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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Substituted isoxazoles as potent inhibitors of p38 MAP kinase.

In a continuous effort to develop improved p38 MAP (mitogen-activated protein) kinase inhibitors, we focused our attention on the suitability of the isoxazole ring as a bioisosteric replacement for the imidazole ring of SB-203580. 3,4- and 4,5-disubstituted as well as 3,4,5-trisubstituted isoxazole derivatives were synthesized. These compounds were tested in an in vitro enzyme-linked immunosorbent assay of isolated p38 MAP kinase and for inhibitory potency against cytochrome P450. Compound 4 a displays a highly promising profile for development as an anti-inflammatory agent owing to its enhanced suppression of cytokine release, decreased affinity for cytochrome P450 and a twofold decrease in IC50 toward isolated p38 MAP kinase.[1]

References

  1. Substituted isoxazoles as potent inhibitors of p38 MAP kinase. Laufer, S.A., Margutti, S., Fritz, M.D. ChemMedChem (2006) [Pubmed]
 
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