Table 3. Mouse microsomal stability and in vivo mouse pharmacokinetic data of 1 and fluorinated analogs 20a, c, d.
| Parameter | 1 | 20a | 20c | 20d |
|---|---|---|---|---|
| Microsomal t1/2 (min) | ∼10a | ∼10a | 214 | 16 |
| t max (h)b | 0.25 | nd | 0.5 | nd |
| C max (μM)b | 46.1 | nd | 19.9 | nd |
| AUC0-inf (h μM)b | 88 | nd | 114 | nd |
| CLobs (mL min−1 kg−1) | 12.1 | nd | 8.85 | nd |
| t 1/2 (h)c | 8.5 | nd | 5.2 | nd |
| % F | 57 | nd | 58 | nd |
| V d (L) | 3.5 | nd | 3.8 | nd |
a
Approximate, see SI.
b
Oral dosing 40 mg kg−1, first oral time point is 0.25 h.
c
Oral, 40 mg kg−1, reflects elimination phase only (4–24 h).