Table 9 ADMET properties of selected compounds.
Pharmacokinetic parameters | CI | CII | CIII | CIV | CV | CVI |
|---|---|---|---|---|---|---|
Water solubility | − 5.2 | − 7.3 | − 7.2 | − 4.80 | − 4.7 | − 4.8 |
Caco-permeability | 1.211 | 1.192 | 1.204 | 0.77 | 0.79 | 0.79 |
HIA | 0.999 | 0.995 | 0.994 | 0.997 | 1.00 | 0.99 |
Skin permeability | − 2.84 | − 2.61 | − 2.84 | − 2.71 | − 2.18 | − 2.73 |
P-glycoprotein substrate | Yes | No | Yes | No | Yes | Yes |
BBB permeability | 0.9 | 0.96 | 0.98 | 0.96 | 0.97 | 0.96 |
CNS permeability | − 2.89 | − 2.11 | − 1.59 | − 1.4 | − 1.70 | − 1.42 |
Gastrointestinal absorption | Yes | Yes | Yes | Yes | Yes | Yes |
Skin sensitization | No | Yes | No | No | No | No |
Subcellular localization | Mt | Mt | Lysosome | Lysosome | Lysosome | Lysosome |
Inhibitor of CYP1A2 | None | None | None | None | None | None |
Inhibitor of CYP2C19 | Yes | None | None | None | None | None |
Inhibitor of CYP2C9 | None | None | None | None | None | None |
Inhibitor of CYP2D6 | None | None | None | None | None | None |
Inhibitor of CYP3A4 | None | None | None | None | None | None |
AMES toxicity | No | No | No | No | No | No |
Hepatotoxicity | Yes | Yes | No | No | No | No |
Tolerated dose in human | 0.277 | − 0.527 | − 0.57 | − 0.303 | − 0.576 | − 0.351 |
ROT (LD50) | 1.652 | 1.583 | 3.09 | 2.83 | 2.6 | 3.2 |
Chronic rat toxicity | 2.7 | 0.925 | 0.747 | 0.806 | 0.855 | 0.855 |
Drug plasma clearance | 1.964 | 1.425 | 0.529 | 0.262 | 0.628 | 0.388 |
T. pyriformis toxicity | 0.345 | 1.229 | 0.586 | 0.305 | 0.43 | 0.294 |
Minnow toxicity | 0.943 | − 0.816 | − 1.029 | − 1.928 | − 1.802 | − 1.714 |
hERG I inhibitor | No | No | No | No | No | No |
hERG II inhibitor | No | Yes | Yes | Yes | Yes | Yes |
Renal OCT2 substrate | No | No | No | No | No | Yes |
