TABLE 5.
Pharmacological profiling of compounds (D2R binding and functional activity) (Yan et al., 2021).
| Cmpd | Structure | D2R binding Ki nM (pKi±SEM) | D2R Gαi1 BRET EC50 nM (Emax%) (pEC50 ± SEM) | D2R β-arrestin2 BRET EC50 nM (Emax%) (pEC50 ± SEM) |
|---|---|---|---|---|
| 64 |
|
61.9 (7.21 ± 0.04) | 49.0 (25 ± 2%) (7.31 ± 0.09) | 67.6 (30 ± 1%) (7.17 ± 0.07) |
| 65 |
|
59.9 (7.22 ± 0.13) | 26.3 (52 ± 1%) (7.58 ± 0.08) | 32.4 (53 ± 2%) (7.49 ± 0.14) |
| 66 |
|
125.7 (6.90 ± 0.08) | 9.30 (58 ± 3%) (8.03 ± 0.01) | 10.0 (52 ± 1) (8.00 ± 0.11) |
| 67 |
|
155.7 (6.81 ± 0.03) | 11.2 (65 ± 3%) (7.95 ± 0.04) | 7.08 (60 ± 1%) (8.15 ± 0.12) |
| 68 |
|
259.2 (6.59 ± 0.05) | 891.2 (12 ± 1%) (6.05 ± 0.42) | 416.9 (14 ± 4%) (6.38 ± 0.64) |
| 69 |
|
217.8 (6.66 ± 0.08) | 77.6 (18 ± 1%) (7.11 ± 0.12) | 190.6 (19 ± 1%) (6.72 ± 0.49) |
| 70 |
|
977.2 (6.01 ± 0.11) | 8.45 (68 ± 1%) (8.07 ± 0.11) | 9.49 (16 ± 1%) (8.02 ± 0.06) |
| 71 |
|
244.3 (6.61 ± 0.07) | 34.8 (51 ± 5%) (7.46 ± 0.10) | 94.0 (39 ± 4%) (7.03 ± 0.20) |
| 72 |
|
128.1 (6.89 ± 0.112) | 14.73 (66 ± 3%) (7.83 ± 0.12) | 27.6 (33 ± 1%) (7.56 ± 0.09) |
| (1S,2S)-73a |
|
20.8 (7.68 ± 0.06) | 9.43 (29 ± 3%) (8.03 ± 0.05) | 3.63 (18 ± 1%) (8.44 ± 0.17) |
| (1R,2R)-73b |
|
43.8 (7.36 ± 0.07) | 12.9 (13 ± 3%) (7.89 ± 0.14) | 1.86 (10 ± 2%) (8.71 ± 0.15) |
| (1S,2S)-74a |
|
6.58 (8.18 ± 0.04) | 4.12 (55 ± 2%) (8.39 ± 0.08) | 4.66 (29 ± 1%) (8.33 ± 0.15) |
| (1R,2R)-74b |
|
362.5 (6.44 ± 0.07) | 62.0 (7 ± 1%) (7.21 ± 0.16) | 14.7 (17 ± 1%) (7.83 ± 0.12) |
| (1S,2S)-75a |
|
11.5 (7.94 ± 0.07) | 8.9 (40 ± 2%) (8.05 ± 0.04) | 2.50 (20 ± 1%) (8.60 ± 0.10) |
| (1R,2R)-75b |
|
30.1 (7.52 ± 0.02) | NT | NT |
| (1S,2S)-76a |
|
12.8 (7.89 ± 0.05) | 3.41 (71 ± 3%) (8.47 ± 0.08) | 8.30 (47 ± 2%) (8.08 ± 0.06) |
| (1R,2R)-76b |
|
317.0 (6.50 ± 0.04) | 197.2 (41 ± 5%) (6.71 ± 0.05) | 70.1 (18 ± 3%) (7.15 ± 0.15) |