Evolution of a Series of Peptidoleukotriene Antagonists: Synthesis and Structure-Activity Relationships of 1,6-Disubstituted Indoles and Indazoles

Article abstract of DOI:10.1021/jm00168a036

A perception of structural similarities between two independent series of leukotriene antagonists (one emanating from FPL 55712 and one based upon the leukotrienes themselves) led to the discovery of a novel class of indole and indazole derived antagonists of peptidoleukotrienes.A systematic exploration of C-6 substituted 4-(indol-1-ylmethyl)-3-methoxybenzoic acids identified cyclopentylacetamide and cyclopentylurethane as preferred substituents.The corresponding indazoles were equipotent.These compounds are selective leukotriene antagonists with pK_B values of 7.5-7.8 vs LTE4 on guinea pig trachea.