Design, synthesis and evaluation of 7-azaindazolyl-indolyl-maleimides as glycogen synthase kinase-3β (GSK-3β) inhibitors

Qing Ye; Yanhong Shen; Yubo Zhou; Dan Lv; Jianrong Gao; Jia Li; Yongzhou Hu

doi:10.1016/j.ejmech.2013.07.046

Design, synthesis and evaluation of 7-azaindazolyl-indolyl-maleimides as glycogen synthase kinase-3β (GSK-3β) inhibitors

Eur J Med Chem. 2013 Oct:68:361-71. doi: 10.1016/j.ejmech.2013.07.046. Epub 2013 Aug 9.

Authors

Qing Ye¹, Yanhong Shen, Yubo Zhou, Dan Lv, Jianrong Gao, Jia Li, Yongzhou Hu

Affiliation

¹ ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, China.

PMID: 23994329
DOI: 10.1016/j.ejmech.2013.07.046

Abstract

A series of 7-azaindazolyl-indolyl-maleimides were designed, synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited potent activity against GSK-3β. Among them, compounds 17a, 17b, 17g, 17i, 29a and 30 significantly reduced Aβ-induced Tau hyperphosphorylation, showin;g the inhibition of GSK-3β at the cell level. Preliminary structure-activity relationships were discussed based on the experimental data obtained.

Keywords: 7-Azaindazolyl-indolyl-maleimides; Cellular activity; Enzymatic activity; GSK-3β inhibitors.

MeSH terms

Aza Compounds / chemical synthesis
Aza Compounds / chemistry
Aza Compounds / pharmacology
Blotting, Western
Cell Line, Tumor
Drug Design*
Enzyme Activation / drug effects
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology
Inhibitory Concentration 50
Maleimides* / chemical synthesis
Maleimides* / chemistry
Maleimides* / pharmacology
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology

Substances

Aza Compounds
Indoles
Maleimides
Protein Kinase Inhibitors
Glycogen Synthase Kinase 3