Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2.

نویسندگان

  • Christopher G Nasveschuk
  • Alexandre Gagnon
  • Shivani Garapaty-Rao
  • Srividya Balasubramanian
  • Robert Campbell
  • Christina Lee
  • Feng Zhao
  • Louise Bergeron
  • Richard Cummings
  • Patrick Trojer
  • James E Audia
  • Brian K Albrecht
  • Jean-Christophe P Harmange
چکیده

The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.

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عنوان ژورنال:
  • ACS medicinal chemistry letters

دوره 5 4  شماره 

صفحات  -

تاریخ انتشار 2014