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

…, EA O'Neill, S Luell, E Carballo-Jane…

Index: Lin, Songnian; Lombardo, Matthew; Malkani, Sunita; Hale, Jeffrey J.; Mills, Sander G.; Chapman, Kevin; Thompson, James E.; Zhang, Wen Xiao; Wang, Ruixiu; Cubbon, Rose M.; O'Neill, Edward A.; Luell, Silvi; Carballo-Jane, Ester; Yang, Lihu Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 12 p. 3238 - 3242

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Citation Number: 20

Abstract

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 15nM, 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 ...