| Structural highlights
Publication Abstract from PubMed
The synthesis and structure-activity relationships (SAR) of p38alpha MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2j was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38alpha is also disclosed.
5-Amino-pyrazoles as potent and selective p38alpha inhibitors.,Das J, Moquin RV, Dyckman AJ, Li T, Pitt S, Zhang R, Shen DR, McIntyre KW, Gillooly K, Doweyko AM, Newitt JA, Sack JS, Zhang H, Kiefer SE, Kish K, McKinnon M, Barrish JC, Dodd JH, Schieven GL, Leftheris K Bioorg Med Chem Lett. 2010 Dec 1;20(23):6886-9. Epub 2010 Oct 13. PMID:21035336[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Das J, Moquin RV, Dyckman AJ, Li T, Pitt S, Zhang R, Shen DR, McIntyre KW, Gillooly K, Doweyko AM, Newitt JA, Sack JS, Zhang H, Kiefer SE, Kish K, McKinnon M, Barrish JC, Dodd JH, Schieven GL, Leftheris K. 5-Amino-pyrazoles as potent and selective p38alpha inhibitors. Bioorg Med Chem Lett. 2010 Dec 1;20(23):6886-9. Epub 2010 Oct 13. PMID:21035336 doi:10.1016/j.bmcl.2010.10.034
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