Table 3.
Binding affinity assays and biological assays for design of nonpeptide opioid receptor-selective ligands based on TMT1-DPDPE
| Compound | Binding affinity assays | Biological assays | ||
|---|---|---|---|---|
| vs[3H]pCl-DPDPE IC50 (nM) | vs[3H]DAMGO IC50 (nM) | MVD EC50 (nM) | GPI EC50 (nM) | |
| [2S,3R]TMT1-DPDPE | 5.0 | 4,300 | 1.8 | antagonist |
| I A; R = H | 6,400 | 8,100 | – | – |
| I B; R = Me | 610 | 780 | – | – |
| I C; R = i-Bu | 420 | 2,100 | – | – |
| I D; R = C6H3 | 34 | 500 | 174 | 1,250 |
| I E; R = p-tBu-C6H4 | 8.4 | 17,000 | 85 | 39,000 |
| I E (+); R = p-tBu-C6H4 | 42 | 11,000 | 210 | 3,000 |
| I E (−); R = p-tBu-C6H4 | 41 | 7,700 | 360 | 7,600 |
| [MeO-Tyr1]DPDPE | 230 | 11,000 | – | – |
|
II; m-CH3O, R = p-tBu-C6H4 |
1,800 | >8,000 | – | – |
| DPDPE | 1.6 | 610 | 4.1 | 7,300 |
Abbreviations: DAMGO, [D-Ala2,N-MePhe4,Gly-ol]enkephalin; DPDPE, c[D-Pen2,D-Pen5]enkephalin; GPI, guinea pig ileum; MVD, mouse vas deferens; ND, not determined; TMT, β-methyl-2′,6′-dimethyltyrosine (trimethyltyrosine).