Table 2.
Calculated physicochemical and ADME properties of compounds 5b and 5d.
| Property | 5b | 5d |
|---|---|---|
| Molecular weight | 385.50 g/mol | 385.50 g/mol |
| Num. heavy atoms | 29 | 29 |
| Num. arom. heavy atoms | 21 | 21 |
| Fraction Csp 3 | 0.24 | 0.24 |
| Num. rotatable bonds | 9 | 6 |
| Num. H-bond acceptors | 2 | 2 |
| Num. H-bond donors | 1 | 1 |
| Molar Refractivity | 118.71 | 119.18 |
| TPSA | 42.94 Å2 | 42.94 Å2 |
| GI absorption | High | High |
| BBB permeant | Yes | Yes |
| P-gp substrate | Yes | Yes |
| CYP1A2 inhibitor | Yes | Yes |
| CYP2C19 inhibitor | Yes | Yes |
| CYP2C9 inhibitor | Yes | Yes |
| CYP2D6 inhibitor | Yes | Yes |
| CYP3A4 inhibitor | Yes | Yes |
| Log Kp (skin permeation) | −5.02 cm/s | −4.91 cm/s |
| Lipinski | Yes; 1 violation: MLOGP>4.15 | Yes; 1 violation: MLOGP>4.15 |
| Ghose | Yes | Yes |
| Veber | Yes | Yes |
| Egan | Yes | Yes |
| Muegge | No; 1 violation: XLOGP3>5 | No; 1 violation: XLOGP3>5 |
| Bioavailability Score | 0.55 | 0.55 |