title: Design, synthesis, and evaluation of 3-aryl-4-pyrrolyl-maleimides as glycogen synthase kinase-3β inhibitors.
abstract: A series of 3-aryl-4-pyrrolyl-maleimides were designed, synthesized, and evaluated for their glycogen synthase kinase-3β (GSK-3β) inhibitory activity. Most compounds exhibited potent activity against GSK-3β. Among them, compounds 11a, 11c, 11h, 11i, and 11j significantly reduced Aβ-induced Tau hyperphosphorylation, showing the inhibition of GSK-3β at the cellular level. Structure-activity relationships were discussed based on the experimental data obtained.
authors.affiliation: State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Yu-Bo
authors.initials: YB
authors.lastname: Zhou
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Cao
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Gao
authors.forename: Yong-Zhou
authors.initials: YZ
authors.lastname: Hu
authors.forename: Jia
authors.initials: J
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013329:Structure-Activity Relationship; D016875:tau Proteins / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008301:Maleimides; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3