Discovery and structure-activity relationship of N-(ureidoalkyl)-benzyl-piperidines as potent small molecule CC chemokine receptor-3 (CCR3) antagonists

被引：46

作者：

De Lucca, GV ^{[1
]}

Kim, UT ^{[1
]}

Johnson, C ^{[1
]}

Vargo, BJ ^{[1
]}

Welch, PK ^{[1
]}

Covington, M ^{[1
]}

Davies, P ^{[1
]}

Solomon, KA ^{[1
]}

Newton, RC ^{[1
]}

Trainor, GL ^{[1
]}

Decicco, CP ^{[1
]}

Ko, SK ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Expt Stn, Wilmington, DE 19880 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 17期

关键词：

D O I：

10.1021/jm0201767

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity relationship (SAR) studies of initial screening hits from our corporate library of compounds and a structurally related series of CCR1 receptor antagonists were used to determine that an N-(alkyl)benzylpiperidine is an essential pharmacophore for selective CCR3 antagonists. Further SAR studies that introduced N-(ureidoalkyl) substituents improved the binding potency of these compounds from the micromolar to the low nanomolar range. This new series of compounds also displays highly potent, in vitro functional CCR3-mediated antagonism of eotaxin-induced Ca2+ mobilization and chemotaxis of human eosinophils.

引用

页码：3794 / 3804

页数：11

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