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.
Gapinski
D M
DM
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Mallett
B E
BE
Froelich
L L
LL
Jackson
W T
WT
D001577:Benzophenones / Q000494:pharmacology*; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D009504:Neutrophils; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D013329:Structure-Activity Relationship
D001577:Benzophenones; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4