CN107428734A - 用于雄激素受体的靶向降解的化合物和方法 - Google Patents

用于雄激素受体的靶向降解的化合物和方法 Download PDF

Info

Publication number
CN107428734A
CN107428734A CN201680014250.8A CN201680014250A CN107428734A CN 107428734 A CN107428734 A CN 107428734A CN 201680014250 A CN201680014250 A CN 201680014250A CN 107428734 A CN107428734 A CN 107428734A
Authority
CN
China
Prior art keywords
optionally substituted
alkyl
independently
substituted
halo
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.)
Pending
Application number
CN201680014250.8A
Other languages
English (en)
Chinese (zh)
Inventor
M·金
A·P·克鲁
H·董
J·王
C·费拉罗
X·陈
Y·钱
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.)
Arvinas Inc
Original Assignee
Arvinas Inc
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 Arvinas Inc filed Critical Arvinas Inc
Publication of CN107428734A publication Critical patent/CN107428734A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • 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
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyrrole Compounds (AREA)
  • Secondary Cells (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Developing Agents For Electrophotography (AREA)
  • Lubricants (AREA)
CN201680014250.8A 2015-01-20 2016-01-20 用于雄激素受体的靶向降解的化合物和方法 Pending CN107428734A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562105210P 2015-01-20 2015-01-20
US62/105,210 2015-01-20
PCT/US2016/014187 WO2016118666A1 (en) 2015-01-20 2016-01-20 Compounds and methods for the targeted degradation of the androgen receptor

Publications (1)

Publication Number Publication Date
CN107428734A true CN107428734A (zh) 2017-12-01

Family

ID=56417710

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201680014250.8A Pending CN107428734A (zh) 2015-01-20 2016-01-20 用于雄激素受体的靶向降解的化合物和方法

Country Status (11)

Country Link
US (3) US11352351B2 (enExample)
EP (1) EP3247708A4 (enExample)
JP (3) JP6817962B2 (enExample)
KR (5) KR102564925B1 (enExample)
CN (1) CN107428734A (enExample)
AU (4) AU2016209349B2 (enExample)
BR (1) BR112017015497A2 (enExample)
CA (1) CA2974367A1 (enExample)
HK (2) HK1245791A1 (enExample)
MX (2) MX390189B (enExample)
WO (1) WO2016118666A1 (enExample)

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019120079A1 (zh) * 2017-12-19 2019-06-27 刘秀云 硫代咪唑二酮类雄激素受体拮抗剂及其用途
WO2019218904A1 (zh) * 2018-05-18 2019-11-21 四川科伦博泰生物医药股份有限公司 非天然氨基酸类衍生物、其制备方法及用途
CN110506039A (zh) * 2016-10-11 2019-11-26 阿尔维纳斯股份有限公司 用于雄激素受体靶向降解的化合物和方法
CN110684046A (zh) * 2018-07-06 2020-01-14 江苏恒瑞医药股份有限公司 一种新的咪唑啉类衍生物的制备方法
CN110845348A (zh) * 2019-12-10 2020-02-28 苏州国匡医药科技有限公司 一种arv-110中间体的制备方法
WO2020211822A1 (zh) * 2019-04-18 2020-10-22 成都海创药业有限公司 一类靶向降解雄激素受体的双功能嵌合体杂环化合物及其用途
CN111944012A (zh) * 2019-05-17 2020-11-17 成都海创药业有限公司 一种芳香胺类靶向ar和bet的蛋白降解嵌合体化合物及用途
WO2021012659A1 (zh) * 2018-07-23 2021-01-28 上海美志医药科技有限公司 具有降解雄激素受体活性的化合物
CN112390852A (zh) * 2019-08-14 2021-02-23 上海济煜医药科技有限公司 作为蛋白降解剂的化合物及其制备方法和应用
CN112457366A (zh) * 2019-09-06 2021-03-09 江西济民可信集团有限公司 作为蛋白降解剂的并环类化合物及其制备方法和应用
CN112457367A (zh) * 2019-09-06 2021-03-09 上海济煜医药科技有限公司 作为蛋白降解剂的连环类化合物及其制备方法和应用
CN112574278A (zh) * 2019-09-29 2021-03-30 江西济民可信集团有限公司 作为蛋白降解剂杂环类化合物及其制备方法和医药应用
CN113087704A (zh) * 2019-12-23 2021-07-09 上海济煜医药科技有限公司 一种蛋白降解剂化合物的制备方法和应用
CN113149981A (zh) * 2020-01-22 2021-07-23 苏州德亘生物医药有限公司 一种降解雄激素受体的蛋白降解靶向嵌合体
CN113387930A (zh) * 2020-03-11 2021-09-14 苏州开拓药业股份有限公司 一种双官能化合物及其制备方法和用途
CN113527273A (zh) * 2020-10-28 2021-10-22 中国药科大学 靶向泛素化降解hmgcr的化合物或其可药用的盐、制备方法及用途
CN113677668A (zh) * 2019-01-30 2021-11-19 蒙特利诺治疗公司 用于雄激素受体靶向泛素化的双官能化合物和方法
CN114163444A (zh) * 2020-09-11 2022-03-11 江苏恒瑞医药股份有限公司 一种用于雄激素受体蛋白靶向降解的嵌合体化合物、其制备方法及其在医药上的应用
CN114181277A (zh) * 2020-09-15 2022-03-15 江苏恒瑞医药股份有限公司 一种用于雄激素受体蛋白靶向降解的嵌合体化合物、其制备方法及其在医药上的应用
CN114262319A (zh) * 2020-12-01 2022-04-01 南昌奥瑞药业有限公司 一类双功能分子、其制备方法及其应用
WO2022262782A1 (zh) * 2021-06-17 2022-12-22 南京明德新药研发有限公司 戊二酰亚胺取代的异噁唑稠环化合物及其应用
CN117209433A (zh) * 2023-08-04 2023-12-12 南开大学 一种以降冰片胺为疏水基团的蛋白降解剂及其制备方法、药物组合物和应用
WO2024037616A1 (zh) * 2022-08-19 2024-02-22 正大天晴药业集团股份有限公司 包含环己基的化合物
WO2024165050A1 (en) * 2023-02-10 2024-08-15 Aubrak Therapeutics Proteolysis-targeting chimera (protac) compounds and uses thereof field
RU2825000C2 (ru) * 2019-04-18 2024-08-19 Хинова Фармасьютикалс Инк. Класс бифункциональных химерных гетероциклических соединений для направленного разрушения андрогенных рецепторов и их применение

