The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor, antagonists

被引：17

作者：

Porter, David W. ^{[1
]}

Bradley, Michelle ^{[1
]}

Brown, Zarin ^{[1
]}

Charlton, Steven J. ^{[1
]}

Cox, Brian ^{[1
]}

Hunt, Peter ^{[1
]}

Janus, Diana ^{[1
]}

Lewis, Sarah ^{[1
]}

Oakley, Paul ^{[1
]}

O'Connor, Des ^{[1
]}

Reilly, John ^{[1
]}

Smith, Nichola ^{[1
]}

Press, Neil J. ^{[1
]}

机构：

[1] Horsham Res Ctr, Novartis Inst BioMed Res, Horsham RH12 5AB, W Sussex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 15期

关键词：

CXCR2; Chemokines; Pyrimidine; Neutrophils; COPD;

D O I：

10.1016/j.bmcl.2014.06.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrimidine 2-((2,6-dichlorobenzyl)thio)-5-isocyano-6-phenylpyrimidin-4-ol 4, resulting in the discovery of CXCR2 receptor antagonist 24(2,3-difluorobenzyl)thio)-6-(2-(hydroxymethyl)cyclopropyl)-5-isocyanopyrimidin-4-ol 24. The SAR was investigated by systematic variation of the aromatic group at c-6, the linker between c-2 and the halogenated ring, and the c-5 nitrile moiety. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3285 / 3290

页数：6

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