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

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

− 0.32

1.64

2.52

2.14

2.54

Stability

t_1/2 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