Families Citing this family (134)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3608317A1 (en) 2012-01-12 2020-02-12 Yale University Compounds & methods for the enhanced degradation of targeted proteins & other polypeptides by an e3 ubiquitin ligase
GB201311891D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compound
GB201311888D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
KR102564925B1 (ko) 2015-01-20 2023-08-07 아비나스 오퍼레이션스, 인코포레이티드 안드로겐 수용체의 표적화된 분해를 위한 화합물 및 방법
GB201504314D0 (en) 2015-03-13 2015-04-29 Univ Dundee Small molecules
EP3270917A4 (en) 2015-03-18 2018-08-08 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
EP3302482A4 (en) 2015-06-05 2018-12-19 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
US20170008904A1 (en) * 2015-07-10 2017-01-12 Arvinas, Inc. Mdm2-based modulators of proteolysis and associated methods of use
WO2017024319A1 (en) 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Tunable endogenous protein degradation
EP3337476A4 (en) 2015-08-19 2019-09-04 Arvinas, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US9963433B2 (en) * 2016-01-29 2018-05-08 Wayne State University Anticancer drugs including the chemical structures of an androgen receptor ligand and a histone deacetylase inhibitor
JP6968823B2 (ja) 2016-04-22 2021-11-17 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 Ｅｇｆｒの分解のための二官能性分子、及び使用方法
WO2017197051A1 (en) 2016-05-10 2017-11-16 C4 Therapeutics, Inc. Amine-linked c3-glutarimide degronimers for target protein degradation
WO2017197036A1 (en) 2016-05-10 2017-11-16 C4 Therapeutics, Inc. Spirocyclic degronimers for target protein degradation
EP3455218A4 (en) 2016-05-10 2019-12-18 C4 Therapeutics, Inc. C3 CARBON-BASED GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN REDUCTION
EP3454856B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
GB2554071A (en) * 2016-09-14 2018-03-28 Univ Dundee Small molecules
WO2018053354A1 (en) 2016-09-15 2018-03-22 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
CA3042260C (en) 2016-11-01 2023-10-03 Arvinas, Inc. Tau-protein targeting protacs and associated methods of use
US10689366B2 (en) * 2016-11-01 2020-06-23 Cornell University Compounds for MALT1 degredation
RS64976B1 (sr) 2016-12-01 2024-01-31 Arvinas Operations Inc Derivati tetrahidronaftalena i tetrahidroizohinolina kao degradatori estrogenih receptora
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
JP2020505327A (ja) 2016-12-23 2020-02-20 アルビナス・オペレーションズ・インコーポレイテッドＡｒｖｉｎａｓ Ｏｐｅｒａｔｉｏｎｓ， Ｉｎｃ． Ｅｇｆｒタンパク質分解標的化キメラ分子およびその関連する使用方法
CN110741004B (zh) 2016-12-23 2023-10-17 阿尔维纳斯运营股份有限公司 用于迅速加速性纤维肉瘤多肽的靶向降解的化合物和方法
WO2018118598A1 (en) 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
AU2018211975B2 (en) 2017-01-26 2022-05-26 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
KR102747905B1 (ko) 2017-01-31 2024-12-31 아비나스 오퍼레이션스, 인코포레이티드 세레블론 리간드 및 이를 포함하는 이작용성 화합물
JP7227912B2 (ja) 2017-02-08 2023-02-24 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 キメラ抗原受容体の調節
CN110545853A (zh) 2017-04-28 2019-12-06 石英治疗有限公司 Raf降解偶联化合物
AU2018261331C1 (en) 2017-05-01 2022-08-04 Spg Therapeutics, Inc. Tripartite androgen receptor eliminators, methods and uses thereof
CN108976278B (zh) * 2017-06-05 2021-04-06 海创药业股份有限公司 一种嵌合分子及其制备和应用
CN110769822A (zh) 2017-06-20 2020-02-07 C4医药公司 用于蛋白降解的n/o-连接的降解决定子和降解决定子体
SG10202110500TA (en) 2017-06-22 2021-11-29 Catalyst Biosciences Inc Modified membrane type serine protease 1 (mtsp-1) polypeptides and methods of use
BR112020001825A2 (pt) * 2017-07-28 2020-07-21 Arvinas Operations, Inc. compostos e métodos para a degradação direcionada de receptor de androgênio
WO2019043214A1 (en) 2017-09-04 2019-03-07 F. Hoffmann-La Roche Ag glutarimide
WO2019043208A1 (en) 2017-09-04 2019-03-07 F. Hoffmann-La Roche Ag DIHYDROQUINOLINONES
EP3679027A1 (en) 2017-09-04 2020-07-15 C4 Therapeutics, Inc. Dihydrobenzimidazolones
AU2018332634A1 (en) * 2017-09-12 2020-04-30 Agency For Science, Technology And Research Compounds useful as inhibitors of isoprenylcysteine carboxyl methyltransferase
IL322809A (en) 2017-09-22 2025-10-01 Kymera Therapeutics Inc Protein Decomposers and Their Uses
US11358948B2 (en) 2017-09-22 2022-06-14 Kymera Therapeutics, Inc. CRBN ligands and uses thereof
WO2019099868A2 (en) 2017-11-16 2019-05-23 C4 Therapeutics, Inc. Degraders and degrons for targeted protein degradation
US11065231B2 (en) 2017-11-17 2021-07-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
US11512080B2 (en) 2018-01-12 2022-11-29 Kymera Therapeutics, Inc. CRBN ligands and uses thereof
WO2019140380A1 (en) 2018-01-12 2019-07-18 Kymera Therapeutics, Inc. Protein degraders and uses thereof
EP3743066A4 (en) 2018-01-26 2021-09-08 Yale University IMIDE-BASED PROTEOLYSIS MODULATORS AND RELATED METHODS OF USE
