Pyrazolo-Pyrimidines: A Novel Heterocyclic Scaffold for Potent and Selective p38alpha Inhibitors
Journal Article
·
· BioOrganic and Medicinal Chemistry Letters
The synthesis and structure-activity relationships (SAR) of p38a 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 p38a MAP kinase with excellent cellular potency toward the inhibition of TNFa production. Compound 2x was highly efficacious in vivo in inhibiting TNFa production in an acute murine model of TNFa production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38a is also disclosed.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 959850
- Report Number(s):
- BNL-82836-2009-JA; TRN: US201016%%994
- Journal Information:
- BioOrganic and Medicinal Chemistry Letters, Vol. 18
- Country of Publication:
- United States
- Language:
- English
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