3-DEAZA-5'-NORARISTEROMYCIN AND 7-DEAZA-5'-NORARISTEROMYCIN AND THEIR ANTIVIRAL PROPERTIES

An enantiospecific synthesis of 3-deaza-5'noraristeromycin as its dihydrochloride ((-)-6) has been accomplished in six steps beginning with the reaction of (+)-(1R,4S)d-hydroxy-2-cyclopenten-1-yl acetate with 4-chloro-1H-imidazo[4,5-c]pyridine. The preparation of 7-deaza-5'-noraristeromycin ((-)-7) was described previously. Compounds (-)-6 and (-)-7 were evaluated for antiviral activity against a large number of viruses. Compound (-)-6 produced an antiviral activity pattern similar to 5'-noraristeromycin but was less potent. Compound (-)-6 inhibited CEM cell proliferation at a 50% inhibitory concentration of 27 mu g/mL but proved not inhibitory to HEL cell proliferation and not toxic to E(6)SM, HeLa, Vero, and MDCK cells at concentrations up to 200 mu g/mL. While (-)-6 showed inhibition of S-adenosyl-L-homocysteine (AdoHcy) hydrolase, it was less inhibitory than 5'-noraristeromcyin. Compound(-)-7 displayed no antiviral properties or inhibitory effects toward AdoHcy hydrolase.