6-Methyl-5-Azacytidine-Synthesis, Conformational Properties and Biological Activity. A Comparison of Molecular Conformation with 5-Azacytidine

Abstract The title compound was prepared by the isocyanate procedure and the tri-methylsilyl method. The measurement of 1H NMR spectrum of 6-methyl-5-azacytidine (1) revealed a preference of γt (46%) rotamer around C(5′)-C(4′) bond, a predominance of N conformation of the ribose ring (Keq 0.33) and a preference of syn conformation around the C-N glycosyl bond. An analogous measurement of 5-azacytidine has shown a preference of γ+ (60%) rotamer around the C(5′)-C(4′) bond, a predominance of N conformation of the ribose ring (Keq 0.41) and a preference of anti conformation around the C-N glycosyl bond. 6-Methyl-5-azacytidine (1) inhibits the growth of bacteria E. coli to the extent of 85% at 4000 μM concentration and the growth of LoVo/L, a human colon carcinoma cell line, to the extent of 30% at 100 μM concentration but did not inhibit L1210 cells at ≤ 100 μM concentration. 6-Methyl-5-azacytidine (1) exhibited no in vitro antiviral activity at ≤ 1 μM concentration. + Present address: Beckman, 2500 Harbor B...

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