Synthesis and biological evaluation of (2S)-and (2R)-2-(3′-phosphonobicyclo[1.1.1]pentyl)glycines as novel group III selective metabotropic glutamate receptor ligands

被引：28
|
作者：
Filosa, Rosanna
Marinozzi, Maura
Costantino, Gabriele
Hermit, Mette Brunsgaard
Thomsen, Christian
Pellicciari, Roberto
机构：
[1] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06123 Perugia, Italy
[2] H Lundbeck & Co AS, DK-2500 Copenhagen, Denmark
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 11期
关键词：
metabotropic glutamate receptors; neuroprotection; propellane;
D O I：
10.1016/j.bmc.2006.01.027
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The synthesis of (2S)- and (2R)-2-(3'-phosphonobicyclo[1.1.1]pentyl)glycine isomers (10 and 11), characterized by the bioisosteric replacement of the distal carboxylic group of 2-(3'-carboxybicyclo[1.1.1]pent-1-yl)glycine by the phosphonate moiety, was accomplished by a stereoselective Ugi condensation. The two isomers were tested for their activity against an array of metabotropic glutamate receptors, and the S-isomer (10) turned out to be a moderately potent and selective mGluR4 agonist. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3811 / 3817
页数：7
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