title: 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.
abstract: 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 [(11)C]phosgene ([(11)C]COCl(2)) as a labeling agent with the expectation that [(11)C]2 could become a positron emission tomography ligand for the imaging of proteasome and kinase in tumors. The strategy for the radiosynthesis of [(11)C]2 was to react hydrochloride of 3,5-bis(trifluoromethyl)aniline (4·HCl) with [(11)C]COCl(2) to possibly give isocyanate [(11)C]6, followed by the reaction of [(11)C]6 with N-(2-aminoethyl)glycyrrhetinamide (3).
authors.affiliation: Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Asakawa
authors.forename: Masanao
authors.initials: M
authors.lastname: Ogawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010705:Phosgene / Q000737:chemistry*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049268:Positron-Emission Tomography; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002250:Carbon Radioisotopes; C568507:N-(2-(3-(3,5-bis(trifluoromethyl)phenyl)ureido)ethyl)glycyrrhetinamide; D010671:Phenylurea Compounds; D061988:Proteasome Inhibitors; D019275:Radiopharmaceuticals; D010705:Phosgene; D010770:Phosphotransferases; D046988:Proteasome Endopeptidase Complex; D006034:Glycyrrhetinic Acid