Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas as potent inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2)

被引：17

作者：

Lin, Songnian ^{[1
]}

Lombardo, Matthew ^{[1
]}

Malkani, Sunita ^{[1
]}

Hale, Jeffrey J. ^{[1
]}

Mills, Sander G. ^{[1
]}

Chapman, Kevin ^{[1
]}

Thompson, James E. ^{[1
]}

Zhang, Wen Xiao ^{[1
]}

Wang, Ruixiu ^{[1
]}

Cubbon, Rose M. ^{[1
]}

O'Neill, Edward A. ^{[1
]}

Luell, Silvi ^{[1
]}

Carballo-Jane, Ester ^{[1
]}

Yang, Lihu ^{[1
]}

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 12期

关键词：

MAPKAP kinase 2; MK-2; TNF alpha; Inflammation; Rheumatoid arthritis; Aminopyrazine; Thiourea; RHEUMATOID-ARTHRITIS;

D O I：

10.1016/j.bmcl.2009.04.088

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas are described as inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). These compounds demonstrate potent in vitro activity against the enzyme with IC50 values as low as 15 nM, and suppress expression of TNF alpha in THP-1 cells and in vivo in an acute inflammation model in mice. The synthesis, structure-activity relationship (SAR), and biological evaluation of these compounds are discussed. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3238 / 3242

页数：5

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