title: 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.
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.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
authors.forename: J Y
authors.initials: JY
authors.lastname: Gauthier
authors.forename: T
authors.initials: T
authors.lastname: Jones
authors.forename: E
authors.initials: E
authors.lastname: Champion
authors.forename: L
authors.initials: L
authors.lastname: Charette
authors.forename: R
authors.initials: R
authors.lastname: Dehaven
authors.forename: A W
authors.initials: AW
authors.lastname: Ford-Hutchinson
authors.forename: K
authors.initials: K
authors.lastname: Hoogsteen
authors.forename: A
authors.initials: A
authors.lastname: Lord
authors.forename: P
authors.initials: P
authors.lastname: Masson
authors.forename: H
authors.initials: H
authors.lastname: Piechuta
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008968:Molecular Conformation; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011422:Propionates; D011804:Quinolines; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; C059141:verlukast