Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate:: Discovery of potent S1P receptor agonists
Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate:: Discovery of potent S1P receptor agonists
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DOI：
10.1016/s0960-894x(03)00812-6
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发表时间：
2003-10-20
影响因子：
2.7
通讯作者：
Macdonald, TL
中科院分区：
文献类型：
--
作者：
Clemens, JJ;Davis, MD;Macdonald, TL
1-磷酸鞘氨醇 (S1P) 是一种具有生物活性的溶血磷脂，能够通过与 G 蛋白偶联受体 S1P 家族的相互作用诱导广泛的细胞反应。该报告描述了几种有效的 S1P 受体激动剂的合成。例如，使用[γ-S-35]GTP结合测定，化合物9c对S1P(1)受体显示EC50＝8.6nM，相比之下内源配体的EC50＝4.5nM。我们还报告了与在类似物的“接头”和“亲脂尾”区域之间引入苯环相关的影响，例如 S1P(2) 的活性完全丧失和 S1P(5) 的激动作用增加。 (C) 2003 Elsevier Ltd. 保留所有权利。
Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, compound 9c displayed an EC50=8.6 nM at the S1P(1) receptor using a [gamma-S-35]GTP binding assay as compared to an EC50=4.5 nM for the endogenous ligand. We also report the effects associated with introduction of a phenyl ring between the 'linker' and 'lipophilic tail' regions of the analogues, for example total loss of activity at S1P(2) and increased agonism at S1P(5). (C) 2003 Elsevier Ltd. All rights reserved.