发现碳-11 标记的磺胺衍生物：一种用于脑 NLRP3 炎性小体成像的 PET 示踪剂。
Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome.
机构信息
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, United States.
出版信息
Bioorg Med Chem Lett. 2021 Feb 15;34:127777. doi: 10.1016/j.bmcl.2021.127777. Epub 2021 Jan 6.
Abstract
We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain. [C]1, thus suggesting the potential to serve as a useful tool for imaging NLRP3 inflammasome in living brains.
摘要
我们在此报告了一种正电子发射断层扫描 (PET) 示踪剂的发现，用于（NOD）样受体蛋白 3 (NLRP3)。我们最近在开发基于磺胺的 NLRP3 抑制剂的药物化学研究中，得到了一个带有甲氧基取代基的类似物 1，该取代基适合用碳-11 标记。PET/CT 成像研究表明，[C]1 具有快速的血脑屏障 (BBB) 穿透能力和中等的脑摄取能力，以及在大脑中的可阻断摄取能力。[C]1，因此表明其有可能成为在活体大脑中成像 NLRP3 炎性小体的有用工具。
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