Table 3.
ADMET profile for the active hybrids 5a, 5f, 8b, 8c, 8e, and 8g.
| Comp. | HIA | Caco2 | MDCK | BBB | CYP3A4 inhibition | PgP inhibition | Carcinogenicity |
|---|---|---|---|---|---|---|---|
| 5a | 77.05 | 0.79 | 1.98 | 0.10 | Non | Inhibitor | Negative |
| 5f | 94.80 | 0.99 | 1.03 | 0.21 | Inhibitor | Inhibitor | Negative |
| 8b | 98.38 | 37.30 | 0.55 | 1.74 | Non | Inhibitor | Negative |
| 8c | 97.94 | 41.54 | 0.02 | 1.86 | Non | Inhibitor | Positive |
| 8e | 99.08 | 25.04 | 0.87 | 1.65 | Non | Inhibitor | Negative |
| 8g | 100.00 | 23.56 | 0.26 | 0.35 | Inhibitor | Inhibitor | Negative |
| Epalrestat | 99.52 | 21.44 | 99.45 | 0.18 | Non | Inhibitor | Negative |
HIA: human intestinal absorption (%); Caco2: permeability through cells derived from human colon adenocarcinoma (nm/s); MDCK: permeability through Madin-Darby canine kidney cells (nm/s); tool for rapid permeability; BBB: blood–brain barrier penetration; CYP3A4: cytochrome P450 3A4; PgP: P-glycoprotein.