Skip to main content

Advertisement

Table 1 Structure, log P value, stability, and pharmacokinetics of DAC and 5′-O-trialkylsilylated DACs

From: Novel prodrugs of decitabine with greater metabolic stability and less toxicity

  DAC OR-2003 OR-2009 OR-2100 OR-2102
  R 1 H H H H H
R 2 H H H H H
R3 = R4 H H H H H
R 5 Methyl Methyl Ethyl Ethyl
R 6 Methyl Methyl Ethyl Ethyl
R 7 n-Propyl c-Hexyl Ethyl n-Propyl
Log P value − 0.32 1.64 2.52 2.14 2.54
Stability t1/2 in PBS 20 h* 20** + 1 h 20** + 14 h 20** + 16 h 20** + 19 h
Enzymatic Complete degradation after 0.5 h Retain 52% after 1 h Retain 75% after 2 h Retain 84% after 2 h Retain 46% after 2 h
AUC 0 → lim (μM·hr) OR compound 0.305 0.314 0.168 0.081
DAC 0.378 0.338 0.238 0.266 0.285
Total 0.378 0.643 0.552 0.434 0.366
  1. DAC decitabine, PBS phosphate-buffered saline
  2. *Reference: Yoo C.B. et al. Cancer Research 2007; 67:6400–6408
  3. **20 h: t1/2 in PBS of DAC