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 Rioja & 9 others Gail A. Seal, Tracy Shipley, Onkar Singh, Colin J. Suckling, Joanna Taylor, Pamela Thomas, David M. Wilson, Kevin Lee, Rab K. Prinjha

Research output: Contribution to journalArticle

38 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

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Histone Demethylases
pyridine
pyrido(4,3-d)pyrimidin-4(3H)-one

Keywords

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

Cite this

Westaway, Susan M. ; Preston, Alex G. S. ; Barker, Michael D. ; Brown, Fiona ; Brown, Jack A. ; Campbell, Matthew ; Chung, Chun-Wa ; Drewes, Gerard ; Eagle, Robert ; Garton, Neil ; Gordon, Laurie ; Haslam, Carl ; Hayhow, Thomas G. ; Humphreys, Philip G. ; Joberty, Gerard ; Katso, Roy ; Kruidenier, Laurens ; Leveridge, Melanie ; Pemberton, Michelle ; Rioja, Inma ; Seal, Gail A. ; Shipley, Tracy ; Singh, Onkar ; Suckling, Colin J. ; Taylor, Joanna ; Thomas, Pamela ; Wilson, David M. ; Lee, Kevin ; Prinjha, Rab K. / Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 4. pp. 1370-1387.
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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.",
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Westaway, SM, Preston, AGS, Barker, MD, Brown, F, Brown, JA, Campbell, M, Chung, C-W, Drewes, G, Eagle, R, Garton, N, Gordon, L, Haslam, C, Hayhow, TG, Humphreys, PG, Joberty, G, Katso, R, Kruidenier, L, Leveridge, M, Pemberton, M, Rioja, I, Seal, GA, Shipley, T, Singh, O, Suckling, CJ, Taylor, J, Thomas, P, Wilson, DM, Lee, K & Prinjha, RK 2016, 'Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives', Journal of Medicinal Chemistry, vol. 59, no. 4, pp. 1370-1387. https://doi.org/10.1021/acs.jmedchem.5b01538

Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives. / Westaway, Susan M.; Preston, Alex G. S.; Barker, Michael D.; Brown, Fiona; Brown, Jack A.; Campbell, Matthew; Chung, Chun-Wa; Drewes, Gerard; Eagle, Robert; Garton, Neil; Gordon, Laurie; Haslam, Carl; Hayhow, Thomas G.; Humphreys, Philip G.; Joberty, Gerard; Katso, Roy; Kruidenier, Laurens; Leveridge, Melanie; Pemberton, Michelle; Rioja, Inma; Seal, Gail A.; Shipley, Tracy; Singh, Onkar; Suckling, Colin J.; Taylor, Joanna; Thomas, Pamela; Wilson, David M.; Lee, Kevin; Prinjha, Rab K.

In: Journal of Medicinal Chemistry, Vol. 59, No. 4, 25.02.2016, p. 1370-1387.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives

AU - Westaway, Susan M.

AU - Preston, Alex G. S.

AU - Barker, Michael D.

AU - Brown, Fiona

AU - Brown, Jack A.

AU - Campbell, Matthew

AU - Chung, Chun-Wa

AU - Drewes, Gerard

AU - Eagle, Robert

AU - Garton, Neil

AU - Gordon, Laurie

AU - Haslam, Carl

AU - Hayhow, Thomas G.

AU - Humphreys, Philip G.

AU - Joberty, Gerard

AU - Katso, Roy

AU - Kruidenier, Laurens

AU - Leveridge, Melanie

AU - Pemberton, Michelle

AU - Rioja, Inma

AU - Seal, Gail A.

AU - Shipley, Tracy

AU - Singh, Onkar

AU - Suckling, Colin J.

AU - Taylor, Joanna

AU - Thomas, Pamela

AU - Wilson, David M.

AU - Lee, Kevin

AU - Prinjha, Rab K.

PY - 2016/2/25

Y1 - 2016/2/25

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KW - molecular medicine

KW - drugs

KW - drug discovery

KW - gene expression

KW - epigenetics

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DO - 10.1021/acs.jmedchem.5b01538

M3 - Article

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SP - 1370

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

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