trans-3,4-Dimethyl-4-(3-carboxamidophenyl)piperidines: A novel class of μ-Selective opioid antagonists

trans-3,4-Dimethyl-4-(3-carboxamidophenyl)piperidines constitute a novel class of μ opioid receptor antagonists. The CONH2 group was found to be an effective isostere of the phenolic OH moiety. Structure–activity relationships at the piperidine nitrogen position led to the identification of several ligands displaying high affinity toward the cloned human μ opioid receptors, good selectivity μ/δ, μ/κ, and potent in vitro antagonist activity.