WO2012178208A3 - Selective inhibitors of histone deacetylase isoform 6 and methods thereof - Google Patents

Selective inhibitors of histone deacetylase isoform 6 and methods thereof Download PDF

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Publication number
WO2012178208A3
WO2012178208A3 PCT/US2012/044087 US2012044087W WO2012178208A3 WO 2012178208 A3 WO2012178208 A3 WO 2012178208A3 US 2012044087 W US2012044087 W US 2012044087W WO 2012178208 A3 WO2012178208 A3 WO 2012178208A3
Authority
WO
WIPO (PCT)
Prior art keywords
histone deacetylase
methods
hdac
selective inhibitors
deacetylase isoform
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2012/044087
Other languages
French (fr)
Other versions
WO2012178208A2 (en
Inventor
Chandima ABEYWICKRAMA
James E. Bradner
Shashikanth PONNALA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dana Farber Cancer Institute Inc
Stevens Institute of Technology
Original Assignee
Dana Farber Cancer Institute Inc
Stevens Institute of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dana Farber Cancer Institute Inc, Stevens Institute of Technology filed Critical Dana Farber Cancer Institute Inc
Priority to US14/129,108 priority Critical patent/US20150197497A1/en
Priority to EP12803036.8A priority patent/EP2723338A2/en
Priority to CA2840380A priority patent/CA2840380A1/en
Publication of WO2012178208A2 publication Critical patent/WO2012178208A2/en
Anticipated expiration legal-status Critical
Publication of WO2012178208A3 publication Critical patent/WO2012178208A3/en
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • 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
    • A61K31/41—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
    • A61K31/4192—1,2,3-Triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08—Radicals containing only hydrogen and carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/10—Radicals substituted by halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/26—Oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The described invention provides histone deacetylase (HDAC) inhibitor compounds with substituted benzimidazole, benzimidazolone and benzotriazole heterocycles showing selective inhibition of histone deacetylase isoform HDAC6. The described invention further provides methods of making such compounds and methods of inhibiting HDAC, treating HDAC- associated diseases, including cell proliferative disorders, such as cancer, autoimmune or inflammatory diseases and neurodegenerative diseases.
PCT/US2012/044087 2011-06-24 2012-06-25 Selective inhibitors of histone deacetylase isoform 6 and methods thereof Ceased WO2012178208A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US14/129,108 US20150197497A1 (en) 2011-06-24 2012-06-25 Selective inhibitors of histone deacetylase isoform 6 and methods thereof
EP12803036.8A EP2723338A2 (en) 2011-06-24 2012-06-25 Selective inhibitors of histone deacetylase isoform 6 and methods thereof
CA2840380A CA2840380A1 (en) 2011-06-24 2012-06-25 Selective inhibitors of histone deacetylase isoform 6 and methods thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161500785P 2011-06-24 2011-06-24
US61/500,785 2011-06-24

Publications (2)

Publication Number Publication Date
WO2012178208A2 WO2012178208A2 (en) 2012-12-27
WO2012178208A3 true WO2012178208A3 (en) 2014-05-08

Family

ID=47423274

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/044087 Ceased WO2012178208A2 (en) 2011-06-24 2012-06-25 Selective inhibitors of histone deacetylase isoform 6 and methods thereof

Country Status (4)

Country Link
US (1) US20150197497A1 (en)
EP (1) EP2723338A2 (en)
CA (1) CA2840380A1 (en)
WO (1) WO2012178208A2 (en)

