Novel N1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists

被引：30

作者：

Curtis, NR

Diggle, HJ

Kulagowski, JJ

London, C

Grimwood, S

Hutson, PH

Murray, F

Richards, P

Macaulay, A

Wafford, KA

机构：

[1] Merck Sharp & Dohme Res Labs, Dept Med Chem, Ctr Res Neurosci, Harlow CM20 2QR, Essex, England

[2] Merck Sharp & Dohme Res Labs, Dept Behav Neurosci, Ctr Res Neurosci, Harlow CM20 2QR, Essex, England

[3] Merck Sharp & Dohme Res Labs, Dept Pharmacol, Ctr Res Neurosci, Harlow CM20 2QR, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(02)01060-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel (E)-N-1-(benzyl)cinnamamidines were prepared and evaluated as NR2B subtype NMDA receptor ligands. Excellent affinity was achieved by appropriate substitution of either phenyl ring. The 2-methoxybenzyl compound 1h had similar to1000-fold lower IC50 in NR2B than NR2A-containing cells. Replacement of the styryl unit by 2-naphthl was well tolerated. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：693 / 696

页数：4

共 12 条

[1] Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn
Boyce, S
Wyatt, A
Webb, JK
O'Donnell, R
Mason, G
Rigby, M
Sirinathsinghji, D
Hill, RG
Rupniak, NMJ
[J]. NEUROPHARMACOLOGY, 1999, 38 (05) : 611 - 623
[2] Chenard BL, 1999, CURR PHARM DESIGN, V5, P381
[3] NMDA receptor antagonists as analgesics: focus on the NR2B subtype
Chizh, BA
Headley, PM
Tzschentke, TM
[J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2001, 22 (12) : 636 - 642
[4] CLAIBORNE CF, BIOORG MED CHEM LETT
[5] Dingledine R, 1999, PHARMACOL REV, V51, P7
[6] AN EFFICIENT CONVERSION OF NITRILES TO AMIDINES
GARIGIPATI, RS
[J]. TETRAHEDRON LETTERS, 1990, 31 (14) : 1969 - 1972
[7] Characterisation of N-methyl-D-aspartate receptor-specific[3H]ifenprodil binding to recombinant human NR1a/NR2B receptors compared with native receptors in rodent brain membranes
Grimwood, S
Richards, P
Murray, F
Harrison, N
Wingrove, PB
Hutson, PH
[J]. JOURNAL OF NEUROCHEMISTRY, 2000, 75 (06) : 2455 - 2463
[8] GRIMWOOD S, 1995, MOL PHARMACOL, V48, P841
[9] DEVELOPMENTAL AND REGIONAL EXPRESSION IN THE RAT-BRAIN AND FUNCTIONAL-PROPERTIES OF 4 NMDA RECEPTORS
MONYER, H
BURNASHEV, N
LAURIE, DJ
SAKMANN, B
SEEBURG, PH
[J]. NEURON, 1994, 12 (03) : 529 - 540
[10] NR2B selective NMDA receptor antagonists
Nikam, SS
Meltzer, LT
[J]. CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (10) : 845 - 855

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