Table 3.
N-Phenyl SAR: Physicochemical, In Vitro ADME, Antimalarial, and Cytotoxicity Data
| ||||||
|---|---|---|---|---|---|---|
| Compd | LogD7.4 | PSA (Å2) | Kinetic Sol6.5 (μg/mL) | h/m CLint(μL/min/mg protein) | P. falciparumIC50 (μM) | L6 IC50 (μM) |
| 17 | 2.1 | 55.4 | 50–100 | 23/440a | 0.037 | 47 |
| 18 | 2.6 | 72.5 | >50 | 100/910a,b | 0.041 | 15 |
| 19 | <0 | 86.3 | >100 | 12/<7 | 160 | 220 |
| 20 | 0.8 | 89.3 | >100 | <7/10 | 24 | >340 |
| 21 | 1.3 | 75.7 | >100 | 11/15 | 7.8 | >270 |
| 22 | 2.1 | 70.0 | 25–50 | 23/20c | 0.70 | 160 |
| 23 | 1.6 | 80.3 | >100 | 46/19 | 5.3 | >300 |
| 24 | 2.2 | 46.2 | >100 | 38/74c | 0.056 | 110 |
| 25 | 3.0 | 46.2 | 25–50 | 240/79c | 0.0094 | 9.0 |
| 26 | 3.1 | 55.4 | 6.3–12.5 | 240/110c | 0.0042 | 44 |
| 27 | 3.3 | 46.2 | 6.3–12.5 | 190/71b | 0.0042 | 2.8 |
| 28 | 2.5 | 46.2 | 50–100 | 17/58b | 0.0070 | 86 |
| 29 | 1.2 | 59.1 | >100 | 13/26 | 8.9 | 60 |
Rapid metabolic degradation, estimate only.
Apparent non-NADPH-mediated degradation detected.
Apparent non-NADPH-mediated degradation to form the lactam hydrolysis product.