Octahydropyrrolo[3,4-c]pyrrole: A Diamine Scaffold for Construction of Either α4β2 or α7-Selective Nicotinic Acetylcholine Receptor (nAChR) Ligands. Substitutions that Switch Subtype Selectivity

被引：22

作者：

Bunnelle, William H. ^{[1
]}

Tietje, Karin R. ^{[1
]}

Frost, Jennifer M. ^{[1
]}

Peters, Dan ^{[2
]}

Ji, Jianguo ^{[1
]}

Li, Tao ^{[1
]}

Scanio, Marc J. C. ^{[1
]}

Shi, Lei ^{[1
]}

Anderson, David J. ^{[1
]}

Dyhring, Tino ^{[2
]}

Gronlien, Jens H. ^{[1
]}

Ween, Hilde ^{[1
]}

Thorin-Hagene, Kirsten ^{[1
]}

Meyer, Michael D. ^{[1
]}

机构：

[1] Abbott Labs, Neurosci Res, Dept R47W, Abbott Pk, IL 60064 USA

[2] NeuroSearch AS, DK-2750 Ballerup, Denmark

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 14期

关键词：

ANTINOCICEPTIVE PROPERTIES; COGNITIVE DEFICITS; EXTRACELLULAR DOMAIN; VENTRAL HIPPOCAMPUS; POTENTIAL TREATMENT; PARTIAL AGONIST; KNOCKOUT MICE; SUBUNIT GENE; BINDING-SITE; H-3; CYTISINE;

D O I：

10.1021/jm900249k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 5-(pyridine-3-yl)octahydropyrrolo[3,4-c]pyrroles have been prepared that exhibit high affinity to alpha 4 beta 2 and/or alpha 7 nicotinic acetylcholine receptors (nAChRs). Simple substitution patterns have been identified that allow construction of ligands that are highly selective for either nAChR subtype. The effects of substitution on subtype selectivity provide some insight into the differences in the ligand binding domains of the alpha 4 beta 2 and alpha 7 receptors, especially in regions removed from the cation binding pocket.

引用

页码：4126 / 4141

页数：16

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