Table 3. . Physicochemical properties, binding affinities and functional potencies of investigational triple reuptake inhibitors.
| Compound | Mol wt. | CLogP | LE | Potency [3H]DA:[3H]NA:[3H]5-HT IC50 (nM) | Affinity DAT:NET:SERT Ki (nM/l) | Ref. |
|---|---|---|---|---|---|---|
| DOV-220,075 |
209.72 |
2.2 |
27.4 |
910:55:117 |
5.2:5.0:2.4 (μM) |
[103] |
| RO-84650 |
322.23 |
5.0 |
15.3 |
16.8:15.7:51 |
10.9:8.8:10.3 |
[105,106] |
| NS-2214 |
327.25 |
4 |
54 |
03:13:13 |
0.79:3.13:18.0 (EC50) |
[107,108] |
| NS-2330 |
314.25 |
3.6 |
10.9 |
01:07.7 |
N/A |
[80] |
| DOV-216,303 |
228.12 |
3 |
22.5 |
78:21:14 |
210:260:100 |
[109] |
| DOV-102,677 |
228.12 |
3 |
22.5 |
129:103:133 |
220:1000:740 |
[110] |
| EB-1020 |
209.29 |
2.9 |
30.5 |
0.2773495 |
N/A |
[111] |
| Lu-AA24530 |
283.43 |
4.5 |
22.6 |
X:23:8 |
DA<NE<SE |
[112] |
| Lu-AA21004 |
298.45 |
4.9 |
27.3 |
890:140:5.4 |
N/A:113:1.6 |
[113] |
| PRC-025 |
311.46 |
4.9 |
14.3 |
53:10:06 |
53:10:06 |
[114] |
| PRC-050 |
291.3 |
4.2 |
13.6 |
53:10:06 |
53:10:06 |
[114] |
| PRC200-SS |
291.3 |
4.2 |
13.6 |
18:0.6:2 (Kd) |
61:1.5:2.1 |
[115] |
| WF-23 |
307.43 |
4.2 |
17.9 |
0.65:0.32:0.47 |
0.12:0.39:2.9 |
[116] |
| 1 |
286.24 |
5.3 |
13.9 |
30:57:81 |
N/A |
[117] |
| 2 |
300.27 |
5.8 |
14.8 |
36:10:12 |
N/A |
[117] |
| 3 |
281.44 |
5.7 |
21.6 |
28:21:<1 |
N/A |
[117] |
|
SKF83959 |
317.81 |
4 |
6.7 |
1375:381:242 |
9010:600:1430 |
[118] |
| 4 |
255.35 |
2.9 |
17.4 |
12:06.8 |
N/A |
[119] |
| 5 |
289.37 |
4.6 |
21.3 |
35:8.3:3.1 |
N/A |
[119] |
| 6 |
270.2 |
4.7 |
17.9 |
140:150:53 (pIC50) |
N/A |
[120] |
| 5-APB |
175.23 |
2.3 |
16.2 |
6.3:6.3:5.8 (pKi) |
265:180:811 |
[121] |
| JZ-IV-10 |
354.94 |
3.1 |
13.2 |
|
1.0:0.8:1.1 |
[122] |
| Lu 19–005 |
292.2 |
4.8 |
21 |
11.9:8.8:5.1 |
1.7:5.8:0.42 |
[105,123] |
| JNJ-39836966 |
273.37 |
4.4 |
37.1 |
|
1.6:4.1:0.3 |
[124] |
| 7 |
300.19 |
2.7 |
|
19:08.8 |
N/A |
[125] |
| 8 |
328.28 |
5.6 |
7.3 |
N/A |
8.6:8.2:8.2 (pKi) |
[126] |
| 9 |
279.42 |
5.5 |
25.3 |
86:28:9 |
41:99:3.6 |
[127] |
| 10 |
306.23 |
4.9 |
19.7 |
72:73:107 |
N/A |
[128] |
| 11 |
300.22 |
3.6 |
10.6 |
8.0:8.9:8.6 |
7.0:8.4:9.5 |
[129] |
| DOV-21,947 |
228.12 |
3 |
22.5 |
96:23:12 |
213:262:99 |
[93] |
| SEP-225289 | 251.79 | 4.9 | 15.9 | 8 ± 7:17 ± 3:10 ± 8 | 49:20:15 | [130] |
DA:NA:5-HT: Dopamine:norepinephrine:serotonin; IC50: Concentration required for 50% inhibition in vitro; Ki: Binding affinity of the inhibitor; LE: Ligand efficiency; N/A: Not available.