Piperazinyl benzamidines: Synthesis and affinity for the delta opioid receptor

Piperazinyl benzamidines were prepared and found to bind to the rat delta (δ) opioid receptor. The most active compounds had a N,N-diethylcarboxamido group and a N-benzyl piperazine. The most potent among these was N,N-diethyl-4-[4-(phenylmethyl)-1-piperazinyl][2-(trifluoromethyl)phenyl]iminomethyl]benzamide (27) with a 1.22 nM Ki for the rat δ opioid receptor and ca. 1000× selectivity relative to the μ opioid subtype.