Synthesis and evaluation of [ 123 I]‐indomethacin derivatives as COX‐2 targeted imaging agents

A novel series of iodinated indomethacin derivatives was synthesized, and evaluated as selective inhibitors of COX‐2. Two candidate compounds N ‐( p ‐iodobenzyl)‐2‐(1‐( p ‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1 H ‐indol‐3‐yl)acetamide (3) and 1‐( p ‐iodobenzyl)‐5‐methoxy‐2‐methyl‐3‐indoleacetic acid (9) possessed optimum properties suitable for potential in vivo imaging. Arylstannane precursors for radioiododestannylation were synthesized in 70–85% yield from the iodo compounds by reaction with hexabutylditin and tetrakis (triphenylphosphine)palladium(0) in refluxing dioxane. Radioiododestannylation was conducted by reaction with carrier‐added Na[ 123 I] in the presence of Chloramine‐T in an EtOAc/H 2 O binary system under acidic conditions (pH 3.5), allowing direct isolation of the labeled products by separation of the organic phase. Radioiodinated products [ 123 I]3 and [ 123 I]9 were recovered in a decay‐corrected radiochemical yield of 86–87% and radiochemical purity of 98–99%. Copyright © 2009 John Wiley & Sons, Ltd.