Scaffold-hopping with zwitterionic CCR3 antagonists: Identification and optimisation of a series with good potency and pharmacokinetics leading to the discovery of AZ12436092

被引：18

作者：

Bahl, Ash ^{[2
]}

Barton, Patrick ^{[1
]}

Bowers, Keith ^{[2
]}

Caffrey, Moya V. ^{[1
]}

Denton, Rebecca ^{[3
]}

Gilmour, Peter ^{[2
]}

Hawley, Shaun ^{[2
]}

Linannen, Tero ^{[1
]}

Luckhurst, Christopher A. ^{[1
]}

Mochel, Tobias ^{[1
]}

Perry, Matthew W. D. ^{[1
]}

Riley, Robert J. ^{[3
]}

Roe, Emma ^{[3
]}

Springthorpe, Brian ^{[1
]}

Stein, Linda ^{[1
]}

Webborn, Peter ^{[3
]}

机构：

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

[2] AstraZeneca R&D Charnwood, Dept Biosci, Loughborough LE11 5RH, Leics, England

[3] AstraZeneca R&D Charnwood, Dept Discovery DMPK, Loughborough LE11 5RH, Leics, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 21期

关键词：

Chemokine; Antagonist; Bioavailability; CHEMOKINE RECEPTOR CCR3; AIRWAY SMOOTH-MUSCLE; EXPRESSION; CELLS; EOSINOPHILS; EOTAXIN;

D O I：

10.1016/j.bmcl.2012.08.103

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and optimisation of a series of zwitterionic CCR3 antagonists is described. Optimisation of the structure led to AZ12436092, a compound with excellent selectivity over activity at hERG and outstanding pharmacokinetics in preclinical species. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：6694 / 6699

页数：6

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