WO2019191112A1 (en) 2018-03-26 2019-10-03 C4 Therapeutics, Inc. Cereblon binders for the degradation of ikaros
EP3774789B1 (en) * 2018-04-01 2025-03-05 Arvinas Operations, Inc. Brm targeting compounds and associated methods of use
BR112020020307A2 (pt) 2018-04-04 2021-01-12 Arvinas Operations, Inc. Moduladores de proteólise e métodos de uso associados
EP3781156A4 (en) 2018-04-16 2022-05-18 C4 Therapeutics, Inc. SPIROCYCLIC COMPOUNDS
EA202092436A1 (ru) 2018-05-14 2021-05-04 Нувейшн Био Инк. Противораковые соединения, нацеливающие на ядерные гормональные рецепторы
EP3578561A1 (en) 2018-06-04 2019-12-11 F. Hoffmann-La Roche AG Spiro compounds
US11292792B2 (en) 2018-07-06 2022-04-05 Kymera Therapeutics, Inc. Tricyclic CRBN ligands and uses thereof
EP3817822A4 (en) 2018-07-06 2022-07-27 Kymera Therapeutics, Inc. PROTEIN DEGRADANTS AND USES THEREOF
EP3831811A4 (en) 2018-07-31 2022-04-20 Fimecs, Inc. HETEROCYCLIC COMPOUND
US11707452B2 (en) 2018-08-20 2023-07-25 Arvinas Operations, Inc. Modulators of alpha-synuclein proteolysis and associated methods of use
EP3846800A4 (en) 2018-09-04 2022-08-24 C4 Therapeutics, Inc. Compounds for the degradation of brd9 or mth1
CA3119773A1 (en) 2018-11-30 2020-06-04 Kymera Therapeutics, Inc. Irak degraders and uses thereof
AU2019387370A1 (en) 2018-11-30 2021-06-10 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
CN109762045A (zh) * 2018-12-14 2019-05-17 中山大学附属第一医院 一种双靶点构建protac的方法及其用途
DK3897636T3 (da) 2018-12-19 2025-01-13 Celgene Corp Substituerede 3-((3-aminophenyl)amino)piperidin-2,6-dionforbindelser, sammensætninger heraf og fremgangsmåde til behandling hermed
KR102864064B1 (ko) 2018-12-19 2025-09-24 셀진 코포레이션 치환된 3-((3-아미노페닐)아미노)피페리딘-2,6-디온 화합물, 이의 조성물, 및 이를 사용한 치료 방법
WO2020132561A1 (en) 2018-12-20 2020-06-25 C4 Therapeutics, Inc. Targeted protein degradation
US20220081435A1 (en) * 2019-01-03 2022-03-17 The Regents Of The University Of Michigan Androgen receptor protein degraders
US11547759B2 (en) 2019-01-30 2023-01-10 Montelino Therapeutics, Inc. Bi-functional compounds and methods for targeted ubiquitination of androgen receptor
CN113660937A (zh) * 2019-02-08 2021-11-16 佛罗里达大学研究基金公司 治疗剂和治疗方法
US20200297725A1 (en) * 2019-03-22 2020-09-24 Yale University Allosteric bcr-abl proteolysis targeting chimeric compounds
BR112021019508A2 (pt) * 2019-04-02 2022-02-01 Hinova Pharmaceuticals Inc Composto de amina aromática e uso do mesmo na preparação de reguladores e inibidores duplos de ar e brd4
CN113939300A (zh) 2019-04-05 2022-01-14 凯麦拉医疗公司 Stat降解剂和其用途
EA202192738A1 (ru) 2019-04-12 2022-03-17 С4 Терапьютикс, Инк. Трициклические соединения, обеспечивающие разрушение белка ikaros и белка aiolos
WO2020214555A1 (en) 2019-04-16 2020-10-22 Northwestern University Bifunctional compounds comprising apcin-a and their use in the treatment of cancer
US20220296595A1 (en) 2019-05-05 2022-09-22 Qilu Regor Therapeutics Inc. Cdk inhibitors
GB201906705D0 (en) 2019-05-13 2019-06-26 Phoremost Ltd Methods
CA3138197A1 (en) 2019-05-14 2020-11-19 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
CN114502158A (zh) 2019-06-28 2022-05-13 凯麦拉医疗公司 Irak降解剂及其用途
CN114867727B (zh) 2019-07-17 2025-02-21 阿尔维纳斯运营股份有限公司 Tau蛋白靶向化合物及相关使用方法
CN114667147B (zh) 2019-08-26 2024-09-06 阿尔维纳斯运营股份有限公司 用四氢萘衍生物作为雌激素受体降解剂的治疗乳腺癌的方法
EP4045496A1 (en) 2019-10-17 2022-08-24 Arvinas Operations, Inc. Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
US11952349B2 (en) 2019-11-13 2024-04-09 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
JP2023509366A (ja) 2019-12-17 2023-03-08 カイメラ セラピューティクス， インコーポレイテッド Ｉｒａｋ分解剤およびそれらの使用
US11591332B2 (en) 2019-12-17 2023-02-28 Kymera Therapeutics, Inc. IRAK degraders and uses thereof
PH12022551486A1 (en) 2019-12-19 2023-11-13 Arvinas Operations Inc Compounds and methods for the targeted degradation of androgen receptor
US11679109B2 (en) 2019-12-23 2023-06-20 Kymera Therapeutics, Inc. SMARCA degraders and uses thereof
CN115279370B (zh) 2020-03-05 2025-01-10 C4医药公司 用于brd9的靶向降解的化合物
PH12022552458A1 (en) 2020-03-19 2024-01-22 Kymera Therapeutics Inc Mdm2 degraders and uses thereof
AU2021273458A1 (en) 2020-05-09 2022-12-01 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same
US20230357249A1 (en) * 2020-05-14 2023-11-09 The Regents Of The University Of Michigan Androgen receptor protein degraders with a tricyclic cereblon ligand
WO2021236695A1 (en) * 2020-05-18 2021-11-25 Montelino Therapeutics, Inc. Bi-functional compounds and methods for targeted ubiquitination of androgen receptor
TW202210483A (zh) 2020-06-03 2022-03-16 美商凱麥拉醫療公司 Irak降解劑之結晶型
CR20230007A (es) 2020-06-12 2023-06-01 Shanghai Jemincare Pharmaceuticals Co Ltd Compuesto de ftalazinona, y método de preparación y uso médico de este.
US11739075B2 (en) 2020-06-24 2023-08-29 Celgene Corporation Cereblon binding compounds, compositions thereof, and methods of treatment therewith
