JP7656922B2 - Ｒａｄ５１阻害薬としての求電子剤および求電子剤プロドラッグ - Google Patents

Ｒａｄ５１阻害薬としての求電子剤および求電子剤プロドラッグ Download PDF

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JP7656922B2
JP7656922B2 JP2021525753A JP2021525753A JP7656922B2 JP 7656922 B2 JP7656922 B2 JP 7656922B2 JP 2021525753 A JP2021525753 A JP 2021525753A JP 2021525753 A JP2021525753 A JP 2021525753A JP 7656922 B2 JP7656922 B2 JP 7656922B2
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cells
carbon
electron
mda
rad51
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JP2022507265A5 (https=
JP2022507265A (ja
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ブルース エー． フリーマン，
キャロラ ノイマン，
フランシスコ ジェイ． ショップファー，
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University of Pittsburgh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A61K31/10—Sulfides; Sulfoxides; Sulfones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/50—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1092—Details
    • A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2021525753A 2018-11-14 2019-11-14 Ｒａｄ５１阻害薬としての求電子剤および求電子剤プロドラッグ Active JP7656922B2 (ja)

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Application Number Priority Date Filing Date Title
US201862767424P 2018-11-14 2018-11-14
US62/767,424 2018-11-14
PCT/US2019/061474 WO2020102529A1 (en) 2018-11-14 2019-11-14 Electrophiles and electrophile pro-drugs as rad51 inhibitors

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JP2022507265A JP2022507265A (ja) 2022-01-18
JP2022507265A5 JP2022507265A5 (https=) 2022-11-18
JP7656922B2 true JP7656922B2 (ja) 2025-04-04

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US (1) US12390435B2 (https=)
EP (1) EP3880188A4 (https=)
JP (1) JP7656922B2 (https=)
CN (1) CN112996493A (https=)
CA (1) CA3114406A1 (https=)
WO (1) WO2020102529A1 (https=)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12390435B2 (en) 2018-11-14 2025-08-19 University of Pittsburgh—of the Commonwealth System of Higher Education Electrophiles and electrophile pro-drugs as RAD51 inhibitors
WO2023025263A1 (en) * 2021-08-25 2023-03-02 Ensem Therapeutics Holding (Singapore) Pte. Ltd. Systems and methods for post-translational modification-inspired drug design and screening
KR20230102353A (ko) * 2021-12-30 2023-07-07 주식회사 대웅제약 삼중음성유방암의 예방 또는 치료용 약학적 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009155439A2 (en) 2008-06-19 2009-12-23 University Of Utah Research Foundation Use of nitrated lipids for treatment of side effects of toxic medical therapies
WO2011041639A2 (en) 2009-10-02 2011-04-07 Miller Raymond A Heteroatom containing substituted fatty acids
WO2017151938A1 (en) 2016-03-04 2017-09-08 University Of Pittsburgh- Of The Commonwealth System Of Higher Education Prevention, treatment and reversal of disease using therapeutically effective amounts of dicarboxylic acid compounds
JP2018514511A (ja) 2015-04-14 2018-06-07 アトッサ ジェネティックス インク． 乳房障害とエストロゲン関連障害の処置のための組成物と方法

Family Cites Families (8)

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US7776916B2 (en) 2004-04-28 2010-08-17 The Uab Research Foundation Nitrated lipids and methods of making and using thereof
WO2009017802A1 (en) 2007-08-01 2009-02-05 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Nitro-fattyacid modulation of type ii diabetes
JP2011519373A (ja) 2008-05-01 2011-07-07 コンプレクザ インコーポレイテッド ビニル置換脂肪酸
EP3045167A1 (en) 2009-07-31 2016-07-20 University of Pittsburgh - Of the Commonwealth System of Higher Education Keto fatty acids as anti-inflammatory agents
WO2013116753A1 (en) 2012-02-03 2013-08-08 University Of Pittsburgh-Of The Commonwelth System Of Higher Education Fatty acids as anti-inflammatory agents
CN109803648A (zh) 2016-10-05 2019-05-24 高等教育联邦系统-匹兹堡大学 可逆保护的硫醇化亲电脂肪酸作为前药
US10765652B2 (en) 2016-10-05 2020-09-08 University of Pittsburgh—of the Commonwealth System of Higher Education Reversible nitroxide derivatives of nitroalkenes that mediate nitrosating and alkylating reactions
US12390435B2 (en) 2018-11-14 2025-08-19 University of Pittsburgh—of the Commonwealth System of Higher Education Electrophiles and electrophile pro-drugs as RAD51 inhibitors

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009155439A2 (en) 2008-06-19 2009-12-23 University Of Utah Research Foundation Use of nitrated lipids for treatment of side effects of toxic medical therapies
WO2011041639A2 (en) 2009-10-02 2011-04-07 Miller Raymond A Heteroatom containing substituted fatty acids
JP2018514511A (ja) 2015-04-14 2018-06-07 アトッサ ジェネティックス インク． 乳房障害とエストロゲン関連障害の処置のための組成物と方法
WO2017151938A1 (en) 2016-03-04 2017-09-08 University Of Pittsburgh- Of The Commonwealth System Of Higher Education Prevention, treatment and reversal of disease using therapeutically effective amounts of dicarboxylic acid compounds

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Anti-infammatory nitro-fatty acids suppress tumor growth by triggering mitochondrial dysfunction and activation of the intrinsic apoptotic pathway in colorectal cancer cells，Biochemical Pharmacology，2018年06月15日，155，pp.48-60，https://doi.org/10.1016/j.bcp.2018.06.014
Electrophilic Nitroalkenes Inhibit Triple Negative Breast Cancer Metastasis，The FASEB Journal，2016年04月01日，vol.30, IssueS1，p.714.7，https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.30.1_supplement.714.7，[オンライン], [検索日 2023.11.27]
Nitro-fatty acid inhibition of triple-negative breast cancer cell viability, migration, invasion, and tumor growth，J.Biol.Chem，2017年11月20日，293(4)，pp.1120-1137，DOI:10.1074/jbc.M117.814368
Redox Regulation of RAD51 and Homologous Recombination by Peroxiredoxin 1 and Electrophilic Nitro- fatty Acids ，Free Radical Biology and Medicine，2011年，vol.112, supplement1，pp.100-101，DOI: 10.1016/j.freeradbiomed.2017.10.151
Selective Inhibition of Triple Negative Breast Cancer Cell Mobility and Viability by Nitro-Oleic Acid，Free Radical Biology and Medicine，2017年，vol.112, supplement1，p.99，DOI: 10.1016/j.freeradbiomed.2017.10.148

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Publication number Publication date
US20220040134A1 (en) 2022-02-10
EP3880188A4 (en) 2022-08-17
CA3114406A1 (en) 2020-05-22
US12390435B2 (en) 2025-08-19
EP3880188A1 (en) 2021-09-22
WO2020102529A1 (en) 2020-05-22
CN112996493A (zh) 2021-06-18
JP2022507265A (ja) 2022-01-18

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