Table 1.
IC50 Values of the “Series 7” against HDAC4 and HDAC8 a
| |||
|---|---|---|---|
| compound | Ar group | HDAC4 IC50 (μM) | HDAC8 IC50 (μM) |
| 7a | phenyl | 2.1 ± 0.3 | 4.5 ± 0.2 |
| 7b | 4-fluorophenyl | 1.6 ± 0.3 | 6.6 ± 0.2 |
| 7c | 4-methylphenyl | 1.7 ± 0.3 | 9.0 ± 0.2 |
| 7d | 4-methoxyphenyl | 4.7 ± 0.1 | >50 |
| 7e | 3-trifluoromethylphenyl | 2.5 ± 0.4 | >50 |
| 7f | 3-chlorophenyl | 3.8 ± 0.1 | >50 |
| 7g | 3-methoxyphenyl | 1.6 ± 0.2 | 7.6 ± 0.2 |
| 7h | 3,4-dichlorophenyl | 5.5 ± 0.3 | >50 |
| 7i | 2-bromo-4,6-difluorophenyl | 1.1 ± 1.7 | >50 |
| 7j | 2-phenoxyphenyl | 5.2 ± 0.5 | >50 |
| 7k | 2,4-difluorophenyl | 3.9 ± 0.1 | >50 |
| 7l | 4-bromo-2-methylphenyl | 0.55 ± 0.05 | 7.4 ± 0.3 |
| 7m | pyridin-2-yl | 17 ± 0.7 | >50 |
| 7n | 6-methylpyridin-2-yl | 1.1 ± 1.2 | 7.5 ± 0.2 |
| 7o | 4-Br phenyl | 2.9 ± 0.1 | 16 ± 0.5 |
| 7p | 3-chloro-5 (trifluoromethyl)phenyl | 4.0 ± 0.2 | >50 |
| 7q | 4-nitrophenyl | 1.7 ± 0.4 | 4.0 ± 0.2 |
| 7r | 4-bromo-2-fluorophenyl | 1.9 ± 0.1 | >50 |
| 7s | 6-fluoropyridin-2-yl | 0.84 ± 0.22 | 7.2 ± 0.2 |
| 7t | 5-methylisoxazol-3-yl | 1.7 ± 0.8 | >50 |
| 7u | 3-chloro-4-methylphenyl | 1.1 ± 0.4 | >50 |
| 7v | 3,4-dibromophenyl | 4.9 ± 0.3 | >50 |
| 7w | benzo[d]thiazol-2-yl | 0.42 ± 0.05 | 2.7 ± 0.2 |
| 7x | 4-methylbenzo[d]thiazol-2-yl | 1.2 ± 0.4 | 5.8 ± 0.1 |
| 7y | 6-ethoxybenzo[d]thiazol-2-yl | 3.6 ± 0.3 | 17 ± 0.3 |
| Cpd 6 57 | - | 0.22 | >50 |
| PCI-34051 59 | - | 10 | 0.024 |
a
Data represent mean ± sd (standard deviations), n = 3. Compounds with less than 40% residual enzyme activity were taken further to determine IC50 values.