Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 4. Addition of chromone moiety enhances leukotriene D4 receptor binding affinity

J Med Chem. 1991 May;34(5):1704-7. doi: 10.1021/jm00109a025.

Abstract

The combination of the benzopyran-4-one ring, a moiety found in the prototype leukotriene antagonist, FPL 55,712, with the (2-quinolinylmethoxy)phenyl group led to a significant increase in leukotriene receptor binding affinity. This modification resulted in a 10,000-fold improvement in binding affinity compared to FPL 55,712. Compound 7 (RG 12553), with a Ki value of 0.1 nM, has higher affinity than the natural agonist LTD4 and is one of the most potent LTD4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Chromones / chemical synthesis*
  • Chromones / metabolism
  • Chromones / pharmacology
  • Guinea Pigs
  • Indazoles / metabolism
  • Indazoles / pharmacology
  • Lung / drug effects
  • Lung / metabolism
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology
  • Radioligand Assay
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Leukotriene
  • SRS-A / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Chromones
  • Indazoles
  • Quinolines
  • Receptors, Immunologic
  • Receptors, Leukotriene
  • SRS-A
  • ICI 198615
  • FPL 55712