Binding affinities of derivative at σ1 and σ2 receptorsa.
| |||||||
|---|---|---|---|---|---|---|---|
| Compound | R1 | R2 | R3 | R4 | K i σ1 (nM) | K i σ2 (nM) | Selectivity (Ki σ2/Ki σ1) |
| 7b | –CH3 | –H | –H | –H | 1.8 ± 0.2 | 307 ± 56 | 171 |
| 17 | –CH3 | –F | –H | –H | 1.9 ± 0.0 | 91.5 ± 7.5 | 48 |
| 18 | –CH3 | –H | –F | –H | 0.9 ± 0.1 | 78.5 ± 19.5 | 87 |
| 19 | –CH3 | –Br | –H | –H | 0.8 ± 0.1 | 105 ± 21 | 131 |
| 20 | –CH3 | –H | –Br | –H | 5.5 ± 1.3 | 86.6 ± 16.8 | 16 |
| 21 | –CH3 | –F | –F | –H | 1.7 ± 0.3 | 153 ± 37 | 90 |
| 22 | –CH3 | –F | –H | –F | 2.4 ± 1.2 | 57.0 ± 20.1 | 24 |
| 23 | –CH3 | –Cl | –Cl | –H | 3.2 ± 1.6 | 36.0 ± 9.7 | 11 |
| 24 | –CH3 | –Cl | –H | –Cl | 7.8 ± 3.2 | 22.8 ± 11.1 | 3.0 |
| 25 | –CH3 | –Cl | –F | –H | 1.3 ± 0.4 | 32.0 ± 6.0 | 25 |
| 26 | –CH3 | –CF3 | –H | –H | 4.0 ± 1.2 | 38.0 ± 2.0 | 9.5 |
| 27 | –CH3 | –CH3 | –H | –H | 4.2 ± 1.9 | 124 ± 68 | 29.5 |
| 28 | –H | –H | –H | –H | 0.2 ± 0.0 | 198 ± 64 | 990 |
| 29 | –H | –Cl | –H | –H | 0.4 ± 0.1 | 64.5 ± 13.2 | 161 |
| 30 |
|
–H | –H | –H | 16.0 ± 5.0 | 53.5 ± 0.5 | 3.3 |
a
See Experimental section. Radioligands: σ1: [3H]-(+)-pentazocine; σ2: [3H] DTG (ditolylguanidine). Evaluation platform: σ1: Guinea pig homogenate; σ2: PC12 cells.
b
The Ki values for compound 7 are cited from the literature.27 Data are expressed as the mean ± SEM and each performed from three independent experiments.