Table 4.
Effect of Benzimidazolylethyl/ Benzimidazolylazetidine/ Benzimidazolylpiperazine Amide Substituents on the Phenyl Ring of Benzylidene Moiety
 |
||||||
|---|---|---|---|---|---|---|
| Compd | Position | R | PARP-1 IC50 (nM)a | pIC50 ± S.D (nM) | PARP-2 IC50 (nM)a | pIC50 ± S.D (nM) |
| 51 | - | - | 35 | 7.50 ± 0.20 | 2.1 | 8.69 ± 0.01 |
| 60 | - | - | 68 | 7.17 ± 0.08 | NT | - |
| 93 | 4- |  |
36 | 7.45 ± 0.10 | ~10 (50%c) | - |
| 94 | 4- |  |
22 | 7.66 ± 0.02 | 5 | 8.32 ± 0.12 |
| 95 | 4- |  |
51 | 7.31 ± 0.14 | >10 (33%) | - |
| 96 | 3- |  |
88 | 7.07 ± 0.10 | >10 (18%) | - |
| 97 | 3- |  |
97 | 7.02 ± 0.07 | >10 (24%) | - |
| 98 | 4- |  |
28 | 7.55 ± 0.02 | >10 (44%) | - |
| 99 | 4- |  |
4 | 8.41 ± 0.11 | 0.7 | 9.19 ± 0.03 |
| 100 | 4- |  |
>50 (33%b) | - | >10 (22%) | - |
| 101 | 4- |  |
>50 (49%) | - | >10 (48%) | - |
| 102 | 4- |  |
30 | 7.54 ± 0.10 | >10 (44%) | - |
| 103 | 4- |  |
18 | 7.77 ± 0.15 | 4 | 8.40 ± 0.08 |
| 104 | 4- |  |
58 | 7.24 ± 0.05 | >10 (28%) | - |
| 105 | 4- |  |
98 | 7.01 ± 0.02 | NT | - |
| Olad | - | - | 1.2 | 8.93 ± 0.07 | 0.5 | 9.40 ± 0.30 |
| Vele | - | - | 1.5 | 8.83 ± 0.06 | <10 nM | - |
a
Data shown are mean values obtained from two independent experiments performed in duplicates.
b
% inhibition screening at a single concentration (50 nM unless otherwise specified) was performed in duplicates and data shown is an average of two independent experiments;
c
% inhibition screening of PARP-2, was performed at 10 nM concentration, in duplicates by one experiment.
d
Olaparib;
e
Veliparib.
Not tested (NT).