Table 2.
Structure-activity relationships for compounds in which other 5-membered hetero-aromatic rings were used to replace the pyrrole in the initial lead compound 4
| Compound ID |
Core | Binding Affinities (IC50 ± SD, nM) |
Cell growth inhibition (IC50 ± SD, nM) |
Compound ID |
Core | Binding Affinities (IC50 ± SD, nM) |
Cell growth inhibition (IC50 ± SD, nM) |
||
|---|---|---|---|---|---|---|---|---|---|
|
|
|
||||||||
| Bcl-2 | Bcl-XL | H-146 | Bcl-2 | Bcl-XL | H-146 | ||||
| 7 |
|
99 ± 5 | 11 ± 6 | >10,000 | 4 |
|
1.3 ± 0.2 | 6 ± 1 | 61 ± 39 |
| 12 |
|
0.9 ± 0.2 | 5 ± 1 | 38 ± 22 | |||||
| 18 |
|
46 ± 10 | 18 ± 1 | >10,000 | 23 |
|
3.8 ± 1.1 | 8.3 ± 0.7 | >1,000 |
| 19 |
|
110 ± 4 | 32 ± 9 | >10,000 | 24 |
|
5.4 ± 1.1 | 5 ± 2 | >1,000 |
| 20 |
|
210 ± 28 | 15 ± 1 | >10,000 | 25 |
|
7.1 ± 1.6 | 6.1 ± 2.2 | >1,000 |
| 21 |
|
140 ± 53 | 26 ± 3 | >10,000 | 26 |
|
3.7 ± 0.6 | 5.9 ± 1.7 | 541 ± 76 |
| 22 |
|
350 ± 146 | 22 ± 7 | >10,000 | 27 |
|
3.8 ± 1.0 | 4.7 ± 0.2 | 199 ± 46 |