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 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 K(i) value of 0.1 nM, has higher affinity than the natural agonist LTD4 and one of the most potent LTD4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed.