Table 3. SAR of bicyclic amide substituents.
| ID |
|
EC50(Nurr1) (max. activation) a |
|---|---|---|
| 32 |
|
0.4±0.1 μM (2.0±0.1-fold) |
| 33 |
|
0.12±0.04 μM (1.5±0.1-fold) |
| 34 |
|
0.10±0.03 μM (1.8±0.1-fold) |
| 35 |
|
0.13±0.04 μM (1.7±0.1-fold) |
| 36 |
|
0.13±0.04 μM (1.8±0.1-fold) |
| 37 |
|
0.06±0.02 μM (1.9±0.1-fold) |
| 38 |
|
1.4±0.5 μM (1.5±0.1-fold) |
| 39 |
|
inactive (10 μM) |
| 40 |
|
inactive (10 μM) |
| 41 |
|
inactive (10 μM) |
| 42 |
|
0.5±0.2 μM (1.4±0.1-fold) |
| 43 |
|
0.24±0.07 μM (1.5±0.1-fold) |
| 44 |
|
0.31±0.05 μM (2.1±0.1-fold) |
| 45 |
|
0.4±0.2 μM (2.1±0.1-fold) |
| 46 |
|
0.10±0.04 μM (2.0±0.1-fold) |
| 47 |
|
0.10±0.04 μM (1.5±0.1-fold) |
Nurr1 modulation was determined in a Gal4-Nurr1 hybrid reporter gene assay. Max. activation refers to the maximum effect vs. 0.1% DMSO control. Data are the mean±SD; n≥3.