title: Quinolines as potent 5-lipoxygenase inhibitors: synthesis and biological profile of L-746,530.
abstract: Leukotriene biosynthesis inhibitors have potential as new therapeutic agents for asthma and inflammatory diseases. A series of novel substituted 2-cyanoquinolines have been synthesized and the structure activity relationships were evaluated with respect to their ability to inhibit the formation of leukotrienes via the 5-lipoxygenase enzyme. [1S,5R]-2-Cyano-4-(3-furyl)-7-¿3-fluoro-5-[3-(3 alpha-hydroxy-6,8-dioxabicyclo[3.2.1]-octanyl)]phenoxymethyl ¿quinoline (L-746,530) 3 represents a distinct class of inhibitors and possesses in vitro and in vivo potency comparable or superior to naphthalenic analog (L-739,010) 2.
authors.affiliation: Merck Frosst Centre For Therapeutic Research, Québec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Dubé
authors.forename: M
authors.initials: M
authors.lastname: Blouin
authors.forename: C
authors.initials: C
authors.lastname: Brideau
authors.forename: C C
authors.initials: CC
authors.lastname: Chan
authors.forename: S
authors.initials: S
authors.lastname: Desmarais
authors.forename: D
authors.initials: D
authors.lastname: Ethier
authors.forename: J P
authors.initials: JP
authors.lastname: Falgueyret
authors.forename: R W
authors.initials: RW
authors.lastname: Friesen
authors.forename: M
authors.initials: M
authors.lastname: Girard
authors.forename: Y
authors.initials: Y
authors.lastname: Girard
authors.forename: J
authors.initials: J
authors.lastname: Guay
authors.forename: D
authors.initials: D
authors.lastname: Riendeau
authors.forename: P
authors.initials: P
authors.lastname: Tagari
authors.forename: R N
authors.initials: RN
authors.lastname: Young
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
chemical_list: D001643:Bridged Bicyclo Compounds; C100578:L 746530; D016859:Lipoxygenase Inhibitors; D009281:Naphthalenes; D011804:Quinolines; D011994:Recombinant Proteins; D007975:Leukotriene B4