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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

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
Volume59
Issue number4
Early online date15 Jan 2016
DOIs
Publication statusPublished - 25 Feb 2016

Keywords

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

Fingerprint

Dive into the research topics of 'Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives'. Together they form a unique fingerprint.

Cite this