Table 4. Antileishmanial Activity of Pyrazoles 4–21.
| MRC5a |
HLM | HamLM | ||||||
|---|---|---|---|---|---|---|---|---|
| compound | R1 | R2 | intramacrophage L. infantum EC50 (μM)a | PMMa CC50 (μM) | CC50 (μM) | SIb | Clint (μL/min/mg) | |
| 3 | 2.7 | >64 | >64 | >24 | 0.8 | n.d. | ||
| 4 | CF3 | CF3 | 2.1 | >64 | >64 | >31 | <11.9 | 1,035 |
| 5 | CF3 | CH2CF3 | 1.6 | 50 | >64 | >40 | <11.9 | 41 |
| 6 | CF3 | (CH2)2CF3 | 1.3 | 38 | 49 | 38 | <11.9 | 114 |
| 7 | CH3 | (CH2)2CF3 | 5.7 | >64 | >64 | >11 | n.d. | n.d. |
| 8 | CH3 | c-butyl | 16 | >64 | >64 | >4 | <11.9 | 57 |
| 9 | CF3 | c-butyl | 0.59 | 32 | 26 | 53 | <11.9 | 337 |
| 10 | CF3 | 4-THP | 3.0 | >64 | >64 | >21 | <11.9 | 109 |
| 11 | CH3 | 2-pyridyl | 5.7 | >64 | >64 | >11 | <11.9 | n.d. |
| 12 | CF3 | 2-pyridyl | 0.64 | 2.0 | 1.1 | 1.6 | n.d. | n.d. |
| 13 | CF3 | 4-Cl-phenyl | 1.3 | 8.0 | 2.6 | 2 | n.d. | n.d. |
| 14 | CH3 | 2-MeO-phenyl | 2.2 | >64 | 15.7 | 7.3 | n.d. | n.d. |
| 15 | CH3 | (CH2)2CF3 | 14 | >64 | >64 | >5 | <11.9 | 48 |
| 16 | CH3 | 2-pyridyl | 3.1 | 59 | 61 | 15 | <11.9 | 57 |
| 17 | CH3 | 2-pyridyl-6-OMe | 1.4 | >64 | 40 | 31 | <11.9 | 40 |
| 18 | CH3 | 2-pyridyl-6-Me | 1.6 | >64 | 41 | 25 | <11.9 | 44 |
| 19 | H | 2-pyridyl | 0.5 | 32 | 4.0 | 8 | <11.9 | 253 |
| 20 | CH3 | 2-pyridyl | 34 | >64 | >64 | >2 | 18 | 121 |
| 21 | CH3 | 2-pyridyl | 1.8 | >64 | 54 | 31 | 14 | 106 |
| miltefosine | 10 | 33 | >64 | >6.2 | n.d. | n.d. | ||
a
Geometric mean value of at least two independent tests.
b
Selectivity index representing the ratio of CC50/EC50; data are presented as the geometric mean value of ratios calculated using separate data from at least two independent tests. n.d., not determined.