Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors

Stephen T. Wrobleski, Shuqun Lin, John Hynes, Hong Wu, Sidney Pitt, Ding Ren Shen, Rosemary Zhang, Kathleen M. Gillooly, David J. Shuster, Kim W. McIntyre, Arthur M. Doweyko, Kevin F. Kish, Jeffrey A. Tredup, Gerald J. Duke, John S. Sack, Murray McKinnon, John Harold Dodd, Joel C. Barrish, Gary L. Schieven, Katerina Leftheris

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Abstract

A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38α MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38α enzyme.

Original languageEnglish (US)
Pages (from-to)2739-2744
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number8
DOIs
Publication statusPublished - Apr 15 2008

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All Science Journal Classification (ASJC) codes

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

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