TABLE 7.
Pharmacokinetic parameters important for good oral bioavailability and drug likeness of targets compounds 3a–3i, 4a–4i, and 6a–6e.
| Compound | % ABS | TPSA (Å2) | n-ROTB | MW | miLogP | HBD | HBA | Lipinski’s violation | LogBB |
|---|---|---|---|---|---|---|---|---|---|
| Rule | — | — | <10 | <500 | ≤5 | ≤5 | ≤10 | ≤1 | — |
| 3a | 94.1 | 43.09 | 1 | 196.21 | 1.51 | 0 | 4 | 0 | −0.27 |
| 3b | 94.1 | 43.09 | 1 | 214.20 | 1.68 | 0 | 4 | 0 | −0.24 |
| 3c | 94.1 | 43.09 | 1 | 230.66 | 2.19 | 0 | 4 | 0 | −0.17 |
| 3d | 94.1 | 43.09 | 1 | 230.66 | 2.15 | 0 | 4 | 0 | −0.17 |
| 3e | 94.1 | 43.09 | 1 | 265.10 | 2.80 | 0 | 4 | 0 | −0.07 |
| 3f | 94.1 | 43.09 | 1 | 275.11 | 2.32 | 0 | 4 | 0 | −0.15 |
| 3g | 78.3 | 88.92 | 2 | 241.21 | 1.47 | 0 | 7 | 0 | −0.95 |
| 3h | 94.1 | 43.09 | 1 | 210.24 | 1.96 | 0 | 4 | 0 | −0.20 |
| 3i | 90.9 | 52.33 | 2 | 226.24 | 1.57 | 0 | 5 | 0 | −0.40 |
| 4a | 98.6 | 30.20 | 1 | 195.22 | 2.25 | 0 | 3 | 0 | 0.03 |
| 4b | 98.6 | 30.20 | 1 | 213.22 | 2.41 | 9 | 3 | 0 | 0.06 |
| 4c | 98.6 | 30.20 | 1 | 229.67 | 2.88 | 0 | 3 | 0 | 0.13 |
| 4d | 98.6 | 30.20 | 1 | 229.67 | 2.92 | 0 | 3 | 0 | 0.14 |
| 4e | 98.6 | 30.20 | 1 | 264.12 | 3.53 | 0 | 3 | 0 | 0.23 |
| 4f | 98.6 | 30.20 | 1 | 274.12 | 3.06 | 0 | 3 | 0 | 0.16 |
| 4g | 82.8 | 76.02 | 2 | 240.22 | 2.21 | 0 | 6 | 0 | −0.65 |
| 4h | 98.6 | 30.20 | 1 | 209.25 | 2.69 | 0 | 3 | 0 | 0.10 |
| 4i | 95.4 | 39.43 | 2 | 225.25 | 2.30 | 0 | 4 | 0 | −0.09 |
| 6a | 90.9 | 52.33 | 4 | 254.29 | 2.45 | 0 | 5 | 0 | −0.26 |
| 6b | 90.9 | 52.33 | 5 | 268.32 | 3.01 | 0 | 5 | 0 | −0.18 |
| 6c | 90.9 | 52.33 | 6 | 282.35 | 3.52 | 0 | 5 | 0 | −0.10 |
| 6d | 90.9 | 52.33 | 7 | 296.37 | 4.02 | 0 | 5 | 0 | −0.02 |
| 6e | 90.9 | 52.33 | 4 | 302.34 | 3.17 | 0 | 5 | 0 | −0.15 |
%ABS, percentage of absorption; TPSA, topological polar surface area; MW, molecular weight; miLogP, Log P calculated by Molinspiration online services; HBD, number of H-bond donors; HBA, number of H-bond acceptors; n-ROTB, number of rotatable bonds; LogBB, the ratio of the steady-state concentrations of a compound between the brain and the blood [i.e., log (Cbrain/Cblood)]. logBB = −0.0148 × PSA + 0.152 × clogP + 0.139.