Trisubstituted benzene leukotriene B4 receptor antagonists: synthesis and structure-activity relationships.
Trisubstituted benzene leukotriene B4 receptor antagonists: synthesis and structure-activity relationships.
复制标题
三取代苯白三烯 B4 受体拮抗剂：合成和构效关系。
DOI：
10.1016/s0968-0896(97)00089-8
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发表时间：
1997
影响因子：
3.5
通讯作者：
N. Hamanaka
中科院分区：
文献类型：
--
作者：
M. Konno;T. Nakae;S. Sakuyama;Y. Odagaki;H. Nakai;N. Hamanaka
制备了一系列具有白三烯 B4(LTB4, 1) 受体亲和力的三取代苯。我们实验室以前的三取代苯对 LTB4 受体表现出高亲和力，但在功能测定中表现出激动剂活性。化合物 3a 是该新系列的初始先导化合物，仅表现出中等亲和力（IC50 = 0.20 μM）。然而，3a 是一种受体拮抗剂，在浓度高达 30 μM 时没有明显的激动剂活性。对脂质尾部和芳基头基区域的进一步修饰导致了 3b (ONO-4057) 的发现。该化合物不具有激动剂活性，对 LTB4 受体具有高亲和力 (Ki= 3.7±0.9 nM)。
A series of trisubstituted benzenes which demonstrate leukotriene B4(LTB4, 1) receptor affinity was prepared. Previous trisubstituted benzenes from our laboratory showed high affinity to the LTB4receptor but demonstrated agonist activity in functional assays. Compound 3a, the initial lead compound of this new series, showed only modest affinity (IC50= 0.20 μM). However, 3a was a receptor antagonist with no demonstrable agonist activity up to 30 μM. Further modification of the lipid tail and aryl head groups region led to the discovery of 3b (ONO-4057). This compound, free of agonist activity, possesses high affinity to the LTB4receptor (Ki= 3.7±0.9 nM).