KR20230027214A (ko) 2020-06-24 2023-02-27 셀진 코포레이션 세레블론 결합 화합물, 이의 조성물, 및 이에 의한 치료 방법
IL299256A (en) 2020-06-24 2023-02-01 Celgene Corp Cerebellum binding compounds, their compounds and methods of treatment with them
WO2022032026A1 (en) 2020-08-05 2022-02-10 C4 Therapeutics, Inc. Compounds for targeted degradation of ret
US12180193B2 (en) 2020-08-28 2024-12-31 Arvinas Operations, Inc. Accelerating fibrosarcoma protein degrading compounds and associated methods of use
CR20230162A (es) 2020-09-14 2023-06-02 Arvinas Operations Inc Formas cristalinas y amorfas de un compuesto para la degradación dirigida del receptor de estrógenos
WO2022120355A1 (en) 2020-12-02 2022-06-09 Ikena Oncology, Inc. Tead degraders and uses thereof
JP7434265B2 (ja) * 2020-12-30 2024-02-20 財團法人工業技術研究院 アンドロゲン受容体結合分子およびその使用
MX2023007852A (es) 2020-12-30 2023-07-07 Kymera Therapeutics Inc Degradadores de cinasas asociadas al receptor de interleucina-1 (irak) y usos de los mismos.
EP4277901A1 (en) 2021-01-13 2023-11-22 Monte Rosa Therapeutics, Inc. Isoindolinone compounds
EP4291187A4 (en) 2021-02-15 2025-01-15 Kymera Therapeutics, Inc. Irak4 degraders and uses thereof
IL306010A (en) 2021-03-23 2023-11-01 Nuvation Bio Inc Anticancer compounds against the nuclear hormone receptor
AU2022259683A1 (en) 2021-04-16 2023-10-19 Arvinas Operations, Inc. Modulators of bcl6 proteolysis and associated methods of use
JP2024516024A (ja) 2021-05-03 2024-04-11 ニューベイション・バイオ・インコーポレイテッド 抗がん核内ホルモン受容体標的化化合物
IL308219A (en) 2021-05-05 2024-01-01 Biogen Ma Inc Compounds to Target Broton Tyrosine Kinase Degradation
CN117715904A (zh) 2021-05-07 2024-03-15 凯麦拉医疗公司 Cdk2降解剂和其用途
CN117561249A (zh) * 2021-06-25 2024-02-13 细胞基因公司 Cereblon结合化合物、其组合物及其用于治疗的方法
EP4359406A4 (en) * 2021-06-25 2025-05-21 Celgene Corporation CEREBLON-BINDING COMPOUNDS, COMPOSITIONS THEREOF AND METHODS OF TREATMENT USING THEM
US20250018046A1 (en) 2021-07-07 2025-01-16 Biogen Ma Inc Compounds for targeting degradation of irak4 proteins
IL309941A (en) 2021-07-07 2024-03-01 Biogen Ma Inc Compounds to target degradation of IRAK4 proteins
CN115772210A (zh) * 2021-09-08 2023-03-10 苏州开拓药业股份有限公司 硫代乙内酰脲化合物或其药用盐的无定形物、晶体、药物组合物、制备方法和用途
WO2023039601A1 (en) * 2021-09-13 2023-03-16 Montelino Therapeutics, Inc. Bi-functional compounds and methods for targeted ubiquitination of androgen receptor
US11981672B2 (en) 2021-09-13 2024-05-14 Montelino Therapeutics Inc. Bi-functional compounds and methods for targeted ubiquitination of androgen receptor
US20240425456A1 (en) 2021-09-30 2024-12-26 Aska Pharmaceutical Co., Ltd. Degrader
AU2022378463A1 (en) 2021-10-25 2024-05-09 Kymera Therapeutics, Inc. Tyk2 degraders and uses thereof
EP4422635A4 (en) 2021-10-29 2025-11-26 Kymera Therapeutics Inc IRAQ4 DEGRADATION AGENTS AND THEIR SYNTHESIS
AU2022397695A1 (en) 2021-11-25 2024-06-06 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Chimeric compound for targeted degradation of androgen receptor protein, preparation method therefor, and medical use thereof
AU2023214044A1 (en) 2022-01-31 2024-08-08 Kymera Therapeutics, Inc. Irak degraders and uses thereof
KR20250021314A (ko) 2022-06-06 2025-02-12 씨4 테라퓨틱스, 인코포레이티드 비시클릭-치환된 글루타르이미드 세레블론 결합제
WO2024006776A1 (en) 2022-06-27 2024-01-04 Relay Therapeutics, Inc. Estrogen receptor alpha degraders and medical use thereof
JP2025521686A (ja) 2022-06-27 2025-07-10 リレー セラピューティクス， インコーポレイテッド エストロゲン受容体アルファ分解剤及びその使用
WO2024050016A1 (en) 2022-08-31 2024-03-07 Oerth Bio Llc Compositions and methods for targeted inhibition and degradation of proteins in an insect cell
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
WO2024064358A1 (en) 2022-09-23 2024-03-28 Ifm Due, Inc. Compounds and compositions for treating conditions associated with sting activity
WO2024073507A1 (en) 2022-09-28 2024-04-04 Theseus Pharmaceuticals, Inc. Macrocyclic compounds and uses thereof
EP4655073A2 (en) 2023-01-26 2025-12-03 Arvinas Operations, Inc. Cereblon-based kras degrading protacs ans uses related thereto
WO2024211154A2 (en) * 2023-04-03 2024-10-10 Wisconsin Alumni Research Foundation Ferritin-targeting protacs and methods of inducing pyroptosis
WO2025049555A1 (en) 2023-08-31 2025-03-06 Oerth Bio Llc Compositions and methods for targeted inhibition and degradation of proteins in an insect cell
WO2025068704A1 (en) 2023-09-28 2025-04-03 Phoremost Limited Methods of protein engineering and functional screening
WO2025122895A1 (en) 2023-12-08 2025-06-12 Arvinas Operations, Inc. Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140356322A1 (en) * 2012-01-12 2014-12-04 Yale University Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase
WO2015000867A1 (en) * 2013-07-03 2015-01-08 Glaxosmithkline Intellectual Property Development Limited Benzothiophene derivatives as estrogen receptor inhibitors

