Design, synthesis and biological evaluation of β-carboline derivatives as novel inhibitors targeting B-Raf kinase

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4783-6. doi: 10.1016/j.bmcl.2012.05.053. Epub 2012 May 24.

Abstract

β-Carboline family of compounds is a large group of alkaloids widely distributed in nature and exhibits broad-spectrum anti-tumor activities. We designed and synthesized two series of novel 1-carboxamide- and 6-sulfonamide-substituted β-carboline derivatives 7a-p and 12a-b, and their wild type B-Raf kinase inhibitory activities were described. Most compounds showed moderate to excellent inhibitory activities. Among them, 1-carboxamide-6-(N-(3-(dimethylamino)propyl)-sulfamoyl)-β-carboline, 7e exhibited potent activity (IC(50)=1.62 μM), showing the potential for further investigation as a lead compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbolines / chemical synthesis*
  • Carbolines / pharmacology
  • Drug Design
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Carbolines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf