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Tác giả: Yves P Auberson, Emmanuelle Briard, Christopher J Farady, Christian Fischer, Nadège Graveleau, Joel Karrer, Klemens Kaupmann, Guillaume Lapointe, Angela Mackay, Linjing Mu, Lisa Reichert, David M Whitehead, Michael Wright

Ngôn ngữ: eng

Ký hiệu phân loại: 920.71 Men

Thông tin xuất bản: Germany : ChemMedChem , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 159979

We describe the identification of a candidate positron emission tomography (PET) imaging agent for the NLRP3 protein. NLRP3 plays a critical role in the immune system and has proven a difficult target for the development of imaging agents due to its low and cell-specific expression profile. A recently described series of pyridazine-based inhibitors, with improved permeability and brain-penetration properties, was used as a starting point for the development of a suitable PET imaging agent. Optimization of affinity, non-specific binding and pharmacokinetic properties led to the identification of aminopyridazine (R)-2-(6-((1-cyclopropylpiperidin-3-yl)amino)pyridazin-3-yl)-5-fluoro-3-methylphenol (17 b), which meets the preclinical profile of a successful imaging agent, and whose tritiated version demonstrated excellent specificity in a radioligand saturation binding assay, confirming its imaging potential.
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