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

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 receptoro binding affinity. This modification resulted in a 10000-fold improvement in binding affinity compared to FPL 55,712. Compound 7 (RG 12553) with a K i value of 0.1 nM, has higher affinity than the natural agonist LTD 4 and is one of the most potent LTD 4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed