The Role of the Side Chain in Determining Relative δ- and κ-Affinity in C5‘-Substituted Analogues of Naltrindole

Abstract
The role of the side chain in 5‘-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the κ receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the δ receptor.