Discovery of novel triazole-based opioid receptor antagonists

We report the computer-aided design, chemical synthesis, and biological evaluation of a novel family of delta opioid receptor (DOR) antagonists containing a 1,2,4-triazole core structure that are structurally distinct from other known opioid receptor active ligands. Among those delta antagonists sharing this core structure, 8 exhibited strong binding affinity (K-i = 50 nM) for the DOR and appreciable selectivity for delta over mu and kappa opioid receptors (delta/mu = 80; delta/kappa > 200).