Novel, acidic CCR2 receptor antagonists: Lead optimization

被引：23

作者：

Dasse, O. A.

Evans, J. L.

Zhai, H.-X.

Zou, D.

Kintigh, J. T.

Chan, F.

Hamilton, K.

Hill, E.

Eckman, J. B.

Higgins, P. J.

Volosov, A.

Collart, P.

Nicolas, J.-M.

Kondru, R. K.

Schwartz, C. E.

机构：

[1] UCB Res Inc, Cambridge, MA 02139 USA

[2] BioFocus Ltd, Saffron Walden CB10 1XL, Essex, England

[3] UCB Pharma, B-1420 Braine lAlleud, Belgium

来源：

LETTERS IN DRUG DESIGN & DISCOVERY | 2007年 / 4卷 / 04期

关键词：

MCP-1; CCR2; chemokine receptor; antagonist; medicinal chemistry; lead optimization; CoMFA; pharmacophore;

D O I：

10.2174/157018007784619989

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A unique pyrrolidinone-based CCR2 antagonist with sub-micromolar in vitro activities, good selectivity, and reasonable ADME properties was identified following a screening campaign and subsequent hit-to-lead medicinal chemistry efforts. We now describe further modification of this lead molecule to provide compounds with excellent DMPK profiles and significantly enhanced in vitro activities.

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收藏

页码：263 / 271

页数：9

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