Synthesis and Evaluation of 1- and 2-Substituted Fentanyl Analogues for Opioid Activity

Article abstract of DOI:10.1021/jm00357a007

We synthesized fentanyl analogues that posses key groups common to the opioid peptides to investigate whether or not these two classes of compounds interact with common subsites on opioid receptors.The design of the analogues was based on the possibility of structural analogy between the two aromatic rings of fentanyl and the Tyr¹ and Phe⁴ residues of the opioid peptides.The synthesized compounds showed very week or no opioid activity as tested in the electrically stimulated longitudinal muscle of the guinea pig ileum or mouse vas deferens preparations.These results, together with those of reported studies, suggest that fentanyl and the opioid peptides interact with diffrent subsites on either μ or δ receptors.Studies using the irreversible μ opioid receptor antagonist, β-funaltrexamine, indicate that fentanyl interacts preferentially with μ opioid receptors.