CN110291087B - 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物 - Google Patents

作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物 Download PDF

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CN110291087B
CN110291087B CN201780085150.9A CN201780085150A CN110291087B CN 110291087 B CN110291087 B CN 110291087B CN 201780085150 A CN201780085150 A CN 201780085150A CN 110291087 B CN110291087 B CN 110291087B
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CN110291087A (zh
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安德鲁·P·克鲁
Y·钱
H·董
J·王
基思·R·霍恩伯格
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Arvinas Inc
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Priority to CN202410799699.6A priority patent/CN118834201A/zh
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CN201780085150.9A 2016-12-01 2017-12-01 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物 Active CN110291087B (zh)

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Application Number Priority Date Filing Date Title
CN202210386845.3A CN114656452B (zh) 2016-12-01 2017-12-01 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物
CN202010214256.8A CN111454248A (zh) 2016-12-01 2017-12-01 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物
CN202410799699.6A CN118834201A (zh) 2016-12-01 2017-12-01 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物

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Families Citing this family (155)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
JP6817962B2 (ja) 2015-01-20 2021-01-20 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． ターゲティングされたアンドロゲン受容体分解のための化合物および方法
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
WO2016197114A1 (en) 2015-06-05 2016-12-08 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
EP3319944A4 (en) 2015-07-10 2019-04-24 Arvinas, Inc. MDM2-BASED MODULATORS OF PROTEOLYSIS AND RELATED USE METHODS
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US20170281784A1 (en) 2016-04-05 2017-10-05 Arvinas, Inc. Protein-protein interaction inducing technology
EP3454856B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
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
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
US20180072711A1 (en) 2016-09-15 2018-03-15 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
US10683387B2 (en) 2016-10-04 2020-06-16 Massachusetts Institute Of Technology Bottlebrush copolymers and uses thereof
MX2019005007A (es) 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
BR112019011200B1 (pt) * 2016-12-01 2021-12-28 Arvinas Operations, Inc Derivados de tetrahidronaftaleno e tetrahidroisoquinolina como degradadores do receptor de estrogênio
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
KR20250117470A (ko) 2016-12-23 2025-08-04 아비나스 오퍼레이션스, 인코포레이티드 급속 진행성 섬유육종 폴리펩티드의 표적화 분해를 위한 화합물 및 방법
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, 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
BR112019015312A2 (pt) 2017-01-26 2020-03-10 Arvinas Operations, Inc. Moduladores da proteólise pelo receptor de estrogênio e métodos de uso associados
IL312367A (en) 2017-01-31 2024-06-01 Arvinas Operations Inc Cereblon ligands and bifunctional compounds comprising the same
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
CN118108706A (zh) 2017-09-04 2024-05-31 C4医药公司 戊二酰亚胺
WO2019043208A1 (en) 2017-09-04 2019-03-07 F. Hoffmann-La Roche Ag DIHYDROQUINOLINONES
WO2019043217A1 (en) 2017-09-04 2019-03-07 F. Hoffmann-La Roche Ag DIHYDROBENZIMIDAZOLONES
CN111372585A (zh) 2017-11-16 2020-07-03 C4医药公司 用于靶蛋白降解的降解剂和降解决定子
EP3710443A1 (en) 2017-11-17 2020-09-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides
WO2019148055A1 (en) 2018-01-26 2019-08-01 Yale University Imide-based modulators of proteolysis and methods of use
EP3773576A4 (en) 2018-03-26 2021-12-29 C4 Therapeutics, Inc. Cereblon binders for the degradation of ikaros
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
WO2019195609A2 (en) 2018-04-04 2019-10-10 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
WO2019196812A1 (zh) * 2018-04-09 2019-10-17 上海科技大学 蛋白降解靶向化合物、其抗肿瘤应用、其中间体及中间体应用
