Table 7. In Vitro Data for Key Compounds.
| 1 | 27 | 35 | 47 | 55 | |
|---|---|---|---|---|---|
| T. brucei EC50 (μM)a | 0.03 | 0.03 | 0.02 | 0.06 | 0.08 |
| Hill slope | 3.5 | 2.0 | 2.8 | 4.4 | |
| selectivity vs MRC-5 | >1800 | >1800 | >2700 | >860 | >720 |
| MWT | 345 | 344 | 328 | 312 | 346 |
| clogP | 2.4 | 2.4 | 1.9 | 2.0 | 2.1 |
| PSA | 59 | 59 | 59 | 49 | 58 |
| solubility | >100 μg/mL | ND | ND | 64 μg/mL | >100 μg/mL |
| plasma protein binding | Fu = 0.26 (mouse) | Fu = 0.16 (rat) | Fu = 0.42 (mouse) | Fu = 0.59 (mouse) | Fu = 0.33 (mouse) |
| brain tissue binding (rat) | Fu = 0.15 | ND | ND | Fu = 0.43 | Fu = 0.29 |
| microsomal intrinsic clearance (m/h) (mL min–1 g–1)b | 4.4/2.6 | 3.6/ND | 1.2/ND | 1.9/ND | 1.3/<0.5 |
a
EC50 values are shown as mean values of two or more determinations. Standard deviation is typically within 2–3-fold from the EC50.
b
m/h = mouse/human. ND = not determined. cLogP and PSA calculated using StarDrop. MWT = molecular weight; PSA = polar surface area; Fu = fraction unbound.