Opioid Affinity of Diazacyclic Peptidomimetic Compounds Derived from Reduced Polyamides

Diaza-peptidomimetics are constrained compounds that mimic the biological efficacy of peptides while offering increased stability. We have previously reported the synthesis of bis-cyclic guanidine heterocyclic peptidomimetics as opioid ligands with mixed μ-, κ- and δ-opioid receptor interactions and their potential activity as novel analgesics. Using the same approach, we report here the synthesis of sulfonated and piperazine-tethered bis-cyclic guanidines and their in vitro screening results from radioligand competition binding assays at the μ- (MOR), δ- (DOR), and κ- (KOR) opioid receptors.