Table 8.
ADME profile of compounds 12d, 12i, and 12 l
| Parameter | 12d | 12i | 12l |
|---|---|---|---|
| Physicochemical properties | |||
| Molecular weight | 383.46 | 447.51 | 451.93 |
| Num. heavy atoms | 27 | 32 | 31 |
| Num. H-bond acceptors | 4 | 5 | 4 |
| Num. H-bond donors | 2 | 2 | 2 |
| Molar Refractivity | 107.02 | 125.24 | 123.75 |
| TPSA | 109.53 Ų | 118.76 Ų | 109.53 Ų |
| Consensus Log Po/w | 3.34 | 3.98 | 4.48 |
| Log S (ESOL) | Moderately soluble | Moderately soluble | Moderately soluble |
| Drug likeness | |||
| Lipinski violations | Yes; 0 violation | Yes; 0 violation | Yes; 0 violation |
| Ghose violations | Yes | Yes | Yes |
| Veber violations | Yes | Yes | Yes |
| Bioavailability Score | 0.55 | 0.55 | 0.55 |
| Pharmacokinetics | |||
| GI absorption | High | Low | Low |
| BBB permeant | No | No | No |
| CYP1A2 inhibitor | Yes | Yes | Yes |
| CYP2C19 inhibitor | Yes | Yes | Yes |
| CYP2C9 inhibitor | Yes | Yes | Yes |
| CYP2D6 inhibitor | Yes | Yes | Yes |
| CYP3A4 inhibitor | Yes | Yes | Yes |