Table 4.
Metabolic Stability with Human and Mouse Liver Microsomesa and Aqueous Solubility of Compounds 18, 20, 55, and 57
| compd | % remaining at 30 minb
|
solubility (μM)b,d | |
|---|---|---|---|
| human liver microsomes | mouse liver microsomes | ||
| 18 | 48.6 ± 1.9 | 10.3 ± 0.4 | 64.5 ± 0.7 |
| 20 | 12.0 ± 1.1 | 0.6 ± 0.1 | 4.0 ± 0.1 |
| 55 | 19.3 ± 0.9 | 2.8 ± 0.3 | 20.5 ± 0.7 |
| 57 | 17.7 ± 0.5 | 7.9 ± 0.2 | 5.0 ± 0.1 |
| 7-ethoxycoumarinc | 6.6 ± 0.2 | 0.07 ± 0.02 | |
| propranololc | 54.1 ± 0.4 | 20.6 ± 0.5 | |
a
Metabolic stability: >50, good; 10–50, medium; <10, low.
b
Results are expressed as mean ± SD, n = 2.
c
The standard compounds 7-ethoxycoumarin and propranolol showed metabolic stability in agreement with the literature and internal validation data.36
d
pH 7.4, high throughput screening solubility assay.