Synthesis and biological evaluation of 3-benzisoxazolyl-4-indolylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3β.

TitleSynthesis and biological evaluation of 3-benzisoxazolyl-4-indolylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3β.
Publication TypeJournal Article
Year of Publication2013
AuthorsYe Q, Li M, Zhou Y, Pang T, Xu L, Cao J, Han L, Li Y, Wang W, Gao J, Li J
JournalMolecules (Basel, Switzerland)
Volume18
Issue5
Pagination5498-516
Date Published2013
Abstract

A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC₅₀ value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N¹-position of the indole ring had varying degrees of influence on the GSK-3β inhibitory potency. Compounds 7c, 7f, 7j-l and 7o-q could obviously reduce Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β in a cell-based functional assay.

DOI10.1364/OE.21.010772
Alternate JournalMolecules