Fig. 1

Synthesis and isolation of hydrophilic compounds with disparate stability. a Structures of 5′-O-trialkylsilylated AZAs or DACs. A variety of 5′-O-trialkylsilylated DACs were synthesized that were potentially resistant to deamination by cytidine deaminase and spontaneous hydrolytic cleavage of the triazine ring. b Luciferase activity of DAC, guadecitabine, and four compounds. From the 5′-O-trialkylsilylated DACs that showed a strong luciferase activity, OR-2003, OR-2009, OR-2100, and OR-2102 were selected. c Comparison of plasma concentrations of the four compounds with DAC. Pharmacokinetics of the four compounds were analyzed using mice administered a compound at the same molar concentrations as DAC. d Depletion of DNMT1 by DAC, OR-2003, and OR-2100. Levels of DNMT1 protein in cells treated with a compound were analyzed using western blotting. The DNMT1 protein showed a dose-dependent decrease, and at doses higher than 3 μM, DNMT1 was depleted