Due to the varied and potent biological activity of 3-deazaguanine (20), 3-deaza-7-i3-~-ribofuranosylguanine, 3deazaguanosine (22). and 3-deazaguanylic acid (21). several 3-deazaguanines, mainly wit,h modification in the 7 and 9 positions, were prepared. 7-(5-Deoxy-r)-~-ribofuranosyl)-and 7-(tetrahydropyran-2-yl)-3-deazaguanine (12 and 13) were obtained by ammonolysis of the corresponding 1-substituted methyl 4-(cyanomethyl)imidazole-5-carboxylates, 6 and 8, and subsequent in situ cyclization. 9-(5-Deoxy-i3-D-ribofiiranosyl)-and 9-(t,etrahydropyran-2-yl)-3-deazaguanine (14 and 15) were obtained by ammonolysis of the corresponding 1 -substituted methyl 5-(cyanomethyl)imidazole-4-carboxylates, 5 and 7, to provide 1-(5-deoxy-3-D-ribofuranosyI)-and l-itet,rah~dropyran-2-y1)-5-(cyanoniethyl)imidazole-4-carboxamides (9 and 10, respectively), which were subsequently cyclized with aqueous potassium carbonate. Methyl 4-(cyanomethyl)-lor -3-(5-deoxy-2,3-di-0-acetyl-~-~-ribofuranosyl)imidazole~~-carhoxylates, 5 and 6, were obtained from the stannic chloride catalyzed condensation of methyl 5(4)-(cyanomethyl)-l-(trimethylsilyl)imidazole-4(5)-carboxylate (2) and ~-deoxy-l,2,3-tri-~-acety~-3-D-rihof~ira~iose (3). Methyl 4(5)-(cya. nomethyl)imidazole-5(4)-carhoxylate i 1 ) and dihydropyran in the presence of acid provided the tetrahydropyran-2-yl derivatives 7 and 8. The in vitro antiviral and antihacterial activity of these :<-deazaguanines, their imidazolecarboxamide precursors, and several acetylated derivatives were compared with kleazaguanine (20),3-deazaguanosine (22). and 3-deazaguanylic acid (241, their imidazolecarboxamde precursors, 4(5)-(cyanomethyl)imidazole-5(4)carboxamide (191, 6-(cyanomethyl)-l-,~-~-ribofuranosylimidazole-4-carboxamide (21). and 5-(cyanon~ethyl)-1-3-D-ribofuranosylimidazole-4-carhoxamide 5'-phosphate (23), and ribavirin. The most active compounds. 19. 21, and 23, possessed an in vitro antiviral spectrum similar to, hut generally less potent than, the corresponding ring-closed compounds 20, 22, and 21. Compound 23 was found to he a potent, specific inhibitor of IMP dehydrogenase. Data are presented which support the antiviral activity of 19.21, and 23 independent of the possible enzymatic cycliz,at,ion to the corresponding imidazo[4,5-~]pyidine.
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