Benzophenone Dicarboxylic Acid Antagonists of Leukotriene B4. 1. Structure-Activity Relationships of the Benzophenone Nucleus

Article abstract of DOI:10.1021/jm00172a019

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 lead 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.