Table 1.
Kinase inhibitory activities of compounds 5a–5d and 5–9 against PAK4.
| Compd. | R1 | PAK4 Ki (μmol/L)a | cLogPb | PSAb | LEc |
|---|---|---|---|---|---|
| 5 |  |
0.066 | 3.85 | 72.53 | 0.39 |
| 6 |  |
0.040 | 3.24 | 85.96 | 0.40 |
| 7 |  |
0.036 | 3.20 | 85.50 | 0.40 |
| 8 |  |
0.013 | 3.21 | 84.39 | 0.42 |
| 9 |  |
0.183 | 3.40 | 84.25 | 0.36 |
| 5a |  |
0.082 | 4.11 | 72.59 | 0.38 |
| 5b |  |
0.370 | 2.91 | 97.82 | 0.33 |
| 5c |  |
0.229 | 3.80 | 72.77 | 0.36 |
| 5d |  |
0.182 | 4.08 | 72.34 | 0.35 |
| CZh-226 | 0.005 | 2.75 | 99.49 | 0.39 | |
| GNE-2861 | 0.035 (reported 0.003)21 | 3.41 | 103.30 | 0.34 |
a
PAK4 kinase inhibition was determined using a homogeneous time-resolved fluorescence (HTRF) assay. The Ki values are the average of two independent experiments reported as the mean value.
b
The clogP values and polar surface area (PSA) were calculated by the Qikprop software.
c
Ligand efficiency = (−1.4 Log Ki)/(n heavy atoms).