5-phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition

被引：195

作者：

Auberson, YP ^{[1
]}

Allgeier, H ^{[1
]}

Bischoff, S ^{[1
]}

Lingenhoehl, K ^{[1
]}

Moretti, R ^{[1
]}

Schmutz, M ^{[1
]}

机构：

[1] Novartis Pharma AG, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(02)00074-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

NMDA antagonists derived from 5-phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione (3a) are potent anticonvulsant agents, and display strong protective effects in the electroshock-induced convulsion assay in mice. Their preference for the human NMDAR 1A/2A over 1A/2B subunit composition was optimized, leading to (1RS, 1'S)-PEAQX (9r), which shows a > 100-fold selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：1099 / 1102

页数：4

相关论文

共 15 条

[1] 5-aminomethylquinoxaline-2,3-diones, Part III: Arylamide derivatives as highly potent and selective glycine-site NMDA receptor antagonists [J].

Acklin, P ;

Allgeier, H ;

Auberson, YP ;

Bischoff, S ;

Ofner, S ;

Sauer, D ;

Schmutz, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (05) :493-498

[2] SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS VIA SILYL ESTERS OF PHOSPHORUS-ACIDS [J].

AFARINKIA, K ;

REES, CW ;

CADOGAN, JIG .

TETRAHEDRON, 1990, 46 (20) :7175-7196

[3] N-Phosphonoalkyl-5-aminomethylquinoxaline-2,3-diones:: in vivo active AMPA and NMDA(glycine) antagonists. [J].

Auberson, YP ;

Acklin, P ;

Bischoff, S ;

Moretti, R ;

Ofner, S ;

Schmutz, M ;

Veenstra, SJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (02) :249-254

[4] 5-Aminomethylquinoxaline-2,3-diones. Part II: N-aryl derivatives as novel NMDA/glycine and AMPA antagonists. [J].

Auberson, YP ;

Acklin, P ;

Allgeier, H ;

Biollaz, M ;

Bischoff, S ;

Ofner, S ;

Veenstra, SJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (01) :71-74

[5] 5-Aminomethylquinoxaline-2,3-diones. Part I: A novel class of AMPA receptor antagonists. [J].

Auberson, YP ;

Bischoff, S ;

Moretti, R ;

Schmutz, M ;

Veenstra, SJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (01) :65-70

[6]

Baron BM, 1996, J PHARMACOL EXP THER, V279, P62

[7]

Herrling P.L., 1997, EXCITATORY AMINO ACI, P7

[8]

Hess SD, 1996, J PHARMACOL EXP THER, V278, P808

[9] THE BINDING OF [AMPA-H-3, A STRUCTURAL ANALOG OF GLUTAMIC-ACID, TO RAT-BRAIN MEMBRANES [J].

HONORE, T ;

LAURIDSEN, J ;

KROGSGAARDLARSEN, P .

JOURNAL OF NEUROCHEMISTRY, 1982, 38 (01) :173-178

[10]

LEHMANN J, 1988, J PHARMACOL EXP THER, V246, P65