Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3beta (GSK-3beta) inhibitors.

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Ye Q, Xu G, Lv D, Cheng Z, Li J, Hu Y

Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3beta (GSK-3beta) inhibitors.

Bioorg Med Chem. 2009 Jul 1;17(13):4302-12. doi: 10.1016/j.bmc.2009.05.031. Epub 2009 May 18.

PubMed ID

19481464 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Staurosporine	Glycogen synthase kinase-3 beta	IC 50 (nM)	56	N/A	N/A	Details
Staurosporine	Glycogen synthase kinase-3 beta	IC 50 (nM)	200	N/A	N/A	Details