Table 1. Binding Affinities of Compounds 6a–6t for the Opioid Receptors MOR, DOR, and KOR, Reported as Ki, or Percentage for the Displacement of Each of the Radio-Labeled Ligands at 1.0 μM, or the Testing Concentration if Totally Inactive.
|
Ki (±SEM, nM)
or inhibition (%) |
|||||
|---|---|---|---|---|---|
| compd | R1 | R2 | MORa | DORb | KORc |
| 6a | CH3 | H | >104d | >104 | 37 ± 1% |
| 6b | CH3 | o-OCH3 | >104 | 37.9 ± 0.2% | >104 |
| 6c | CH3 | m-OCH3 | >104 | >104 | >104 |
| 6d | CH3 | p-OCH3 | >104 | >104 | >104 |
| 6e | CH3 | p-CF3 | >104 | >104 | >104 |
| 6f | CH3 | p-Cl | >104 | >104 | >104 |
| 6g | CH3 | m,p-diCl | >104 | >104 | >104 |
| 6h | CH3 | o-CH3 | >104 | 13 ± 2% | 16.2 ± 0.3% |
| 6i | H | H | 20 ± 1% | 22 ± 1% | 140 ± 9 |
| 6j | H | o-OCH3 | >104 | 4.7 ± 0.1 | 17.7 ± 0.1% |
| 6k | H | m-OCH3 | >104 | 43 ± 1% | 15 ± 1% |
| 6l | H | p-OCH3 | >104 | 32 ± 2% | >104 |
| 6m | H | p-CF3 | >104 | >104 | >104 |
| 6n | H | p-Cl | >104 | 17 ± 1% | 8.9 ± 0.2% |
| 6o | H | m,p-diCl | >104 | >104 | >104 |
| 6p | H | o-CH3 | >104 | 140 ± 4 | >104 |
| 6q | H | o-F | >104 | 720 ± 89 | >104 |
| 6r | H | o-Cl | >104 | 160 ± 58 | >104 |
| 6s | H | o-CF3 | >104 | 65 ± 4 | >104 |
| 6t | H | o-OCF3 | >104 | 260 ± 26 | >104 |
| (+)-6j | H | o-OCH3 | >104 | >104 | >104 |
| (−)-6j | H | o-OCH3 | >104 | 2.7 ± 0.6 | >104 |
| ( ± )-tramadol | 9.6 ± 0.4% | >104 | >104 | ||
| ( ± )-M1 | 13.0 ± 0.5 | >104 | >104 | ||
a
Displacement of [3H]DAMGO from CHO cell membranes expressing human MOR.
b
Displacement of [3H]DPDPE from CHO cell membrane expressing human DOR.
c
Displacement of [3H]U69593 from CHO cells expressing human KOR.
d
No binding affinity could be determined up to 104 nM. The binding-assay was performed three times for each compound, and the result was reported as mean ± standard error of the mean.