Table 6.
Physicochemical properties, drug-likeness prediction, and medicinal chemistry of the most active pyrazole and pyrazolo[1,5-a]pyrimidine derivatives compared with acetazolamide as positive control.
| Test Items | Most-Active Pyrazole and Pyrazolo[1,5-a]pyrimidine Derivatives Compared with Acetazolamide | ||||||
|---|---|---|---|---|---|---|---|
| 3a | 5a | 6 | 9a | 10a | ACZ | ||
| Molecular Properties | |||||||
| SwissADME | Xlog P3 | 1.52 | 3.62 | 2.77 | 3.68 | 4.01 | -0.26 |
| TPSA ( °A2) | 131.74 | 121.32 | 107.23 | 160.28 | 154.49 | 151.66 | |
| M. Wt. | 274.28 | 405.45 | 338.36 | 469.50 | 470.48 | 222.25 | |
| nHBA (NO) | 5 | 6 | 6 | 7 | 8 | 6 | |
| nHBD (OHNH) | 3 | 2 | 1 | 2 | 2 | 2 | |
| NRB | 5 | 8 | 5 | 7 | 7 | 3 | |
| Log S (ESOL) | −2.58 | −4.53 | −3.80 | −5.05 | −5.27 | −1.14 | |
| Solubility Class | Soluble | M Soluble | Soluble | M Soluble | M Soluble | Soluble | |
| Drug-Likeness and Medicinal Chemistry Prediction | |||||||
| PAINS | 1 (N=N) | 1 (N=N) | 1 (N=N) | 1 (N=N) | 1 (N=N) | 0 | |
| Lead-Likeness | Yes | No (2) | Yes | No (2) | No (2) | No (1) | |
| Synthetic Accessibility | 2.68 | 2.89 | 3.22 | 3.84 | 3.91 | 3.00 | |
| Bioavailability Score | 0.55 | 0.55 | 0.55 | 0.56 | 0.55 | 0.55 | |
| Lipinski Rule (Violation) | Yes (0) | Yes (0) | Yes (0) | Yes (0) | Yes (0) | Yes (0) | |
| Veber Rule (Violation) | Yes (0) | Yes (0) | Yes (0) | No (1) | No (1) | No (1) | |