Table 9.
ADME properties of compounds 4c–e.
| Entry | Compounds | ||
|---|---|---|---|
| 4c | 4d | 4e | |
| Physicochemical properties/lipophilicity/druglikeness | |||
| Molecular weight (g/mol) | 257.25 | 242.19 | 238.20 |
| Num. heavy atoms | 19 | 18 | 18 |
| Num. arom. heavy | 11 | 11 | 11 |
| Fraction Csp3 | 0.17 | 0.00 | 0.00 |
| Num. rotatable bonds | 4 | 3 | 1 |
| Num. H-bond acceptor | 6 | 6 | 5 |
| Num. H-bond donors | 1 | 1 | 2 |
| Molar refractivity | 67.09 | 62.93 | 64.43 |
| TPSA (Å2) | 96.71 | 124.07 | 107.35 |
| Consensus log Po/w | 1.20 | 0.69 | 0.42 |
| Lipinskiˈs rule | Yes | Yes | Yes |
| Bioavailability score | 0.56 | 0.56 | 0.56 |
| Pharmacokinetics | |||
| GI absorption | High | High | High |
| BBB permeant | No | No | No |
| P-gp substrate | No | No | No |
| CYP1A2 inhibitor | No | No | No |
| CYP2C19 inhibitor | No | No | No |
| CYP2C9 inhibitor | No | No | No |
| CYP2D6 inhibitor | No | No | No |
| CYP3A4 inhibitor | No | No | No |
| Log Kp (cm/s) | − 6.94 | − 6.93 | − 7.70 |