Table 2.
Antimalarial potency of the test articles measured by (a) efficacy against the drug-resistant (W2) and drug-sensitive (3D7) strains of P. falciparum, and (b) RBC partitioning efficiency of the compounds (concentration in blood versus plasma, B/P ratio).
| Compound Name | Region of Modification | In Vitro Efficacy 3D7 IC50, nM | In Vitro Efficacy W2 IC50, nM | RBC Partitioning | |
|---|---|---|---|---|---|
| B/P, 1 μM | B/P, 10 μM | ||||
| CQ | 17 | 382 | 3.76 | 4.08 | |
| 1 | Heterocycle ring | 115 | 267 | 4.80 | 21.31 |
| 2 | Heterocycle ring | 62 | 287 | 6.12 | 6.79 |
| 3 | Heterocycle ring | 51 | 290 | 4.94 | 5.45 |
| 4 | 3°Amine Side Chain | 14.5 | 17.3 | 2.58 | 3.67 |
| 5 | 3°Amine Side Chain | 20.9 | 34.6 | 3.29 | 5.17 |
| 6 | 3°Amine Side Chain | 50 | 50 | 3.21 | 3.68 |
| 7 | 3°Amine Side Chain | 45 | 70 | 5.69 | 5.36 |
| 8 | 3°Amine Side Chain | 2.0 | 3.0 | 1.55 | 2.58 |
| 9 | 3°Amine Side Chain | 63 | 66 | 3.13 | 2.48 |
| 10 | 3°Amine Side Chain | 5.0 | 9.3 | 2.85 | 2.52 |
| 11 | 3°Amine Side Chain | 6.0 | 8.0 | 3.01 | 1.92 |
| 12 | 3°Amine Side Chain | 7.4 | 10.9 | 2.00 | 1.89 |
| 13 | 3°Amine Side Chain | 1.0 | 3.9 | 3.13 | 2.48 |
| 14 | 3°Amine Side Chain | 71 | 100 | 3.20 | 3.36 |
| 15 | 3°Amine Side Chain | 8.1 | 80 | 2.44 | 2.36 |
| 16 | 3°Amine Side Chain | 13 | 34 | 2.74 | 2.23 |
| 17 | 3°Amine Side Chain | 5.0 | 12 | 2.34 | 2.13 |
| 18 | 2°Amine Side Chain | 2.5 | 5.6 | 5.15 | 3.33 |
| 19 | 2°Amine Side Chain | 13 | 183.6 | 5.73 | 8.77 |
| 20 | 2°Amine Side Chain | 4.7 | 45.3 | 2.66 | 0.91 |