IL302595A (en) * 2018-04-13 2023-07-01 Arvinas Operations Inc Servalon ligands and bifunctional compounds containing them
EP3781156A4 (en) 2018-04-16 2022-05-18 C4 Therapeutics, Inc. SPIROCYCLIC COMPOUNDS
FI3784663T3 (fi) 2018-04-23 2023-10-06 Celgene Corp Substituoituja 4-aminoisoindoliini-1,3-dioniyhdisteitä ja niiden käyttö lymfooman hoitamiseksi
EP3578561A1 (en) 2018-06-04 2019-12-11 F. Hoffmann-La Roche AG Spiro compounds
BR122022012697B1 (pt) * 2018-07-10 2023-04-04 Novartis Ag Usos de derivados de 3-(5-hidróxi-1-oxoisoindolin-2-il)piperidina-2,6- diona, e kit
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
WO2020027225A1 (ja) 2018-07-31 2020-02-06 ファイメクス株式会社 複素環化合物
JP7297053B2 (ja) 2018-08-20 2023-06-23 アルビナス・オペレーションズ・インコーポレイテッド 神経変性疾患を治療するためのｅ３ユビキチンリガーゼ結合活性を有するキメラ（ｐｒｏｔａｃ）化合物を標的とし、アルファ－シヌクレインタンパク質を標的とするタンパク質分解
WO2020051235A1 (en) 2018-09-04 2020-03-12 C4 Therapeutics, Inc. Compounds for the degradation of brd9 or mth1
SG11202105256QA (en) 2018-11-21 2021-06-29 Accutar Biotechnology Inc Novel compounds having estrogen receptor alpha degradation activity and uses thereof
CN120698983A (zh) 2018-12-20 2025-09-26 C4医药公司 靶向蛋白降解
KR20210106437A (ko) * 2018-12-20 2021-08-30 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물
CN113614076A (zh) * 2019-01-03 2021-11-05 密执安大学评议会 雌激素受体蛋白降解剂
CN113874016A (zh) 2019-01-29 2021-12-31 福宏治疗公司 化合物及其用途
EP3922632A4 (en) * 2019-02-07 2023-02-15 Korea Research Institute of Chemical Technology DEGRADATION AGENT THAT INDUCES DEGRADATION OF A TARGET EED PROTEIN, METHOD FOR ITS MANUFACTURE AND PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF DISEASES ASSOCIATED WITH EED, EZH2 OR PRC2 USING SUCH AGENT AS THE ACTIVE SUBSTANCE
CN113490528B (zh) * 2019-02-15 2024-12-03 诺华股份有限公司 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途
CA3123519A1 (en) * 2019-02-15 2020-08-20 Novartis Ag Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
CN111606883B (zh) 2019-02-25 2023-05-09 上海科技大学 基于戊二酰亚胺骨架的含硫化合物及其应用
ES2995214T3 (en) 2019-03-06 2025-02-07 C4 Therapeutics Inc Heterocyclic compounds for medical treatment
US20240108747A1 (en) 2019-03-21 2024-04-04 Lonza Sales Ag Extracellular vesicle conjugates and uses thereof
EP3941607A1 (en) 2019-03-21 2022-01-26 Codiak BioSciences, Inc. Process for preparing extracellular vesicles
TW202102497A (zh) 2019-03-29 2021-01-16 瑞典商阿斯特捷利康公司 化合物及它們在治療癌症中之用途
WO2020214555A1 (en) 2019-04-16 2020-10-22 Northwestern University Bifunctional compounds comprising apcin-a and their use in the treatment of cancer
US12331061B2 (en) 2019-04-18 2025-06-17 Accutar Biotechnology Inc. Compounds having BET, estrogen receptor, and androgen receptor degradation activity and uses thereof
EP3971176A4 (en) * 2019-05-17 2023-01-25 Hinova Pharmaceuticals Inc. AR AND BET AROMATIC AMINE TARGETING PROTEIN DEGRADATION CHIMERIC COMPOUND AND USE THEREOF
WO2021011868A1 (en) 2019-07-17 2021-01-21 Kymera Therapeutics, Inc. Irak degraders and uses thereof
EP3999182A1 (en) 2019-07-17 2022-05-25 Arvinas Operations, Inc. Tau-protein targeting compounds and associated methods of use
WO2021018118A1 (en) * 2019-07-29 2021-02-04 Janssen Pharmaceutica Nv Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 1 proteins
WO2021022163A2 (en) 2019-07-31 2021-02-04 Foghorn Therapeutics Inc. Compounds and uses thereof
WO2021023233A1 (zh) 2019-08-05 2021-02-11 上海科技大学 Egfr蛋白降解剂及其抗肿瘤应用
KR20220054347A (ko) 2019-08-26 2022-05-02 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 유도체로 유방암을 치료하는 방법
JP7307796B2 (ja) * 2019-09-23 2023-07-12 アキュター バイオテクノロジー インコーポレイテッド アンドロゲン受容体分解活性を有する新規の置換キノリン－８－カルボニトリル誘導体およびその使用
CN118930604A (zh) * 2019-09-29 2024-11-12 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包含其的药物组合物和应用
CA3154386A1 (en) 2019-10-17 2021-04-22 Michael Berlin Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
JP7629459B2 (ja) 2019-11-19 2025-02-13 ブリストル－マイヤーズ スクイブ カンパニー Ｈｅｌｉｏｓタンパク質の阻害剤として有用な化合物
MX2022006133A (es) 2019-12-06 2022-06-17 Celgene Corp Procesos para preparar 2-(4-clorofenil)-n-((2-(2,6-dioxopiperidin- 3-il)-1-oxoisoindolin-5-il)metil)-2,2-difluoroacetamida.
