CN112888460A - Lrkk2的野生型及突变型的降解剂 - Google Patents

Lrkk2的野生型及突变型的降解剂 Download PDF

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Publication number
CN112888460A
CN112888460A CN201980068658.7A CN201980068658A CN112888460A CN 112888460 A CN112888460 A CN 112888460A CN 201980068658 A CN201980068658 A CN 201980068658A CN 112888460 A CN112888460 A CN 112888460A
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Prior art keywords
compound
bifunctional compound
formula
lrrk2
structure represented
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Pending
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CN201980068658.7A
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English (en)
Chinese (zh)
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N·S·格雷
J·哈彻
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Dana Farber Cancer Institute Inc
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Dana Farber Cancer Institute Inc
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Publication of CN112888460A publication Critical patent/CN112888460A/zh
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    • 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
    • A61K47/545—Heterocyclic compounds
    • 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
    • A61K47/555—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 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
CN201980068658.7A 2018-10-16 2019-10-16 Lrkk2的野生型及突变型的降解剂 Pending CN112888460A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862746283P 2018-10-16 2018-10-16
US62/746,283 2018-10-16
US201962884410P 2019-08-08 2019-08-08
US62/884,410 2019-08-08
PCT/US2019/056537 WO2020081682A1 (en) 2018-10-16 2019-10-16 Degraders of wild-type and mutant forms of lrrk2

Publications (1)

Publication Number Publication Date
CN112888460A true CN112888460A (zh) 2021-06-01

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Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980068658.7A Pending CN112888460A (zh) 2018-10-16 2019-10-16 Lrkk2的野生型及突变型的降解剂

Country Status (7)

Country Link
US (1) US20210361774A1 (https=)
EP (1) EP3866801A4 (https=)
JP (2) JP7640454B2 (https=)
CN (1) CN112888460A (https=)
AU (1) AU2019361964C1 (https=)
CA (1) CA3115818A1 (https=)
WO (1) WO2020081682A1 (https=)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115697990A (zh) * 2020-03-21 2023-02-03 阿维纳斯企业公司 基于吲唑的化合物和相关使用方法
US12559506B2 (en) 2021-03-19 2026-02-24 Arvinas Operations, Inc. Indazole based compounds and associated methods of use
US12589156B2 (en) 2023-09-28 2026-03-31 Arvinas Operations, Inc. Benzimidazole and benzimidazolone based protac compounds for the targeted degradation of leucine rich repeat kinase 2 (LRRK2)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021194878A1 (en) * 2020-03-21 2021-09-30 Arvinas Operations, Inc. Selective modulators of mutant lrrk2 proteolysis and associated methods of use
CN117321046A (zh) * 2021-03-19 2023-12-29 阿维纳斯企业公司 基于吲唑的化合物和相关使用方法
US20240308982A1 (en) * 2021-07-08 2024-09-19 Dana-Farber Cancer Institute, Inc. Degraders of wild-type and mutant forms of lrrk2 and uses thereof
KR20240171138A (ko) * 2022-04-04 2024-12-06 브레닉 테라퓨틱스 인코포레이티드 Lrrk2 저해제
EP4276097A1 (en) 2022-05-10 2023-11-15 University Of Dundee Aminopyrimidinyl derivatives for the treament of parkinson's disease
KR20250054737A (ko) * 2023-10-16 2025-04-23 주식회사 아스트로젠 신규한 분자 접착제의 용도

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103987698A (zh) * 2011-11-29 2014-08-13 霍夫曼-拉罗奇有限公司 作为激酶lrrk2调节剂用于治疗帕金森病的2-苯基氨基嘧啶衍生物
WO2014134774A1 (en) * 2013-03-04 2014-09-12 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
US20150141439A1 (en) * 2012-07-11 2015-05-21 Korea Research Institute Of Chemical Technology Pharmaceutical composition for the prevention or treatment of brain tumor or temodal resistant glioblastoma multiform comprising azathioprine as an active ingredient
CN107257800A (zh) * 2014-12-23 2017-10-17 达纳-法伯癌症研究所股份有限公司 通过双功能分子诱导靶蛋白降解的方法
CN108366992A (zh) * 2015-11-02 2018-08-03 耶鲁大学 蛋白水解靶向嵌合体化合物及其制备和应用方法

