Synthesis and biological evaluation of phosphonic and thiophosphoric acid derivative's of lysophosphatidic acid

被引：26

作者：

Santos, WL

Heasley, BH

Jarosz, R

Carter, KM

Lynch, KR

Macdonald, TL

机构：

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

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

[3] Dept Chem & Chem Biol, Cambridge, MA 02138 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 13期

关键词：

lysophosphatidic acid; phosphonic acid; thiophosphoric acids; phosphatase;

D O I：

10.1016/j.bmcl.2004.04.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using an N-oleoyl ethanolamide scaffold, a series of phosphate polar head group analogues of LPA comprised of various alpha-substituted phosphonates and thiophosphates was prepared. In a broken cell GTP[gamma(35)S] binding assay, agonist activity was evaluated at the three LPA receptors of the endothelial differentiation gene (Edg) family. This study has resulted in the discovery of a nonhydrolyzable LPA(1)-selective agonist (11). Additionally, thiophosphate 19 bears an isosteric phosphate mimetic that confers agonism at the LPA(1) receptor but not LPA(2). (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3473 / 3476

页数：4

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