Table 6. Physical Properties, ADME/PK Profiles.
| compound ID | GLS4 | 28a | |
|---|---|---|---|
| MW/tPSA | 508/76 | 484/100 | |
| CLogP/LogD | 4.7/4.4 | 2.7/2.8 | |
| KS (μM) | 14 | 22 | |
| liver/plasma ratio of AUC0–4h (μM·h) | 9 | 10 | |
| CYP (μM) 1A2/2C9/2C19/2D6/3A4 | >50/16/4/52/2 | >50/28/39/>50/11 | |
| IV (1 mpk) | T1/2 (h) | 1.5 ± 0.1 | 1.1 ± 0.1 |
| Vdss (L/kg) | 4.1 ± 0.6 | 2.0 ± 0.2 | |
| Cl (mL/min/kg) | 56 ± 7 | 21 ± 3 | |
| AUC0-last (μM·h) | 0.6 ± 0.1 | 1.7 ± 0.2 | |
| POa,b (10 mpk) | Cmax (μM) | 0.7 ± 0.1 | 4.7 ± 0.3 |
| AUC0-last (μM·h) | 0.8 ± 0.1 | 9.1 ± 1.5 | |
| F% | 14 | 54 | |
a
The single-dose pharmacokinetics of GLS4 and 28a was carried out in female Balb/c mice (n = 3) according to standard procedures.
b
Vehicle: 1.00 mg/mL in 0.5% HEC.