Design,synthesis and activity evaluation of pyridinylcyclopropanecarboxamides targeting GSK-3β in brains
JIA Jian-hua
YANG Mei-xian
QIU Da-chuan
Abstract：Objective:A series of pyridinylcyclopropanecarboxamide derivatives were designed and synthesized to screen excellent lead compounds for the development of small-molecule inhibitors of glycogen synthase kinase-3β(GSK-3β)and positron emission computed tomography(PET)imaging agents for Alzheimer's disease(AD).Methods:A Suzuki coupling reaction catalyzed by Pd was applied to produce the target compounds.The inhibitory activity of the compounds against GSK-3β was evaluated by enzyme inhibition assay.The blood-brain barrier(BBB)permeability was predicted by SwissADME.Results:The structures of compounds were confirmed by 1 H-NMR,13 C-NMR and HRMS.Fluoro-amide compounds(17～20)indicated high affinities to GSK-3β and feasible BBB permeability.Conclusion:Pyridinylcyclopropanecarboxamide compounds have the potential to be developed as GSK-3β inhibitors and PET probes for the treatment and imaging of AD.
Keywords：pyridinylcyclopropanecarboxamide derivativessynthesisinhibitory activityglycogen synthase kinase-3β inhibitorspositron emission tomography imaging agents
Publication Date：2024-02-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 279-284 )