2,5-Disubstituted pyridines:: The discovery of a novel series of 5-HT2A ligands

被引：23

作者：

Wilson, Kevin J. ^{[1
]}

van Niel, Monique B. ^{[1
]}

Cooper, Laura ^{[1
]}

Bloomfield, Dawn ^{[1
]}

O'Connor, Desmond ^{[1
]}

Fish, Rebecca ^{[1
]}

MacLeod, Angus M. ^{[1
]}

机构：

[1] Merck Sharp & Dohme Ltd, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 09期

关键词：

5-HT2A ligand; pyridine; styrene;

D O I：

10.1016/j.bmcl.2007.01.098

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This report describes the effect of replacing the central basic amine present in many known 5-HT2A ligands with an aromatic residue. We targeted the isomeric phenethylpyridines 2 and 3 and these compounds proved to be excellent leads, possessing good 5-HT2A receptor binding affinity and selectivity over the 5-HT2C subtype. Optimization of one isomer led to the identification of 25, a compound with sub-nanomolar 5-HT2A affinity and selectivity over 5-HT2C of greater than 4600-fold. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2643 / 2648

页数：6

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