Table 3. Profiling of Lead Molecules.
| compound | 31 (NDT-30347) | 36 (NDT-30408) | 50 (NDT-30805) | 51 (NDT-30744) |
|---|---|---|---|---|
| MW | 398 | 405 | 414 | 421 |
| c log P (ChemAxon) | 4.8 | 4.4 | 5.1 | 5.2 |
| tPSA | 85 | 78 | 68 | 64 |
| PAMPA, nm/s | <0.18 | 0.38 | <0.18 | <0.004 |
| thermodynamic solubility, mg/mL [μM] | 0.0009 [2.4] | 0.0097 [24] | 0.61 [1500] | 0.31 [730] |
| PPB, % | Hu = 99.8 | Hu = 99.9 | Hu = 98.1 | Hu = 99.9 |
| Rat = 100 | Rat = 100 | Rat = 98.5 | Rat = 99.8 | |
| Mu = 99.8 | Mu = 99.6 | Mu = 99.6 | ||
| PBMC IL-1β IC50, μM | 0.26 (n = 2), range 0.22–0.31 | 1.9 ± 1.1(n = 5) | 0.013 ± 0.0007(n = 3) | 0.13 ± 0.13(n = 4) |
| WB IL-1β IC50, μM | >40 (n = 2) | >40 (n = 1) | 1.5 ± 0.63(n = 3) | 8.9 ± 7.6(n = 4) |
| ASC speck inh IC50, μM | 0.24 (n = 1) | 1.3 (n = 1) | 0.034 (n = 1) | 0.19 (n = 1) |
| PBMC IL-6 IC50, μM | >40 (n = 1) | >40 (n = 1) | >40 (n = 1) | >20 (n = 1) |
| PBMC TNFα IC50, μM | >40 (n = 1) | >40 (n = 1) | >40 (n = 1) | >20 (n = 1) |