Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors

被引：63

作者：

Das, J ^{[1
]}

Furch, JA ^{[1
]}

Liu, CJ ^{[1
]}

Moquin, RV ^{[1
]}

Lin, J ^{[1
]}

Spergel, SH ^{[1
]}

McIntyre, KW ^{[1
]}

Shuster, DJ ^{[1
]}

O'Day, KD ^{[1
]}

Penhallow, B ^{[1
]}

Hung, CY ^{[1
]}

Doweyko, AM ^{[1
]}

Kamath, A ^{[1
]}

Zhang, HJ ^{[1
]}

Marathe, P ^{[1
]}

Kanner, SB ^{[1
]}

Lin, TA ^{[1
]}

Dodd, JH ^{[1
]}

Barrish, JC ^{[1
]}

Wityak, J ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 14期

关键词：

amino-(thioaryl)thiazoles; selective Itk inhibitor;

D O I：

10.1016/j.bmcl.2006.04.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：3706 / 3712

页数：7

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