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

详细信息    查看全文

• 作者：Songnian Lin ; Matthew Lombardo ; Sunita Malkani ; Jeffrey J. Hale ; S ; er G. Mills ; Kevin Chapman ; James E. Thompson ; Wen Xiao Zhang ; Ruixiu Wang ; Rose M. Cubbon ; Edward A. O’ ; Neill ; Silvi Luell ; Es
• 关键词：MAPKAP kinase 2 ; MK-2 ; TNFα ; Inflammation ; Rheumatoid arthritis ; Aminopyrazine ; Thiourea
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 June 2009
• 年：2009
• 卷：19
• 期：12
• 页码：3238-3242
• 全文大小：660 K

文摘

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 TNFα 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.