Discovery of novel modulators of metabotropic glutamate receptor subtype-5

被引：36

作者：

Wang, BW

Vernier, JM

Rao, S

Chung, J

Anderson, JJ

Brodkin, JD

Jiang, XH

Gardner, MF

Yang, XQ

Munoz, B

机构：

[1] Merck Res Labs, Dept Chem, San Diego, CA 92121 USA

[2] Merck Res Labs, Dept Neuropharmacol, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 01期

关键词：

D O I：

10.1016/j.bmc.2003.10.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of potent and selective mGluR5 antagonists were synthesized and evaluated in vitro and in vivo. It was found that a pyridyl functionality is a potential replacement for acetonitrile in the lead structure, with 2-pyridyl being most favored. Additionally, the benzoxazole moiety could also be replaced by other heterobicyclic rings such as imidazothiazole. (C) 2003 Elsevier Ltd. All rights reserved.

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页码：17 / 21

页数：5

相关论文

共 18 条

[1] In vivo receptor occupancy of mGlu5 receptor antagonists using the novel radioligand [3H]3-methoxy-5-(pyridin-2-ylethynyl)pyridine) [J].

Anderson, JJ ;

Bradbury, MJ ;

Giracello, DR ;

Chapman, DF ;

Holtz, G ;

Roppe, J ;

King, C ;

Cosford, NDP ;

Varney, MA .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 473 (01) :35-40

[2]

Awad H, 2000, J NEUROSCI, V20, P7871

[3] Peripheral group I metabotropic glutamate receptors modulate nociception in mice [J].

Bhave, G ;

Karim, F ;

Carlton, SM ;

Gereau, RW .

NATURE NEUROSCIENCE, 2001, 4 (04) :417-423

[4] Involvement of mGluR5 on acute nociceptive transmission [J].

Bordi, F ;

Ugolini, A .

BRAIN RESEARCH, 2000, 871 (02) :223-233

[5] Anxiolytic-like activity of the mGluR5 antagonist MPEP - A comparison with diazepam and buspirone [J].

Brodkin, J ;

Busse, C ;

Sukoff, SJ ;

Varney, MA .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2002, 73 (02) :359-366

[6] Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective [J].

Bruno, V ;

Ksiazek, I ;

Battaglia, G ;

Lukic, S ;

Leonhardt, T ;

Sauer, D ;

Gasparini, F ;

Kuhn, R ;

Nicoletti, F ;

Flor, PJ .

NEUROPHARMACOLOGY, 2000, 39 (12) :2223-2230

[7] Anticonvulsant activity of two metabotropic glutamate Group I antagonists selective for the mGlu5 receptor: 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and (E)-6-methyl-2-styryl-pyridine (SIB 1893) [J].

Chapman, AG ;

Nanan, K ;

Williams, M ;

Meldrum, BS .

NEUROPHARMACOLOGY, 2000, 39 (09) :1567-1574

[8] Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice [J].

Chiamulera, C ;

Epping-Jordan, MP ;

Zocchi, A ;

Marcon, C ;

Cottiny, C ;

Tacconi, S ;

Corsi, M ;

Orzi, F ;

Conquet, F .

NATURE NEUROSCIENCE, 2001, 4 (09) :873-874

[9] Tin(II) chloride-mediated synthesis of 2-substituted benzoxazoles [J].

Cho, CS ;

Kim, DT ;

Zhang, JQ ;

Ho, SL ;

Kim, TJ ;

Shim, SC .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2002, 39 (02) :421-423

[10] 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity [J].

Cosford, NDP ;

Tehrani, L ;

Roppe, J ;

Schweiger, E ;

Smith, ND ;

Anderson, J ;

Bristow, L ;

Brodkin, J ;

Jiang, XH ;

McDonald, I ;

Rao, S ;

Washburn, M ;

Varney, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (02) :204-206