From ATP to AZD6140:: The discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis

被引：194

作者：

Springthorpe, Brian ^{[1
]}

Bailey, Andrew ^{[1
]}

Barton, Patrick ^{[1
]}

Birkinshaw, Timothy N. ^{[1
]}

Bonnert, Roger V. ^{[1
]}

Brown, Roger C. ^{[1
]}

Chapman, David ^{[1
]}

Dixon, John ^{[1
]}

Guile, Simon D. ^{[1
]}

Humphries, Robert G. ^{[1
]}

Hunt, Simon F. ^{[1
]}

Ince, Francis ^{[1
]}

Ingall, Anthony H. ^{[1
]}

Kirk, Ian P. ^{[1
]}

Leeson, Paul D. ^{[1
]}

Leff, Paul ^{[1
]}

Lewis, Richard J. ^{[1
]}

Martin, Barrie P. ^{[1
]}

McGinnity, Dermot F. ^{[1
]}

Mortimore, Michael P. ^{[1
]}

Paine, Stuart W. ^{[1
]}

Pairaudeau, Garry ^{[1
]}

Patel, Anil ^{[1
]}

Rigby, Aaron J. ^{[1
]}

Riley, Robert J. ^{[1
]}

Teobald, Barry J. ^{[1
]}

Tomlinson, Wendy ^{[1
]}

Webborn, Peter J. H. ^{[1
]}

Willis, Paul A. ^{[1
]}

机构：

[1] Astra Zeneca R&D Charnwood, Loughborough LE11 5RH, Leics, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 21期

关键词：

ATP; P2Y(12) receptor antagonist; thrombosis; AZD16140;

D O I：

10.1016/j.bmcl.2007.07.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y(12) receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：6013 / 6018

页数：6

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