Design, synthesis, and biological evaluation of aminopyrazine derivatives as inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2)

被引：9

作者：

Lin, Songnian ^{[1
]}

Malkani, Sunita ^{[1
]}

Lombardo, Matthew ^{[1
]}

Yang, Lihu ^{[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
]}

Hale, Jeffrey J. ^{[1
]}

机构：

[1] Merck Res Labs, Early Dev & Discovery Sci, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 22期

关键词：

MAPKAP kinase 2; MK-2; TNF alpha; Inflammation; Rheumatoid arthritis; Aminopyrazine; Guanidine; Thiourea replacement; TUMOR-NECROSIS-FACTOR; IN-VITRO SAR; RHEUMATOID-ARTHRITIS; BENZOTHIOPHENE INHIBITORS; FACILE SYNTHESIS; PHASE SYNTHESIS; PART; POTENT; DISCOVERY; THIOUREA;

D O I：

10.1016/j.bmcl.2015.09.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several series of novel non-thiourea-containing aminopyrazine derivatives were designed based on the MK-2 inhibitors 1-(2-aminopyrazin-3-yl)methyl-2-thioureas. These compounds were synthesized and evaluated for their inhibitory activity against MK-2 enzyme in vitro. Compounds with low micromolar to sub-micromolar IC50 values were identified, and several compounds were also found to be active in suppressing the lipopolysaccharide (LPS)-stimulated TNF alpha production in THP-1 cells with minimum shift compared to their enzyme activity. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：5402 / 5408

页数：7

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