Discovery and structure -: Activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors

被引：187

作者：

Bodnar, AL ^{[1
]}

Cortes-Burgos, LA ^{[1
]}

Cook, KK ^{[1
]}

Dinh, DM ^{[1
]}

Groppi, VE ^{[1
]}

Hajos, M ^{[1
]}

Higdon, NR ^{[1
]}

Hoffmann, WE ^{[1
]}

Hurst, RS ^{[1
]}

Myers, JK ^{[1
]}

Rogers, BN ^{[1
]}

Wall, TM ^{[1
]}

Wolfe, ML ^{[1
]}

Wong, E ^{[1
]}

机构：

[1] Pfizer Inc, Dept Neurosci, Global Res & Dev, Groton, CT USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 04期

关键词：

D O I：

10.1021/jm049363q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A library of benzamides was tested for alpha7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have alpha7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT3 receptor, a structural homologue of the alpha7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native alpha7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.

引用

页码：905 / 908

页数：4

共 38 条

[1] ADLER LE, 1993, AM J PSYCHIAT, V150, P1856
[2] Arneric S. P., 1999, NEURONAL NICOTINIC R
[3] Recent Progress in the Development of Subtype Selective Nicotinic Acetylcholine Receptor Ligands
Astles, P. C.
Baker, S. R.
Boot, J. R.
Broad, L. M.
Dell, C. P.
Keenan, M.
[J]. CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2002, 1 (04) : 337 - 348
[4] Brioni JD, 1996, MED CHEM RES, V6, P487
[5] Design of Ligands for the nicotinic acetylcholine receptors: The quest for selectivity
Bunnelle, WH
Dart, MJ
Schrimpf, MR
[J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (03) : 299 - 334
[6] CLEMENTI F, 2000, HDB EXPT PHARM NEURO
[7] Overview of nicotinic receptors and their roles in the central nervous system
Dani, JA
[J]. BIOLOGICAL PSYCHIATRY, 2001, 49 (03) : 166 - 174
[8] DEFIEBRE CM, 1995, MOL PHARMACOL, V47, P164
[9] CHIMERIC NICOTINIC SEROTONERGIC RECEPTOR COMBINES DISTINCT LIGAND-BINDING AND CHANNEL SPECIFICITIES
EISELE, JL
BERTRAND, S
GALZI, JL
DEVILLERSTHIERY, A
CHANGEUX, JP
BERTRAND, D
[J]. NATURE, 1993, 366 (6454) : 479 - 483
[10] Serotoninergic 5-HT3 and 5-HT4 receptor activities of dihydrobenzofuran carboxylic acid derivatives.
Fancelli, D
Caccia, C
Fornaretto, MG
McArthur, R
Severino, D
Vaghi, F
Varasi, M
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (03) : 263 - 266

← 1 2 3 4 →