EP3835298B1 (en) * 2019-12-12 2024-06-26 Accutar Biotechnology Inc. Novel chroman derivatives having estrogen receptor degradation activity and uses thereof
US20230099031A1 (en) * 2019-12-17 2023-03-30 Orionis Biosciences, Inc. Bifunctional agents for protein recruitment and/or degradation
WO2021126973A1 (en) * 2019-12-17 2021-06-24 Orionis Biosciences, Inc. Compounds modulating protein recruitment and/or degradation
PH12022551482A1 (en) 2019-12-18 2023-11-29 Novartis Ag 3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
AU2020405129A1 (en) 2019-12-19 2022-06-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
JP2023508357A (ja) * 2019-12-23 2023-03-02 アキュター バイオテクノロジー インコーポレイテッド エストロゲン受容体分解剤とサイクリン依存性キナーゼ阻害剤との癌治療用組み合わせ
WO2021141662A1 (en) * 2020-01-10 2021-07-15 Massachusetts Institute Of Technology Proteolysis targeting chimeric molecules (protacs) with functional handles and uses thereof
US12528825B2 (en) 2020-01-29 2026-01-20 Foghorn Therapeutics Inc. Compounds and uses thereof
EP4096651A4 (en) * 2020-01-29 2024-01-24 Foghorn Therapeutics Inc. COMPOUNDS AND THEIR USES
AU2021226514B2 (en) * 2020-02-25 2023-10-19 Shanghaitech University Glutarimide skeleton-based compounds and application thereof
TW202146412A (zh) 2020-03-05 2021-12-16 美商Ｃ４醫藥公司 用於標靶降解brd9之化合物
TW202140441A (zh) * 2020-03-23 2021-11-01 美商必治妥美雅史谷比公司 經取代之側氧基異吲哚啉化合物
CN111393409A (zh) * 2020-03-27 2020-07-10 苏州昊帆生物股份有限公司 蛋白降解靶向嵌合体化合物、应用及其制备方法
CN115803030A (zh) * 2020-04-06 2023-03-14 阿维纳斯企业公司 用于kras靶向降解的化合物和方法
WO2021237100A1 (en) 2020-05-21 2021-11-25 Codiak Biosciences, Inc. Methods of targeting extracellular vesicles to lung
JP2023530030A (ja) 2020-06-19 2023-07-12 シーフォー セラピューティクス， インコーポレイテッド Ｂｒａｆ分解剤
CN115916769B (zh) * 2020-06-28 2024-09-10 深圳扬厉医药技术有限公司 并环吲唑类化合物
IL300397A (en) 2020-08-05 2023-04-01 C4 Therapeutics Inc Compounds for targeted knockdown of RET
WO2022047145A1 (en) 2020-08-28 2022-03-03 Arvinas Operations, Inc. Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use
WO2022056368A1 (en) * 2020-09-14 2022-03-17 Arvinas Operations, Inc. Crystalline forms of a compound for the targeted degradation of estrogen receptor
CN112094275A (zh) * 2020-09-16 2020-12-18 迪嘉药业集团有限公司 一种（右）佐匹克隆光降解杂质的制备方法
WO2022066928A2 (en) 2020-09-23 2022-03-31 Codiak Biosciences, Inc. Process for preparing extracellular vesicles
WO2022099117A1 (en) 2020-11-06 2022-05-12 Prelude Therapeutics Incorporated Brm targeting compounds and associated methods of use
US20240058318A1 (en) * 2020-12-10 2024-02-22 Mayo Foundation For Medical Education And Research Degrading pkcb1 to treat cancer
AU2021401580A1 (en) 2020-12-14 2023-06-22 Arvinas Operations, Inc. Methods of treating breast cancer with tetrahydronaphthalene derivatives as estrogen receptor degraders
AU2022207648A1 (en) 2021-01-13 2023-07-27 Monte Rosa Therapeutics Ag Isoindolinone compounds
CN116438177B (zh) * 2021-01-28 2025-09-16 江苏亚虹医药科技股份有限公司 靶向嵌合化合物、含其的药物组合物及其制备方法和用途
WO2022166879A1 (zh) * 2021-02-04 2022-08-11 正大天晴药业集团股份有限公司 苯并七元环类双功能化合物及其应用
CN116867494A (zh) 2021-02-15 2023-10-10 凯麦拉医疗公司 Irak4降解剂和其用途
CA3211378A1 (en) 2021-03-29 2022-10-06 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Tetrahydronaphthalene compound, and preparation method therefor and use thereof in medicine
AU2022253450A1 (en) 2021-04-05 2023-11-16 Bristol-Myers Squibb Company Pyridinyl substituted oxoisoindoline compounds for the treatment of cancer
EP4320112B1 (en) 2021-04-06 2025-05-14 Bristol-Myers Squibb Company Pyridinyl substituted oxoisoindoline compounds
KR20230171979A (ko) 2021-04-16 2023-12-21 아비나스 오퍼레이션스, 인코포레이티드 Bcl6 단백질 분해의 조절제 및 관련 사용 방법
AU2022270089A1 (en) * 2021-05-03 2023-11-16 Nurix Therapeutics, Inc. Compounds for inhibiting or degrading target proteins, compositions, comprising the same, methods of their making, and methods of their use
TW202309039A (zh) 2021-05-05 2023-03-01 美商百健Ｍａ公司 用於靶向布魯頓氏酪胺酸激酶降解之化合物
WO2022254362A1 (en) 2021-06-03 2022-12-08 Novartis Ag 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and medical uses thereof
