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• W1997625667 abstract "Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic properties, of which compound 16 displayed the most desirable profile. Oral dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease in TNFalpha production." @default.
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• W1997625667 date "2008-09-26" @default.
• W1997625667 modified "2023-10-18" @default.
• W1997625667 title "Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold" @default.
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• W1997625667 doi "https://doi.org/10.1021/jm8005417" @default.
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