Table 7.
ADME measurements of 1 and analogs
| Compound | Aqueous Solubility (uM) |
Human PPB (%) |
HLM Clint (µL/min/mg) |
HLM t1/2 (min) |
Rat Hepatocyte Clint (µL/min/106) |
Rat Hepatocyte t1/2 (min) |
logD 7.4 |
|---|---|---|---|---|---|---|---|
| 1 | 6.33 | > 99.9 | 24 | * | 24.9 | * | 4.0 |
| 46 | 298 | 98.61 | 22.6 | * | 81.4 | * | 2.0 |
| 47a | 4.02 | 99.8 | 15.5 | * | 17.2 | * | 4.3 |
| 47b | 12.2 | 99.8 | 12.9 | * | 29.3 | * | 4.5 |
| 47c | < 1 | 99.9 | 34.2 | * | 33.6 | * | 4.0 |
| 47d | 3.77 | > 99.9 | 43.8 | * | 49.7 | * | 4.1 |
| 47e | 19 | * | 80.9 | 8.6 | 98.8 | 7 | * |
| 47f | 32 | * | 142 | 4.9 | 33.3 | 20.8 | * |
| 47g | * | * | * | * | 7.96 | 87.1 | * |
| 48a | 21 | 99.8 | 36 | * | 30.7 | * | 4.3 |
| 48b | 4.26 | 99.9 | 22.5 | * | 17 | * | 3.7 |
| 48c | 11.7 | > 99.9 | 135 | * | 61.7 | * | 4.0 |
| 48d | * | * | * | * | > 300 | < 2.3 | * |
| 48e | * | > 99.9 | 51.6 | * | 100 | * | 4.9 |
| 48f | < 1 | > 99.9 | 33.9 | * | 22.5 | * | 4.3 |
| 48g | 1.39 | > 99.9 | 27.3 | * | 18.7 | * | 4.7 |
| 48h | 11 | > 100 | 64.2 | * | 115 | * | 4.0 |
| 48j | 0.3 | 100 | * | * | 38.8 | * | 4.4 |
| 48k | < 1 | 99.0 | 21.1 | * | 12.8 | * | 4.9 |
*
Not obtained