EP4367113A1 (en) 2021-07-07 2024-05-15 Biogen MA Inc. Compounds for targeting degradation of irak4 proteins
US20250018046A1 (en) 2021-07-07 2025-01-16 Biogen Ma Inc Compounds for targeting degradation of irak4 proteins
CA3227425A1 (en) 2021-07-26 2023-02-02 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound
CA3235512A1 (en) * 2021-10-22 2023-04-27 Xiaobao Yang Crbn e3 ligase ligand compound, protein degrader developed based thereon and their applications
EP4431511A4 (en) 2021-11-09 2025-10-15 Hangzhou Glubio Pharmaceutical Co Ltd WEE1 PROTEIN KINASE DEGRADING AGENT AND ITS USE
US12122764B2 (en) 2021-12-22 2024-10-22 Gilead Sciences, Inc. IKAROS zinc finger family degraders and uses thereof
WO2023116835A1 (zh) * 2021-12-24 2023-06-29 苏州开拓药业股份有限公司 一种具有酰亚胺骨架的多蛋白降解剂
KR20240128831A (ko) 2021-12-30 2024-08-27 베이진 스위찰랜드 게엠베하 브루톤 티로신 키나아제(btk) 억제제와 e3 리가아제 리간드의 접합에 의한 btk의 분해 및 사용 방법
CN114085213B (zh) * 2022-01-20 2022-03-25 苏州国匡医药科技有限公司 一种arv-471的制备方法
WO2023178181A1 (en) 2022-03-17 2023-09-21 Gilead Sciences, Inc. Ikaros zinc finger family degraders and uses thereof
AU2023239642A1 (en) 2022-03-25 2024-11-07 Shenzhen Pharmacin Co., Ltd. Pharmaceutical compositions of protac compounds and uses thereof
TW202404643A (zh) 2022-04-20 2024-02-01 大陸商同宜醫藥（蘇州）有限公司 化合物及用途
CA3249074A1 (en) 2022-06-06 2023-12-14 C4 Therapeutics, Inc. BICYCLIC SUBSTITUTION GLUTARIMIDE CEREBLON BINDERS
CN117229286A (zh) * 2022-06-14 2023-12-15 海创药业股份有限公司 一种芳香类化合物及其制备方法及在制备雌激素受体降解剂中的用途
WO2023242598A1 (en) * 2022-06-16 2023-12-21 Amphista Therapeutics Limited Bifunctional molecules for targeted protein degradation
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
WO2024006776A1 (en) * 2022-06-27 2024-01-04 Relay Therapeutics, Inc. Estrogen receptor alpha degraders and medical use thereof
IL317333A (en) * 2022-06-30 2025-01-01 Bristol Myers Squibb Co WEE1 reducing agents and their uses
US20260028354A1 (en) * 2022-07-12 2026-01-29 Regent Of The University Of Michigan Tetrahydronaphthalene derivatives as estrogen receptor degraders
CN120112291A (zh) 2022-08-31 2025-06-06 阿尔维纳斯运营股份有限公司 雌激素受体降解剂的给药方案
TW202416992A (zh) 2022-08-31 2024-05-01 美商亞文納營運公司 雌激素受體降解劑之給藥方案
WO2024054591A1 (en) 2022-09-07 2024-03-14 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use
EP4584259A1 (en) * 2022-09-09 2025-07-16 Innovo Therapeutics, Inc. Ck1alpha and dual ck1alpha / gspt1 degrading compounds
WO2024073507A1 (en) 2022-09-28 2024-04-04 Theseus Pharmaceuticals, Inc. Macrocyclic compounds and uses thereof
JP2025533592A (ja) * 2022-09-29 2025-10-07 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司 テトラリン系誘導体の薬学的に許容される塩、結晶型及び調製方法
IL320302A (en) 2022-10-17 2025-06-01 Astrazeneca Ab SERD combinations for cancer treatment
US20240180893A1 (en) 2022-11-17 2024-06-06 Astrazeneca Ab Methods of treatment of breast cancer
KR102794861B1 (ko) * 2022-11-25 2025-04-11 재단법인 대구경북첨단의료산업진흥재단 선택적 에스트로겐 수용체 조절제로서의 신규 화합물
WO2024119081A1 (en) 2022-12-02 2024-06-06 Arvinas Operations, Inc. Method of treating breast cancer
CN116751186B (zh) * 2022-12-23 2024-10-18 南京知和医药科技有限公司 一种雌激素受体调节剂的制备及其用途
WO2024140638A1 (zh) * 2022-12-27 2024-07-04 标新生物医药科技(上海)有限公司 基于硫/氧取代戊二酰亚胺基异吲哚啉酮骨架的化合物及其应用
CN118271284A (zh) * 2022-12-30 2024-07-02 江苏威凯尔医药科技有限公司 雌激素受体调节剂及其用途
US12448399B2 (en) 2023-01-26 2025-10-21 Arvinas Operations, Inc. Cereblon-based KRAS degrading PROTACs and uses related thereto
WO2024167904A1 (en) 2023-02-07 2024-08-15 Arvinas Operations, Inc. Dosage regimens of estrogen receptor degraders in combination with an mtor inhibitor
TW202440096A (zh) 2023-03-24 2024-10-16 美商亞文納營運公司 雌激素受體降解劑之給藥方案
TW202508573A (zh) 2023-05-11 2025-03-01 瑞典商阿斯特捷利康公司 用於治療癌症之組合療法
CN121368483A (zh) 2023-06-02 2026-01-20 辉瑞公司 雌激素受体降解剂与cdk4抑制剂的组合
EP4719399A1 (en) 2023-06-02 2026-04-08 Arvinas Operations, Inc. Combinations of estrogen receptor degraders and akt inhibitors
IL325099A (en) 2023-06-12 2026-02-01 Arvinas Operations Inc Oral solid estrogen receptor antagonist dosage forms
