Table 3.
Antiprotozoal activity and toxicity of 6-substituted imidazo[1,2-b]pyridazines.
| Cmpd | R1 | NR3R4 | M.W. | cLogPa | tPSAa | IC50 (nM) |
|
|---|---|---|---|---|---|---|---|
| G.l.b | MRC-5c | ||||||
| 21 | NO2 |  |
207.2 | 1.4 | 76.6 | 22.0 ± 3.0 | >6.4 × 104 |
| 22 | NO2 |  |
233.2 | 1.8 | 76.6 | 2.3 ± 0.4 | >6.4 × 104 |
| 23 | NO2 |  |
247.3 | 2.2 | 76.6 | 3.6 ± 0.8 | 28,100 ± 1,400 |
| 24d | NO2 |  |
308.3 | 1.2 | 79.8 | 144.0 ± 31.0 | >6.4 × 104 |
| 25d | NO2 |  |
316.4 | 1.8 | 79.8 | 5.8 ± 0.9 | >6.4 × 104 |
| 26 | NO2 |  |
323.4 | 3.7 | 76.6 | 8.2 ± 1.0 | >6.4 × 104 |
| 27 | NO2 |  |
324.3 | 3.1 | 79.8 | 0.7 ± 0.1 | >6.4 × 104 |
| 28 | NO2 |  |
337.4 | 4.1 | 76.6 | 0.5 ± 0.1 | 7,960 ± 210 |
| 29 | NO2 |  |
351.4 | 3.2 | 93.6 | 1.1 ± 0.2 | >6.4 × 104 |
| 30 | NO2 |  |
313.3 | 2.9 | 85.8 | 10.3 ± 1.5 | >6.4 × 104 |
| 31 | H |  |
202.3 | 2.2 | 33.4 | >104 | >6.4 × 104 |
| 2 (MET) | - | 171.2 | −0.5 | 81.2 | 800 ± 100 | - | |
a
cLogP, tPSA are calculated using CDD Vault.
b
mean values ± standard errors are given for quadruplicates, the standard errors correspond to the 95% confidence intervals as calculated via the logit-log algorithm.
c
mean values ± standard deviations, n ≥ 2.
d
formate.