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.
MeSH terms
-
Animals
-
Chemical Phenomena
-
Chemistry
-
Chromones / chemical synthesis*
-
Chromones / metabolism
-
Chromones / pharmacology
-
Guinea Pigs
-
Indazoles / metabolism
-
Indazoles / pharmacology
-
Lung / drug effects
-
Lung / metabolism
-
Quinolines / chemical synthesis*
-
Quinolines / pharmacology
-
Radioligand Assay
-
Receptors, Immunologic / antagonists & inhibitors*
-
Receptors, Immunologic / metabolism
-
Receptors, Leukotriene
-
SRS-A / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Chromones
-
Indazoles
-
Quinolines
-
Receptors, Immunologic
-
Receptors, Leukotriene
-
SRS-A
-
ICI 198615
-
FPL 55712