Table 4.
ADMET profiling of the best 10 hits.
| ADMET Parameters | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
|---|---|---|---|---|---|---|---|---|---|---|
| Absorption | ||||||||||
| Water solubility (log mol/L) | −1.88 | −2.24 | −3.1 | −2.01 | −4.12 | −3.561 | −2.929 | −3.808 | −4.441 | −2.97 |
| Caco2 permeability (log Papp in 10−6 cm/s) | 0.14 | −0.31 | −0.17 | −0.49 | 0.67 | 1.337 | 1.027 | 1.21 | 1.376 | 0.108 |
| Intestinal absorption (human) (% Absorbed) | 42.81 | 32.3 | 45 | 25.50 | 93.15 | 95.325 | 96.606 | 96.34 | 91.364 | 61.309 |
| P-glycoprotein substrate (Yes/No) | NO | Yes | Yes | Yes | Yes | No | No | Yes | No | No |
| Distribution | ||||||||||
| BBB permeability (log BB) | −0.71 | −1.007 | −1.38 | −1.09 | −0.04 | −0.007 | −0.313 | 0.142 | 0.098 | −0.953 |
| CNS permeability (log PS) | −3.18 | −4.15 | −3.80 | −3.92 | −2.132 | −2.176 | −2.333 | −2.135 | −3.22 | −3.414 |
| Metabolism | ||||||||||
| CYP2D6 substrate (Yes/No) | No | No | No | No | No | No | No | Yes | No | No |
| CYP3A4 substrate (Yes/No) | No | No | No | No | Yes | Yes | Yes | Yes | No | No |
| CYP1A2 inhibitor (Yes/No) | No | No | No | No | Yes | No | No | No | No | No |
| CYP2C19 inhibitor (Yes/No) | No | No | No | No | No | No | No | No | Yes | No |
| CYP2C9 inhibitor (Yes/No) | No | No | No | No | No | No | No | No | No | No |
| CYP2D6 inhibitor (Yes/No) | No | No | No | No | No | No | No | No | No | No |
| CYP3A4 inhibitor (Yes/No) | No | No | No | No | No | No | No | No | No | No |
| Excretion | ||||||||||
| Total Clearance (log mL/min/kg) | 0.93 | 1.04 | 0.225 | 0.524 | 0.196 | 1.101 | 0.506 | 0.762 | −0.374 | 1.05 |
| Renal OCT2 substrate (Yes/No) | No | No | No | No | No | Yes | No | Yes | No | No |
| Toxicity | ||||||||||
| AMES toxicity (Yes/No) | No | No | No | No | No | No | No | No | No | No |
| Max. tolerated dose (human) (log mg/kg/day) | 0.89 | 1.50 | 0.847 | −0.224 | 0.039 | −0.465 | 0.2 | −0.741 | 0.171 | 0.906 |
| hERG I inhibitor (Yes/No) | No | No | No | No | No | No | No | No | No | No |
| Hepatotoxicity (Yes/No) | Yes | Yes | Yes | No | Yes | No | No | No | No | Yes |