Chemistry and structure--activity relationships of leukotriene receptor antagonists

Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 2):S220-5; discussion S225-6, S247-8.


Several strategies have been employed by medicinal chemists in the design of potent and selective leukotriene receptor antagonists-leukotriene structural analogs, FPL 55712 analogs, and random screening of corporate compound banks. Lead compounds were optimized, often through the exchange of ideas with groups working on other chemical series of leukotriene antagonists. Pranlukast can likely be traced to a lead compound identified by random screening that was initially modified by incorporating structural components present in FPL 55712. Montelukast originated from an early quinoline lead, which was modified with leukotriene structural elements. Zafirlukast is based on a lead compound that incorporated structural components from both FPL 55712 and the leukotrienes. Therefore, each medicinal chemistry strategy that was originally employed has successfully identified clinically effective leukotriene receptor antagonists.

Publication types

  • Review

MeSH terms

  • Acetates / chemistry
  • Anti-Asthmatic Agents / chemical synthesis
  • Anti-Asthmatic Agents / chemistry*
  • Biological Availability
  • Chromones / chemistry
  • Cyclopropanes
  • Indoles
  • Leukotriene Antagonists*
  • Leukotrienes / chemistry*
  • Lipoxygenase Inhibitors / chemistry
  • Phenylcarbamates
  • Quinolines / chemistry
  • SRS-A / chemistry
  • Structure-Activity Relationship
  • Sulfides
  • Sulfonamides
  • Tosyl Compounds / chemistry


  • Acetates
  • Anti-Asthmatic Agents
  • Chromones
  • Cyclopropanes
  • Indoles
  • Leukotriene Antagonists
  • Leukotrienes
  • Lipoxygenase Inhibitors
  • Phenylcarbamates
  • Quinolines
  • SRS-A
  • Sulfides
  • Sulfonamides
  • Tosyl Compounds
  • FPL 55712
  • montelukast
  • pranlukast
  • zafirlukast