Family Cites Families (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ302378B6 (cs) 1996-07-24 2011-04-20 Celgene Corporation Optický izomer (S)-1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindolin a farmaceutická kompozice s jeho obsahem
CA2287387C (en) 1997-05-14 2010-02-16 Sloan-Kettering Institute For Cancer Research Methods and compositions for destruction of selected proteins
US6306663B1 (en) 1999-02-12 2001-10-23 Proteinex, Inc. Controlling protein levels in eucaryotic organisms
CA2372176A1 (en) 1999-05-05 2000-11-09 Merck & Co., Inc. Novel prolines as antimicrobial agents
AU2001288213B2 (en) * 2000-06-28 2005-04-14 Bristol-Myers Squibb Company Selective androgen receptor modulators and methods for their identification, design and use
US7208157B2 (en) 2000-09-08 2007-04-24 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
WO2002020740A2 (en) 2000-09-08 2002-03-14 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
US20030045552A1 (en) 2000-12-27 2003-03-06 Robarge Michael J. Isoindole-imide compounds, compositions, and uses thereof
CA2432932A1 (en) 2001-02-16 2002-08-29 Mark A. Scialdone Angiogenesis-inhibitory tripeptides, compositions and their methods of use
HN2002000136A (es) 2001-06-11 2003-07-31 Basf Ag Inhibidores de la proteasa del virus hiv, compuestos que contienen a los mismos, sus usos farmaceuticos y los materiales para su sintesis
TWI263640B (en) * 2001-12-19 2006-10-11 Bristol Myers Squibb Co Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function
JP4541882B2 (ja) 2002-07-02 2010-09-08 ノバルティス アーゲー Ｓｍａｃタンパク質のアポトーシスタンパク質阻害物質（ｉａｐ）との結合に対するペプチド阻害剤
WO2005007621A2 (en) 2003-05-30 2005-01-27 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
CN1960728A (zh) 2004-01-16 2007-05-09 密歇根大学董事会 构象受限的smac模拟物及其应用
JP5122275B2 (ja) 2004-03-23 2013-01-16 ジェネンテック， インコーポレイテッド Ｉａｐのアザビシクロ−オクタンインヒビター
ME02125B (me) 2004-04-07 2013-04-30 Novartis Ag Inhibitori protein apoptoze (iap)
WO2006014361A1 (en) 2004-07-02 2006-02-09 Genentech, Inc. Inhibitors of iap
WO2006006065A1 (en) 2004-07-08 2006-01-19 Warner-Lambert Company Llc Androgen modulators
TW200621723A (en) * 2004-09-09 2006-07-01 Chugai Pharmaceutical Co Ltd Novel imidazolidine derivative and use thereof
ATE477254T1 (de) 2004-12-20 2010-08-15 Genentech Inc Pyrrolidine als inhibitoren von iap
EA012810B1 (ru) 2005-02-25 2009-12-30 Тетралоджик Фармасеутикалс Димерные ингибиторы ингибиторов белков апоптоза (iap)
CN100383139C (zh) 2005-04-07 2008-04-23 天津和美生物技术有限公司 可抑制细胞释放肿瘤坏死因子的哌啶-2，6-二酮衍生物
WO2006113942A2 (en) 2005-04-20 2006-10-26 Schering Corporation Method of inhibiting cathepsin activity
AU2007245022A1 (en) 2006-03-29 2007-11-08 The Regents Of The University Of California Diarylthiohydantoin compounds
KR101332889B1 (ko) * 2005-05-13 2013-11-26 더 리전트 오브 더 유니버시티 오브 캘리포니아 디아릴히단토인 화합물
CA2822094C (en) 2005-08-31 2015-10-27 Celgene Corporation Isoindole-imide compounds and compositions comprising and methods of using the same
JP2009529008A (ja) 2006-03-03 2009-08-13 ノバルティス アクチエンゲゼルシャフト Ｎ−ホルミルヒドロキシルアミン化合物
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
CN101032483B (zh) * 2006-03-09 2011-05-04 陈德桂 调节雄激素受体活性的乙内酰脲衍生物及其应用
JP5230610B2 (ja) 2006-05-05 2013-07-10 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン 二価ｓｍａｃ模倣物およびその使用
AU2007275415A1 (en) 2006-07-20 2008-01-24 Ligand Pharmaceuticals Incorporated Proline urea CCR1 antagonists for the treatment of autoimmune diseases or inflammation
US20100056495A1 (en) 2006-07-24 2010-03-04 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
RU2448101C2 (ru) 2006-08-30 2012-04-20 Селджин Корпорейшн 5-замещенные изоиндолиновые соединения
JP5523831B2 (ja) 2006-08-30 2014-06-18 セルジーン コーポレイション ５−置換イソインドリン化合物
WO2008054827A2 (en) 2006-11-03 2008-05-08 Pharmacyclics, Inc. Bruton's tyrosine kinase activity probe and method of using
WO2008109057A1 (en) 2007-03-02 2008-09-12 Dana-Farber Cancer Institute, Inc. Organic compounds and their uses
BRPI0810178A2 (pt) 2007-04-12 2014-09-23 Joyant Pharmaceuticals Inc Dímeros e trímeros miméticos de smac úteis como agentes anticâncer
EP2139490B1 (en) 2007-04-13 2014-07-02 The Regents of the University of Michigan Diazo bicyclic smac mimetics and the uses thereof
BRPI0809867A2 (pt) 2007-04-30 2014-09-30 Genentech Inc Composto, método de indução da apoptose em uma célula, método de sensibilização de uma célula para um sinal apoptótico, método para inibir a ligação de uma proteína iap a uma proteína caspase e métodos
US20100203012A1 (en) 2007-05-30 2010-08-12 Aegera Therapeutics, Inc. Iap bir domain binding compounds
KR20100038108A (ko) 2007-07-25 2010-04-12 브리스톨-마이어스 스큅 컴퍼니 트리아진 키나제 억제제
JP2010535213A (ja) * 2007-07-31 2010-11-18 アンドロサイエンス コーポレーション アンドロゲン受容体分解（ａｒｄ）エンハンサーを含む組成物ならびに皮膚疾患および脱毛の予防的または治療的処理方法
EP2058312A1 (en) 2007-11-09 2009-05-13 Universita' degli Studi di Milano SMAC mimetic compounds as apoptosis inducers
EP3354646A1 (en) 2008-10-29 2018-08-01 Celgene Corporation Isoindoline compounds for use in the treatment of cancer
US20120135089A1 (en) 2009-03-17 2012-05-31 Stockwell Brent R E3 ligase inhibitors
WO2010141805A1 (en) 2009-06-05 2010-12-09 Janssen Pharmaceutica Nv Heterocyclic amides as modulators of trpa1
EP2453908B1 (en) 2009-07-13 2018-03-14 President and Fellows of Harvard College Bifunctional stapled polypeptides and uses thereof
AR078793A1 (es) 2009-10-27 2011-12-07 Orion Corp Derivados de carboxamidas no esteroidales y acil hidrazona moduladores de receptores androgenicos de tejido selectivo (sarm), composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento del cancer de prostata entre otros
EP2784076A1 (en) 2009-10-28 2014-10-01 Joyant Pharmaceuticals, Inc. Dimeric SMAC mimetics
SG10201501062SA (en) 2010-02-11 2015-04-29 Celgene Corp Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
KR101819199B1 (ko) * 2010-02-16 2018-01-16 아라곤 파마슈티컬스, 인코포레이티드 안드로겐 수용체 조절제 및 이의 용도
AU2011272860A1 (en) 2010-06-30 2013-02-07 Brandeis University Small-molecule-targeted protein degradation
