Table 6.
In silico drug-likeness and ADMET properties of the most inhibitory compounds.
| Drug-likeness | Compounds |
||||
|---|---|---|---|---|---|
| 5 | 11 | 16 | 22 | 24 | |
| Partition coefficient (logP) | 4.700 | 3.770 | 3.990 | 3.520 | 3.100 |
| Molecular weight | 469.550 | 577.690 | 563.710 | 547.660 | 491.060 |
| Number of H-bond acceptors | 5 | 8 | 8 | 7 | 7 |
| Number of H-bond donors | 1 | 1 | 1 | 1 | 1 |
| Number of rotatable bonds | 7 | 11 | 11 | 9 | 8 |
| Lipinski's violations | 0 | 1 | 1 | 1 | 0 |
| Water solubility (log mol/L) | −5.193 | −4.159 | −3.440 | −2.849 | −2.563 |
| Polar surface area (Å2) | 54.460 | 87.240 | 70.170 | 78.010 | 60.940 |
| PAINS alert | 0 | 0 | 0 | 0 | 0 |
| Absorption | |||||
| Caco-2 permeability (log cm/s) | −4.935 | −4.989 | −5.197 | −5.134 | −4.899 |
| Human intestinal absorption (%) | 99.700 | 99.900 | 99.900 | 99.800 | 99.300 |
| Distribution | |||||
| Volume distribution (L/kg) | 2.328 | 1.830 | 2.109 | 2.319 | 2.357 |
| BBB penetration (log cm/s) | −0.188 | −0.072 | −0.038 | −0.041 | −0.010 |
| Metabolism | |||||
| CYP1A2 inhibitor | No | No | No | No | No |
| CYP2C19 inhibitor | No | Yes | Yes | Yes | No |
| CYP2C9 inhibitor | Yes | Yes | No | No | No |
| CYP2D6 inhibitor | Yes | Yes | Yes | Yes | Yes |
| CYP3A4 inhibitor | Yes | Yes | Yes | Yes | Yes |
| Excretion | |||||
| Half-life | 0.015 | 0.017 | 0.017 | 0.072 | 0.029 |
| Toxicity | |||||
| Ames toxicity | 0.833 | 0.289 | 0.046 | 0.030 | 0.144 |
| Rat oral acute toxicity | 0.436 | 0.426 | 0.326 | 0.786 | 0.429 |
| Carcinogenicity | 0.092 | 0.388 | 0.088 | 0.125 | 0.088 |