Synthesis, stability, and implications of phosphothioate agonists of sphingosine-1-phosphate receptors

被引：22

作者：

Foss, FW

Clemens, JJ

Davis, MD

Snyder, AH

Zigler, MA

Lynch, KR

Macdonald, TL

机构：

[1] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA

[2] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22904 USA

[3] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22904 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 20期

关键词：

sphingosine-l-phosphate; phosphothioate; lymphopenia;

D O I：

10.1016/j.bmcl.2005.07.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphothioates may provide metabolic stability when compared to their phosphate counterparts, while retaining the potency and efficacy as agonists at sphingosine-1 -phosphate (SIP) G-protein coupled receptors. Unlike their phosphate precursors, phosphothioate compounds with SIP-receptor profiles similar to that of FTY720, an emerging immunomodulator, were shown to evoke prolonged lymphopenia in vivo. Analysis of mouse plasma concentrations for a series of related alcohol/phosphate/phosphothioate compounds showed the conversion of the phosphate to alcohol. These preliminary data highlight the importance of metabolic regulation of SIP receptor ligands. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4470 / 4474

页数：5

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