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

  • Bioorg Med Chem Lett. 2008 Jun 15;18(12):3632-7. doi: 10.1016/j.bmcl.2008.04.059.
Sanath K Meegalla  1 ,  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
Affiliations
  • 1. Johnson & Johnson Pharmaceutical Research & Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
PMID: 18495479 DOI: 10.1016/j.bmcl.2008.04.059
Abstract

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.

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