Table 6.
Binding affinities and agonist potencies of differently 5-substituted N-methylmorphinan-6-ones 2, 4, 17 and 21.
| Binding Affinity (Ki, nM) a | Agonist Activity (EC50, nM; %stim) b | ||||||
|---|---|---|---|---|---|---|---|
| MOP | DOP | KOP | Ki Ratios MOP/DOP/KOP | MOP | DOP | KOP | |
| 2 | 0.10 | 4.8 | 10.2 | 1/48/102 | 1.21; 95 23.7; 103 d |
38.5; 102 | 135; 65.6 |
| 4 | 0.15 | 13.3 | 25.2 | 1/89/168 | 2.66; 99 63.0; 99 d |
36.8; 100 | 181; 68.9 |
| 17 | 0.20 | 0.14 | 0.40 | 1/0.7/2 | - c | - | - |
| 21 | 0.31 | 13.1 | 22.8 | 1/42/73 | 1.86; 95 e 13.8; 85 d |
31.7; 126 e | 116; 59.0 e |
a Determined in competition radioligand binding assays using membranes from rat brain (MOP and DOP receptors) or guinea pig brain (KOP receptors). b Determined in the [35S]GTPγS binding assays using CHO stably expressing human opioid receptors; percentage stimulation relative to the standard full agonists DAMGO (MOP), DPDPE (DOP) or U69,593 (KOP). c not determined. d Determined in the [35S]GTPγS binding assay using rat brain membranes; percentage of stimulation relative to the standard full agonist DAMGO (MOP). e unpublished data. Data from [90,94,102]. For compound structures, refer to Scheme 1, Scheme 7 and Scheme 8.