Table 2.
Binding affinity data for compounds derived from 2 primary pharmacophore. Radioligand competition binding assays performed on HEK293 cells stably expressing hD2R and hD3R, in presence of [3H]-(R)-(+)-7-OH-DPAT.
| vs. [3H]-(R)-(+)-7-OH-DPAT | ||||||
|---|---|---|---|---|---|---|
| Compound | Structure | D2R Ki ± SEM [nM] | D3R Ki ± SEM [nM] | D4R Ki ± SEM [nM] | D2R/D3R | D4R/D3R |
| 2 |  |
1,740 ± 348 (n=5) | 185 ± 20.5 (n=8) | 292 ± 22.2 (n=3) | 9.41 | 1.58 |
| 20 |  |
8,240 ± 1,670 (n=3) | 21,100 ± 2,310 (n=5) | >100,000 | 0.391 | >4.74 |
| 22 |  |
113 ± 22.7 (n=4) | 173 ± 48.2 (n=5) | 3,220 ± 842 (n=3) | 0.653 | 18.6 |
| 23a |  |
7,100 ± 402 (n=3) | 1,520 ± 183 (n=3) | ND | 4.67 | ND |
| 23b |  |
2,340 ± 458 (n=3) | 424 ± 32.4 (n=3) | ND | 5.52 | ND |
| 24 |  |
2,660 ± 370 (n=3) | 24,200 ± 4,500 (n=3) | ND | 0.110 | ND |
| 26 |  |
34.6 ± 4.86 (n=3) | 31.2 ± 8.72 (n=3) | ND | 1.11 | ND |
| 25 |  |
5,220 ± 735 (n=3) | 6,470 ± 675 (n=3) | ND | 0.807 | ND |
| 27 |  |
134 ± 21.6 (n=4) | 5.96 ± 0.477 (n=4) | 357 ± 71.8 (n=3) | 22.5 | 59.9 |
| 30 |  |
21,100 ± 2,100 (n=3) | 73,000 ± 2,810 (n=3) | ND | 0.289 | ND |
| 31 |  |
341±27.6 (n=3) | 1,150±210 (n=3) | ND | 0.297 | ND |
| rac-trans-36 |  |
14,100 ± 1,790 (n=3) | 66,200 ± 25,600 (n=3) | ND | 0.213 | ND |
| trans-37a |  |
216 ± 32.6 (n=3) | 1,190 ± 165 (n=3) | ND | 0.182 | ND |
| trans-37b |  |
707 ± 19.8 (n=3) | 404 ± 34 (n=3) | ND | 1.75 | ND |
| cis-38a |  |
1,070 ± 40.9 (n=3) | 2,150 ± 159 (n=3) | ND | 0.498 | ND |
| cis-38b |  |
120 ± 16.6 (n=3) | 276 ± 30 (n=4) | ND | 0.435 | ND |
| cis-39a |  |
11,300 ± 2,280 (n=3) | 26,200 ± 2,520 (n=3) | ND | 0.431 | ND |
| cis-39b |  |
7,730 ± 2,070 (n=3) | 32,900 ± 2,700 (n=3) | ND | 0.235 | ND |
| rac-trans-53 |  |
106 ± 7.94 (n=5) | 2.84 ± 0.462 (n=5) | 315 ± 16.2 (n=3) | 37.3 | 111 |
| 53a |  |
87.8±9.81 (n=3) | 1.85±0.137 (n=3) | 286 ± 23.9 (n=3) | 47.5 | 155 |
| 53b |  |
831±99.5 (n=3) | 282±24 (n=3) | 2,930 ± 719 (n=3) | 2.95 | 10.4 |
Equilibrium dissociation constants (Ki) were derived from IC50 values using the Cheng–Prusoff equation. Each Ki value represents the arithmetic mean ± S.E.M; n = number of independent experiments, each performed in triplicate. ND = Not Determined.