Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT6 agonists

被引：18

作者：

Bernotas, Ronald C. ^{[1
]}

Lenicek, Steven ^{[2
]}

Antane, Schuyler ^{[2
]}

Cole, Derek C. ^{[3
]}

Harrison, Boyd L. ^{[2
]}

Robichaud, Albert J. ^{[2
]}

Zhang, Guo Ming ^{[4
]}

Smith, Deborah ^{[4
]}

Platt, Brian ^{[4
]}

Lin, Qian ^{[4
]}

Li, Ping ^{[4
]}

Coupet, Joseph ^{[4
]}

Rosenzweig-Lipson, Sharon ^{[4
]}

Beyer, Chad E. ^{[4
]}

Schechter, Lee E. ^{[4
]}

机构：

[1] Wyeth Res, Chem Sci, Collegeville, PA 19426 USA

[2] Wyeth Ayerst Res, Chem Sci, Princeton, NJ 08543 USA

[3] Wyeth Res, Chem Sci, Pearl River, NY 10965 USA

[4] Wyeth Ayerst Res, Neurosci, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 14期

关键词：

Serotonin; 5-Hydroxytryptamine-6; receptor; 7-Azaindole; Agonist; Adenylyl cyclase assay; Binding; Sulfone; Pyrrolo[2,3-b]pyridine; RECEPTOR LIGANDS; SEROTONIN RECEPTORS; ANTAGONISTS; DERIVATIVES; DISCOVERY; OXIDATION; SULFIDES; AGENTS;

D O I：

10.1016/j.bmc.2009.05.055

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 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines 10a-z was prepared as novel 5-HT6 ligands. The best compounds were high affinity, full agonists at 5-HT6 receptors. Several agonists demonstrated good selectivity over other serotonergic and dopaminergic receptors. Acute administration of selective agonist 10e significantly increased extracellular GABA concentrations in rat frontal cortex. This compound also reduced adjunctive drinking behavior in the rat schedule-induced polydipsia assay, possibly predictive of efficacy in obsessive compulsive disorder and other anxiety related disorders. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5153 / 5163

页数：11

共 22 条

[1] Indene-Based Scaffolds. 2. An Indole-Indene Switch: Discovery of Novel Indenylsulfonamides as 5-HT6 Serotonin Receptor Agonists [J].