Radioiodinated (+)-4-[(αR)-α-[(2S, 5R)-4-(iodopropen-2-yl)-2,5- dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N, N-diethylbenzamide: A potential ligand for in vitro and in vivo investigations of δ-opioid receptors

(+)-4-[(αR)-α-[(2S, 5R)-4-(Iodopropen-2-yl)-2,5-dimethyl-1- piperazinyl]-3-hydroxybenzyl]-N, N-diethylbenzamide (1), a novel radioiodinated derivative of the selective δ-opioid antagonist (+)-BW373U86, was synthesized and evaluated in vitro for binding to opioid receptor subtypes. This new compound was found to have high affinity (Ki = 0.57 ± 0.10 nM) and good selectivity for delta (δ) opioid receptors over mu (μ) (Ki μ/δ = 13.6) and kappa (κ) (Ki κ/δ = 175) receptors. The corresponding ¹²³I and ¹²⁵I derivatives were prepared by oxidative radioiododestannylation from a trans-vinyltributyltin precursor. The radiochemical yield was 72-78% EOS (74.3 ± 2.6%, n = 3) for ¹²⁵I-1 and 40-62% EOS (53.9 ± 9.8%, n = 3) for ¹²³I-1. The specific activities were 200-300 mCi/μmol and >5,000 mCi/μmol for the ¹²⁵I and ¹²³I-labeled tracers, respectively.