| No.a | Structureb | TR IC50 (μM)c |
GR IC50 (μM)c |
Selectivity for TRe |
T. brucei EC50 (μM)f |
||
|---|---|---|---|---|---|---|---|
|
| |||||||
| R1 | R2 | R3 | |||||
| 5a | NMe2.HCl | - | - | 2.9 (±1.4) | 20.4 (±6.3) | 7 | 0.55 (±0.04) |
| 5b | N-piperidyl | - | - | 7.8 (±3.7) | 105 (±36) | 13 | 0.95 (±0.09) |
| 6a | NMe2.HCl | - | - | 0.34 (±0.13) | 20.3 (±8.4) | 59 | 0.68 (±0.10) |
| 6b | NH-4-(CO2-nBu)Ph | - | - | 2.4 (±0.92) | > 135d | >56 | 0.96 (±0.11) |
| 6c | NHPh | - | - | 1.7 (±0.78) | 58.0 (±16) | 35 | 1.01 (±0.07) |
| 6d | NH-2,3-diMePh | - | - | 1.5 (±0.71) | 86.3 (±41) | 58 | 5.87, 0.68, 0.15g |
| 6e | NH-3-FPh | - | - | 3.3 (±1.1) | > 173 | >52 | 0.82 (±0.16) |
| 7a | tBu | N((CH2)2OH).HCl | - | 2.0 (±0.21) | 24.9 (±6.0) | 13 | 3.01 (±0.30) |
| 7b | iPr | NMe2 | - | 11.8 (±3.2) | 79.3 (±25) | 6.7 | > 50 |
| 7c | tBu | N-homopiperidyl | - | 38.8 (±5.0) | > 155 | >4 | 3.30 (±0.30) |
| 8a | Cl | Cl | R3 = NMe2.HCl | 3.3 (±2.2) | 64.8 (±18) | 20 | 1.00 (±0.21) |
| 8b | Cl | H | R3 = N-morpholinyl | 148 (±31) | > 212 | >1.4 | 0.98 (±0.07) |
| 8c | Cl | Cl | R3 = NH-4-EtPh | 107 (±0.71) | > 157 | >1.5 | 1.65 (±0.18) |
a
All compounds were purchased from ChemBridge, except for 5a and 5b (Peakdale).
b
Dash signifies that this chemotype did not possess variable groups at this position.
c
Values are means of two experiments, standard deviation is given in parentheses.
d
IC50 value greater than the highest tested inhibitor concentration.
e
GR IC50/TR IC50.
f
Values are weighted means of three independent experiments, standard errors are given in parentheses. IC50 values for pentamidine are 4.6 (± 0.2) nM.
g
Compound 6d gave highly variable EC50 results, all three are listed.