BENZOPHENONE DICARBOXYLIC-ACID ANTAGONISTS OF LEUKOTRIENE-B4 .1. STRUCTURE-ACTIVITY-RELATIONSHIPS OF THE BENZOPHENONE NUCLEUS
BENZOPHENONE DICARBOXYLIC-ACID ANTAGONISTS OF LEUKOTRIENE-B4 .1. STRUCTURE-ACTIVITY-RELATIONSHIPS OF THE BENZOPHENONE NUCLEUS
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DOI：
10.1021/jm00172a019
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发表时间：
1990-10-01
影响因子：
7.3
通讯作者：
JACKSON, WT
中科院分区：
文献类型：
--
作者：
GAPINSKI, DM;MALLETT, BE;JACKSON, WT
制备了一系列亲脂性二苯甲酮二羧酸衍生物，其抑制有效的趋化因子白三烯B4与其在完整的人中性粒细胞上的受体的结合。用放射性配体结合试验作为受体亲和力的量度，研究了该系列的构效关系。这两个酸性残基都是受体结合活性所需的。两个酸性基团的相对取向对于最佳结合是重要的。用各种极性和非极性连接基团取代二苯甲酮的羰基仅导致结合亲和力的微小变化，表明连接基团可能不参与受体识别。该系列中的进一步结构-活性关系在随附的论文中报道。
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.