Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives

Susan M. Westaway, Alex G. S. Preston, Michael D. Barker, Fiona Brown, Jack A. Brown, Matthew Campbell, Chun-Wa Chung, Gerard Drewes, Robert Eagle, Neil Garton, Laurie Gordon, Carl Haslam, Thomas G. Hayhow, Philip G. Humphreys, Gerard Joberty, Roy Katso, Laurens Kruidenier, Melanie Leveridge, Michelle Pemberton, Inma RiojaGail A. Seal, Tracy Shipley, Onkar Singh, Colin J. Suckling, Joanna Taylor, Pamela Thomas, David M. Wilson, Kevin Lee, Rab K. Prinjha

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46 Citations (Scopus)


Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochemical and target-specific, cellular mechanistic assays.

Original languageEnglish
Pages (from-to)1370-1387
Number of pages18
JournalJournal of Medicinal Chemistry
Issue number4
Early online date15 Jan 2016
Publication statusPublished - 25 Feb 2016


  • molecular medicine
  • drugs
  • drug discovery
  • gene expression
  • epigenetics

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