BENZOPHENONE DICARBOXYLIC-ACID ANTAGONISTS OF LEUKOTRIENE-B4 .1. STRUCTURE-ACTIVITY-RELATIONSHIPS OF THE BENZOPHENONE NUCLEUS

A series of lipophilic benzophenone dicarboxylic acid derivatives was prepared which inhibited the binding of the potent chemotaxin leukotriene B4.to its receptor(s) on intact human neutrophils. With a radioligand-binding assay as a measure of receptor affinity, a structure-activity relationship for this series was investigated. Both acidic residues were required for receptor-binding activity. The relative orientation of the two acidic groups was important for optimal binding. Replacement of the carbonyl group of the benzophenone with a variety of polar and nonpolar linking groups led to only small changes in binding affinity, indicating the linking group may not be involved in receptor recognition. Further structure-activity relationships within this series are reported in an accompanying paper. © 1990, American Chemical Society. All rights reserved.