Table 1. Physiochemical Properties and CREB Inhibition Activity of 3a–j.
| compd | PSAa (Å2) | cLogPa | CREB inhibition IC50 (μM)b |
|---|---|---|---|
| 3a | 123.2 | 5.30 | 2.22 ± 0.38 |
| 3b | 86.9 | 6.41 | 4.69 ± 1.28 |
| 3c | 98.0 | 4.91 | 10.05 ± 2.29 |
| 3d | 97.9 | 4.92 | 5.30 ± 1.41 |
| 3e | 96.1 | 5.42 | >50 |
| 3f | 92.45 | 5.87 | 18.53 ± 8.68 |
| 3g | 105.8 | 5.26 | 7.30 ± 1.66 |
| 3h | 100.2 | 4.43 | 0.30 ± 0.12 |
| 3i | 100.2 | 4.83 | 0.081 ± 0.04 |
| 3j | 100.0 | 5.39 | 5.23 ± 0.36 |
a
The polar surface area (PSA) and calculated log P (cLogP) values were computed from their global energy minima using QikProp.
b
CREB inhibition refers to inhibition of CREB-mediated gene transcription in HEK 293T cells using a CREB reporter assay. The IC50 was presented as the mean ± SD of at least two independent experiments in triplicate or >50 in the cases where the IC50 was not reached at the highest tested concentration (50 μM).