| Compound | Substituent | Mcl-1/Bim a | Bcl-xL/Bim a | pKa 1 b | pKa 2 b | pKa 3/4 b | pKa 5/6 b | Clog p b |
|---|---|---|---|---|---|---|---|---|
| (±)-1 | R = H | 8.9 ± 1.0 | 16.4 ± 3.3 | 7.8 | 8.4 | − | − | 5.6 |
| (+)-1 | R = H | 12.7 ± 1.0 | 19.7 ± 3.6 | 7.8 | 8.4 | − | − | 5.6 |
| (–)-1 | R = H | 12.5 ± 1.4 | 12.0 ± 2.8 | 7.8 | 8.4 | − | − | 5.6 |
| 4a | R = COOMe | 16.9 ± 2.3 | >100 | 7.5 | 8.1 | − | − | 5.9 |
| 5a | R = PO(EtO)2 | 7.7 ± 2.2 | >100 | 6.8 | 7.4 | − | − | 6.7 |
| 7a | R = COOH | 61.4 ± 7.6 | >100 | 7.8 | 8.4 | 3.8 | 3.2 | 4.6 |
| 8a | R = PO(OH)2 | 10.9 ± 3.1 | 27.3 ± 7.2 | 7.8 | 8.1 | 0.7/5.5 c | 1.0/5.8 c | 2.4 |
| 9 | Tetrabromo-(±)-1 | 4.5 ± 0.9 | 7.3 ± 0.9 | 7.8 | 8.4 | − | − | 6.7 |
a IC50 in micromolar (average ± SEM, n ≥ 3); b calculated using ChemAxon Software Version 5.12.3; c pKa values from two hydroxyl groups.