Table 5.
PI3K/HDAC Enzyme Inhibitory Activities of 5-Substituted Quinazolinones with Amino-pyrimidine Hinge Bindersa
| IC50 (nM) | HDAC6 isoform selectivityb | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Compound | L | R1 | R2 | PI3K | HDAC6 | ||||
| α | β | γ | δ | ||||||
| 46a | ![]() |
Et | ![]() |
52 | 33 | 3 | 0.7 | 69 | >13 |
| 46b | ![]() |
Et | ![]() |
9 | 12 | 2 | 0.2 | 28 | >36 |
| 46c | ![]() |
Et | ![]() |
5210 | 1769 | 96 | 45 | >22 | |
| 46d | ![]() |
Et | ![]() |
13 | 26 | 2 | 0.2 | 77 | >7 |
| 48a | ![]() |
Et | ![]() |
186 | 279 | 8 | 5 | 1238 | >2 |
| 48b | ![]() |
Et | ![]() |
50 | 842 | 45 | 32 | 4 | >73 |
| 48c | ![]() |
Et | ![]() |
47 | 9 | 7.0 | 12 | >39 | |
| 48d | ![]() |
Et | ![]() |
4 | >58 | ||||
| 48e | ![]() |
Et | ![]() |
444 | 752 | 60 | 4 | >113 | |
| 48f | ![]() |
Et | ![]() |
133 | 4 | >5 | |||
| 48g | ![]() |
Et | ![]() |
189 | 3 | >81 | |||
| 48h | ![]() |
Et | ![]() |
663 | 22 | >15 | |||
| 48i | ![]() |
Et | ![]() |
491 | 14 | >20 | |||
| 48j | ![]() |
Et | ![]() |
269 | 9 | >24 | |||
| 48k | ![]() |
Et | ![]() |
52 | >13 | ||||
| 481 | ![]() |
Et | ![]() |
47 | >9 | ||||
| 48m | ![]() |
Et | ![]() |
222 | 390 | 27 | >6 | ||
| 48n | ![]() |
Me | ![]() |
42 | 159 | 4 | 4 | 6 | >31 |
| 48o | ![]() |
Me | ![]() |
75 | 188 | 2 | 4 | 8 | >15 |
| 51 | ![]() |
Me | ![]() |
18 | 379 | 10 | 0.7 | 16 | >6 |
| 54 | ![]() |
Me | ![]() |
42 | 293 | 15 | 3 | 3 | >25 |
| PI-103 | - | - | - | 4 | 7 | 55 | 5 | NT | - |
| TSA | - | - | - | NT | NT | NT | NT | 6 | - |
| TMP269 | - | - | - | NT | NT | NT | NT | NT | - |









































