Table 6.
Summary of in vitro pharmacokinetic properties for ML240 and ML241.
| Compd | Aqueous solubility [μg mL−1]a | PAMPA Pe [×10−6 cm s−1]b | PPB [%]c | PS [%]d | HMS [%]e | LC50 [μm]f | |
|---|---|---|---|---|---|---|---|
| human | mouse | ||||||
| ML240 | 0.35 (5.0)/0.33 (6.2)/0.27 (7.4) | 357 (5.0)/628 (6.2)/<60.3 (7.4) | 99.53/99.71 | 99.73/99.63 | 100/100 | 54.28/0.63 | 8.5 |
| ML241 | 28 (5.0)/0.13 (6.2)/0.20 (7.4) | 1164 (5.0)g/2504 (6.2)g/2278 (7.4)g | 99.97/99.95 | 99.95/99.91 | 100/100 | 18.97/2.57 | >50 |
a
In aqueous buffer, pH 5.0/6.2/7.4.
b
In aqueous buffer, donor compartment pH 5.0/6.2/7.4; acceptor compartment pH 7.4.
c
Plasma protein bound, 1 μm/10 μm.
d
Plasma stability, percent remaining at 3 h; human/mouse.
e
Hepatic microsome stability, percent remaining at 1 h; human/mouse.
f
Hepatic toxicity toward Fa2N-4 immortalized human hepatocytes.
g
In the presence of 20% CH3CN.