AU2011305315A1 (en) 2010-09-24 2013-03-28 The Regents Of The University Of Michigan Deubiquitinase inhibitors and methods for use of the same
EP2649099A4 (en) 2010-12-07 2016-10-19 Univ Yale SMALL MOLECULAR HYDROPHOBIC LABELING OF FUSION PROTEINS AND INDUCED REMOVAL FROM THIS
US20140243282A1 (en) 2010-12-31 2014-08-28 Satish Reddy Kallam Methods and compositions for designing novel conjugate therapeutics
ES2541295T3 (es) * 2011-04-21 2015-07-17 Orion Corporation Carboxamidas que modulan el receptor de andrógenos
WO2013049250A1 (en) 2011-09-27 2013-04-04 Amgen Inc. Heterocyclic compounds as mdm2 inhibitors for the treatment of cancer
WO2013067151A1 (en) * 2011-11-02 2013-05-10 Medivation Prostate Therapeutics, Inc. Treatment methods using diarylthiohydantoin derivatives
WO2013067142A1 (en) * 2011-11-02 2013-05-10 Medivation Technologies, Inc. Compounds and treatment methods
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
EP2776409B1 (en) 2011-11-09 2016-02-03 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2013106646A2 (en) 2012-01-12 2013-07-18 Yale University Compounds and methods for the inhibition of vcb e3 ubiquitin ligase
US20150119435A1 (en) 2012-05-11 2015-04-30 Yale University Compounds useful for promoting protein degradation and methods using same
US9365576B2 (en) 2012-05-24 2016-06-14 Novartis Ag Pyrrolopyrrolidinone compounds
CA2869101A1 (en) 2012-05-30 2013-12-05 F. Hoffmann-La Roche Ag Substituted pyrrolidine-2-carboxamides
WO2014011712A1 (en) 2012-07-10 2014-01-16 Bristol-Myers Squibb Company Iap antagonists
US9371568B2 (en) 2012-07-31 2016-06-21 Novartis Ag Markers associated with human double minute 2 inhibitors
US9453048B2 (en) 2012-08-09 2016-09-27 Bristol-Myers Squibb Company IAP antagonists
SI2894151T1 (sl) * 2012-09-04 2021-01-29 Shanghai Hengrui Pharmaceutical Co. Ltd. Imidazolinski derivati, postopki za njihovo pripravo in njihove uporabe v medicini
TWI586668B (zh) 2012-09-06 2017-06-11 第一三共股份有限公司 二螺吡咯啶衍生物之結晶
EP2897949B1 (en) 2012-09-18 2018-01-10 Bristol-Myers Squibb Company Iap antagonists
WO2014055461A1 (en) 2012-10-02 2014-04-10 Bristol-Myers Squibb Company Iap antagonists
TW201428002A (zh) 2012-11-09 2014-07-16 必治妥美雅史谷比公司 用於抑制細胞凋亡抑制劑之巨環化合物
CA2895504A1 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Substituted imidazopyridines as hdm2 inhibitors
WO2014100071A2 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Substituted pyrrolopyrimidines as hdm2 inhibitors
EP2752191A1 (en) 2013-01-07 2014-07-09 Sanofi Compositions and methods using hdm2 antagonist and mek inhibitor
GB201311910D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel Compounds
NL2011274C2 (en) 2013-08-06 2015-02-09 Illumicare Ip B V 51 Groundbreaking platform technology for specific binding to necrotic cells.
MX368703B (es) 2013-02-28 2019-10-11 Amgen Inc Un inhibidor de mdm2 derivado de acido benzoico para el tratamiento del cancer.
MX374513B (es) 2013-03-14 2025-03-06 Amgen Inc Compuestos de morfolinona de ácido heteroarilo como inhibidores mdm2 para el tratamiento de cáncer.
TW201534586A (zh) * 2013-06-11 2015-09-16 Orion Corp 新穎ｃｙｐ１７抑制劑／抗雄激素劑
GB201311891D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compound
EP3019517A1 (en) 2013-07-12 2016-05-18 Bristol-Myers Squibb Company Iap antagonists
KR20250127179A (ko) * 2014-04-14 2025-08-26 아비나스 오퍼레이션스, 인코포레이티드 단백질분해의 이미드-기초된 조절인자 및 연관된 이용 방법
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
TW201613916A (en) 2014-06-03 2016-04-16 Gilead Sciences Inc TANK-binding kinase inhibitor compounds
US20160022642A1 (en) 2014-07-25 2016-01-28 Yale University Compounds Useful for Promoting Protein Degradation and Methods Using Same
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
JP6815318B2 (ja) * 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 二官能性分子によって標的化タンパク質分解を誘導する方法
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
KR102564925B1 (ko) 2015-01-20 2023-08-07 아비나스 오퍼레이션스, 인코포레이티드 안드로겐 수용체의 표적화된 분해를 위한 화합물 및 방법
GB201504314D0 (en) 2015-03-13 2015-04-29 Univ Dundee Small molecules
EP3270917A4 (en) 2015-03-18 2018-08-08 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
GB201506872D0 (en) 2015-04-22 2015-06-03 Ge Oil & Gas Uk Ltd Novel compounds
EP3302482A4 (en) 2015-06-05 2018-12-19 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
WO2017007612A1 (en) * 2015-07-07 2017-01-12 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US20170008904A1 (en) 2015-07-10 2017-01-12 Arvinas, Inc. Mdm2-based modulators of proteolysis and associated methods of use
CA2988436A1 (en) 2015-07-13 2017-01-19 Arvinas, Inc. Alanine-based modulators of proteolysis and associated methods of use
WO2017024317A2 (en) * 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2017024319A1 (en) * 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Tunable endogenous protein degradation
EP3337476A4 (en) 2015-08-19 2019-09-04 Arvinas, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
RU2018120330A (ru) 2015-11-02 2019-12-04 Йейл Юниверсити Химерные соединения, осуществляющие нацеливание для протеолиза, и способы их получения и применения
US20170281784A1 (en) 2016-04-05 2017-10-05 Arvinas, Inc. Protein-protein interaction inducing technology
HUE061847T2 (hu) 2016-10-11 2023-08-28 Arvinas Operations Inc Androgén receptor célzott degradálására alkalmas vegyületek és eljárások
CA3042260C (en) 2016-11-01 2023-10-03 Arvinas, Inc. Tau-protein targeting protacs and associated methods of use
RS64976B1 (sr) 2016-12-01 2024-01-31 Arvinas Operations Inc Derivati tetrahidronaftalena i tetrahidroizohinolina kao degradatori estrogenih receptora
CN110741004B (zh) 2016-12-23 2023-10-17 阿尔维纳斯运营股份有限公司 用于迅速加速性纤维肉瘤多肽的靶向降解的化合物和方法
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140356322A1 (en) * 2012-01-12 2014-12-04 Yale University Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase
WO2015000867A1 (en) * 2013-07-03 2015-01-08 Glaxosmithkline Intellectual Property Development Limited Benzothiophene derivatives as estrogen receptor inhibitors

