3-(7-Azaindolyl)-4-arylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3

Bioorg Med Chem Lett. 2004 Jun 21;14(12):3245-50. doi: 10.1016/j.bmcl.2004.03.090.


A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3beta and selectivity versus PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3beta (IC(50)=7 and 26 nM, respectively) and exhibited excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3beta.

MeSH terms

  • Cell Line
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Maleimides / chemistry*
  • Maleimides / pharmacology
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology


  • Maleimides
  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3