Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds

T. G. Murali Dhar, Stephen T. Wrobleski, Shuqun Lin, Joseph A. Furch, David S. Nirschl, Yi Fan, Gordon Todderud, Sidney Pitt, Arthur M. Doweyko, John S. Sack, Arvind Mathur, Murray McKinnon, Joel C. Barrish, John H. Dodd, Gary L. Schieven, Katerina Leftheris

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.

Original languageEnglish (US)
Pages (from-to)5019-5024
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number18
DOIs
Publication statusPublished - Sep 15 2007

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Murali Dhar, T. G., Wrobleski, S. T., Lin, S., Furch, J. A., Nirschl, D. S., Fan, Y., ... Leftheris, K. (2007). Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds. Bioorganic and Medicinal Chemistry Letters, 17(18), 5019-5024. https://doi.org/10.1016/j.bmcl.2007.07.029