Structure-activity relationships of novel, highly potent, selective, and orally active CCRI antagonists

被引:17
|
作者
Xie, Yun Feng
Lake, Kirk
Ligsay, Kathleen
Komandla, Mallareddy
Sircar, Ila
Nagarajan, Gobi
Li, Jian
Xu, Kui
Parise, Jason
Schneider, Lisa
Huang, Ding
Liu, Juping
Dines, Kevin
Sakurai, Naoki
Barbosa, Miguel
Jack, Rick
机构
[1] Tanabe Res Labs Inc, Dept Chem, San Diego, CA 92121 USA
[2] Tanabe Res Labs Inc, Dept Biol, San Diego, CA 92121 USA
关键词
chemokine receptor 1; CCR1; antagonist; diaminocyclobutenedione;
D O I
10.1016/j.bmcl.2007.03.104
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCRI antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3367 / 3372
页数:6
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