Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 2. Effects of an additional phenyl ring on receptor affinity

J Med Chem. 1990 Apr;33(4):1194-200. doi: 10.1021/jm00166a017.


This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of changes in the linkage between the two phenyl rings as well as the orientation of the acidic functional group on biological activity are discussed. Many of these compounds have high affinity to the sulfidopeptide leukotriene D4 receptors with Ki values ranging between 2 and 20 nM and are orally active. Compound 27 [RG 12525, 5-[[2-[[4-(2-quinolinylmethoxy)phenoxy]- methyl]phenyl]methyl]-1H-tetrazole] represents the best combination of in vitro and in vivo biological activity in this series and has been selected for further evaluation in clinical studies of asthma.

MeSH terms

  • Animals
  • Azoles / chemical synthesis*
  • Bronchodilator Agents / chemical synthesis*
  • Chemical Phenomena
  • Chemistry
  • Guinea Pigs
  • Leukotriene Antagonists
  • Lung / drug effects
  • Phenyl Ethers / chemical synthesis*
  • Phenyl Ethers / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology
  • Receptors, Immunologic / drug effects*
  • Receptors, Immunologic / metabolism
  • Receptors, Leukotriene B4
  • SRS-A / antagonists & inhibitors
  • Structure-Activity Relationship
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / pharmacology


  • Azoles
  • Bronchodilator Agents
  • Leukotriene Antagonists
  • Phenyl Ethers
  • Quinolines
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
  • SRS-A
  • Tetrazoles
  • RG 12525