Evaluation of a series of bicyclic CXCR2 antagonists

被引：56

作者：

Walters, Iain ^{[1
]}

Austin, Caroline ^{[1
]}

Austin, Rupert ^{[1
]}

Bonnert, Roger ^{[1
]}

Cage, Peter ^{[1
]}

Christie, Mark ^{[1
]}

Ebden, Mark ^{[1
]}

Gardiner, Stuart ^{[1
]}

Graharnes, Caroline ^{[1
]}

Hill, Steven ^{[1
]}

Hunt, Fraser ^{[1
]}

Jewell, Robert ^{[1
]}

Lewis, Shirley ^{[1
]}

Martin, Lain ^{[1
]}

Nicholls, David ^{[1
]}

Robinson, David ^{[1
]}

机构：

[1] AstraZeneca R&D Charnwood, Dept Med Chem Mol Biol & Discovery BioSci, Loughborough LE11 5RH, Leics, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 02期

关键词：

CXCR2; thiazolo[4,5-d]pyrimidine-2(3H)-one;

D O I：

10.1016/j.bmcl.2007.11.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：798 / 803

页数：6

共 24 条

[1] CXC chemokines bind to unique sets of selectivity determinants that can function independently and are broadly distributed on multiple domains of human interleukin-8 receptor B - Determinants of high affinity binding and receptor activitation are distinct [J].