Quinolines as potent 5-lipoxygenase inhibitors: Synthesis and biological profile of L-746,530

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 l...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1998-05, Vol.8 (10), p.1255-1260
Main Authors: Dubé, Daniel, Blouin, Marc, Brideau, Christine, Chan, Chi-Chung, Desmarais, Sylvie, Ethier, Diane, Falgueyret, Jean-Pierre, Friesen, Richard W., Girard, Mario, Girard, Yves, Guay, Jocelyne, Riendeau, Denis, Tagari, Philip, Young, Robert N.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bridged Bicyclo Compounds - pharmacology
Humans
Leukotriene B4 - blood
Lipoxygenase Inhibitors - chemical synthesis
Lipoxygenase Inhibitors - chemistry
Lipoxygenase Inhibitors - pharmacology
Medical sciences
Models, Molecular
Molecular Structure
Naphthalenes - chemistry
Naphthalenes - pharmacology
Neutrophils - drug effects
Neutrophils - physiology
Pharmacology. Drug treatments
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Recombinant Proteins - antagonists & inhibitors
Respiratory system
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Summary: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. [1 S,5 R]-2-Cyano-4-(3-furyl)-7-3-fluoro-5-[3-(3 α-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. A series of novel 5-lipoxygenase inhibitors have been synthesized. Among them quinoline ( 3) showed excellent in vitro and in vivo potency.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(98)00201-7