Table 4:
Replacement of the C2 pyrrole ester with amides
 | |||||||
|---|---|---|---|---|---|---|---|
| Cmpd | Cmpd ID | Ar | R | IC50 (μM) | EC50 (μM) | ||
| PfDHODH | PvDHODH | hDHODH | Pf3D7 cellsa | ||||
| 12 | DSM489 |  |
 |
>100 | >100 | nd | >10 |
| 13 | DSM496 |  |
 |
0.14 (0.12–0.17) | 0.031 (0.023–0.041) | >100 | 0.051 (0.014–0.11) |
| 14 | DSM495 |  |
 |
0.3 (0.27–0.34) | 0.059 (0.05–0.069) | >100 | 0.11 (0.059–0.22) |
| 15 | DSM494 |  |
 |
9.9±1.7 (3) | 1.8, 0.54 | >100 | 0.71 (0.57–0.90) |
| 16 | DSM497 |  |
 |
0.054 (0.049–0.06) | 0.036 (0.03–0.043) | >100 | 0.033 (0.018–0.059) |
| 17 | DSM498 |  |
 |
0.072 (0.066–0.078) | 0.038 (0.034–0.044) | >100 | 0.047 (0.014–0.16) |
| 18 | DSM499 |  |
 |
0.050 ±0.013 (3) | 0.022 (0.019–0.026) | >100 | 0.036±0.0046 (3) |
| 19 | DSM500 |  |
 |
0.072, 0.042 | 0.036 (0.028–0.045) | >100 | 0.066 (0.057–0.077) |
| 20 | DSM508 |  |
 |
0.14±0.035 (3) | nd | nd | 0.13 ± 0.023 (3) |
| 21 | DSM509 |  |
 |
13 (11 – 15) | nd | nd | >10 |
| 22 | DSM517 |  |
 |
>30 | nd | nd | >10 |
| 23 | DSM519 |  |
 |
0.44 (0.38–0.49) | nd | nd | 0.34 (0.31–0.38) |
| 24 | DSM521 |  |
 |
1.8 (1.5–2.0) | 0.6 (0.52–0.7) | >100 | 1.0 (0.99–1.1) |
| 25 | DSM522 |  |
 |
0.41 (0.26–0.65) | 0.22 (0.18–0.27) | >100 | 0.47, 0.68 |
See Table 1 footnote. nd, not determined.