The Ras-mitogen activated protein kinase (MAPK) signaling pathway transmits signals from receptors on the cell membrane to cytoplasmic and nuclear factors that are responsible for cell proliferation and survival. This pathway is frequently disregulated cancer, leading to uncontrolled proliferation and tumor growth.  Thus a potent Raf inhibitor could have a significant impact in treating cancers that are dependent on activated Ras or Raf for survival and proliferation signaling.  A series of imidazopyridine analogs which were designed as inhibitors of B-RafV600E will be described along with the relevant medicinal chemistry employed to explore the SAR for this series and improve selectivity versus p38 and KDR.

Design of novel imidazopyridine Type II B-RAFV600E inhibitors

243rd National Meeting (2012)

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