Table 1. Opioid and NK1 Receptor Affinity (nM) and Activity (nM) of the Synthesized Compounds.
| cmpd | pA2a (NK1R) | hNK1Rb (Ki) | GPIc (IC50) | MVDc (IC50) | MORc (Ki) | DORc (Ki) |
|---|---|---|---|---|---|---|
| 1 | 7.80 | 0.50 | 8.51 | 43.3 | 0.42 | 10.4 |
| 2 | 6.44 | 13.0 | 1.86 | 2.16 | 0.08 | 0.28 |
| 3 | 1.41 | 23.1 | 0.58 | 877 | ||
| 7 | nd | 0.99 | 137 | 384 | 9.91 | 533 |
| 8 | nd | 1.1 | 70.2 | 814 | 54.0 | >1000 |
| 9 | nd | 1.2 | 658 | 349 | 39.8 | 339 |
| 10 | nd | nd | 5.90 | 7.70 | 0.187 | 290 |
| 11 | 8.33 | 2.2 | 538 | 1660 | 20.2 | >1000 |
| 12 | 8.11 | 1.4 | 20.3 | 14.1 | 1.18 | 10.6 |
| 13 | 7.54 | 1.4 | 13.0 | 12.6 | 1.82 | 11.2 |
| 14 | 6.72 | 1.9 | 30.1 | 10.3 | 3.07 | 7.07 |
a
The pA2 values were calculated using Schild’s equation.
b
Binding affinities for hNK1 receptor in CHO cells determined by displacement of [3H]SP.
c
The GPI functional assay is representative of MOR activation, whereas the MVD is a DOR receptor-representative assay. Binding affinities for MOR and DOR opioid receptors were determined by displacement of [3H]DAMGO ([d-Ala2,NMePhe4,Gly-ol5]enkephalin) and [3H]DSLET ([d-Ser2,Leu5]enkephalin-Thr6) from rat brain membrane binding sites, respectively. Values represent means of 3–4 experiments. nd: not determined.