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110506039A (zh) * 2016-10-11 2019-11-26 阿尔维纳斯股份有限公司 用于雄激素受体靶向降解的化合物和方法
WO2019120079A1 (zh) * 2017-12-19 2019-06-27 刘秀云 硫代咪唑二酮类雄激素受体拮抗剂及其用途
WO2019218904A1 (zh) * 2018-05-18 2019-11-21 四川科伦博泰生物医药股份有限公司 非天然氨基酸类衍生物、其制备方法及用途
CN110684046A (zh) * 2018-07-06 2020-01-14 江苏恒瑞医药股份有限公司 一种新的咪唑啉类衍生物的制备方法
CN110684046B (zh) * 2018-07-06 2023-05-12 江苏恒瑞医药股份有限公司 一种新的咪唑啉类衍生物的制备方法
WO2021012659A1 (zh) * 2018-07-23 2021-01-28 上海美志医药科技有限公司 具有降解雄激素受体活性的化合物
CN113677668A (zh) * 2019-01-30 2021-11-19 蒙特利诺治疗公司 用于雄激素受体靶向泛素化的双官能化合物和方法
CN113677668B (zh) * 2019-01-30 2024-09-27 蒙特利诺治疗公司 用于雄激素受体靶向泛素化的双官能化合物和方法
CN119504751A (zh) * 2019-04-18 2025-02-25 海创药业股份有限公司 一类靶向降解雄激素受体的双功能嵌合体杂环化合物及其用途
WO2020211822A1 (zh) * 2019-04-18 2020-10-22 成都海创药业有限公司 一类靶向降解雄激素受体的双功能嵌合体杂环化合物及其用途
CN111825657A (zh) * 2019-04-18 2020-10-27 成都海创药业有限公司 一类靶向降解雄激素受体的双功能嵌合体杂环化合物及其用途
RU2825000C2 (ru) * 2019-04-18 2024-08-19 Хинова Фармасьютикалс Инк. Класс бифункциональных химерных гетероциклических соединений для направленного разрушения андрогенных рецепторов и их применение
CN111944012A (zh) * 2019-05-17 2020-11-17 成都海创药业有限公司 一种芳香胺类靶向ar和bet的蛋白降解嵌合体化合物及用途
CN111944012B (zh) * 2019-05-17 2023-08-29 海创药业股份有限公司 一种芳香胺类靶向ar和bet的蛋白降解嵌合体化合物及用途
CN112390852A (zh) * 2019-08-14 2021-02-23 上海济煜医药科技有限公司 作为蛋白降解剂的化合物及其制备方法和应用
CN112457366B (zh) * 2019-09-06 2024-03-19 江西济民可信集团有限公司 作为蛋白降解剂的并环类化合物及其制备方法和应用
CN112457366A (zh) * 2019-09-06 2021-03-09 江西济民可信集团有限公司 作为蛋白降解剂的并环类化合物及其制备方法和应用
CN112457367A (zh) * 2019-09-06 2021-03-09 上海济煜医药科技有限公司 作为蛋白降解剂的连环类化合物及其制备方法和应用
CN112574278B (zh) * 2019-09-29 2024-08-23 江西济民可信集团有限公司 作为蛋白降解剂杂环类化合物及其制备方法和医药应用
CN112574278A (zh) * 2019-09-29 2021-03-30 江西济民可信集团有限公司 作为蛋白降解剂杂环类化合物及其制备方法和医药应用
CN110845348A (zh) * 2019-12-10 2020-02-28 苏州国匡医药科技有限公司 一种arv-110中间体的制备方法
CN114829342A (zh) * 2019-12-23 2022-07-29 上海济煜医药科技有限公司 一种蛋白降解剂化合物的制备方法和应用
CN113087704B (zh) * 2019-12-23 2023-09-08 上海济煜医药科技有限公司 一种蛋白降解剂化合物的制备方法和应用
CN113087704A (zh) * 2019-12-23 2021-07-09 上海济煜医药科技有限公司 一种蛋白降解剂化合物的制备方法和应用
CN113149981A (zh) * 2020-01-22 2021-07-23 苏州德亘生物医药有限公司 一种降解雄激素受体的蛋白降解靶向嵌合体
CN113149981B (zh) * 2020-01-22 2022-07-05 苏州德亘生物医药有限公司 一种降解雄激素受体的蛋白降解靶向嵌合体
WO2021180160A1 (zh) * 2020-03-11 2021-09-16 苏州开拓药业股份有限公司 一种双官能化合物及其制备方法和用途
CN113387930A (zh) * 2020-03-11 2021-09-14 苏州开拓药业股份有限公司 一种双官能化合物及其制备方法和用途
CN114163444B (zh) * 2020-09-11 2023-07-14 江苏恒瑞医药股份有限公司 一种用于雄激素受体蛋白靶向降解的嵌合体化合物、其制备方法及其在医药上的应用
CN114163444A (zh) * 2020-09-11 2022-03-11 江苏恒瑞医药股份有限公司 一种用于雄激素受体蛋白靶向降解的嵌合体化合物、其制备方法及其在医药上的应用
CN114181277A (zh) * 2020-09-15 2022-03-15 江苏恒瑞医药股份有限公司 一种用于雄激素受体蛋白靶向降解的嵌合体化合物、其制备方法及其在医药上的应用
CN113527273B (zh) * 2020-10-28 2023-08-22 中国药科大学 靶向泛素化降解hmgcr的化合物或其可药用的盐、制备方法及用途
CN113527273A (zh) * 2020-10-28 2021-10-22 中国药科大学 靶向泛素化降解hmgcr的化合物或其可药用的盐、制备方法及用途
CN114262319B (zh) * 2020-12-01 2023-05-05 南昌奥瑞药业有限公司 一类双功能分子、其制备方法及其应用
CN114262319A (zh) * 2020-12-01 2022-04-01 南昌奥瑞药业有限公司 一类双功能分子、其制备方法及其应用
WO2022262782A1 (zh) * 2021-06-17 2022-12-22 南京明德新药研发有限公司 戊二酰亚胺取代的异噁唑稠环化合物及其应用
WO2024037616A1 (zh) * 2022-08-19 2024-02-22 正大天晴药业集团股份有限公司 包含环己基的化合物
WO2024165050A1 (en) * 2023-02-10 2024-08-15 Aubrak Therapeutics Proteolysis-targeting chimera (protac) compounds and uses thereof field
CN117209433A (zh) * 2023-08-04 2023-12-12 南开大学 一种以降冰片胺为疏水基团的蛋白降解剂及其制备方法、药物组合物和应用

