Table 7.
In vitro ADME and in vivo PK.
| Cpd | % turnover by liver microsomes in 30 min |
Mouse Fu,pla | Predicted Fu,plb | clogPc | PO AUC (nM*h) | PO Cmax (nM) | PO Tmax (h) | PO t1/2 (h) | IV clearance (mL/min/kg) | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mouse | Rat | Human | |||||||||
| 44 | 98.2 | 99.2 | 68.1 | 0.015 | 0.020 | 4.33 | 676 | 604 | 0.25 | 1.05 | 182 |
| 48 | 52.1 | 52.7 | 32.8 | 0.007 | 0.006 | 5.25 | 2750 | 958 | 0.75 | 2.49 | 33.5 |
| 49 | 12.5 | 21.8 | 30.6 | ND | 0.048 | 3.25 | 187 | 62.8 | 1.5 | ND | 248 |
a
Fu,pl is the fraction unbound in plasma.
b
Predicted value using a QSAR model built based on data generated for >3000 compounds measured internally (unpublished).
c
clogP was predicted by Chemaxon model (www.chemaxon.com).