Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation

被引：25

作者：

Caroff, Eva ^{[1
]}

Meyer, Emmanuel ^{[1
]}

Treiber, Alexander ^{[1
]}

Hilpert, Kurt ^{[1
]}

Riederer, Markus A. ^{[1
]}

机构：

[1] Actelion Pharmaceut Ltd, Drug Discovery & Preclin Res & Dev, CH-4123 Allschwil, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 17期

关键词：

P2Y(12) receptor; P2Y(12) antagonist; GPCR antagonist; Antiplatelet; Antithrombotic; DIPHOSPHATE RECEPTOR ANTAGONISTS; PRASUGREL ACHIEVES GREATER; ASPIRIN-TREATED PATIENTS; ACUTE CORONARY SYNDROMES; UNSTABLE ANGINA; ARTERY-DISEASE; CLOPIDOGREL; ACTIVATION; MECHANISMS; THERAPIES;

D O I：

10.1016/j.bmcl.2014.06.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y(12) antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：4323 / 4331

页数：9

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