WO2018085833A3 - Selective inhibitors of protein arginine methyl transferase 5 (prmt5) - Google Patents

Selective inhibitors of protein arginine methyl transferase 5 (prmt5) Download PDF

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Publication number
WO2018085833A3
WO2018085833A3 PCT/US2017/060396 US2017060396W WO2018085833A3 WO 2018085833 A3 WO2018085833 A3 WO 2018085833A3 US 2017060396 W US2017060396 W US 2017060396W WO 2018085833 A3 WO2018085833 A3 WO 2018085833A3
Authority
WO
WIPO (PCT)
Prior art keywords
prmt5
selective inhibitors
methyl transferase
arginine methyl
protein arginine
Prior art date
Application number
PCT/US2017/060396
Other languages
French (fr)
Other versions
WO2018085833A2 (en
Inventor
Juan Luengo
Raul A. LEAL
Hong Lin
Rupa SHETTY
Original Assignee
Prelude Therapeutics, Incorporated
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Prelude Therapeutics, Incorporated filed Critical Prelude Therapeutics, Incorporated
Publication of WO2018085833A2 publication Critical patent/WO2018085833A2/en
Publication of WO2018085833A3 publication Critical patent/WO2018085833A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/14—Pyrrolo-pyrimidine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The disclosure is directed to compounds of Formula I, Formula II, and Formula III [Formulas should be inserted here]. Methods of their use and preparation are also described.
PCT/US2017/060396 2016-11-07 2017-11-07 Selective inhibitors of protein arginine methyl transferase 5 (prmt5) WO2018085833A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662418541P 2016-11-07 2016-11-07
US62/418,541 2016-11-07

Publications (2)

Publication Number Publication Date
WO2018085833A2 WO2018085833A2 (en) 2018-05-11
WO2018085833A3 true WO2018085833A3 (en) 2018-10-25

Family

ID=60409439

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2017/060396 WO2018085833A2 (en) 2016-11-07 2017-11-07 Selective inhibitors of protein arginine methyl transferase 5 (prmt5)

Country Status (1)

Country Link
WO (1) WO2018085833A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3072439A1 (en) 2017-08-09 2019-02-14 Prelude Therapeutics, Incorporated Selective inhibitors of protein arginine methyltransferase 5 (prmt5)
CN111971288B (en) 2018-03-14 2023-12-01 普莱鲁德疗法有限公司 Selective inhibitors of protein arginine methyltransferase 5 (PRMT 5)
US10711007B2 (en) 2018-03-14 2020-07-14 Prelude Therapeutics Incorporated Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
WO2020206308A1 (en) * 2019-04-05 2020-10-08 Prelude Therapeutics, Incorporated Selective inhibitors of protein arginine methyltransferase 5

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120329747A1 (en) * 2011-06-21 2012-12-27 Jayaram Hiremagular N Novel hydrazone derivatives having potent antitumor activity toward multi-drug resistant tumor cells
WO2014145214A2 (en) * 2013-03-15 2014-09-18 Ohio State Innovation Foundation Inhibitors of prmt5 and methods of their use
WO2014172330A1 (en) * 2013-04-16 2014-10-23 Sloan-Kettering Institute For Cancer Research Methyltransferase inhibitors for treating cancer
WO2016145150A2 (en) * 2015-03-11 2016-09-15 The Broad Institute Inc. Selective treatment of prmt5 dependent cancer
EP3103802A1 (en) * 2014-06-24 2016-12-14 Taiho Pharmaceutical Co., Ltd. Novel pyrrolopyrimidine compound or salt thereof, pharmaceutical composition containing same, especially agent for prevention and/or treatment of tumors etc based on nae inhibitory effect

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US3657744A (en) 1970-05-08 1972-04-25 Univ Minnesota Method for fixing prosthetic implants in a living body
US4733665C2 (en) 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US5023252A (en) 1985-12-04 1991-06-11 Conrex Pharmaceutical Corporation Transdermal and trans-membrane delivery of drugs
US5061273A (en) 1989-06-01 1991-10-29 Yock Paul G Angioplasty apparatus facilitating rapid exchanges
US5350395A (en) 1986-04-15 1994-09-27 Yock Paul G Angioplasty apparatus facilitating rapid exchanges
US5040548A (en) 1989-06-01 1991-08-20 Yock Paul G Angioplasty mehtod
US4748982A (en) 1987-01-06 1988-06-07 Advanced Cardiovascular Systems, Inc. Reinforced balloon dilatation catheter with slitted exchange sleeve and method
US5001139A (en) 1987-06-12 1991-03-19 American Cyanamid Company Enchancers for the transdermal flux of nivadipine
US4992445A (en) 1987-06-12 1991-02-12 American Cyanamid Co. Transdermal delivery of pharmaceuticals
CA1322628C (en) 1988-10-04 1993-10-05 Richard A. Schatz Expandable intraluminal graft
US6344053B1 (en) 1993-12-22 2002-02-05 Medtronic Ave, Inc. Endovascular support device and method
US5674278A (en) 1989-08-24 1997-10-07 Arterial Vascular Engineering, Inc. Endovascular support device
US5292331A (en) 1989-08-24 1994-03-08 Applied Vascular Engineering, Inc. Endovascular support device

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120329747A1 (en) * 2011-06-21 2012-12-27 Jayaram Hiremagular N Novel hydrazone derivatives having potent antitumor activity toward multi-drug resistant tumor cells
WO2014145214A2 (en) * 2013-03-15 2014-09-18 Ohio State Innovation Foundation Inhibitors of prmt5 and methods of their use
WO2014172330A1 (en) * 2013-04-16 2014-10-23 Sloan-Kettering Institute For Cancer Research Methyltransferase inhibitors for treating cancer
EP3103802A1 (en) * 2014-06-24 2016-12-14 Taiho Pharmaceutical Co., Ltd. Novel pyrrolopyrimidine compound or salt thereof, pharmaceutical composition containing same, especially agent for prevention and/or treatment of tumors etc based on nae inhibitory effect
WO2016145150A2 (en) * 2015-03-11 2016-09-15 The Broad Institute Inc. Selective treatment of prmt5 dependent cancer

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
WEIHONG ZHENG ET AL: "Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 134, no. 43, 31 October 2012 (2012-10-31), pages 18004 - 18014, XP055049439, ISSN: 0002-7863, DOI: 10.1021/ja307060p *
ZHAO QUAN ET AL: "PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing", NAT. STRUCT. MOL. BIOL,, vol. 16, no. 3, 1 March 2009 (2009-03-01), pages 304 - 311, XP002554686, ISSN: 1545-9993, [retrieved on 20090222], DOI: 10.1038/NSMB.1568 *

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WO2018085833A2 (en) 2018-05-11

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