WO2020023700A3 - Oxynitidine derivatives useful as inhibitors of topoisomerase ib (top1) and/or tyrosyl-dna phosphodiesterase 1 (tdp1) - Google Patents

Oxynitidine derivatives useful as inhibitors of topoisomerase ib (top1) and/or tyrosyl-dna phosphodiesterase 1 (tdp1) Download PDF

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Publication number
WO2020023700A3
WO2020023700A3 PCT/US2019/043357 US2019043357W WO2020023700A3 WO 2020023700 A3 WO2020023700 A3 WO 2020023700A3 US 2019043357 W US2019043357 W US 2019043357W WO 2020023700 A3 WO2020023700 A3 WO 2020023700A3
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WO
WIPO (PCT)
Prior art keywords
formula
inhibitors
compounds
oxynitidine
tdp1
Prior art date
Application number
PCT/US2019/043357
Other languages
French (fr)
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WO2020023700A2 (en
Inventor
Lin-kun AN
Xiaoru Zhang
Haowen Wang
Yves Georges POMMIER
Evgeny A. Kiselev
Azhar Ali RAVJI
Keli Kisseh AGAMA
Original Assignee
The United States Of America, As Represented By The Secretary, Department Of Health And Human Services
Sun Yat-Sen University
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Publication date
Priority claimed from CN201810827467.1A external-priority patent/CN110759963A/en
Application filed by The United States Of America, As Represented By The Secretary, Department Of Health And Human Services, Sun Yat-Sen University filed Critical The United States Of America, As Represented By The Secretary, Department Of Health And Human Services
Priority to US17/262,379 priority Critical patent/US20230219895A1/en
Priority to CN201980062917.5A priority patent/CN114555189A/en
Priority to EP19750204.0A priority patent/EP3826717A2/en
Publication of WO2020023700A2 publication Critical patent/WO2020023700A2/en
Publication of WO2020023700A3 publication Critical patent/WO2020023700A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/18—Ring systems of four or more rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/14—Ortho-condensed systems
    • C07D491/153—Ortho-condensed systems the condensed system containing two rings with oxygen as ring hetero atom and one ring with nitrogen as ring hetero atom

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compounds and pharmaceutically acceptable salts thereof of Formula I are disclosed. Certain compounds and salts of Formula I are active as Topl and / or Tdpl inhibitors. The disclosure provides pharmaceutical compositions containing a compound of Formula I as the only active agent, or optionally containing one or more additional active agents. Methods of using compounds of Formula I to treat cancer are provided in this disclosure. The disclosed compounds of Formula I may be used alone to treat cancer, but may also be used in combination with another active agent, such as a Topl inhibitor, for example, camptothecin or a camptothecin analogue.
PCT/US2019/043357 2018-07-25 2019-07-25 OXYNITIDINE DERIVATIVES USEFUL AS INHIBITORS OF TOPOISOMERASE IB (Top1) AND TYROSYL-DNA PHOSPHODIESTERASE 1 (Tdp1) WO2020023700A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US17/262,379 US20230219895A1 (en) 2018-07-25 2019-07-25 Oxynitidine derivatives useful as inhibitors of topoisomerase ib (top1) and tyrosyl-dna phosphodiesterase 1 (tdp1)
CN201980062917.5A CN114555189A (en) 2018-07-25 2019-07-25 Xanthophyllone derivatives as inhibitors of topoisomerase IB (TOP1) and/or tyrosyl-DNA phosphodiesterase 1(TDP1)
EP19750204.0A EP3826717A2 (en) 2018-07-25 2019-07-25 Oxynitidine derivatives useful as inhibitors of topoisomerase ib (top1) and/or tyrosyl-dna phosphodiesterase 1 (tdp1)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN201810827467.1A CN110759963A (en) 2018-07-25 2018-07-25 Condensed ring compound and preparation method and application thereof
CN201810827467.1 2018-07-25
US201862732885P 2018-09-18 2018-09-18
US62/732,885 2018-09-18

Publications (2)

Publication Number Publication Date
WO2020023700A2 WO2020023700A2 (en) 2020-01-30
WO2020023700A3 true WO2020023700A3 (en) 2020-05-07

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Application Number Title Priority Date Filing Date
PCT/US2019/043357 WO2020023700A2 (en) 2018-07-25 2019-07-25 OXYNITIDINE DERIVATIVES USEFUL AS INHIBITORS OF TOPOISOMERASE IB (Top1) AND TYROSYL-DNA PHOSPHODIESTERASE 1 (Tdp1)

Country Status (1)

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WO (1) WO2020023700A2 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000021537A1 (en) * 1998-10-14 2000-04-20 Purdue Research Foundation Novel indenoisoquinolines as antineoplastic agents
US20100256164A1 (en) * 2006-07-31 2010-10-07 Marinus Pharmaceuticals Inc., Pseudobase benzo[c]phenantridines with improved efficacy, stability and safety
US20120172371A1 (en) * 2010-10-27 2012-07-05 National Institutes Of Health Fluoroquinolone derivatives or sulfonamide moiety-containing compounds as inhibitors of tyrosyl-dnaphosphodiesterase (tdp1)
US20130345252A1 (en) * 2012-04-13 2013-12-26 Purdue Research Foundation Synthesis and use of dual tyrosyl-dna phosphodiesterase i (tdp1)- topoisomerase i (top1) inhibitors
WO2018118852A1 (en) * 2016-12-22 2018-06-28 Purdue Research Foundation Azaindenoisoquinoline compounds and uses thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000021537A1 (en) * 1998-10-14 2000-04-20 Purdue Research Foundation Novel indenoisoquinolines as antineoplastic agents
US20100256164A1 (en) * 2006-07-31 2010-10-07 Marinus Pharmaceuticals Inc., Pseudobase benzo[c]phenantridines with improved efficacy, stability and safety
US20120172371A1 (en) * 2010-10-27 2012-07-05 National Institutes Of Health Fluoroquinolone derivatives or sulfonamide moiety-containing compounds as inhibitors of tyrosyl-dnaphosphodiesterase (tdp1)
US20130345252A1 (en) * 2012-04-13 2013-12-26 Purdue Research Foundation Synthesis and use of dual tyrosyl-dna phosphodiesterase i (tdp1)- topoisomerase i (top1) inhibitors
WO2018118852A1 (en) * 2016-12-22 2018-06-28 Purdue Research Foundation Azaindenoisoquinoline compounds and uses thereof

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
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