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
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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 EP12803036.8A priority Critical patent/EP2723338A2/en
Priority to US14/129,108 priority patent/US20150197497A1/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
EP12803036.8A EP2723338A2 (en) 2011-06-24 2012-06-25 Selective inhibitors of histone deacetylase isoform 6 and methods thereof
US14/129,108 US20150197497A1 (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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AR096837A1 (en) 2013-07-08 2016-02-03 Incyte Corp TRICYCLIC HETEROCICLES AS BET PROTEIN INHIBITORS
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
ES2704704T3 (en) * 2013-12-12 2019-03-19 Chong Kun Dang Pharmaceutical Corp New azaindole derivatives as selective inhibitors of histone deacetylase (HDAC) and pharmaceutical compositions comprising them
WO2015095492A1 (en) 2013-12-19 2015-06-25 Incyte Corporation Tricyclic heterocycles as bet protein inhibitors
EA034972B1 (en) 2014-04-23 2020-04-13 Инсайт Корпорейшн 1H-PYRROLO[2,3-c]PYRIDIN-7(6H)-ONES AS INHIBITORS OF BET PROTEINS
US9527864B2 (en) 2014-09-15 2016-12-27 Incyte Corporation Tricyclic heterocycles as BET protein inhibitors
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
JP6815318B2 (en) 2014-12-23 2021-01-20 ダナ−ファーバー キャンサー インスティテュート，インコーポレイテッド How to Induce Targeted Proteolysis by Bifunctional Molecules
SG11201708622UA (en) 2015-02-02 2017-11-29 Forma Therapeutics Inc 3-aryl-4-amido-bicyclic [4,5,0] hydroxamic acids as hdac inhibitors
WO2016126726A1 (en) 2015-02-02 2016-08-11 Forma Therapeutics, Inc. Bicyclic [4,6,0] hydroxamic acids as hdac6 inhibitors
WO2017007612A1 (en) 2015-07-07 2017-01-12 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
TW201722966A (en) 2015-10-29 2017-07-01 英塞特公司 Amorphous solid form of a BET protein inhibitor
CN109641874A (en) 2016-05-10 2019-04-16 C4医药公司 C for target protein degradation3The glutarimide degron body of carbon connection
CN109790143A (en) 2016-05-10 2019-05-21 C4医药公司 The C of amine connection for target protein degradation3Glutarimide degron body
EP3454862B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Spirocyclic degronimers for target protein degradation
EP4491236A3 (en) 2016-05-10 2025-04-02 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
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
KR102643344B1 (en) 2016-06-20 2024-03-07 인사이트 코포레이션 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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CN110621317B (en) * 2017-05-16 2023-05-12 安基生技新药股份有限公司 Histone deacetylase (HDACS) inhibitors
EP4717317A2 (en) 2017-06-20 2026-04-01 C4 Therapeutics, Inc. N/o-linked degrons and degronimers for protein degradation
CN111278816B (en) 2017-09-04 2024-03-15 C4医药公司 Dihydroquinolinone
CN118206529A (en) 2017-09-04 2024-06-18 C4医药公司 Dihydrobenzimidazolone
CN118108706A (en) 2017-09-04 2024-05-31 C4医药公司 Glutarimide
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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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CN119751456A (en) 2018-04-16 2025-04-04 C4医药公司 Spirocyclic compounds
WO2020097398A1 (en) 2018-11-07 2020-05-14 Dana-Farber Cancer Institute, Inc. Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof
EP3877371A4 (en) 2018-11-07 2022-07-27 Dana-Farber Cancer Institute, Inc. IMIDAZOPYRIDINE DERIVATIVES AND AZA-IMIDAZOPYRIDINE DERIVATIVES USED AS JANUS KINASE 2 INHIBITORS AND ASSOCIATED USES
WO2020097396A1 (en) 2018-11-07 2020-05-14 Dana-Farber Cancer Institute, Inc. Benzimidazole derivatives and aza-benzimidazole derivatives as janus kinase 2 inhibitors and uses thereof
CN120698983A (en) 2018-12-20 2025-09-26 C4医药公司 Targeted protein degradation
WO2020181232A1 (en) 2019-03-06 2020-09-10 C4 Therapeutics, Inc. Heterocyclic compounds for medical treatment
AU2020321955A1 (en) 2019-07-30 2022-03-17 Eikonizo Therapapeutics, Inc. HDAC6 inhibitors and uses thereof
EP4074707A4 (en) * 2019-12-10 2024-01-03 Shanghai Zhimeng Biopharma, Inc. Compound having neuroprotective effect, preparation method therefor and use thereof
CN115836054B (en) 2020-05-06 2024-12-10 默沙东有限责任公司 IL4I1 inhibitors and methods of use
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Also Published As

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

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