3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT6 receptor modulators

被引：19

作者：

Bernotas, Ronald C. ^{[1
]}

Antane, Schuyler ^{[2
]}

Shenoy, Rajesh ^{[3
]}

Le, Van-Duc ^{[3
]}

Chen, Ping ^{[3
]}

Harrison, Boyd L. ^{[2
]}

Robichaud, Albert J. ^{[2
]}

Zhang, Guo Ming ^{[4
]}

Smith, Deborah ^{[4
]}

Schechter, Lee E. ^{[4
]}

机构：

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

[2] Wyeth Pharmaceut, Chem Sci, Princeton, NJ 08543 USA

[3] Wyeth Pharmaceut, Neurosci, Princeton, NJ 08543 USA

[4] Albany Mol Res, Albany, NY 12212 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 05期

关键词：

Serotonin; Agonist; Antagonist; 5-HT6; Cyclase; Indole; Sulfone; ANTAGONISTS; DERIVATIVES; POTENT; LIGANDS;

D O I：

10.1016/j.bmcl.2010.01.073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 3-(arylsulfonyl)-1-(azacyclyl)-1H-indoles 6 were synthesized as potential 5-HT6 receptor ligands, based on constraining a basic side chain as either a piperidine or a pyrrolidine. Many of these compounds had good 5-HT6 binding affinity with K-i values <10 nM. Depending on substitution, both agonists (e. g., 6o: EC50 = 60 nM, E-max = 70%) and antagonists (6y: IC50 = 17 nM, I-max = 86%) were identified in a 5-HT6 adenylyl cyclase assay. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1657 / 1660

页数：4

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