Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333

被引：8

作者：

Beinat, Corinne ^{[1
]}

Banister, Samuel D. ^{[1
,2
]}

van Prehn, Saundra ^{[2
]}

Doddareddy, Munikumar Reddy ^{[3
]}

Hibbs, David ^{[3
]}

Sako, Michael ^{[3
]}

Chebib, Mary ^{[3
]}

Thao Tran ^{[4
]}

Al-Muhtasib, Nour ^{[4
]}

Xiao, Yingxian ^{[4
]}

Kassiou, Michael ^{[1
,2
,5
]}

机构：

[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[2] Brain & Mind Res Inst, Sydney, NSW 2050, Australia

[3] Univ Sydney, Sch Pharm, Sydney, NSW 2006, Australia

[4] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC 20057 USA

[5] Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 07期

关键词：

alpha 7 Nicotinic receptors; Molecular modeling; CNS; Structure-activity relationships; ALZHEIMERS-DISEASE; PHARMACOLOGICAL-PROPERTIES; IN-VITRO; SCHIZOPHRENIA; BINDING; PROTEIN; EXPRESSION; SSR180711; SUBUNIT; CORTEX;

D O I：

10.1016/j.bmcl.2012.02.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of ligands based on SEN12333, containing either contracted or elongated alkyl chains, were synthesized and evaluated in molecular docking studies against a homology model of the alpha 7 nicotinic acetylcholine receptor (nAChR) subtype. The predicted binding of all ligands was highly similar, with the exception of the analog containing a 5 methylene unit spacer. However, in vitro competition binding assays revealed that the ligands possessed dissimilar binding affinities, with a K-i range of more than an order of magnitude (K-i = 0.50 to >10 mu M), and only SEN12333 itself exhibited functional activity at the alpha 7 nAChR. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2380 / 2384

页数：5

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