Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.

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Selness SR, Devraj RV, Monahan JB, Boehm TL, Walker JK, Devadas B, Durley RC, Kurumbail R, Shieh H, Xing L, Hepperle M, Rucker PV, Jerome KD, Benson AG, Marrufo LD, Madsen HM, Hitchcock J, Owen TJ, Christie L, Promo MA, Hickory BS, Alvira E, Naing W, Blevis-Bal R

Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.

Bioorg Med Chem Lett. 2009 Oct 15;19(20):5851-6. doi: 10.1016/j.bmcl.2009.08.082. Epub 2009 Aug 27.

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19751974 [ View in PubMed

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Abstract

The identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha. These efforts resulted in the identification of 12r and 19 as orally active inhibitors of p38 with significant efficacy in both acute and chronic models of inflammation.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Neflamapimod	Mitogen-activated protein kinase 14	IC 50 (nM)	70	N/A	N/A	Details