TW202500147A (zh) 2023-06-27 2025-01-01 美商亞文納營運公司 雌激素受體降解劑與ｃｄｋ７抑制劑之組合
WO2025038481A1 (en) 2023-08-11 2025-02-20 Arvinas Operations, Inc. Vepdegestrant dosage regimen in cyp3a-inducer treatment in cancer
WO2025090847A1 (en) * 2023-10-25 2025-05-01 Bpgbio, Inc. Estrogen receptor degraders and their use in the treatment of cancer
WO2025114875A1 (en) 2023-12-01 2025-06-05 Astrazeneca Ab Er degraders and uses thereof
WO2025119380A1 (zh) * 2023-12-08 2025-06-12 江苏威凯尔医药科技股份有限公司 雌激素受体调节剂及其用途
US20250276074A1 (en) 2024-03-01 2025-09-04 Prelude Therapeutics Incorporated Brm and brg1 targeting antibody-drug conjugates and methods of use thereof
TW202543650A (zh) 2024-03-08 2025-11-16 美商海爾達醫療運營公司 異雙官能化合物及其在治療疾病中之用途
WO2025245032A1 (en) 2024-05-20 2025-11-27 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound
WO2026017799A1 (en) 2024-07-18 2026-01-22 Centre Hospitalier Universitaire Vaudois Substituted 3-cyanoquinolines for the prevention and treatment of sexually transmitted diseases
WO2026018182A1 (en) 2024-07-19 2026-01-22 Pfizer Inc. Process for preparing a cis-1,2-diaryltetralin derivative
WO2026044127A1 (en) 2024-08-22 2026-02-26 Arvinas Operations, Inc. Administration of cyp3a inhibitors in the treatment of cancer

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016097071A1 (en) * 2014-12-18 2016-06-23 F. Hoffmann-La Roche Ag Estrogen receptor modulators and uses thereof

Family Cites Families (151)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US5681835A (en) 1994-04-25 1997-10-28 Glaxo Wellcome Inc. Non-steroidal ligands for the estrogen receptor
US5510357A (en) 1995-02-28 1996-04-23 Eli Lilly And Company Benzothiophene compounds as anti-estrogenic agents
DE122007000079I2 (de) 1996-07-24 2010-08-12 Celgene Corp Substituierte 2-(2,6-dioxopiperidin-3-yl)-phthalimide und -1-oxoisoindoline und verfahren zur reduzierung des tnf-alpha-spiegels
US5916916A (en) * 1996-10-10 1999-06-29 Eli Lilly And Company 1-aryloxy-2-arylnaphthyl compounds, intermediates, compositions, and methods
ZA982877B (en) 1997-04-09 1999-10-04 Lilly Co Eli Treatment of central nervous system disorders with selective estrogen receptor modulators.
CA2287387C (en) 1997-05-14 2010-02-16 Sloan-Kettering Institute For Cancer Research Methods and compositions for destruction of selected proteins
WO1999015521A1 (en) 1997-09-23 1999-04-01 Eli Lilly And Company Benzothiophenes
PT966968E (pt) * 1998-06-16 2004-08-31 Pfizer Prod Inc Combinacoes terapeuticas compreendendo um modulador de receptor de estrogenio selectivo e prostaglandina e2
US6306663B1 (en) 1999-02-12 2001-10-23 Proteinex, Inc. Controlling protein levels in eucaryotic organisms
EP1176959B1 (en) 1999-05-05 2006-03-08 Merck & Co., Inc. Novel prolines as antimicrobial agents
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
US7091353B2 (en) 2000-12-27 2006-08-15 Celgene Corporation Isoindole-imide compounds, compositions, and uses thereof
US20030045552A1 (en) 2000-12-27 2003-03-06 Robarge Michael J. Isoindole-imide compounds, compositions, and uses thereof
JP2005507363A (ja) 2001-02-16 2005-03-17 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー 血管新生阻害トリペプチド、組成物およびそれらの使用方法
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
US7030141B2 (en) 2001-11-29 2006-04-18 Christopher Franklin Bigge Inhibitors of factor Xa and other serine proteases involved in the coagulation cascade
WO2004005248A1 (en) 2002-07-02 2004-01-15 Novartis Ag Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap)
EP1651595A2 (en) 2003-05-30 2006-05-03 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
BRPI0506883A (pt) 2004-01-16 2007-05-29 Univ Michigan miméticos de smac conformacionalmente comprimidos e seus usos
AU2005228950B2 (en) 2004-03-23 2012-02-02 Genentech, Inc. Azabicyclo-octane inhibitors of IAP
DK2253614T3 (da) 2004-04-07 2013-01-07 Novartis Ag IAP-inhibitorer
KR100984459B1 (ko) 2004-07-02 2010-09-29 제넨테크, 인크. Ｉａｐ의 억제제
DK1836201T4 (da) 2004-12-20 2013-11-11 Genentech Inc Pyrrolidininhibitorer af IAP.
