Table 4.
Comparative plasma and brain pharmacokinetic properties of parent 2 and lead compound 5B in fasting mice a.
| Cpd 2 (50 mg/kg PO) | Cpd 5B (50 mg/kg PO) | |||
|---|---|---|---|---|
| total Plasma | free Plasma | total Plasma | free Plasma | |
| Cmax (ng/mL) | 39011 | 1428 | 33619 | 1523 |
| T1/2 (h) | 1.280 | 1.67 | ||
| AUC0-last (ng.h/mL) | 30612 | 1121 | 59567 | 2697 |
| MRT0-last (h) | 1.01 | 1.92 | ||
| total Plasma | free Plasma | total Plasma | free Plasma | |
| Cmax (ng/g) | 10001 | 970 | 13480 | 774 |
| T1/2 (h) | 0.999 | 1.77 | ||
| AUC0-last (ng.h/g) | 7392 | 717 | 23465 | 1347 |
| MRT0-last (h) | 0.959 | 1.98 | ||
a
Free compound concentrations were calculated from protein binding assays: 2 – mouse plasma 96.7%, mouse brain 90.3%; 5B – mouse plasma 95.5%, mouse brain 94.3%.