Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Bioorg Med Chem Lett. 2011 Dec 1;21(23):7017-20. doi: 10.1016/j.bmcl.2011.09.102. Epub 2011 Oct 1.
Three ureido-substituted benzenesulfonamides 1a-c have been developed as potent inhibitors for carbonic anhydrase IX, which is overexpressed in hypoxic tumors. In this study, we labeled these unsymmetrical ureas 1a-c using [(11)C]phosgene ([(11)C]COCl(2)) as a labeling agent with the expectation that [(11)C]1a-c could become promising positron tomography probes for imaging carbonic anhydrase IX in tumors. The strategy for radiosynthesis of [(11)C]1a-c was to react hydrochloride of anilines 2a-c with [(11)C]COCl(2) to give isocyanate [(11)C]4a-c, followed by a reaction with 4-aminobenzenesulfonamide (3).
三种脲基取代的苯磺酰胺 1a-c 已被开发为碳酸酐酶 IX 的有效抑制剂，碳酸酐酶 IX 在缺氧肿瘤中过度表达。在这项研究中，我们使用 [(11)C]光气 ([(11)C]COCl(2)) 对这些不对称脲 1a-c 进行标记，期望 [(11)C]1a-c 能够成为用于肿瘤中碳酸酐酶 IX 成像的有前途的正电子断层扫描探针。[(11)C]1a-c 的放射合成策略是使苯胺盐酸盐 2a-c 与 [(11)C]COCl(2)反应得到异氰酸酯 [(11)C]4a-c，然后与 4-氨基苯磺酰胺 (3)反应。
