Table 1.
TDP2 inhibitory activity and PAMPA permeability for the control series.
 | |||
|---|---|---|---|
| Compd | R | TDP2 IC50 (μM)a | PAMPA Pe (10−6 cm/s)b |
| 4ac |  |
0.041 ± 0.003 | 0.003 |
| 4bc | 3′ OH | 0.042 ± 0.004 | 0.01 |
| 4cc | 4′ OH | 0.14 ± 0.01 | 0.008 |
| 4dc | H | 0.64 ± 0.02 | 0.4 |
| 4e | 4′ OCF3 | 1.0 ± 0.1 | 1.1 |
| 4f | 4′ OCHF2 | 0.88 ± 0.06 | 0.3 |
| 4g |  |
0.96 ± 0.02 | 0.5 |
| 4h |  |
1.5 ± 0.1 | 1.1 |
| 31 | -- | 0.32 ± 0.02 | 0.1 |
a
IC50: concentration of a compound producing 50% inhibition, expressed as mean ± standard deviation from three independent experiments performed in triplicate.
b
Pe: effective permeability coefficients determined using the PAMPA, measured in five replicates.
c
Previously reported analogues. Reported IC50 values are 0.04 μM (4a), 0.05 μM (4b), 0.09 μM (4c) and 0.50 μM (4d).15