Synthesis and preliminary evaluation of trans-3,4-conformationally-restricted glutamate and pyroglutamate analogues as novel EAAT2 inhibitors

被引：9
作者：
Denton, TT
Seib, T
Bridges, RJ
Thompson, CM [1 ]
机构：
[1] Univ Montana, Dept Chem, Missoula, MT 59812 USA
[2] Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Pharmaceut Sci, Missoula, MT 59812 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 21期
关键词：
D O I：
10.1016/S0960-894X(02)00520-6
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Select trans-4,5-[bi]cyclohexenylglutamic and pyroglutamic acids (3,4-substituted glutamates) were synthesized in three steps and were screened as potential inhibitors of the sodium dependent excitatory amino acid transporters 2 (EAAT2) and 3 (EAAT3), the chloride dependent glial cystine/glutamate exchanger system x(c)(-), and the glutamate vesicular transport system (VGLUT). Two glutamate analogues and one pyroglutamate analogue were found to inhibit EAAT2 with activity comparable to dihydrokainate. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：3209 / 3213
页数：5
相关论文
共 24 条
[1]  
ARRIZA JL, 1994, J NEUROSCI, V14, P5559
[2]   Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance [J].
Arriza, JL ;
Eliasof, S ;
Kavanaugh, MP ;
Amara, SG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :4155-4160
[3]   Substituted quinolines as inhibitors of L-glutamate transport into synaptic vesicles [J].
Bartlett, RD ;
Esslinger, CS ;
Thompson, CM ;
Bridges, RJ .
NEUROPHARMACOLOGY, 1998, 37 (07) :839-846
[4]   CONFORMATIONALLY DEFINED NEUROTRANSMITTER ANALOGS - SELECTIVE-INHIBITION OF GLUTAMATE UPTAKE BY ONE PYRROLIDINE-2,4-DICARBOXYLATE DIASTEREOMER [J].
BRIDGES, RJ ;
STANLEY, MS ;
ANDERSON, MW ;
COTMAN, CW ;
CHAMBERLIN, AR .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (02) :717-725
[5]   A rational approach to the design of selective substrates and potent nontransportable inhibitors of the excitatory amino acid transporter EAAC1 (EAAT3). New glutamate and aspartate analogues as potential neuroprotective agents [J].
Campiani, G ;
De Angelis, M ;
Armaroli, S ;
Fattorusso, C ;
Catalanotti, B ;
Ramunno, A ;
Nacci, V ;
Novellino, E ;
Grewer, C ;
Ionescu, D ;
Rauen, T ;
Griffiths, R ;
Sinclair, C ;
Fumagalli, E ;
Mennini, T .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (16) :2507-2510
[6]   Quinoline-2,4-dicarboxylic acids: Synthesis and evaluation as inhibitors of the glutamate vesicular transport system [J].
Carrigan, CN ;
Esslinger, CS ;
Bartlett, RD ;
Bridges, RJ ;
Thompson, CM .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (17) :2607-2612
[7]  
Chamberlin AR, 1998, METHOD ENZYMOL, V296, P175
[8]  
CHAMBERLIN AR, 1993, DRUG DESIGN NEUROSCI, P231
[9]  
COREY EJ, 1981, J AM CHEM SOC, V103, P5599, DOI 10.1021/ja00408a067
[10]  
Cotman Carl W., 1995, P75
123