Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase.

Article Details

Citation

Copy to clipboard

Selness SR, Devraj RV, Devadas B, Walker JK, Boehm TL, Durley RC, Shieh H, Xing L, 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, Messing D, Yang J, Mao MK, Yalamanchili G, Vonder Embse R, Hirsch J, Saabye M, Bonar S, Webb E, Anderson G, Monahan JB

Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase.

Bioorg Med Chem Lett. 2011 Jul 1;21(13):4066-71. doi: 10.1016/j.bmcl.2011.04.121. Epub 2011 May 11.

PubMed ID

21641211 [ View in PubMed

]

Abstract

The synthesis and SAR studies of a novel N-aryl pyridinone class of p38 kinase inhibitors are described. Systematic structural modifications to the HTS lead, 5, led to the identification of (-)-4a as a clinical candidate for the treatment of inflammatory diseases. Additionally, the chiral synthesis and properties of (-)-4a are described.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
PH-797804	Mitogen-activated protein kinase 14	IC 50 (nM)	2.5	N/A	N/A	Details
PH-797804	Mitogen-activated protein kinase 14	IC 50 (nM)	2.3	N/A	N/A	Details
PH-797804	Mitogen-activated protein kinase 14	IC 50 (nM)	247	N/A	N/A	Details