GSBS Student Publications

Title

Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors

Publication Date

2008-03-25

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Pathology; Bristol-Myers Squibb Research and Development

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2x was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38 alpha is also disclosed.

DOI of Published Version

10.1016/j.bmcl.2008.03.019

Source

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2652-7. Epub 2008 Mar 10. Link to article on publisher's site

Journal/Book/Conference Title

Bioorganic and medicinal chemistry letters

Related Resources

Link to Article in PubMed

PubMed ID

18359226

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