Table 1. Comparison of the Pyridone and DBF Series Activities.
| BRD4
pIC50a |
||||||
|---|---|---|---|---|---|---|
| Cpd | seriesb | R | BD2 (LE) | BD1 | fold selectivity | ChromLogD @ pH 7.4 |
| 14 | pyridone | H | 6.5 (0.42) | 5.1 | 25 | 2.03 |
| 15 | DBF | 7 (0.42) | 4.8 | 160 | 3.28 | |
| 16 | pyridone | methyl | 6.9 (0.43) | 5.1 | 60 | 2.38 |
| 17 | DBF | 7.5 (0.43) | 4.9 | 400 | 3.55 | |
| 18 | pyridone | ethyl | 6.9 (0.41) | 4.8 | 125 | 2.99 |
| 19 | DBF | 7.4 (0.41) | 4.4 | 1000 | 4.11 | |
| 20 | pyridone | c-Pr | 7.1 (0.41) | 4.8 | 200 | 3.07 |
| 21 | DBF | 7.9 (0.42) | 4.7 | 1600 | 4.24 | |
| 22 | pyridone | CH2CH2OH | 6.2 (0.35) | 4.7 | 30 | 1.9 |
| 23 | DBF | 6.8 (0.36) | <4.3 | >320 | 3.12 | |
| 24 | pyridone | CH2CH2OCH3 | 6.2 (0.34) | 5.1 | 13 | 2.74 |
| 25 | DBF | 6.7 (0.34) | 4.4 | 200 | 3.81 | |
a
BRD4 potencies are representative of the potencies against the BET proteins (see the Supporting Information for full profiling).
b
See ref (4) for all data on the pyridone series.