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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NANJING AOZHAO BIOTECHNOLOGY Co Ltd
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NANJING AOZHAO BIOTECHNOLOGY Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/403Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/407Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/498Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • AHUMAN NECESSITIES
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/4985Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/12Heterocyclic 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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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12Heterocyclic 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
    • C07D495/14Ortho-condensed systems

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  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pain & Pain Management (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 (OSRAM)
EP (1) EP2785720B1 (OSRAM)
JP (1) JP6272773B2 (OSRAM)
CN (1) CN103974956B (OSRAM)
CA (1) CA2857193A1 (OSRAM)
WO (1) WO2013078544A1 (OSRAM)

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PL3080125T3 (pl) 2013-12-12 2019-06-28 Chong Kun Dang Pharmaceutical Corp. Pochodne azaindolu jako selektywne inhibitory deacetylazy histonowej (HDAC) i zawierające je kompozycje farmaceutyczne
KR101685639B1 (ko) * 2014-01-03 2016-12-12 주식회사 종근당 신규한 인돌 유도체 화합물 및 이를 포함하는 약제학적 조성물
JP6757312B2 (ja) 2014-03-27 2020-09-16 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
US10106540B2 (en) 2014-08-04 2018-10-23 Universität Regensburg HDAC6 inhibitors and their uses
ES2935932T3 (es) 2015-07-27 2023-03-13 Chong Kun Dang Pharmaceutical Corp Compuestos de derivados de 1,3,4-oxadiazolsulfonamida como inhibidor de histona desacetilasa 6, y la composición farmacéutica que comprende los mismos
AU2016299485B2 (en) 2015-07-27 2019-02-07 Chong Kun Dang Pharmaceutical Corp. 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same
MX376585B (es) 2015-07-27 2025-03-07 Chong Kun Dang Pharmaceutical Corp Compuestos derivados de sulfamida de 1,3,4-oxadiazol como inhibidor de histona desacetilasa 6, y la composición farmacéutica que comprende los mismos.
AU2016303891B2 (en) * 2015-08-04 2019-08-01 Chong Kun Dang Pharmaceutical Corp. 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same
HUE061967T2 (hu) 2015-10-12 2023-09-28 Chong Kun Dang Pharmaceutical Corp Hiszton deacetiláz-6 inhibitor oxadiazol-amin származékok és az azokat tartalmazó gyógyászati készítmény
BR112018067775B1 (pt) 2016-03-04 2024-02-15 Vanderbilt University Compostos inibidores de mcl-1 indol substituídos, composição farmacêutica compreendendo ditos compostos e usos terapêuticos dos mesmos
WO2018081556A1 (en) * 2016-10-28 2018-05-03 Acetylon Pharmaceuticals, Inc. Pharmaceutical combinations comprising a histone deacetylase inhibitor and epothilone and methods of use thereof
CA3063111C (en) 2017-05-16 2022-10-11 Annji Pharmaceutical Co., Ltd. Histone deacetylases (hdacs) inhibitors
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
PH12021552905A1 (en) 2019-05-31 2022-04-04 Chong Kun Dang Pharmaceutical Corp 1,3,4-oxadiazole homophthalimide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same
BR112022011917A2 (pt) 2019-12-20 2022-09-06 Tenaya Therapeutics Inc Fluoroalquil-oxadiazois e seus usos
EP4326263A1 (en) 2021-04-23 2024-02-28 Tenaya Therapeutics, Inc. Hdac6 inhibitors for use in the treatment of dilated cardiomyopathy
MX2023012875A (es) 2021-05-04 2024-01-12 Tenaya Therapeutics Inc Inhibidores 2-fluoro alquil-l,3,4-oxadiazol-5-il-tiazol de hdac6 para su uso en el tratamiento de enfermedades metabólicas y 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
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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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JP2014533734A (ja) 2014-12-15
US9345905B2 (en) 2016-05-24
US20140322229A1 (en) 2014-10-30
WO2013078544A1 (en) 2013-06-06
EP2785720A1 (en) 2014-10-08
CA2857193A1 (en) 2013-06-06
EP2785720A4 (en) 2015-11-11
EP2785720B1 (en) 2017-08-09
JP6272773B2 (ja) 2018-01-31
CN103974956A (zh) 2014-08-06

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