Table 3.
Molecular properties and drug-like scores of the active compounds. IC50 values of the 14 active compounds toward Kv1.1–1.2(3) (primary target) and Nav1.5, Cav1.2, and hERG (from the cardiac safety panel).
| ID | Set[a] | W[b] [Da] | A[c] | D[c] | Log P[d] | PSA[e] [Å2] | Vol[f] [Å3] | DL[g] | Kv1.1–1.2(3) | Nav1.5 | Cav1.2 | hERG | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AV[h] | SD | n | AV[h] | SD | n | AV[h] | AV[h] | SD | n | |||||||||
| 1 | A | 492 | 6 | 2 | 2.64 | 84 | 489 | 0.63 | 0.71 | 0.19 | 3 | 27.92 | 4.17 | 4 | +30 | +30 | 0 | 3 |
| 2 | A | 485 | 6 | 0 | 3.28 | 65 | 466 | 0.18 | 0.79 | 0.03 | 3 | +30 | 0 | 3 | +30 | +30 | 0 | 3 |
| 3 | A | 493 | 4 | 2 | 3.91 | 73 | 494 | −0.67 | 1.41 | 0.24 | 3 | 24.07 | 10.27 | 3 | 10.44 | 13.26 | 3.97 | 4 |
| 4 | A | 482 | 6 | 1 | 4.34 | 76 | 482 | 0.42 | 1.62 | 0.48 | 4 | 28.38 | 2.81 | 3 | 3.3 | 8.05 | 3.53 | 5 |
| 5 | A | 427 | 2 | 2 | 2.76 | 53 | 432 | 1.00 | 2.98 | 0.35 | 4 | 25.73 | 7.40 | 3 | +30 | +30 | 0 | 4 |
| 6 | A | 492 | 7 | 2 | 3.56 | 105 | 449 | −0.15 | 4.07 | 0.23 | 3 | +30 | 0 | 3 | 15.5 | +30 | 0 | 3 |
| 7 | A,B | 471 | 5 | 1 | 4.29 | 67 | 437 | 0.08 | 1.53 | 0.37 | 3 | +30 | 0 | 3 | 11.43 | +30 | 0 | 3 |
| 8 | B | 490 | 5 | 0 | 5.57 | 56 | 472 | 0.11 | 0.58 | 0.11 | 3 | +30 | 0 | 4 | 2.87 | 7.33 | 4.75 | 3 |
| 9 | B | 468 | 5 | 0 | 5.32 | 57 | 439 | −0.32 | 0.93 | 0.48 | 3 | 29.39 | 1.06 | 3 | 1.55 | 8.62 | 2.74 | 3 |
| 10 | B | 495 | 4 | 0 | 3.89 | 65 | 464 | 0.37 | 1.66 | 0.21 | 4 | +30 | 0 | 4 | 2.52 | 9.46 | 1.23 | 3 |
| 11 | B | 477 | 6 | 0 | 5.59 | 60 | 445 | 0.27 | 2.71 | 0.64 | 6 | 22.73 | 9.22 | 4 | 3.85 | 8.43 | 1.88 | 3 |
| 12 | B | 480 | 5 | 0 | 5.09 | 57 | 445 | −0.27 | 3.70 | 0.60 | 4 | +30 | 0 | 3 | 4.74 | 8.93 | 2.05 | 3 |
| 13 | B | 480 | 5 | 1 | 4.38 | 74 | 458 | 0.40 | 3.77 | 1.07 | 3 | 24.80 | 9.00 | 3 | 9.61 | +30 | 0 | 4 |
| 14 | B | 475 | 6 | 1 | 2.74 | 81 | 448 | 0.07 | 5.94 | 0.67 | 4 | +30 | 0 | 4 | 12.27 | +30 | 0 | 3 |
[a] Implementation that suggested the compound. [b] Molecular weight. [c] Number of hydrogen bond acceptors (A) and donors (D). [d] Partition coefficient. [e] Polar surface area. [f] Molecular volume. [g] Molsoft’s drug-likeness model score. [h] Concentration that produces 50 % inhibition of the respective channel Kv1.1–1.2(3), Nav1.5, Cav1.2, and hERG, respective standard deviation (SD), and number of evaluations (n). No SD or n are given for Cav1.2 results, which were obtained using Flexstation. Molecular properties were calculated with the Molsoft molecular properties calculator.