Abstract
A series of 2',3'-disubstituted pyrrolomorphinans (5a-i) were synthesized to determine the role of steric hindrance at μ and γ receptors in promoting δ opioid receptor antagonist selectivity. In smooth muscle preparations, five members of the series (5a-c,e,f) possessed K(e) values in the range 2-15 nM and were 6 selective. Since the unsubstituted analogue 4 possessed δ antagonist potency of similar magnitude, but was not δ selective, it is suggested that the 2',3'substitution confers δ selectivity by hindering the interaction of the pharmacophore at μ and γ receptors, while not affecting δ receptors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1977-1981 |
| Number of pages | 5 |
| Journal | Journal of medicinal chemistry |
| Volume | 40 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jun 20 1997 |