1-Substituted 4-(3-Hydroxyphenyl)piperazines Are Pure Opioid Receptor Antagonists.

This report describes the discovery that 1-substituted 4-(3-hydroxyphenyl)piperazines are pure opioid receptor antagonists. Compounds in this new series include N-phenylpropyl (3S)-3-methyl-4-(3-hydroxyphenyl)piperazine and (3R)-3-methyl-4-(3-hydroxyphenyl)piperazine, both of which diaplay low nanomolar potencies at μ, δ, and κ receptors and pure antagonist properties in a [(35)S]GTPγS assay.