Quinolines as potent 5-lipoxygenase inhibitors: synthesis and biological profile of L-746,530.
Dubé D, Blouin M, Brideau C, Chan CC, Desmarais S, Ethier D, Falgueyret JP, Friesen RW, Girard M, Girard Y, Guay J, Riendeau D, Tagari P, Young RN.
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.