CN103974956B - 作为hdac6抑制剂和用作抗肿瘤剂的杂环酰胺化合物 - Google Patents

作为hdac6抑制剂和用作抗肿瘤剂的杂环酰胺化合物 Download PDF

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CN103974956B
CN103974956B CN201280058930.1A CN201280058930A CN103974956B CN 103974956 B CN103974956 B CN 103974956B CN 201280058930 A CN201280058930 A CN 201280058930A CN 103974956 B CN103974956 B CN 103974956B
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methyl
indol
hydroxybenzamide
ylsulfanyl
tetrahydropyrazino
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CN103974956A (zh
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王召印
李连海
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Beta Pharma Canada Inc
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    • 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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/4985—Pyrazines or piperazines 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
    • A61K31/495—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
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    • A61P33/10—Anthelmintics
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14—Ortho-condensed systems

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201280058930.1A 2011-11-29 2012-11-29 作为hdac6抑制剂和用作抗肿瘤剂的杂环酰胺化合物 Expired - Fee Related CN103974956B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161629827P 2011-11-29 2011-11-29
US61/629,827 2011-11-29
PCT/CA2012/001101 WO2013078544A1 (en) 2011-11-29 2012-11-29 Heterocyclic amides compounds which are hdac6 inhibitors and used as anti-tumoral agents

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CN103974956A CN103974956A (zh) 2014-08-06
CN103974956B true CN103974956B (zh) 2016-07-06

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US (1) US9345905B2 (cg-RX-API-DMAC10.html)
EP (1) EP2785720B1 (cg-RX-API-DMAC10.html)
JP (1) JP6272773B2 (cg-RX-API-DMAC10.html)
CN (1) CN103974956B (cg-RX-API-DMAC10.html)
CA (1) CA2857193A1 (cg-RX-API-DMAC10.html)
WO (1) WO2013078544A1 (cg-RX-API-DMAC10.html)

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RU2451686C1 (ru) * 2010-12-27 2012-05-27 Александр Васильевич Иващенко ЗАМЕЩЕННЫЕ ГИДРИРОВАННЫЕ ТИЕНО-ПИРРОЛО [3,2-c] ПИРИДИНЫ, ЛИГАНДЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ИХ ПРИМЕНЕНИЯ
HRP20181965T1 (hr) * 2013-12-12 2019-02-08 Chong Kun Dang Pharmaceutical Corp. Novi derivati azaindola kao selektivni inhibitori histonske deacetilaze (hdac) i farmaceutski pripravci koji ih sadrže
KR101685639B1 (ko) * 2014-01-03 2016-12-12 주식회사 종근당 신규한 인돌 유도체 화합물 및 이를 포함하는 약제학적 조성물
US10533010B2 (en) 2014-03-27 2020-01-14 Vanderbilt University Substituted indole Mcl-1 inhibitors
US10106540B2 (en) 2014-08-04 2018-10-23 Universität Regensburg HDAC6 inhibitors and their uses
NZ739211A (en) 2015-07-27 2019-05-31 Chong Kun Dang Pharmaceutical Corp 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same
BR112017027798B1 (pt) 2015-07-27 2023-12-19 Chong Kun Dang Pharmaceutical Corp Compostos de derivado de 1,3,4-oxadiazol sulfamida como inibidor de histona desacetilase 6 e a composição farmacêutica que compreende os mesmos
HRP20230052T1 (hr) 2015-07-27 2023-03-03 Chong Kun Dang Pharmaceutical Corp. Spojevi derivata 1,3,4-oksadiazol sulfonamida kao inhibitori histonske deacetilaze 6, i farmaceutski pripravak koji ih sadrži
HRP20220003T1 (hr) * 2015-08-04 2022-04-01 Chong Kun Dang Pharmaceutical Corp. Spojevi derivata 1,3,4-oksadiazola kao inhibitori histonske deacetilaze 6, i farmaceutski pripravak koji ih sadrži
FI3362445T3 (fi) 2015-10-12 2023-03-21 Chong Kun Dang Pharmaceutical Corp Oksadiatsoliamiinijohdannaisyhdisteitä histonideasetylaasi 6:n inhibiittoreina ja niitä käsittävä farmaseuttinen koostumus
JP7086395B2 (ja) 2016-03-04 2022-06-20 ヴァンダービルト ユニバーシティー 置換インドールMcl-1阻害剤
US11998546B2 (en) 2016-10-28 2024-06-04 Acetylon Pharmaceuticals, Inc. Pharmaceutical combinations comprising a histone deacetylase inhibitor and epothilone and methods of use thereof
JP7254028B2 (ja) 2017-05-16 2023-04-07 アンジー ファーマスーティカル シーオー.,エルティーディー. ヒストンデアセチラーゼ(hdacs)阻害剤
KR20190043437A (ko) 2017-10-18 2019-04-26 씨제이헬스케어 주식회사 단백질 키나제 억제제로서의 헤테로고리 화합물
KR102316234B1 (ko) 2018-07-26 2021-10-22 주식회사 종근당 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물
KR102195348B1 (ko) 2018-11-15 2020-12-24 에이치케이이노엔 주식회사 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물
CN113874369B (zh) 2019-05-31 2024-08-27 株式会社钟根堂 作为组蛋白脱乙酰酶6抑制剂的1,3,4-噁二唑高邻苯二甲酰亚胺衍生化合物及包含其的药物组合物
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
CN113861193A (zh) * 2021-11-04 2021-12-31 西南大学 一种光引发自由基串联反应制备吲哚并四氢吡啶二酮及其衍生物的方法和产品
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
CN121226371B (zh) * 2025-10-28 2026-07-14 百色学院 四氢吡嗪[1,2-a]吲哚类组蛋白去乙酰化酶抑制剂及其制备方法与应用

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CA2760516A1 (en) * 2009-04-29 2011-02-17 Medivation Technologies, Inc. Pyrido[4,3-b]indoles and methods of use
CA2768466A1 (en) * 2009-07-22 2011-01-27 The Board Of Trustees Of The University Of Illinois Hdac inhibitors and therapeutic methods using the same

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EP2785720B1 (en) 2017-08-09
CN103974956A (zh) 2014-08-06
US20140322229A1 (en) 2014-10-30
JP6272773B2 (ja) 2018-01-31
WO2013078544A1 (en) 2013-06-06
US9345905B2 (en) 2016-05-24
EP2785720A4 (en) 2015-11-11
JP2014533734A (ja) 2014-12-15
EP2785720A1 (en) 2014-10-08
CA2857193A1 (en) 2013-06-06

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