Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach.

نویسندگان

  • R A Smith
  • J Barbosa
  • C L Blum
  • M A Bobko
  • Y V Caringal
  • R Dally
  • J S Johnson
  • M E Katz
  • N Kennure
  • J Kingery-Wood
  • W Lee
  • T B Lowinger
  • J Lyons
  • V Marsh
  • D H Rogers
  • S Swartz
  • T Walling
  • H Wild
چکیده

Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54 microM) for a second generation series of heterocyclic urea raf kinase inhibitors.

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عنوان ژورنال:
  • Bioorganic & medicinal chemistry letters

دوره 11 20  شماره 

صفحات  -

تاریخ انتشار 2001