Table 2.
Ketolactam 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) |
| 10 | 1.8 | 64.5 | >100 | 22/76 | >190 | >380 |
| 11 | 2.5 | 50.7 | >100 | 11/54a | 95 | 250 |
| 12 | 1.5 | 49.3 | >100 | 11/27 | 83 | >390 |
| 13 | 2.6 | 29.1 | >25 | 62/81 | 100 | 190 |
| 14 | 2.4 | 37.4 | >100 | 110/220a | 77 | >380 |
| 15 | 2.9 | 37.4 | 25–50 | 310/>870b | 100 | 83 |
| 16 | 3.7 | 43.4 | >100 | 14/16 | 100 | 210 |
Apparent non-NADPH-mediated degradation detected.
Rapid metabolic degradation, estimate only.