Amide-based inhibitors of p38alpha MAP kinase. Part 1: discovery of novel N-pyridyl amide lead molecules.

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Luedtke GR, Schinzel K, Tan X, Tester RW, Nashashibi I, Xu YJ, Dugar S, Levy DE, Jung J

Amide-based inhibitors of p38alpha MAP kinase. Part 1: discovery of novel N-pyridyl amide lead molecules.

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2556-9. doi: 10.1016/j.bmcl.2010.02.088. Epub 2010 Mar 10.

PubMed ID

20346653 [ View in PubMed

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Abstract

A novel series of N-pyridyl amides as potent p38alpha kinase inhibitors is described. Based on the structural similarities between the initial hit and a well-known imidazole pyrimidine series of p38alpha inhibitors, potencies within the newly discovered series were quickly improved by installation of an (S)-alpha-methylbenzyl moiety at the 2-position of the pyridine ring. The proposed binding modes of the new series to p38alpha were evaluated against SAR findings and provided rationale for further development of this series of molecules.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4-[5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine	Mitogen-activated protein kinase 14	IC 50 (nM)	110	N/A	N/A	Details