Table 5.
Calculated logP value, ligand-lipophilicity efficiency (LLE) and solubility data for selected compounds a.
| Compound | logP | LLE | Scalc, pH 7.4 [µM] | Sexp., therm., pH 7.4 [µM] b | Sexp., kin., pH 7.4 [µM] d |
|---|---|---|---|---|---|
| KuFal194 (5) | 4.22 | 4.00 | 13183 | < 0.5 | 5.28 (4.99–5.57) |
| 6a | 2.53 | 2.95 | 525 | 143 ± 6.3c | 116 ± 14 |
| 6b | 2.70 | 3.26 | 224 | 136 ± 11 | 142 ± 14 |
| 6c | 2.86 | 3.53 | 263 | 45.2 (44.8–45.6) | 261 (254–267) |
| 6f | 4.10 | 3.30 | 2.63 | <0.5 | 14.7 ± 4.5 |
| 6g | 4.26 | 3.34 | 1.26 | <0.5 | 14.8 ± 0.26 |
| 6h | 4.42 | 3.58 | 1.66 | <0.5 | 4.57 (4.11–5.03) |
| 6p | 3.21 | 3.89 | 25.1 | n.d. | 10.0 (7.21–12.9) |
| 6r | 3.48 | 3.37 | 37.2 | <0.5 | 38.1 (37.6–38.6) |
| 6s | 4.37 | 2.78 | 3.80 | <0.5 | 16.2 (15.2–17.3) |
| 13f | 4.65 | 1.54 | 12.0 | <0.5 | 37.5 (36.6–38.4) |
| 14 | 1.11 | 4.59 | 912 | 3447 ± 182 c | n.d. |
a The logP und logS values were predicted using the program MarvinSketch [47]. b Thermodynamic solubility: Two or three independent experiments were performed. If the compounds caused signals lower than the limit of quantification in two experiments, the thermodynamic solubility was indicated as <0.5 µM, which was the lowest concentration of the calibration solutions. If two experiments were performed the mean value and range is indicated, for three experiments the mean value ± SD is indicated. c The solubility was determined after 24 h, 48 h, 72 h and 96 h. After 24 h the equilibrium was not reached. Indicated solubility is the mean value of the results after 48 h, 72 h and 96 h. d Kinetic solubility: Two or three independent experiments were performed. If two experiments were performed, the mean value and range is indicated, for three experiments the mean value ± SD is indicated. n.d., not determined