Stereospecific synthesis, assignment of absolute configuration, and biological activity of the enantiomers of 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid, a potent and specific leukotriene D4 receptor antagonist

J Med Chem. 1990 Oct;33(10):2841-5. doi: 10.1021/jm00172a025.

Abstract

The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic intermediate (5), and the biological activity of the enantiomers has been explored. Unexpectedly, the enantiomers are both comparably biologically active with (+)-1 slightly more intrinsically active at the LTD4 receptor in vitro.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Membrane / metabolism
  • Chemical Phenomena
  • Chemistry
  • Guinea Pigs
  • In Vitro Techniques
  • Lung / metabolism
  • Molecular Conformation
  • Propionates / chemical synthesis*
  • Propionates / chemistry
  • Propionates / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / metabolism
  • Receptors, Leukotriene
  • SRS-A / antagonists & inhibitors*
  • SRS-A / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Propionates
  • Quinolines
  • Receptors, Immunologic
  • Receptors, Leukotriene
  • SRS-A
  • verlukast