Table 5. DMPK Data for Selected Compounds.
| cmpd | TbNMT IC50 (nM) | HsNMT IC50 (nM) | T. brucei EC50 (nM) | enzyme selectivity | “S” | Cli mouse microsomes mL–1 min–1 g–1 | mouse brain:blood ratio | mouse PPB (fu) | hERGa IC50/μM |
|---|---|---|---|---|---|---|---|---|---|
| Quinoline Series | |||||||||
| 32 | <5 | 250 | 19 | >50 | 13 | 6.2 | |||
| 34 | <5 | 640 | 40 | >130 | 16 | 6.2 | 0.8 | 0.17 | 1.3 |
| 37 | 6 | 1400 | 59 | 59 | 24 | 1.8 | 0.8 | 0.093 | |
| 41 | 7 | 27000 | 91 | 3900 | 300 | 1.5 | 0.8 | 0.18 | 1.6 |
| Indazole Series | |||||||||
| 54 | <5 | 230 | 5 | >46 | 46 | 2.9 | <0.1 | 0.062 | 3.7 |
| 58 | <5 | 2500 | 31 | >500 | 80 | 3.7 | <0.1 | 3.0 | |
| 60 | 5 | 12000 | 39 | 2500 | 320 | 1.4 | <0.1 | 3.3 | |
| 62 | 7 | 4600 | 220 | 660 | 21 | 20 | 3.1 | ||
| 63 | <5 | 190 | 26 | >38 | 7 | 24 | 5.6 | ||
| 64 | <5 | 130 | 9 | >26 | 14 | 22 | 6.7 | ||
a
hERG values were determined using IonWorks patch-clamp electrophysiology at Essen Bioscience, UK.