Table 6. Physicochemical Properties and Rodent PK Profiles.
| Physicochemical Properties | |||
|---|---|---|---|
| 35 | 36 | WM382 | |
| LDH P. falciparum EC50 (nM) | 0.4 | 2.5 | 0.4 |
| FRET P. falciparum IC50 PMX/PMIX (nM) | 0.06/4.5 | 0.07/2.2 | 0.03/1.4 |
| LLE PMX/PMIX | 7.4/5.5 | 8.1/6.4 | 8.0/6.3 |
| clogP/TPSA | 5.8/95 | 3.6/104 | 4.6/104 |
| logD7.4/kin. sol. (μM) | 2.9/0.2 | 2.1/0.2 | 2.5/0.1 |
| MDCK (A:B) (10–6cm/s) | 16.3 | 8.8 | 11.6 |
| Rodent PK Profiles | ||||||
|---|---|---|---|---|---|---|
|
35 |
36 |
WM382 |
||||
| rat | mouse | rat | mouse | rat | mouse | |
| MRT (h) | 1.1 | 1.1 | 2.7 | 1.3 | 3.7 | 2.5 |
| CLP/CLu (mL min–1 kg–1) | 103/5,648 | 36/3,148 | 79/518 | 68/1,278 | 42/1,022 | 42/774 |
| Vd/Vd,u (L/kg) | 6.7/340 | 2.3/204 | 12/80 | 5.4/102 | 9.4/222 | 6.6/120 |
| F (%) | 6 | 14 | 27 | 4 | 8 | 38 |
| PPB (%) | 98.0 | 98.9 | 84.8 | 94.7 | 95.2 | 94.5 |