Discovery of novel α7 nicotinic receptor antagonists

被引：19

作者：

Peng, Youyi ^{[1
]}

Zhang, Qiang ^{[1
]}

Snyder, Gretchen L. ^{[1
]}

Zhu, Hongwen ^{[1
]}

Yao, Wei ^{[1
]}

Tomesch, John ^{[1
]}

Papke, Roger L. ^{[2
]}

O'Callaghan, James P. ^{[3
]}

Welsh, William J. ^{[4
]}

Wennogle, Lawrence P. ^{[1
]}

机构：

[1] Intracellular Therapies Inc, New York, NY 10032 USA

[2] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA

[3] NIOSH, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA

[4] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 16期

关键词：

Nicotinic acetylcholine receptors; alpha; 7; antagonists; Pharmacophore; Neuroprotection; ACETYLCHOLINE-RECEPTORS; DRUG DISCOVERY; RAT-BRAIN; BINDING; AGONIST; SCHIZOPHRENIA; MEMORY;

D O I：

10.1016/j.bmcl.2010.06.103

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two distinct families of small molecules were discovered as novel alpha 7 nicotinic acetylcholine receptor (nAChR) antagonists by pharmacophore-based virtual screening. These novel antagonists exhibited selectivity for the neuronal alpha 7 subtype over other nAChRs and good brain penetration. Neuroprotection was demonstrated by representative compounds 7i and 8 in a mouse seizure-like behavior model induced by the nerve agent diisopropylfluorophosphate (DFP). These novel nAChR antagonists have potential use as antidote for organophosphorus nerve agent intoxication. (C) 2010 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4825 / 4830

页数：6

相关论文

共 32 条

[1] Neuronal nicotinic receptors: A perspective on two decades of drug discovery research [J].

Arneric, Stephen P. ;

Holladay, Mark ;

Williams, Michael .

BIOCHEMICAL PHARMACOLOGY, 2007, 74 (08) :1092-1101

[2] Recent Progress in the Development of Subtype Selective Nicotinic Acetylcholine Receptor Ligands [J].

Astles, P. C. ;

Baker, S. R. ;

Boot, J. R. ;

Broad, L. M. ;

Dell, C. P. ;

Keenan, M. .

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2002, 1 (04) :337-348

[3] Discovery and structure -: Activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors [J].

Bodnar, AL ;

Cortes-Burgos, LA ;

Cook, KK ;

Dinh, DM ;

Groppi, VE ;

Hajos, M ;

Higdon, NR ;

Hoffmann, WE ;

Hurst, RS ;

Myers, JK ;

Rogers, BN ;

Wall, TM ;

Wolfe, ML ;

Wong, E .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (04) :905-908

[4] The novel α7 nicotinic acetylcholine receptor agonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-[2-(methoxy)phenyl]-1-benzofuran-2-carboxamide improves working and recognition memory in rodents [J].

Boess, Frank G. ;

De Vry, Jean ;

Erb, Christina ;

Flessner, Timo ;

Hendrix, Martin ;

Luithle, Joachim ;

Methfessel, Christoph ;

Riedl, Bernd ;

Schnizler, Katrin ;

van der Staay, Franz-Josef ;

van Kampen, Marja ;

Wiese, Welf Burkhard ;

Koenig, Gerhard .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 321 (02) :716-725

[5] PSAB-OFP, a selective α7 nicotinic receptor agonist, is also a potent agonist of the 5-HT3 receptor [J].

Broad, LM ;

Felthouse, C ;

Zwart, R ;

McPhie, GI ;

Pearson, KH ;

Craig, PJ ;

Wallace, L ;

Broadmore, RJ ;

Boot, JR ;

Keenan, M ;

Baker, SR ;

Sher, E .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 452 (02) :137-144

[6] Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures [J].

Celie, PHN ;

van Rossum-Fikkert, SE ;

van Dijk, WJ ;

Brejc, K ;

Smit, AB ;

Sixma, TK .

NEURON, 2004, 41 (06) :907-914

[7] Looking back on the discovery of α-bungarotoxin [J].

Chang, CC .

JOURNAL OF BIOMEDICAL SCIENCE, 1999, 6 (06) :368-375

[8] Conformational sampling of druglike molecules with MOE and catalyst: Implications for pharmacophore modeling and virtual screening [J].

Chen, I-Jen ;

Foloppe, Nicolas .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2008, 48 (09) :1773-1791

[9] Characterisation of the binding of [3H]methyllycaconitine:: a new radioligand for labelling α7-type neuronal nicotinic acetylcholine receptors [J].

Davies, ARL ;

Hardick, DJ ;

Blagbrough, IS ;

Potter, BVL ;

Wolstenholme, AJ ;

Wonnacott, S .

NEUROPHARMACOLOGY, 1999, 38 (05) :679-690

[10]

FLORES CM, 1992, MOL PHARMACOL, V41, P31

← 1 2 3 4 →