Selective δ-opioid receptor ligands: potential PET ligands based on naltrindole

Two series of δ-selective ligands related to the prototypic δ-antagonist naltrindole have been prepared and evaluated in opioid binding assays with the aim of developing new PET ligands for the δ-opioid receptor. One compound (5d) had significantly higher selectivity than naltrindole, but with substantially reduced binding affinity. For those compounds retaining similar affinity to naltrindole, those having ethyl and fluoroethyl substituents afforded the highest levels of selectivity. However, none of the compounds combined the high level of affinity and selectivity ideally suited to the development of an imaging agent.