Also Published As

Publication number Publication date
KR20220151010A (ko) 2022-11-11
KR20200052995A (ko) 2020-05-15
US20160214972A1 (en) 2016-07-28
MX390189B (es) 2025-03-20
KR20170103977A (ko) 2017-09-13
HK1247204A1 (zh) 2018-09-21
EP3247708A1 (en) 2017-11-29
JP2018502925A (ja) 2018-02-01
EP3247708A4 (en) 2018-09-12
RU2017129429A3 (enExample) 2019-07-17
US20180346461A1 (en) 2018-12-06
BR112017015497A2 (pt) 2018-01-30
JP2020111590A (ja) 2020-07-27
JP2023040072A (ja) 2023-03-22
US11352351B2 (en) 2022-06-07
CA2974367A1 (en) 2016-07-28
AU2020213376A1 (en) 2020-08-27
KR102110566B1 (ko) 2020-05-13
AU2021257970A1 (en) 2021-11-25
KR102564925B1 (ko) 2023-08-07
AU2020213376B2 (en) 2021-07-29
RU2017129429A (ru) 2019-02-21
JP6817962B2 (ja) 2021-01-20
MX2022002016A (es) 2022-03-25
AU2023285742A1 (en) 2024-01-18
WO2016118666A1 (en) 2016-07-28
KR20220029783A (ko) 2022-03-08
MX2017009454A (es) 2017-10-20
KR20230119040A (ko) 2023-08-14
US20240059686A1 (en) 2024-02-22
AU2016209349B2 (en) 2020-05-07
HK1245791A1 (zh) 2018-08-31
AU2016209349A1 (en) 2017-08-10

Similar Documents

Publication Publication Date Title
CN107428734A (zh) 用于雄激素受体的靶向降解的化合物和方法
US20250223265A1 (en) Compounds and methods for the targeted degradation of androgen receptor
JP7178532B2 (ja) アンドロゲン受容体の標的分解のための化合物および方法
CN112218859B (zh) 蛋白水解调节剂及相关使用方法
CN115397821B (zh) 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
US12419960B2 (en) Compounds and methods for the targeted degradation of androgen receptor and associated methods of use
AU2018306606B2 (en) Compounds and methods for the targeted degradation of Androgen Receptor
JP2024023277A (ja) セレブロンリガンド、およびセレブロンリガンドを含有する二官能性化合物
JP2023159166A (ja) 急速進行性線維肉腫ポリペプチドの標的分解のための多環式化合物および方法
RU2830173C2 (ru) Полициклические соединения и способы целенаправленной деградации полипептидов быстро ускоренной фибросаркомы
RU2774863C2 (ru) Соединения и способы для таргетной деградации андрогенового рецептора

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1245791

Country of ref document: HK

CB02 Change of applicant information
CB02 Change of applicant information

Address after: Connecticut USA

Applicant after: Arvinas, Inc.

Address before: Connecticut USA

Applicant before: ARVINAS, Inc.

RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20171201