Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Bioorg Med Chem Lett. 2012 Jun 1;22(11):3594-7. doi: 10.1016/j.bmcl.2012.04.049. Epub 2012 Apr 18.
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).
N-(2-{3-[3,5-双(三氟甲基)]苯甲酰氨基}乙基)甘草次酸酰胺（2）是甘草次酸的脲取代衍生物，已被报道具有很强的蛋白酶体和激酶抑制活性，而这些酶在肿瘤中过度表达。在这项研究中，我们使用 [(11)C]光气 ([(11)C]COCl(2)) 对这个不对称脲 2 进行了标记，期望 [(11)C]2 可以成为正电子发射断层扫描配体，用于肿瘤中蛋白酶体和激酶的成像。[(11)C]2 的放射性合成策略是使 3,5-双(三氟甲基)苯胺盐酸盐（4·HCl）与 [(11)C]COCl(2)反应，可能得到异氰酸酯 [(11)C]6，然后 [(11)C]6 与 N-(2-氨基乙基)甘草次酸酰胺（3）反应。