TW200639163A (en) 2005-02-04 2006-11-16 Genentech Inc RAF inhibitor compounds and methods
MX2007010371A (es) 2005-02-25 2008-01-11 Tetralogic Pharmaceuticals Inhibidores dimericos 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
UA91560C2 (ru) 2005-08-31 2010-08-10 Селджин Корпорэйшн Соединения ряда изоиндолимидов, их композиция и применение
AU2007226715A1 (en) 2006-03-03 2007-09-20 Novartis Ag N-formyl hydroxylamine compounds
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
CA2645566A1 (en) 2006-03-20 2007-09-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions
NZ572531A (en) 2006-05-05 2011-09-30 Univ Michigan Bivalent smac mimetics and the uses thereof
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
CL2007002513A1 (es) 2006-08-30 2008-04-04 Celgene Corp Soc Organizada Ba Compuestos derivados de isoindolina sustituidos, compuestos intermediarios; composicion farmaceutica; y uso en el tratamiento y prevencion de enfermedades tales como cancer, dolor, degeneracion macular, entre otras.
US8877780B2 (en) 2006-08-30 2014-11-04 Celgene Corporation 5-substituted isoindoline compounds
RU2448101C2 (ru) 2006-08-30 2012-04-20 Селджин Корпорейшн 5-замещенные изоиндолиновые соединения
CA2668286C (en) 2006-11-03 2014-09-16 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
JP5454943B2 (ja) 2007-04-12 2014-03-26 ジョイアント ファーマスーティカルズ、インク． 抗癌剤として有用なｓｍａｃ模倣二量体及び三量体
WO2008128171A2 (en) 2007-04-13 2008-10-23 The Regents Of The University Of Michigan Diazo bicyclic smac mimetics and the uses thereof
WO2008134679A1 (en) 2007-04-30 2008-11-06 Genentech, Inc. Inhibitors of iap
US20100203012A1 (en) 2007-05-30 2010-08-12 Aegera Therapeutics, Inc. Iap bir domain binding compounds
MX2009013213A (es) * 2007-06-08 2010-03-30 Abbott Lab Indazoles 5-sustituidos 5-heteroarilo como inhibidores de cinasa.
US8648069B2 (en) 2007-06-08 2014-02-11 Abbvie Inc. 5-substituted indazoles as kinase inhibitors
US8415340B2 (en) 2007-07-25 2013-04-09 Bristol-Myers Squibb Company Triazine kinase inhibitors
ES2534899T3 (es) 2007-08-06 2015-04-30 Janssen Pharmaceutica, N.V. Fenilendiaminas sustituidas como inhibidores de la interacción entre MDM2 y p53
EP2058312A1 (en) 2007-11-09 2009-05-13 Universita' degli Studi di Milano SMAC mimetic compounds as apoptosis inducers
PT2358697E (pt) 2008-10-29 2016-02-03 Celgene Corp Compostos de isoindolina para utilização no tratamento do cancro
DK2376480T3 (en) 2008-12-05 2016-09-12 Abbvie Inc Sulfonamide derivatives AS BCL-2-selective apoptosis inducing agents for the treatment of cancer and immune diseases
US8084620B2 (en) 2008-12-19 2011-12-27 Bristol-Myers Squibb Company Carbazole carboxamide compounds useful as kinase inhibitors
US8063102B2 (en) * 2009-03-13 2011-11-22 N.V. Organon Tetrahydronaphthalen-2-ol derivatives
WO2010107485A1 (en) 2009-03-17 2010-09-23 The Trustees Of Columbia University In The City Of New York E3 ligase inhibitors
WO2010138588A2 (en) 2009-05-26 2010-12-02 Abbott Laboratories Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
WO2010141805A1 (en) 2009-06-05 2010-12-09 Janssen Pharmaceutica Nv Heterocyclic amides as modulators of trpa1
AU2010273220B2 (en) 2009-07-13 2015-10-15 President And Fellows Of Harvard College Bifunctional stapled polypeptides and uses thereof
US8551955B2 (en) 2009-10-28 2013-10-08 Joyant Pharmaceuticals, Inc. Dimeric Smac mimetics
US8440693B2 (en) 2009-12-22 2013-05-14 Novartis Ag Substituted isoquinolinones and quinazolinones
PL3202460T3 (pl) 2010-02-11 2019-12-31 Celgene Corporation Pochodne arylometoksyizoindoliny i zawierające je kompozycje oraz sposoby ich zastosowania
CN103153335A (zh) 2010-06-30 2013-06-12 布兰代斯大学 小分子靶定的蛋白质降解
WO2012040527A2 (en) 2010-09-24 2012-03-29 The Regents Of The University Of Michigan Deubiquitinase inhibitors and methods for use of the same
CN102477017A (zh) * 2010-11-23 2012-05-30 苏州波锐生物医药科技有限公司 四氢萘衍生物及其在制备预防和/或治疗乳腺癌骨质疏松症药物中的用途
CN102477033A (zh) 2010-11-23 2012-05-30 苏州波锐生物医药科技有限公司 苯并噻酚类化合物及其在制备预防和/或治疗乳腺癌骨质疏松症药物中的用途
CA2823837A1 (en) 2010-12-07 2012-06-14 Yale University Small-molecule hydrophobic tagging of fusion proteins and induced degradation of same
WO2012090104A1 (en) 2010-12-31 2012-07-05 Kareus Therapeutics, Sa Methods and compositions for designing novel conjugate therapeutics
