Table 1.
Structure | Receptor Binding Ki (nM) | [35S]GTPγS NOP | [35S]GTPγS μ | [35S]GTPγS κ | ||||||
---|---|---|---|---|---|---|---|---|---|---|
NOP | μ | κ | EC50 nM | % Stim | EC50 nM | % Stim | EC50 nM | % Stim | ||
C-moietypharmaeophore (pipetidine N-substituent) modifications | ||||||||||
1 | 1.39 ± 0.42 | 29.9 ± 2.09 | 42.7 ± 1.02 | 20.8 ± 3.1 | 54 ± 11 | 99 ± 12 | 23.4 ± 3 | 276 ± 75 | 38 ± 3 | |
2 | 7.49 ± 0.78 | 2.70 ± 0.05 | 31.74 ± 4.8 | 28.7 ± 0.6 | 45 ± 5 | 29 ± 10 | 30 ± 0.2 | <10K | ||
3 | 3.96 ± 1.55 | 8.0 ± 0.97 | 148.7 ± 8.7 | 26.5 ± 4.3 | 100± 15 | 73.5 ± 5 | 49 ± 0.45 | <10K | ||
4 | 7.63 ± 1.87 | 5.39 ± 0.16 | 190.2 ± 45 | 107 ± 8 | 62 ± 6 | 595±493 | 28 ± 8 | NTa | NT | |
5 | 15.26 ± 0.29 | 16.13 ± 1.2 | 159.7 ± 4.2 | 83 ± 2 | 18.5 ± 2 | 189 ± 78 | 39 ± 6 | NT | NT | |
6 | 212.8 ± 0.95 | 533 ± 42.3 | NTa | NT | NT | NT | NT | NT | NT | |
7 | 9.98 ± 2.8 | 3.44 ± 0.46 | 43.9 ± 9.2 | 82.3 ± 16 | 60± 10 | 28 ± 3.4 | 80.5 ± 11 | 873±293 | 48 ± 12 | |
8 | 201.3 ± 51.7 | 91.1 ± 16.6 | 84.5 ± 0.76 | 174 ± 51 | 18± 2 | 1981±606 | 36 ± 5 | <10K | ||
9 | 26.9 ± 0.25 | 2.34 ± 0.45 | 29.2 ± 0.06 | 138 ± 34 | 76± 14 | 50.6 ± 7 | 91 ± 4.9 | 422.60 | 37.5 | |
10 | 11.43 ± 0.91 | 79.9 ± 3.86 | 681.3 ± 61 | 46.1 ± 20 | 107± 7.4 | 129 ± 48 | 18 ± 1.6 | <10K |
A-moietypharmaeophore (thepipetidine 4-position heterocyclic ring) | |||||||||
---|---|---|---|---|---|---|---|---|---|
11 | 6.53 ± 1.48 | 3.62 ± 0.38 | 41.77 ± 2.4 | 54.9 ± 41 | 100± 40 | 119.6 | 84.3 | <10K | |
12 | 12.65 ± 1.93 | 10.49 ± 0.4 | 39.2 ± 15.3 | 30.2 ± 0.3 | 40± 10 | 94 ± 1.4 | 53.2± 14 | <10K | |
13 | 5.22 ± 0.65 | 1.07 ± 0.17 | 82.4 ± 16.4 | 8.5 ± 0.8 | 95± 12 | 4.7 ± 1.2 | 44 ± 5.2 | <10K | |
14 | 8.67 ± 0.89 | 16.26 ± 5.2 | 43.4 ± 17.8 | 6.8 ± 0.96 | 62 ± 12 | 37.3 ± 5 | 63 ± 18 | <10K | |
15 | 20.4 ± 5.55 | 7.62 ± 1.01 | 70.04 ± 8.4 | 127 ± 5.3 | 75± 5 | 68 ± 5.9 | 50 ± 0.55 | <10K | |
16 | 18.66 ± 5.05 | 46.97 ± 5.4 | 37.92 ± 32 | 101 ± 20 | 32 ± 2.2 | NT | NT | <10K | |
17 | 40.28 ± 1.8 | 23.27 ± 0.7 | 27.69 ± 3.6 | 94.7 ± 12 | 38 ± 2 | 58 ± 18 | 59 ± 5.1 | <10K |
NT=not tested. In some cases where the binding affinity was above 40 nM, the functional assays were not done.