NR2B selective NMDA antagonists:: The evolution of the ifenprodil-type pharmaeophore

被引：86

作者：

Borza, Istvan ^{[1
]}

Domany, Gyorgy ^{[1
]}

机构：

[1] Gedeon Richter Chem Works Ltd, H-1475 Budapest, Hungary

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2006年 / 6卷 / 07期

关键词：

ifenprodil; NR2B subunit; pharmacophore; side activities; piperidines;

D O I：

10.2174/156802606776894456

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The quest for NR2B subtype selective NMDA antagonists started almost twenty years ago. The structure of ifenprodil, the prototype of this group of compounds, inspired many medicinal chemists in several research units. Different approaches led to the identification of the pharmacophore and several distinct classes of compounds containing this pharmacophore. From these studies a few drug candidates emerged and clinical trials proved the viability of the concept. This article attempted to follow the evolution from ifenprodil, a multiple ligand, to selective NR2B antagonists.

引用

页码：687 / 695

页数：9

共 41 条

[1] Antagonist properties of the stereoisomers of ifenprodil at NR1A/NR2A and NR1A/NR2B subtypes of the NMDA receptor expressed in Xenopus oocytes [J].

Avenet, P ;

Leonardon, J ;

Besnard, F ;

Graham, D ;

Frost, J ;

Depoortere, H ;

Langer, SZ ;

Scatton, B .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 296 (02) :209-213

[2] Oxamides as novel NR2B selective NMDA receptor antagonists [J].

Barta-Szalai, G ;

Borza, I ;

Bozó, É ;

Kiss, C ;

Agai, B ;

Proszenyák, A ;

Keserü, GM ;

Gere, A ;

Kolok, S ;

Galgóczy, K ;

Horváth, C ;

Farkas, S ;

Domány, G .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (15) :3953-3956

[3] Indole-2-carboxamides as novel NR2B selective NMDA receptor antagonists [J].

Borza, I ;

Kolok, S ;

Gere, A ;

Agai-Csongor, É ;

Agai, B ;

Tárkányi, G ;

Horváth, C ;

Barta-Szalai, G ;

Bozó, É ;

Kiss, C ;

Bielik, A ;

Nagy, J ;

Farkas, S ;

Domány, G .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (21) :3859-3861

[4] (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol:: A conformationally restricted analogue of the NR2B subtype-selective NMDA antagonist (1S,2S)-1-(4-hydroxyphenyl)-2(4-hydroxy-4-phenylpiperidino)-1-propanol [J].

Butler, TW ;

Blake, JF ;

Bordner, J ;

Butler, P ;

Chenard, BL ;

Collins, MA ;

DeCosta, D ;

Ducat, MJ ;

Eisenhard, ME ;

Menniti, FS ;

Pagnozzi, MJ ;

Sands, SB ;

Segelstein, BE ;

Volberg, W ;

White, WF ;

Zhao, DY .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (07) :1172-1184

[5]

CARRON C, 1971, ARZNEI-FORSCHUNG, V21, P1992

[6] (1S,2S)-1-(4-HYDROXYPHENYL)-2-(4-HYDROXY-4-PHENYLPIPERIDINO)-1-PROPANOL - A POTENT NEW NEUROPROTECTANT WHICH BLOCKS N-METHYL-D-ASPARTATE RESPONSES [J].

CHENARD, BL ;

BORDNER, J ;

BUTLER, TW ;

CHAMBERS, LK ;

COLLINS, MA ;

DECOSTA, DL ;

DUCAT, MF ;

DUMONT, ML ;

FOX, CB ;

MENA, EE ;

MENNITI, FS ;

NIELSEN, J ;

PAGNOZZI, MJ ;

RICHTER, KEG ;

RONAU, RT ;

SHALABY, IA ;

STEMPLE, JZ ;

WHITE, WF .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (16) :3138-3145

[7]

Chenard BL, 1999, CURR PHARM DESIGN, V5, P381

[8] SEPARATION OF ALPHA-1 ADRENERGIC AND N-METHYL-D-ASPARTATE ANTAGONIST ACTIVITY IN A SERIES OF IFENPRODIL COMPOUNDS [J].

CHENARD, BL ;

SHALABY, IA ;

KOE, BK ;

RONAU, RT ;

BUTLER, TW ;

PROCHNIAK, MA ;

SCHMIDT, AW ;

FOX, CB .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (10) :3085-3090

[9]

Fischer G, 1997, J PHARMACOL EXP THER, V283, P1285

[10] Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist [J].

Gill, R ;

Alanine, A ;

Bourson, A ;

Buttelmann, B ;

Fischer, G ;

Heitz, MP ;

Kew, JNC ;

Levet-Trafit, B ;

Lorez, HP ;

Malherbe, P ;

Miss, MT ;

Mutel, V ;

Pinard, E ;

Roever, S ;

Schmitt, M ;

Trube, G ;

Wybrecht, R ;

Wyler, R ;

Kemp, JA .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 302 (03) :940-948

← 1 2 3 4 5 →