Table 3.
Phase I metabolic stability in liver microsomes t1/2 (min).
| Compd | HLMa | HLMa (+Cobic) | MLMb | MLMb (+Cobic) |
|---|---|---|---|---|
| PF74c | 0.7 | 91 | 0.6 | 34 |
| 3 | 1.2 | -- | 0.5 | -- |
| 7 | 1.8 | -- | 0.6 | -- |
| 16 | 7.0 | -- | 1 | -- |
| 20 | 1.5 | -- | 0.6 | -- |
| 24 | 6.7 | 107 | 1.4 | 34 |
| 25 | 1.8 | -- | 0.5 | -- |
| 27 | 2.7 | >120 | 1.4 | 18 |
| 31 | 0.6 | -- | 0.5 | -- |
| 33 | 1.1 | 102 | 0.6 | 7.4 |
| 37 | 4.7 | -- | 1.2 | -- |
| 46 | 5.2 | -- | 0.7 | -- |
| 47 | 3.3 | -- | 1.2 | -- |
| 48 | 1.1 | -- | 0.5 | -- |
| 50 | 2.5 | >120 | 1.1 | 20 |
a
HLM: human liver microsome
b
MLM: mouse liver microsome
c
Microsomal stability measured in the presence of CYP3A inhibitor Cobi.