Orally efficacious NR2B-selective NMDA receptor antagonists

被引：51
作者：
Claiborne, CF
McCauley, JA [1 ]
Libby, BE
Curtis, NR
Diggle, HJ
Kulagowski, JJ
Michelson, SR
Anderson, KD
Claremon, DA
Freidinger, RM
Bednar, RA
Mosser, SD
Gaul, SL
Connolly, TM
Condra, CL
Bednar, B
Stump, GL
Lynch, JJ
Macaulay, A
Wafford, KA
Koblan, KS
Liverton, NJ
机构：
[1] Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
[2] Merck Sharp & Dohme Res Labs, Dept Med Chem, Ctr Res Neurosci, Harlow CM20 2QR, Essex, England
[3] Merck Res Labs, Dept Mol Pharmacol, W Point, PA 19486 USA
[4] Merck Sharp & Dohme Res Labs, Dept Pharmacol, W Point, PA 19486 USA
[5] 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)01061-2
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel series of benzamidines as synthesized and shogun to exhibit NR2B-subtype selective NMDA antagonist activity. Compound 31 is orally active in a carrageenan-induced rat hyperalgesia model of pain and shows no motor coordination side effects. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：697 / 700
页数：4
相关论文
共 19 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] (1S,2S)-1-(4-HYDROXYPHENYL)-2-(4-HYDROXY-4-PHENYLPIPERIDINO)-1-PROPANOL - A POTENT NEW NEUROPROTECTANT WHICH BLOCKS N-METHYL-D-ASPARTATE RESPONSES
    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
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (16) : 3138 - 3145
  • [3] Chenard BL, 1999, CURR PHARM DESIGN, V5, P381
  • [4] 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
  • [5] NMDA receptor subunits: diversity, development and disease
    Cull-Candy, S
    Brickley, S
    Farrant, M
    [J]. CURRENT OPINION IN NEUROBIOLOGY, 2001, 11 (03) : 327 - 335
  • [6] CURTIS NR, BIOORG MED CHEM LETT
  • [7] DOX AW, 1932, ORG SYNTH C, V6, P5
  • [8] A novel mechanism of activity-dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones
    Kew, JNC
    Trube, G
    Kemp, JA
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1996, 497 (03): : 761 - 772
  • [9] Potential and current use of N-methyl-D-aspartate (NMDA) receptor antagonists in diseases of aging
    Le, DA
    Lipton, SA
    [J]. DRUGS & AGING, 2001, 18 (10) : 717 - 724
  • [10] INTRAVENOUS-INFUSION OF THE NMDA ANTAGONIST, KETAMINE, IN CHRONIC POSTTRAUMATIC PAIN WITH ALLODYNIA - A DOUBLE-BLIND COMPARISON TO ALFENTANIL AND PLACEBO
    MAX, MB
    BYASSMITH, MG
    GRACELY, RH
    BENNETT, GJ
    [J]. CLINICAL NEUROPHARMACOLOGY, 1995, 18 (04) : 360 - 368
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