Table 4. Pharmacokinetic Properties of 4 and 21 (DS21360717) in Mouse.
| compound | metabolic stabilitya (% remaining) | solubility (pH 6.8/FaSSIF)b (μg/mL) | protein bindingc (% bound) | Pe (pH 7.4) (10–6 cm/s) | CLtotd (mL/min/kg) | AUCe (μg·h/mL) | Cmaxe (μg/mL) | BA (%) |
|---|---|---|---|---|---|---|---|---|
| 4 | 100 | 35/49 | 99 | 16 | 12 | 2.4 | 0.42 | 17 |
| 21(DS21360717) | 96 | 0.9/2.1 | 99 | >50 | 12 | 4.8 | 0.36 | 34 |
a
Remaining rate of test compounds (1.0 μM) after incubation for 30 min in mouse liver microsomes (1.0 mg/mL).
b
Solubility: μg/mL in pH 6.8 buffer and FaSSIF.
c
Protein binding was tested by BALB/c mice serum samples.
d
Compounds were dosed iv at 1 mg/kg.
e
Compounds were dosed po at 10 mg/kg. The statistics are shown in the Supporting Information.