Discovery and initial SAR of imidazoquinoxalines as inhibitors of the Src-family kinase p56(Lck)

Bioorg Med Chem Lett. 2002 May 20;12(10):1361-4. doi: 10.1016/s0960-894x(02)00191-9.

Abstract

We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck with excellent potency (IC50s<5 nM) as well as good cellular activity against T-cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the requirement for the core heterocycle in addition to an optimal 2,6-disubstituted aniline group.

MeSH terms

  • Animals
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Kinetics
  • Lymphocyte Activation / drug effects
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Conformation
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / pharmacology
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Quinoxalines
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases