Table 2.
In silico prediction of druglike properties.
| Properties | 1 | 2 | 3 | 4 |
|---|---|---|---|---|
| MW | 382.5 | 420.5 | 330.4 | 340.4 |
| LogP* | 5.76 | 7.29 | 5.72 | 5.38 |
| LogP | 5.27 | 6.98 | 5.11 | 5.57 |
| TPSA** | 54 | 36.9 | 47.9 | 36.9 |
| Solubility** | low | low | low | low |
| Permeability (Caco-2) | moderate | moderate | moderate | moderate |
| Pgp inhibitor | yes | yes | yes | yes |
| Pgp substrate | yes | yes | yes | yes |
| HIA (>/=30%) | yes | yes | yes | yes |
| Oral bioavailability | ≥30% F | ≥20% F | ≥30% | ≥30% |
| Protein binding | moderate | moderate | moderate | moderate |
| Distribution (VD) | low | good | good | good |
| CYP3A4 inhibitor | yes | yes | no | no |
| CYP2C9 inhibitor | no | yes | no | no |
| CYP3A4 substrate | yes | yes | yes | yes |
| CYP2C9 substrate | yes | yes | yes | yes |
| Clearance | low | low | low | low |
| hERG | yes | yes | yes | yes |
| Hepatotoxicity | yes | no | yes | yes |
| AMES | no | no | no | no |
| DILI | yes | yes | yes | yes |
| Phospholipidosis* | no | no | no | no |
| Lilly Med Chem Rules* | phenolic ester | pass | pass | pass |
| PAINs* | no | no | no | no |
ADMETlab was used to predict all values except: *Predicted using FAF-drugs4 and **Predicted using both ADMETlab and FAF-drugs4.