New opioid compounds in analgesia

Abstract

Increasing evidence has accumulated that there are subtypes of opioid receptors and that opioid receptors in the brain, spinal column and periphery have different structural requirements for bioactivity. We have sought to design peptide and peptide mimetic analogs that will interact specifically with δ or κ opioid receptor types and subtypes as well as the recently proposed μδ cx receptor. Using computer assisted design, conformational and topographical stereostructural considerations, asymmetric and macrocyclic synthetic chemistry, and multiple assays and binding methods (1), we have designed conformationally and topographically constrained ligands with high potency, selectivity and efficacy at δ 1 , δ 2 , μδ cx , k 1 and other opioid receptors