title: Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3beta (GSK-3beta) inhibitors.
abstract: A series of novel 4-azaindolyl-indolyl-maleimides were synthesized and evaluated for their GSK-3beta inhibitory activity. Most compounds exhibited high potency to GSK-3beta. Among them, compound 7c was the most promising GSK-3beta inhibitor. Preliminary structure-activity relationships were discussed based on the experimental data obtained and showed that different substituents on the indole ring and side chains at 1-position of indole had varying degrees of influence on the GSK-3beta inhibitory potency. In a cell-based functional assay, compounds 7c and 15a significantly reduced Abeta-induced Tau hyperphosphorylation by inhibiting GSK-3beta.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Guiqing
authors.initials: G
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Lv
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009447:Neuroblastoma / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D013329:Structure-Activity Relationship; D016875:tau Proteins / Q000378:metabolism
chemical_list: D008301:Maleimides; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3