Utilization of [11C]phosgene for radiosynthesis of N-(2-{3-[3,5-bis(trifluoromethyl)]phenyl[11C]ureido}ethyl) glycyrrhetinamide, an inhibitory agent for proteasome and kinase in tumors

Article abstract of DOI:10.1016/j.bmcl.2012.04.049

N-(2-{3-[3,5-Bis(trifluoromethyl)]phenylureido}ethyl)glycyrrhetinamide (2), an ureido-substituted derivative of glycyrrhetinic acid (1), has been reported to display potent inhibitory activity for proteasome and kinase, which are overexpressed in tumors. In this study, we labeled this unsymmetrical urea 2 using [¹¹C]phosgene ([¹¹C]COCl₂) as a labeling agent with the expectation that [¹¹C]2 could become a positron emission tomography ligand for the imaging of proteasome and kinase in tumors. The strategy for the radiosynthesis of [¹¹C]2 was to react hydrochloride of 3,5-bis(trifluoromethyl)aniline (4·HCl) with [ ¹¹C]COCl₂ to possibly give isocyanate [¹¹C]6, followed by the reaction of [¹¹C]6 with N-(2-aminoethyl) glycyrrhetinamide (3).