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US9409858B2 (en) 2012-03-07 2016-08-09 H. Lee Moffitt Cancer Center And Research Institute, Inc. Selective histone deactylase 6 inhibitors
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US9751832B2 (en) 2013-07-30 2017-09-05 H. Lee Moffitt Cancer Center And Research Institute, Inc. Selective histone deactylase 6 inhibitors
WO2015081189A1 (en) 2013-11-26 2015-06-04 Incyte Corporation Bicyclic heterocycles as bet protein inhibitors
US9399640B2 (en) 2013-11-26 2016-07-26 Incyte Corporation Substituted pyrrolo[2,3-c]pyridines and pyrazolo[3,4-c]pyridines as BET protein inhibitors
US9650379B2 (en) * 2013-12-12 2017-05-16 Chong Kun Dang Pharmaceutical Corp. Azaindole derivatives as selective histone deacetylase (HDAC) inhibitors and pharmaceutical compositions comprising the same
WO2015095492A1 (en) 2013-12-19 2015-06-25 Incyte Corporation Tricyclic heterocycles as bet protein inhibitors
PL3134403T3 (en) 2014-04-23 2020-07-13 Incyte Corporation 1h-pyrrolo[2,3-c]pyridin-7(6h)-ones and pyrazolo[3,4-c]pyridin-7(6h)-ones as inhibitors of bet proteins
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WO2016105518A1 (en) 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
TW201636329A (en) 2015-02-02 2016-10-16 佛瑪治療公司 Bicyclo[4,6,0]hydroxamic acid as HDAC inhibitor
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WO2017007612A1 (en) 2015-07-07 2017-01-12 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2017075377A1 (en) 2015-10-29 2017-05-04 Incyte Corporation Amorphous solid form of a bet protein inhibitor
EP3454856B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
ES2990061T3 (en) 2016-05-10 2024-11-28 C4 Therapeutics Inc Spirocyclic degronimers for the degradation of target proteins
CN109790143A (en) 2016-05-10 2019-05-21 C4医药公司 The C of amine connection for target protein degradation3Glutarimide degron body
CN109641874A (en) 2016-05-10 2019-04-16 C4医药公司 C for target protein degradation3The glutarimide degron body of carbon connection
CN107434789B (en) * 2016-05-26 2021-04-13 中国医学科学院药物研究所 Benzotriazole derivatives, their preparation method, pharmaceutical composition and use
EP3472131B1 (en) 2016-06-17 2020-02-19 Forma Therapeutics, Inc. 2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors
CA3028689A1 (en) 2016-06-20 2017-12-28 Incyte Corporation Crystalline solid forms of a bet inhibitor
WO2018064589A1 (en) 2016-09-29 2018-04-05 Dana-Farber Cancer Institute, Inc. Targeted protein degradation using a mutant e3 ubiquitin ligase
WO2018165520A1 (en) 2017-03-10 2018-09-13 Vps-3, Inc. Metalloenzyme inhibitor compounds
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JP7254028B2 (en) * 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． Histone deacetylase (HDACS) inhibitors
CN110769822A (en) 2017-06-20 2020-02-07 C4医药公司 N/O-linked degron and degron bodies for protein degradation
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KR102059027B1 (en) * 2018-01-12 2019-12-24 주식회사 비엔에이치리서치 Pharmaceutical Composition Comprising Inhibitor of HDAC6 for Preventing or Treating Itch
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EP3876939A4 (en) 2018-11-07 2022-08-10 Dana-Farber Cancer Institute, Inc. BENZOTHIAZOLE DERIVATIVES AND 7-AZA-BENZOTHIAZOLE DERIVATIVES AS JANUS KINASE-2 INHIBITORS AND USES THEREOF
US12522583B2 (en) 2018-11-07 2026-01-13 Dana-Farber Cancer Institute, Inc. Benzimidazole derivatives and aza-benzimidazole derivatives as Janus kinase 2 inhibitors and uses thereof
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CN120698983A (en) 2018-12-20 2025-09-26 C4医药公司 Targeted protein degradation
ES2995214T3 (en) 2019-03-06 2025-02-07 C4 Therapeutics Inc Heterocyclic compounds for medical treatment
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Also Published As

Publication number Publication date
EP2723338A2 (en) 2014-04-30
WO2012178208A2 (en) 2012-12-27
US20150197497A1 (en) 2015-07-16
CA2840380A1 (en) 2012-12-27

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