Synthesis and biological evaluation of 5-arylamino-6-chloro-1H-indazole-4,7-diones as inhibitors of protein kinase B/Akt

Bioorg Med Chem Lett. 2006 Dec 1;16(23):6001-5. doi: 10.1016/j.bmcl.2006.08.120. Epub 2006 Sep 20.

Abstract

A series of 5-arylamino-6-chloro-1H-indazole-4,7-diones were synthesized and evaluated for their inhibitory activity on protein kinase B/Akt. The compounds exhibited a potent Akt1 inhibitory activity. Further mechanistic study revealed that they might have dual inhibitory effects on both activity and phosphorylation of Akt1 in PC-3 tumor cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Catalysis
  • Cell Line, Tumor
  • Chlorine / chemistry*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Indazoles / chemical synthesis
  • Indazoles / chemistry*
  • Indazoles / pharmacology*
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Indazoles
  • Protein Kinase Inhibitors
  • Chlorine
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3