CN110382463B - Hdac6选择性抑制剂及其制备方法和应用 - Google Patents

Hdac6选择性抑制剂及其制备方法和应用 Download PDF

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Publication number
CN110382463B
CN110382463B CN201880006463.5A CN201880006463A CN110382463B CN 110382463 B CN110382463 B CN 110382463B CN 201880006463 A CN201880006463 A CN 201880006463A CN 110382463 B CN110382463 B CN 110382463B
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compound
pharmaceutically acceptable
acceptable salt
stereoisomer
solution
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Chinese (zh)
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CN110382463A (zh
Inventor
吴颢
韦昌青
郭强
张贵芬
刘斌
廖勇刚
肖瑶
陈曙辉
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Shenshi Biomedical (Shanghai) Co.,Ltd.
CStone Pharmaceuticals Shanghai Co Ltd
CStone Pharmaceuticals Suzhou Co Ltd
CStone Pharmaceuticals
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CStone Pharmaceuticals Shanghai Co Ltd
CStone Pharmaceuticals Suzhou Co Ltd
CStone Pharmaceuticals
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • A61K31/16—Amides, e.g. hydroxamic 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • 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
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further 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
    • A61K31/435—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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • 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
    • A61K31/69—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
    • C07D211/86—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/06—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Furan Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201880006463.5A 2017-01-10 2018-01-10 Hdac6选择性抑制剂及其制备方法和应用 Active CN110382463B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2017100172872 2017-01-10
CN201710017287 2017-01-10
PCT/CN2018/072088 WO2018130155A1 (zh) 2017-01-10 2018-01-10 Hdac6选择性抑制剂及其制备方法和应用

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CN110382463A CN110382463A (zh) 2019-10-25
CN110382463B true CN110382463B (zh) 2022-11-04

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US (1) US10745389B2 (enExample)
EP (1) EP3569592B8 (enExample)
JP (1) JP7237010B2 (enExample)
KR (1) KR102549606B1 (enExample)
CN (1) CN110382463B (enExample)
AU (1) AU2018208160B2 (enExample)
ES (1) ES2927352T3 (enExample)
IL (1) IL267968B (enExample)
MX (1) MX394624B (enExample)
SA (1) SA519402090B1 (enExample)
SG (1) SG11201906361YA (enExample)
WO (1) WO2018130155A1 (enExample)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020007329A1 (zh) * 2018-07-04 2020-01-09 基石药业（苏州）有限公司 Hdac6选择性抑制剂的晶型及其应用
CN115443329A (zh) 2019-06-27 2022-12-06 乔治华盛顿大学国会特许非营利公司 Hdac6激活的巨噬细胞、其组合物及用途
WO2021110121A1 (zh) * 2019-12-05 2021-06-10 基石药业（苏州）有限公司 Hdac6选择性抑制剂及其组合疗法
KR20220119653A (ko) 2019-12-20 2022-08-30 테나야 테라퓨틱스, 인코포레이티드 플루오로알킬-옥사디아졸 및 이의 용도
EP4326263A1 (en) 2021-04-23 2024-02-28 Tenaya Therapeutics, Inc. Hdac6 inhibitors for use in the treatment of dilated cardiomyopathy
US20240252502A1 (en) 2021-05-04 2024-08-01 Tenaya Therapeutics, Inc. Hdac6 inhibitors for treatment of metabolic disease and hfpef
WO2024123700A1 (en) * 2022-12-05 2024-06-13 The General Hospital Corporation Histone deacetylase inhibitors
WO2025215092A1 (en) 2024-04-10 2025-10-16 Institut National de la Santé et de la Recherche Médicale Selective hdac6 inhibitors for use in the treatment of myotonic dystrophy type 1

Citations (1)

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CN103429574A (zh) * 2010-11-16 2013-12-04 阿塞蒂隆制药公司 作为蛋白质去乙酰化酶抑制剂的嘧啶羟基酰胺化合物和其使用方法

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JP2005517007A (ja) * 2002-02-07 2005-06-09 アクシス・ファーマスーティカルズ ヒストンデアセチラーゼ阻害剤としての新規二環式ヒドロキサメート
CN101641338A (zh) * 2006-09-11 2010-02-03 柯瑞斯公司 作为抗增殖制剂的多功能小分子
KR20110038159A (ko) 2008-07-28 2011-04-13 길리애드 사이언시즈, 인코포레이티드 사이클로알킬리덴 및 헤테로사이클로알킬리덴 히스톤 데아세틸라아제 억제제 화합물
WO2011106632A1 (en) 2010-02-26 2011-09-01 Millennium Pharmaceuticals, Inc. Substituted hydroxamic acids and uses thereof
US8404738B2 (en) 2011-01-21 2013-03-26 Hoffmann-La Roche Inc. 4-amino-N-hydroxy-benzamides for the treatment of cancer
EP2826769A1 (en) * 2013-07-18 2015-01-21 Institut de Recherche pour le Développement ( IRD) Compounds for the treatment and/or prevention of parasitic diseases and method of production thereof
CA2933907A1 (en) * 2013-12-23 2015-07-02 The Trustees Of Columbia University In The City Of New York Selective hdac6 inhibitors
US9464073B2 (en) * 2014-02-26 2016-10-11 Acetylon Pharmaceuticals, Inc. Pyrimidine hydroxy amide compounds as HDAC6 selective inhibitors

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
CN103429574A (zh) * 2010-11-16 2013-12-04 阿塞蒂隆制药公司 作为蛋白质去乙酰化酶抑制剂的嘧啶羟基酰胺化合物和其使用方法

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Publication number Publication date
EP3569592B1 (en) 2022-08-24
US20190375735A1 (en) 2019-12-12
EP3569592B8 (en) 2022-11-30
IL267968A (en) 2019-10-31
RU2019124962A (ru) 2021-02-15
CA3049834A1 (en) 2018-07-19
JP7237010B2 (ja) 2023-03-10
JP2020505440A (ja) 2020-02-20
ES2927352T8 (es) 2022-11-18
EP3569592A4 (en) 2020-08-12
KR102549606B1 (ko) 2023-06-29
IL267968B (en) 2022-06-01
SA519402090B1 (ar) 2022-05-30
KR20190103286A (ko) 2019-09-04
RU2019124962A3 (enExample) 2021-05-11
SG11201906361YA (en) 2019-08-27
AU2018208160A1 (en) 2019-08-15
CN110382463A (zh) 2019-10-25
WO2018130155A1 (zh) 2018-07-19
MX394624B (es) 2025-03-24
US10745389B2 (en) 2020-08-18
ES2927352T3 (es) 2022-11-04
EP3569592A1 (en) 2019-11-20
MX2019008181A (es) 2019-12-09
AU2018208160B2 (en) 2021-03-04
BR112019014152A2 (pt) 2020-03-31

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