Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3 [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 547.2 Organic chemical reactions formerly 547.139
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2021
• Mô tả vật lý: Size: Article No. 109760 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 259735
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 60 applied life sciences; 3. Chemistry; 4. Copper-mediated radiofluorination; 5. Fluorine-18; 6. Glycogen synthase kinase 3; 7. Gsk-3; 8. Neuroimaging; 9. Pet imaging

Tóm tắt

 Glycogen synthase kinase 3 (GSK-3) is an enzyme that is dysregulated in oncology neurodegeneration, neuroinflammation and several mental health illnesses. As such, GSK-3 is a long-sought after target for positron emission tomography (PET) imaging and therapeutic intervention. Herein, we report on the development and radiofluorination of two oxazole-4- carboxamides, including one bearing a non-activated aromatic ring. Both compounds demonstrated excellent selectivity in a kinase screen and inhibit GSK-3 with high affinity. [<
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 F]OCM-49 was synthesized from [<
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 18<
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 F]fluoride using a copper-mediated reaction of an aryl boronic acid precursor, while [<
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 18<
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 F]OCM-50 used a trimethylammonium triflate precursor, and both radiotracers were translated for preclinical PET imaging in rodents. Due to superior radiochemical yields and brain uptake (peak standardized uptake value of ~2.0), [<
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 18<
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 F]OCM-50 was further evaluated in non-human primate and also showed good brain uptake and rapid clearance. Finally, further studies to consider clinical translation of both radiotracers are underway.