Design, synthesis, and evaluation of 3-aryl-4-pyrrolyl-maleimides as glycogen synthase kinase-3β inhibitors

Arch Pharm (Weinheim). 2013 May;346(5):349-58. doi: 10.1002/ardp.201300008. Epub 2013 Apr 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Maleimides / chemical synthesis
  • Maleimides / chemistry
  • Maleimides / pharmacology*
  • Phosphorylation / drug effects
  • Structure-Activity Relationship
  • tau Proteins / metabolism

Substances

  • Enzyme Inhibitors
  • Maleimides
  • tau Proteins
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3