 -, N^- and -glycosylated regioisomers (12-15). The a- and p-anomers of the N^-glycosylated isomer 26 and 27 were also synthesized through the gly- cosylation of 8-aza-l-deazaadenine with l-acetoxy-2,3-dideoxy-5-0-[(l,l-di- methyiethyl)dimethylsilyl]-D-,g /ycer6 >-pentofuranose. These dideoxynucleo- sides and a series of previously synthesized 8-aza-l-deazapurine nucleosides were tested for activity against several DNA and RNA vinises, HIV-1 inchided. The a- and p-anomers of 7-chloro-3-(2-deoxy-D-eryf/zr <9 -pentofuranosyl)-3//- l,2,3-triazolo[4,5-£]pyridine (3a and 4) showed activities against Sb-1 and Coxs viruses. The a- and p-anomers of 2\3'-dideoxy-8-aza-l-deazaadenosine (20 and 21) were found active as inhibitors of adenosine deaminase. In vitro, 8-azapurine and 1-deazapurine nucleosides are endowed with a wide range of pharmacological activities. Following the discovery of the antibacterial and antitumor activity of 8-azaguanine, a variety of a and p anomers of 8-azaadenine nucleosides have been shown cytotoxic to tumor cells 1>2 or active as antiviral agents. 3 Previous studies from our laboratory have pointed out the activity of 1- deazaadenosine as an inhibitor of adenosine deaminase (ADA) 4 and blood platelet aggregation,^ as an adenosine receptor agonist,^ and as an antitumor agent. 7 1739 Copyright © 1994 by Marcel Dekker, Inc.