Discovery and characterization of the N-phenyl-N'-naphthylurea class of p38 kinase inhibitors.

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Cirillo PF, Hickey ER, Moss N, Breitfelder S, Betageri R, Fadra T, Gaenzler F, Gilmore T, Goldberg DR, Kamhi V, Kirrane T, Kroe RR, Madwed J, Moriak M, Netherton M, Pargellis CA, Patel UR, Qian KC, Sharma R, Sun S, Swinamer A, Torcellini C, Takahashi H, Tsang M, Xiong Z

Discovery and characterization of the N-phenyl-N'-naphthylurea class of p38 kinase inhibitors.

Bioorg Med Chem Lett. 2009 May 1;19(9):2386-91. doi: 10.1016/j.bmcl.2009.03.104. Epub 2009 Mar 26.

PubMed ID

19356929 [ View in PubMed

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Abstract

An effort aimed at exploring structural diversity in the N-pyrazole-N'-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N-phenyl-N'-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-alpha production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Doramapimod	Mitogen-activated protein kinase 14	Kd (nM)	0.1	N/A	N/A	Details