Table 1.
Binding affinity data for compounds derived from 1 primary pharmacophore. Radioligand competition binding assays performed on HEK293 cells stably expressing hD2R, hD3R, and hD4R 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 |
| Pramipexole |  |
11.1 ± 0.532 (n=3) | 1.32 ± 0.200 (n=5) | ND | 8.41 | ND |
| 1 |  |
20.5 ± 2.87 (n=6) | 1.69 ± 0.0892 (n=8) | 26.6 ± 3.97 (n=4) | 12.1 | 15.7 |
| 3 |  |
2,510 ± 553 (n=3) | 1,190 ± 151 (n=3) | ND | 2.11 | ND |
| 5 |  |
6,710 ± 741 (n=3) | 806 ± 185 (n=5) | ND | 8.33 | ND |
| 6 |  |
3,860 ± 975 (n=3) | 613 ± 50.6 (n=3) | ND | 6.30 | ND |
| 7 |  |
9,450 ± 3,130 (n=3) | 6,010 ± 1,540 (n=4) | ND | 1.57 | ND |
| 8 |  |
5,510 ± 182 (n=3) | 1,330 ± 263 (n=3) | ND | 4.14 | ND |
| 9 |  |
9,160 ± 276 (n=3) | 2,130 ± 402 (n=3) | ND | 4.30 | ND |
| 10 |  |
27,000 ± 11,400 (n=3) | 8,660 ± 3,660 (n=3) | ND | 3.12 | ND |
| 11 |  |
10,100 ± 3,590 (n=3) | 1,590 ± 30.9 (n=3) | ND | 6.35 | ND |
| 15 |  |
4,250 ± 1,320 (n=3) | 403 ± 5.55 (n=3) | ND | 10.5 | ND |
| 16 |  |
6,260 ± 179 (n=3) | 11,300 ± 1,070 (n=3) | ND | 0.554 | ND |
| 19a |  |
245 ± 32 (n=3) | 354 ± 45.1 (n=3) | ND | 0.710 | ND |
| 19b |  |
1,430 ± 210 (n=3) | 1,770 ± 241 (n=3) | ND | 0.808 | ND |
| 57 |  |
1.86 ± 0.591 (n=3) | 40.9 ± 12.9 (n=3) | ND | 0.0455 | ND |
| 58 |  |
0.844 ± 0.163 (n=3) | 2.42 ± 0.340 (n=3) | ND | 0.349 | ND |
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.