title: Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 4. Addition of chromone moiety enhances leukotriene D4 receptor binding affinity.
abstract: The combination of the benzopyran-4-one ring, a moiety found in the prototype leukotriene antagonist, FPL 55,712, with the (2-quinolinylmethoxy)phenyl group led to a significant increase in leukotriene receptor binding affinity. This modification resulted in a 10,000-fold improvement in binding affinity compared to FPL 55,712. Compound 7 (RG 12553), with a Ki value of 0.1 nM, has higher affinity than the natural agonist LTD4 and is one of the most potent LTD4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed.
authors.affiliation: Rhone-Poulenc Rorer Central Research, King of Prussia, Pennsylvania 19406.
authors.forename: F C
authors.initials: FC
authors.lastname: Huang
authors.forename: R A
authors.initials: RA
authors.lastname: Galemmo
authors.forename: G B
authors.initials: GB
authors.lastname: Poli
authors.forename: K S
authors.initials: KS
authors.lastname: Learn
authors.forename: M M
authors.initials: MM
authors.lastname: Morrissette
authors.forename: W H
authors.initials: WH
authors.lastname: Johnson
authors.forename: W P
authors.initials: WP
authors.lastname: Dankulich
authors.forename: H F
authors.initials: HF
authors.lastname: Campbell
authors.forename: G W
authors.initials: GW
authors.lastname: Carnathan
authors.forename: R G
authors.initials: RG
authors.lastname: VanInwegen
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002867:Chromones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D007191:Indazoles / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002867:Chromones; D007191:Indazoles; D011804:Quinolines; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; C054217:ICI 198615; C006312:FPL 55712