4-[(8-Alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-diethylbenzamides: high affinity, selective ligands for the delta opioid receptor illustrate factors important to antagonist activity

The tropane derived compounds, 4-[(8-alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-diethylbenzamides (5a–d), were synthesized and found to have high affinity and selectivity for the δ receptor. Compounds 5a–d are structurally similar to the full agonist (−)-RTI-5989-54 (3); yet, efficacy studies for compounds in this series (5a–d) reveal greatly diminished agonist activity as well as antagonism not found in piperidine-based compounds like 3.