US8889684B2 (en) 2011-02-02 2014-11-18 Boehringer Ingelheim International Gmbh Azaindolylphenyl sulfonamides as serine/threonine kinase inhibitors
AU2012249491B2 (en) 2011-04-29 2016-12-15 Celgene Corporation Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor
US9376425B2 (en) 2011-09-27 2016-06-28 Amgen, Inc. Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer
EP2776409B1 (en) 2011-11-09 2016-02-03 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
CN103159736B (zh) 2011-12-10 2015-05-13 通化济达医药有限公司 取代的吡唑激酶抑制剂
PL2797888T3 (pl) 2011-12-31 2016-12-30 Połączone związki tricykliczne jako inhibitory kinazy raf
WO2013106646A2 (en) 2012-01-12 2013-07-18 Yale University Compounds and methods for the inhibition of vcb e3 ubiquitin ligase
KR102668696B1 (ko) * 2012-01-12 2024-05-29 예일 유니버시티 E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법
US20150141470A1 (en) 2012-05-08 2015-05-21 The Broad Institute, Inc. Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy
WO2013170147A1 (en) 2012-05-11 2013-11-14 Yale University Compounds useful for promoting protein degradation and methods using same
EP2855483B1 (en) 2012-05-24 2017-10-25 Novartis AG Pyrrolopyrrolidinone compounds
BR112014029530A2 (pt) 2012-05-30 2017-06-27 Hoffmann La Roche compostos, composição farmacêutica e uso de um composto
US9345740B2 (en) 2012-07-10 2016-05-24 Bristol-Myers Squibb Company IAP antagonists
ES2742285T3 (es) 2012-07-31 2020-02-13 Novartis Ag Marcadores asociados con la sensibilidad a inhibidores del doble minuto humano 2 (MDM2)
ES2885769T3 (es) 2012-08-09 2021-12-15 Celgene Corp Una forma sólida de clorhidrato de (s)-3-(4-((4-morpholinometil)bencil)oxi)-1-oxoisoindolin-2-il)piperidina-2,6-diona
US9453048B2 (en) 2012-08-09 2016-09-27 Bristol-Myers Squibb Company IAP antagonists
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
US9783573B2 (en) 2012-09-18 2017-10-10 Bristol-Myers Squibb Company IAP antagonists
US9603889B2 (en) 2012-10-02 2017-03-28 Bristol-Myers Squibb Company IAP antagonists
CA2930030A1 (en) 2012-11-09 2014-05-15 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis
KR102196882B1 (ko) 2012-12-20 2020-12-30 머크 샤프 앤드 돔 코포레이션 Hdm2 억제제로서의 치환된 이미다조피리딘
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.
WO2014134201A1 (en) 2013-02-28 2014-09-04 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of 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.
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
US9637518B2 (en) 2013-07-12 2017-05-02 Bristol-Myers Squibb Company IAP antagonists
BR122022015241B1 (pt) 2013-12-20 2023-09-26 Astex Therapeutics Limited Compostos heterocíclicos bicíclicos intermediários para a preparação de um composto de fórmula (i)
WO2015136016A2 (en) * 2014-03-13 2015-09-17 F. Hoffmann-La Roche Ag Therapeutic combinations with estrogen receptor modulators
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
RU2738833C9 (ru) * 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
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
DK3200615T3 (da) * 2014-10-03 2019-08-19 Conagen Inc Kaloriefrie sødestoffer og fremgangsmåder til syntetisering
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2016105518A1 (en) 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
JP6817962B2 (ja) 2015-01-20 2021-01-20 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． ターゲティングされたアンドロゲン受容体分解のための化合物および方法
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
IL315294A (en) * 2015-03-03 2024-10-01 Pharmacyclics Llc Pharmaceutical formulations of bruton's tyrosine kinase inhibitor
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
GB201506871D0 (en) 2015-04-22 2015-06-03 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201506872D0 (en) 2015-04-22 2015-06-03 Ge Oil & Gas Uk Ltd Novel compounds
WO2016197114A1 (en) 2015-06-05 2016-12-08 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
EP3319944A4 (en) 2015-07-10 2019-04-24 Arvinas, Inc. MDM2-BASED MODULATORS OF PROTEOLYSIS AND RELATED USE METHODS
BR112017028269A2 (pt) 2015-07-13 2018-09-04 Arvinas Inc composto, composição farmacêutica, uso de uma quantidade efetiva de um composto, estado ou condição de doença, e, método para identificar um composto.
