CN113164775A - 用于迅速加速性纤维肉瘤多肽的靶向降解的多环化合物和方法 - Google Patents

用于迅速加速性纤维肉瘤多肽的靶向降解的多环化合物和方法 Download PDF

Info

Publication number
CN113164775A
CN113164775A CN201980073600.1A CN201980073600A CN113164775A CN 113164775 A CN113164775 A CN 113164775A CN 201980073600 A CN201980073600 A CN 201980073600A CN 113164775 A CN113164775 A CN 113164775A
Authority
CN
China
Prior art keywords
optionally substituted
alkyl
substituted
ulm
aryl
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
CN201980073600.1A
Other languages
English (en)
Chinese (zh)
Inventor
安德鲁·P·克鲁
基思·R·霍恩伯格
J·王
克雷格·M·克鲁斯
绍尔·J-F
H·董
Y·钱
库尔特·齐默尔曼
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.)
Yale University
Arvinas Inc
Arvinas Operations Inc
Original Assignee
Yale University
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 Yale University, Arvinas Inc filed Critical Yale University
Publication of CN113164775A publication Critical patent/CN113164775A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D401/14—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 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
    • C07D417/14—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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
    • 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
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N

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)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201980073600.1A 2018-09-07 2019-09-07 用于迅速加速性纤维肉瘤多肽的靶向降解的多环化合物和方法 Pending CN113164775A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862728581P 2018-09-07 2018-09-07
US62/728,581 2018-09-07
PCT/US2019/050114 WO2020051564A1 (en) 2018-09-07 2019-09-07 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides

Publications (1)

Publication Number Publication Date
CN113164775A true CN113164775A (zh) 2021-07-23

Family

ID=68051923

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980073600.1A Pending CN113164775A (zh) 2018-09-07 2019-09-07 用于迅速加速性纤维肉瘤多肽的靶向降解的多环化合物和方法

Country Status (9)

Country Link
EP (1) EP3846907A1 (ja)
JP (2) JP2022500368A (ja)
KR (2) KR102642203B1 (ja)
CN (1) CN113164775A (ja)
AU (2) AU2019335516B2 (ja)
CA (1) CA3109981A1 (ja)
IL (1) IL281188A (ja)
MX (1) MX2021002559A (ja)
WO (1) WO2020051564A1 (ja)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023025091A1 (en) * 2021-08-24 2023-03-02 Biofront Ltd (Cayman) Hpk1 degraders, compositions thereof, and methods of using the same
CN115806503A (zh) * 2022-12-02 2023-03-17 中国海洋大学 一种选择性组蛋白去乙酰化酶抑制剂及其制备方法和应用
CN115894450A (zh) * 2021-11-30 2023-04-04 知和(山东)大药厂有限公司 一种新型多环类化合物及其组合物和用途
WO2023066350A1 (zh) * 2021-10-22 2023-04-27 标新生物医药科技(上海)有限公司 Crbn e3连接酶配体化合物、基于该配体化合物开发的蛋白降解剂及它们的应用
WO2023098656A1 (en) * 2021-11-30 2023-06-08 Beigene, Ltd. Compounds for the degradation of egfr kinase

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3710002A4 (en) 2017-11-16 2021-07-07 C4 Therapeutics, Inc. DEGRADER AND DEGRONE FOR TARGETED PROTEIN DEGRADATION
CN111902141A (zh) 2018-03-26 2020-11-06 C4医药公司 用于ikaros降解的羟脑苷脂结合剂
EP3781156A4 (en) 2018-04-16 2022-05-18 C4 Therapeutics, Inc. SPIROCYCLIC COMPOUNDS
US20230099031A1 (en) * 2019-12-17 2023-03-30 Orionis Biosciences, Inc. Bifunctional agents for protein recruitment and/or degradation
WO2021201036A1 (ja) * 2020-03-31 2021-10-07 田辺三菱製薬株式会社 ヒドロキシピロリジン誘導体およびその医薬用途
CN115996719A (zh) 2020-06-19 2023-04-21 C4医药公司 Braf降解剂
WO2021255213A1 (en) * 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Heterobifunctional compounds as degraders of braf
JP2023539663A (ja) * 2020-08-28 2023-09-15 アルビナス・オペレーションズ・インコーポレイテッド 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法
EP4277901A1 (en) 2021-01-13 2023-11-22 Monte Rosa Therapeutics, Inc. Isoindolinone compounds
WO2022266206A1 (en) * 2021-06-16 2022-12-22 Erasca, Inc. Kras inhibitor conjugates
CA3223447A1 (en) 2021-06-25 2022-12-29 Korea Research Institute Of Chemical Technology Novel bifunctional heterocyclic compound having btk degradation function via ubiquitin proteasome pathway, and use thereof
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
WO2024089272A1 (en) * 2022-10-28 2024-05-02 Institut National De La Sante Et De La Recherche Medicale New inhibitors of phosphatidylinositol 3-kinase

