Structure-based optimization of a potent class of arylamide FMS inhibitors

Sanath K. Meegalla, Mark J. Wall, Jinsheng Chen, Kenneth J. Wilson, Shelley K. Ballentine, Renee L. DesJarlais, Carsten Schubert, Carl S. Crysler, Yanmin Chen, Christopher J. Molloy, Margery A. Chaikin, Carl L. Manthey, Mark R. Player, Bruce E. Tomczuk, Carl R. Illig

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions.

Original languageEnglish (US)
Pages (from-to)3632-3637
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number12
StatePublished - Jun 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

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


  • Anti-inflammatory activity
  • CSF-1R
  • Colony-stimulating factor-1
  • FMS
  • Idiosyncratic drug reactions
  • M-CSF
  • Macrophages
  • cFMS


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