WO2017024318A1 (en) 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Targeted protein degradation to attenuate adoptive t-cell therapy associated adverse inflammatory responses
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
GB201516243D0 (en) 2015-09-14 2015-10-28 Glaxosmithkline Ip Dev Ltd Novel compounds
BR112018008918A8 (pt) 2015-11-02 2019-02-26 Univ Yale compostos de quimera proteólise dirigida e métodos para preparação e uso dos mesmos
AU2017235450A1 (en) * 2016-03-15 2018-08-16 Merrimack Pharmaceuticals, Inc. Methods for treating ER+, HER2-, HRG+ breast cancer using combination therapies comprising an anti-ErbB3 antibody
BR112018068906A2 (pt) 2016-03-16 2019-01-22 H. Lee Moffitt Cancer Center And Research Institute, Inc. composição, método, método de redução de risco, prevenção ou tratamento de um indivíduo que tem uma doença ou distúrbio autoimune, método de indução de degradação de uma proteína-alvo numa célula, método para reduzir o risco, prevenir ou tratar um estado da doença ou afecção num paciente em que a atividade proteica desregulada é responsável pelo referido estado da doença ou afecção, método para reduzir o risco, prevenir ou tratar câncer num indivíduo e método de tratamento de uma doença ou distúrbio genético num indivíduo
US20170281784A1 (en) 2016-04-05 2017-10-05 Arvinas, Inc. Protein-protein interaction inducing technology
SG11201808728QA (en) * 2016-04-06 2018-11-29 Univ Michigan Regents Mdm2 protein degraders
AU2017254713C1 (en) 2016-04-22 2021-04-29 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for degradation of EGFR and methods of use
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
US10245258B2 (en) 2016-06-06 2019-04-02 Celgene Corporation Treatment of a hematologic malignancy with 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide
US10646488B2 (en) 2016-07-13 2020-05-12 Araxes Pharma Llc Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
US20180072711A1 (en) 2016-09-15 2018-03-15 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
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
MX2019005007A (es) 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
WO2018098280A1 (en) 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Degradation of protein kinases by conjugation of protein kinase inhibitors with e3 ligase ligand and methods of use
BR112019011200B1 (pt) 2016-12-01 2021-12-28 Arvinas Operations, Inc Derivados de tetrahidronaftaleno e tetrahidroisoquinolina como degradadores do receptor de estrogênio
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
KR20250117470A (ko) 2016-12-23 2025-08-04 아비나스 오퍼레이션스, 인코포레이티드 급속 진행성 섬유육종 폴리펩티드의 표적화 분해를 위한 화합물 및 방법
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
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
BR112019015312A2 (pt) 2017-01-26 2020-03-10 Arvinas Operations, Inc. Moduladores da proteólise pelo receptor de estrogênio e métodos de uso associados
IL312367A (en) 2017-01-31 2024-06-01 Arvinas Operations Inc Cereblon ligands and bifunctional compounds comprising the same
WO2019060742A1 (en) 2017-09-22 2019-03-28 Kymera Therapeutics, Inc AGENTS FOR DEGRADING PROTEINS AND USES THEREOF
CA3121930A1 (en) 2018-12-06 2020-06-11 Radius Pharmaceuticals, Inc. Methods for treating cancer resistant to cdk4/6 inhibitors
KR20220054347A (ko) 2019-08-26 2022-05-02 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 유도체로 유방암을 치료하는 방법
JP7307796B2 (ja) 2019-09-23 2023-07-12 アキュター バイオテクノロジー インコーポレイテッド アンドロゲン受容体分解活性を有する新規の置換キノリン－８－カルボニトリル誘導体およびその使用
EP3835298B1 (en) 2019-12-12 2024-06-26 Accutar Biotechnology Inc. Novel chroman derivatives having estrogen receptor degradation activity and uses thereof
WO2022056368A1 (en) 2020-09-14 2022-03-17 Arvinas Operations, Inc. Crystalline forms of a compound for the targeted degradation of estrogen receptor
AU2021401580A1 (en) 2020-12-14 2023-06-22 Arvinas Operations, Inc. Methods of treating breast cancer with tetrahydronaphthalene derivatives as estrogen receptor degraders
CA3227425A1 (en) 2021-07-26 2023-02-02 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound
CN113816927B (zh) 2021-11-23 2022-02-25 苏州国匡医药科技有限公司 一种arv-471中间体的制备方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016097071A1 (en) * 2014-12-18 2016-06-23 F. Hoffmann-La Roche Ag Estrogen receptor modulators and uses thereof

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