Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists

被引：29

作者：

Guay, Daniel ^{[1
]}

Beaulieu, Christian ^{[1
]}

Belley, Michel ^{[1
]}

Crane, Sheldon N. ^{[1
]}

DeLuca, Jeancarlo ^{[1
]}

Gareau, Yves ^{[1
]}

Hamel, Martine ^{[1
]}

Henault, Martin ^{[1
]}

Hyjazie, Huda ^{[1
]}

Kargman, Stacia ^{[1
]}

Chan, Chi Chung ^{[1
]}

Xu, Lijing ^{[1
]}

Gordon, Robert ^{[1
]}

Li, Lianhai ^{[1
]}

Mamane, Yael ^{[1
]}

Morin, Nicolas ^{[1
]}

Mancini, Joseph ^{[1
]}

Therien, Michel ^{[1
]}

Tranmer, Geoffrey ^{[1
]}

Vouy Linh Truong ^{[1
]}

Wang, Zhaoyin ^{[1
]}

Black, W. Cameron ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 10期

关键词：

PROTEIN-COUPLED RECEPTOR; AGONISTS; DISEASE; PURINE; CELLS; UDP;

D O I：

10.1016/j.bmcl.2011.03.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A weak antagonist of the pyrimidinergic receptor P2Y(14) containing a dihydropyridopyrimidine core was identified through high-throughput screening. Subsequent optimization led to potent, non-UTP competitive antagonists and represent the first reported non-nucleotide antagonists of this receptor. Compound 18q was identified as a 10 nM P2Y(14) antagonist with good oral bioavailability and provided sufficient exposure in mice to be used as a tool for future in vivo studies. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2832 / 2835

页数：4

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