Table 6. In Vitro Metabolic and Plasma Stability of Compounds 5, 8, 10, and 28.
| model system | 5 | 8 | 10 | 28 | |
|---|---|---|---|---|---|
| mouse liver S9 | T1/2 [min]a | 23 ± 3 | 11 ± 3 | 20 ± 5 | 23 ± 3 |
| Clint [μL/min/mg]a | 31 ± 4 | 66 ± 20 | 36 ± 10 | 31 ± 4 | |
| human liver S9 | T1/2 [min]a | 91 ± 19 | 53 ± 11 | 69 ± 12 | >120 |
| Clint [μL/min/mg]a | 8 ± 2 | 14 ± 3 | 10 ± 2 | <5 | |
| mouse plasma | T1/2 [min]a | >150 | >150 | >150 | >150 |
| % at 2.5 ha | >100 | >100 | >100 | >100 | |
| human plasma | T1/2 [min]a | >150 | >150 | >150 | >150 |
| % at 2.5 ha | >100 | >100 | >100 | >100 | |
| PPB mouse [%] | 98.9 ± 0.1 | 98.2 ± 0.3 | 96.9 ± 0.1 | 99.7 ± 0.1 | |
| PPB human [%] | 99.9 ± 0.1 | 98.1 ± 0.1 | 96.3 ± 0.3 | 99.7 ± 0.1 | |
| HepG2 cytotoxicity | CC50 [μM]a | 29 ± 7 | 62 ± 15 | 40 ± 5 | >100 |
a
Assays were performed in duplicate as independent experiments (n = 2); values are shown as mean ± SD.