Table 2.
The Effect of Substituted Piperazine/Piperidine Substituents on the Phenyl Portion of Benzylidene Moiety
 | |||||
|---|---|---|---|---|---|
| Compd | Position | R | PARP-1 IC50 (nM)a | pIC50 ± S.D (nM) | PARP-2 IC50 (nM)a |
| 51 | - | - | 35 | 7.50 ± 0.20 | 2.1 |
| 60 | - | - | 68 | 7.17 ± 0.08 | NT |
| 61 | 4- |  |
>50 (19%b) | - | NT |
| 62 | 4- |  |
66 | 7.18 ± 0.01 | NT |
| 63 | 4- |  |
55 | 7.27 ± 0.10 | <50 (89%c) |
| 64 | 4- |  |
77 | 7.12 ± 0.04 | <50 (89%) |
| 65 | 4- |  |
>50 (8%) | - | NT |
| 66 | 4- |  |
>50 (22%) | - | NT |
| 67 | 4- |  |
>50 (10%) | - | NT |
| 68 | 4- |  |
66 | 7.18 ± 0.04 | NT |
| 69 | 4- |  |
66 | 7.18 ± 0.05 | <50 (92%) |
| 70 | 4- |  |
>50 (34%) | - | NT |
| 71 | 4- |  |
>50 (36%) | - | <50 (98%) |
| 72 | 3- |  |
58 | 7.24 ± 0.06 | <50 (89%) |
| 73 | 3- |  |
>50 (32%) | - | <50 (96%) |
| 74 | 3- |  |
>50 (16%) | - | <50 (88%) |
| 75 | 4- |  |
197 | 6.71 ± 0.08 | NT |
| 76 | 4- |  |
>50 (NA) | - | <50 (51%) |
| 77 | 4- |  |
112 | 6.95 ± 0.01 | NT |
| 78 | 4- |  |
>50 (3%) | - | >50 (21%) |
| Olad | - | - | 1.2 | 8.93 ± 0.07 | 0.50 ± 0.30 |
| Vele | - | - | 1.5 | 8.83 ± 0.06 | 100% @ 10 nM |
a
Data shown are mean 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 50 nM concentration, in duplicates by one experiment;
d
Olaparib;
e
Veliparib;
No activity (NA);
Not tested (NT).