Optically pure (−)-4-[(N-allyl-3-methyl-4-piperidinyl)phenyl-amino]-N,N-diethylbenzamide displays selective binding and full agonist activity for the δ opioid receptor

The optical isomers of 4-[(N-allyl-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylbenzamide (3) have been prepared and tested in both binding and functional assays. The data show that (−)-3 is responsible for the δ opioid activity demonstrated by the racemic material. This compound displays a binding affinity of 5.5 nM for the δ opioid receptor as well as a 470-fold δ versus μ selectivity. Importantly, (−)-3 is a full agonist at the δ receptor in comparison with SNC-80 (2). Taken together, the data suggest that (−)-3 behaves more like the prototypical δ agonists, BW373U86 or SNC-80, and less like the peptidomimetic compound SL-3111 (5).