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- W4323660143 abstract "Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that regulates numerous cellular processes, including metabolism, proliferation, and cell survival. Due to its multifaceted role, GSK-3 has been implicated in a variety of diseases, including Alzheimer's disease, type 2 diabetes, cancer, and mood disorders. GSK-3β has been linked to the formation of the neurofibrillary tangles associated with Alzheimer's disease that arise from the hyperphosphorylation of tau protein. The design and synthesis of a series of imidazo[1,2-b]pyridazine derivatives that were evaluated as GSK-3β inhibitors are described herein. Structure-activity relationship studies led to the identification of potent GSK-3β inhibitors. In vivo studies with 47 in a triple-transgenic mouse Alzheimer's disease model showed that this compound is a brain-penetrant, orally bioavailable GSK-3β inhibitor that significantly lowered levels of phosphorylated tau." @default.
- W4323660143 created "2023-03-10" @default.
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- W4323660143 date "2023-03-09" @default.
- W4323660143 modified "2023-09-30" @default.
- W4323660143 title "Design, Structure–Activity Relationships, and In Vivo Evaluation of Potent and Brain-Penetrant Imidazo[1,2-<i>b</i>]pyridazines as Glycogen Synthase Kinase-3β (GSK-3β) Inhibitors" @default.
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- W4323660143 doi "https://doi.org/10.1021/acs.jmedchem.3c00133" @default.
- W4323660143 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36950863" @default.
- W4323660143 hasPublicationYear "2023" @default.
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