.kappa. Opioid Receptor Selective Affinity Labels: Electrophilic Benzeneacetamides as .kappa.-Selective Opioid Antagonists

2-(3,4-Dichlorophenyl)-N-methyl-N-[1-(3- or 4-substituted phenyl)-2-(1-pyrrolidinyl)ethyl]-acetamides 3-6 were synthesized as κ-selective affinity labels and evaluated for opioid activity. In smooth muscle preparations, the non-electrophilic parent compound (+)-S-2 and the affinity labels 3-6 behaved as κ agonists in that they were potently antagonized by norbinaltorphimine (norBNI). In addition to the high binding affinity and selectivity of the 3-isothiocyanate 3 (DIPPA) to κ opioid receptors, wash studies have suggested that this involves covalent binding