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE20110220A1 (es) 2006-08-02 2011-04-11 Novartis Ag DERIVADOS DE 2-OXO-ETIL-AMINO-PROPIONAMIDA-PIRROLIDIN-2-IL-SUSTITUIDOS COMO INHIBIDORES DEL ENLACE DE LA PROTEINA Smac AL INHIBIDOR DE LA PROTEINA DE APOPTOSIS
WO2008128171A2 (en) 2007-04-13 2008-10-23 The Regents Of The University Of Michigan Diazo bicyclic smac mimetics and the uses thereof
US8461147B2 (en) * 2007-12-03 2013-06-11 Boehringer Ingelheim International Gmbh Diaminopyridines for the treatment of diseases which are characterised by excessive or anomal cell proliferation
ES2577829T3 (es) * 2010-06-04 2016-07-19 F. Hoffmann-La Roche Ag Derivados de aminopirimidina como moduladores de la LRRK2
FR2983607B1 (fr) 2011-12-02 2014-01-17 Morpho Procede et dispositif de suivi d'un objet dans une sequence d'au moins deux images
GB201218864D0 (en) 2012-10-19 2012-12-05 Astex Therapeutics Ltd Bicyclic heterocycle compounds and their uses in therapy
GB201218862D0 (en) 2012-10-19 2012-12-05 Astex Therapeutics Ltd Bicyclic heterocycle compounds and their uses in therapy
BR122022015241B1 (pt) 2013-12-20 2023-09-26 Astex Therapeutics Limited Compostos heterocíclicos bicíclicos intermediários para a preparação de um composto de fórmula (i)
IL286427B2 (en) 2014-01-28 2024-08-01 Mayo Found Medical Education & Res Inhibitors bcl-2 anti-apoptotic protein family members for treatment of non cancer pulmonary disease or an opthalmic disease
US9694084B2 (en) * 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
EP3270917A4 (en) * 2015-03-18 2018-08-08 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
GB201519196D0 (en) 2015-10-30 2015-12-16 Heptares Therapeutics Ltd CGRP Receptor Antagonists
ES2990061T3 (es) 2016-05-10 2024-11-28 C4 Therapeutics Inc Degronímeros espirocíclicos para la degradación de proteínas diana
CN109790143A (zh) * 2016-05-10 2019-05-21 C4医药公司 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体
EP3454856B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
CN109641874A (zh) 2016-05-10 2019-04-16 C4医药公司 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体
GB201610147D0 (en) * 2016-06-10 2016-07-27 Glaxosmithkline Ip Dev Ltd Novel compounds
WO2018064589A1 (en) * 2016-09-29 2018-04-05 Dana-Farber Cancer Institute, Inc. Targeted protein degradation using a mutant e3 ubiquitin ligase
AU2018219292B2 (en) * 2017-02-08 2024-09-26 Dana-Farber Cancer Institute, Inc. Tunable endogenous protein degradation with heterobifunctional compounds
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
KR101923852B1 (ko) * 2017-02-24 2018-11-29 재단법인 대구경북첨단의료산업진흥재단 혈액 뇌관문을 통과할 수 있는 화합물을 유효성분으로 함유하는 뇌암의 예방 또는 치료용 약학적 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103987698A (zh) * 2011-11-29 2014-08-13 霍夫曼-拉罗奇有限公司 作为激酶lrrk2调节剂用于治疗帕金森病的2-苯基氨基嘧啶衍生物
US20150141439A1 (en) * 2012-07-11 2015-05-21 Korea Research Institute Of Chemical Technology Pharmaceutical composition for the prevention or treatment of brain tumor or temodal resistant glioblastoma multiform comprising azathioprine as an active ingredient
WO2014134774A1 (en) * 2013-03-04 2014-09-12 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
CN107257800A (zh) * 2014-12-23 2017-10-17 达纳-法伯癌症研究所股份有限公司 通过双功能分子诱导靶蛋白降解的方法
CN108366992A (zh) * 2015-11-02 2018-08-03 耶鲁大学 蛋白水解靶向嵌合体化合物及其制备和应用方法

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115697990A (zh) * 2020-03-21 2023-02-03 阿维纳斯企业公司 基于吲唑的化合物和相关使用方法
US12053469B2 (en) 2020-03-21 2024-08-06 Arvinas Operations, Inc. Indazole based compounds and associated methods of use
CN115697990B (zh) * 2020-03-21 2025-06-13 阿维纳斯企业公司 基于吲唑的化合物和相关使用方法
US12559506B2 (en) 2021-03-19 2026-02-24 Arvinas Operations, Inc. Indazole based compounds and associated methods of use
US12589156B2 (en) 2023-09-28 2026-03-31 Arvinas Operations, Inc. Benzimidazole and benzimidazolone based protac compounds for the targeted degradation of leucine rich repeat kinase 2 (LRRK2)

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JP2024156881A (ja) 2024-11-06
US20210361774A1 (en) 2021-11-25
WO2020081682A1 (en) 2020-04-23
JP2022504762A (ja) 2022-01-13
JP7640454B2 (ja) 2025-03-05
AU2019361964B2 (en) 2025-01-23
EP3866801A1 (en) 2021-08-25
AU2019361964A1 (en) 2021-03-18
AU2019361964C1 (en) 2025-06-26
CA3115818A1 (en) 2020-04-23
EP3866801A4 (en) 2022-11-09

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