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180179183A1 (en) * 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2005206929B2 (en) 2004-01-16 2008-01-24 The Regents Of The University Of Michigan Conformationally constrained Smac mimetics and the uses thereof
EP1740173A4 (en) 2004-03-23 2009-05-27 Genentech Inc AZABICYCLOOCTAN IAP INHIBITORS
DK2253614T3 (da) 2004-04-07 2013-01-07 Novartis Ag IAP-inhibitorer
RU2401840C2 (ru) 2004-07-02 2010-10-20 Дженентек, Инк. Ингибиторы iap
JP5007235B2 (ja) 2004-12-20 2012-08-22 ジェネンテック， インコーポレイテッド Ｉａｐのピロリジンインヒビター
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
WO2008014236A1 (en) 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
US8278293B2 (en) 2007-04-13 2012-10-02 The Regents Of The University Of Michigan Diazo bicyclic Smac mimetics and the uses thereof
CA2823837A1 (en) 2010-12-07 2012-06-14 Yale University Small-molecule hydrophobic tagging of fusion proteins and induced degradation of same
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
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
WO2014055461A1 (en) 2012-10-02 2014-04-10 Bristol-Myers Squibb Company Iap antagonists
US9637518B2 (en) 2013-07-12 2017-05-02 Bristol-Myers Squibb Company IAP antagonists
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
WO2015160845A2 (en) * 2014-04-14 2015-10-22 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
GB201504314D0 (en) * 2015-03-13 2015-04-29 Univ Dundee Small molecules
BR112017019751A2 (pt) * 2015-03-18 2018-05-29 Arvinas Inc composto bifuncional, composição farmacêutica, e, métodos para tratar ou prevenir uma doença ou um distúrbio, e para degradar uma proteína alvo em uma célula
AU2017363257B2 (en) * 2016-11-22 2021-08-19 Dana-Farber Cancer Institute, Inc. Degradation of protein kinases by conjugation of protein kinase inhibitors with E3 ligase ligand and methods of use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180179183A1 (en) * 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
WO2018119448A1 (en) * 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023025091A1 (en) * 2021-08-24 2023-03-02 Biofront Ltd (Cayman) Hpk1 degraders, compositions thereof, and methods of using the same
WO2023066350A1 (zh) * 2021-10-22 2023-04-27 标新生物医药科技(上海)有限公司 Crbn e3连接酶配体化合物、基于该配体化合物开发的蛋白降解剂及它们的应用
CN115894450A (zh) * 2021-11-30 2023-04-04 知和(山东)大药厂有限公司 一种新型多环类化合物及其组合物和用途
WO2023098656A1 (en) * 2021-11-30 2023-06-08 Beigene, Ltd. Compounds for the degradation of egfr kinase
CN115894450B (zh) * 2021-11-30 2023-09-12 山东如至生物医药科技有限公司 一种新型多环类化合物及其组合物和用途
CN115806503A (zh) * 2022-12-02 2023-03-17 中国海洋大学 一种选择性组蛋白去乙酰化酶抑制剂及其制备方法和应用

Also Published As

Publication number Publication date
CA3109981A1 (en) 2020-03-12
IL281188A (en) 2021-04-29
JP2023159166A (ja) 2023-10-31
AU2019335516A1 (en) 2021-03-11
JP2022500368A (ja) 2022-01-04
WO2020051564A1 (en) 2020-03-12
EP3846907A1 (en) 2021-07-14
KR102642203B1 (ko) 2024-03-04
AU2019335516B2 (en) 2022-06-16
KR20210073519A (ko) 2021-06-18
KR20240028539A (ko) 2024-03-05
AU2022228150A1 (en) 2022-09-29
MX2021002559A (es) 2021-07-21

Similar Documents

Publication Publication Date Title
CN113164775A (zh) 用于迅速加速性纤维肉瘤多肽的靶向降解的多环化合物和方法
AU2019249231B2 (en) Modulators of proteolysis and associated methods of use
AU2021200099B2 (en) Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
US11384063B2 (en) Modulators of estrogen receptor proteolysis 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
JP2020505327A (ja) 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
CN115397821A (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
US11986531B2 (en) Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
JP2020504089A (ja) エストロゲン受容体分解物質としてのテトラヒドロナフタレン誘導体およびテトラヒドロイソキノリン誘導体
JP2020504741A5 (ja)
AU2016294450A1 (en) Alanine-based modulators of proteolysis and associated methods of use
RU2782458C2 (ru) Соединения и способы нацеленного расщепления полипептидов быстропрогрессирующей фибросаркомы

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination