WO2019192533A1 - Agent de dégradation du récepteur des œstrogènes pour le traitement du cancer du sein - Google Patents

Agent de dégradation du récepteur des œstrogènes pour le traitement du cancer du sein Download PDF

Info

Publication number
WO2019192533A1
WO2019192533A1 PCT/CN2019/081314 CN2019081314W WO2019192533A1 WO 2019192533 A1 WO2019192533 A1 WO 2019192533A1 CN 2019081314 W CN2019081314 W CN 2019081314W WO 2019192533 A1 WO2019192533 A1 WO 2019192533A1
Authority
WO
WIPO (PCT)
Prior art keywords
och
group
compound
formula
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2019/081314
Other languages
English (en)
Chinese (zh)
Inventor
朱程刚
杨铉
徐良亮
张朝春
郭玉函
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.)
Shenzhen Forward Pharmaceuticals Co Ltd
Original Assignee
Shenzhen Forward Pharmaceuticals Co Ltd
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 Shenzhen Forward Pharmaceuticals Co Ltd filed Critical Shenzhen Forward Pharmaceuticals Co Ltd
Priority to CN201980015908.0A priority Critical patent/CN111770924B/zh
Publication of WO2019192533A1 publication Critical patent/WO2019192533A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • 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
    • 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

Definitions

  • R a is selected from the group consisting of H, C 1 -C 6 alkyl, C 2 -C 8 alkenyl, propargyl, C 3 -C 6 cycloalkyl and C 3 -C 6 heterocyclic, optionally selected Substituting one or more groups independently selected from the group consisting of F, Cl, Br, I, CN, OH, OCH 3 and SO 2 CH 3 ;
  • alkanediyl, fluoroalkanediyl, aryldiyl, carbocyclicdiyl, heterocyclic diyl and heteroaryldiyl are optionally substituted with one or more groups independently selected from the group consisting of F, Cl, Br, I, -CN, -CH 3 , -CH 2 CH 3 , -CH(CH 3 ) 2 , -CH 2 CH(CH 3 ) 2 , -CH 2 OH, -CH 2 OCH 3 , -CH 2 CH 2 OH, -C(CH 3 ) 2 OH, -CH(OH)CH(CH 3 ) 2 , -C(CH 3 ) 2 CH 2 OH, -CH 2 CH 2 SO 2 CH 3 , -CH 2 OP ( O) (OH) 2 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 CF 3 , -CH 2 CHF 2 , -CH 2 CHCH 2
  • R 1 , R 2 , R 3 and R 4 are independently selected from H, F, Cl , Br, I, -CN, -CH 3 , -CH 2 CH 3 , -CH(CH 3 ) 2 , -CH 2 CH(CH 3 ) 2 , -CH 2 OH, -CH 2 OCH 3 , -CH 2 CH 2 OH, -C(CH 3 ) 2 OH, -CH(OH)CH(CH 3 ) 2 , -C(CH 3 ) 2 CH 2 OH, -CH 2 CH 2 SO 2 CH 3 , -CH 2 OP (O)(OH) 2 , -CH 2 F, -CHF 2 , -CH 2 NH 2 , -CH 2 NHSO 2 CH 3 , -CH 2 NHCH 3 , -CH 2 N(CH 3 ,
  • a compound of the formula (I), (II) or a pharmaceutically acceptable salt thereof which is an enantiomeric excess (ee%) ⁇ 95%, ⁇ 98% or ⁇ 99 % of a single enantiomer.
  • the single enantiomer is present in an enantiomeric excess (ee%) > 99%.
  • Y 1 is CR b or N
  • Y 2 is -(CH 2 )-;
  • R 8 is H or -CH 3 .
  • estrogen receptor-related disease is a cancer selected from the group consisting of breast cancer, lung cancer, ovarian cancer, endometrial cancer, prostate cancer, and uterine cancer.
  • Solid naphthalene (615 mg, 5.0 mmol) was added to a 100 mL reaction flask, and the sodium block was sheared to dry sodium ether in dry petroleum ether, and then quickly weighed (drying the paper towel to remove the petroleum ether from the surface). , 5.0 mmol) was added to the original reaction flask and the nitrogen was replaced. 25 mL of the re-distilled THF was added to the reaction system with a syringe, and the mixture was stirred at room temperature for 1 h or more to obtain a fresh sodium naphthalene complex (0.2 M in THF), which was dark green.
  • Preparation of 1x protein mixture Prepare 2x GST-ER ⁇ -LBD/MAb anti-GST-Eu mixed solution according to the following table.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

La présente invention concerne certains nouveaux composés ou des sels pharmaceutiquement acceptables de ceux-ci, les composés ayant une activité anticancéreuse et étant par conséquent potentiellement utiles dans des méthodes de traitement chez l'homme ou l'animal. La présente invention concerne également des procédés de production des composés, des compositions pharmaceutiques les comprenant et leurs utilisations dans des méthodes thérapeutiques, par exemple, dans la fabrication de médicaments pour la prévention ou le traitement de cancers chez des animaux à sang chaud tels que des êtres humains, notamment pour la prévention ou le traitement de cancers. La présente invention concerne en outre des composés qui sont des modulateurs pour la régulation négative sélective de récepteurs des œstrogènes.
PCT/CN2019/081314 2018-04-04 2019-04-03 Agent de dégradation du récepteur des œstrogènes pour le traitement du cancer du sein Ceased WO2019192533A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201980015908.0A CN111770924B (zh) 2018-04-04 2019-04-03 用于治疗乳腺癌的雌激素受体降解剂

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNPCT/CN2018/081947 2018-04-04
CN2018081947 2018-04-04

Publications (1)

Publication Number Publication Date
WO2019192533A1 true WO2019192533A1 (fr) 2019-10-10

Family

ID=68100014

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/081314 Ceased WO2019192533A1 (fr) 2018-04-04 2019-04-03 Agent de dégradation du récepteur des œstrogènes pour le traitement du cancer du sein

Country Status (2)

Country Link
CN (2) CN111770924B (fr)
WO (1) WO2019192533A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021139756A1 (fr) * 2020-01-10 2021-07-15 江苏恒瑞医药股份有限公司 Dérivé tétrahydroisoquinoline tricyclique, son procédé de préparation et son application en médecine
WO2022194096A1 (fr) * 2021-03-15 2022-09-22 深圳福沃药业有限公司 Antagoniste du récepteur des oestrogènes

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019192533A1 (fr) * 2018-04-04 2019-10-10 深圳福沃药业有限公司 Agent de dégradation du récepteur des œstrogènes pour le traitement du cancer du sein

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015086496A1 (fr) * 2013-12-09 2015-06-18 Ucb Biopharma Sprl Dérivés de triazolopyridine comme modulateurs de l'activité du tnf
WO2015191506A2 (fr) * 2014-06-13 2015-12-17 Merck Sharp & Dohme Corp. Pyrrolo[2,3-c]pyridines utilisables en tant qu'agents d'imagerie pour les enchevêtrements neurofibrillaires

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4836788B2 (ja) * 2003-07-23 2011-12-14 エグゼリクシス， インコーポレイテッド 未分化リンパ腫キナーゼ変調因子及びその使用法
WO2005105814A1 (fr) * 2004-04-28 2005-11-10 Incyte Corporation Inhibiteurs tetracycliques de janus kinases
EA031077B1 (ru) * 2013-06-19 2018-11-30 Серагон Фармасьютикалз, Инк. Модулятор рецептора эстрогена и его применения
KR102785474B1 (ko) * 2014-12-18 2025-03-26 에프. 호프만-라 로슈 아게 테트라하이드로-피리도[3,4-b]인돌 에스트로겐 수용체 조절제 및 이의 용도
KR102710603B1 (ko) * 2015-10-01 2024-09-27 올레마 파마슈티컬스 인코포레이티드 테트라히드로-1H-피리도[3,4-b]인돌 항에스트로겐 약물
CN109362222B (zh) * 2016-02-05 2021-03-19 益方生物科技(上海)股份有限公司 选择性雌激素受体降解物及其用途
US10125135B2 (en) * 2016-04-20 2018-11-13 Astrazeneca Ab Chemical compounds
WO2018005249A1 (fr) * 2016-06-28 2018-01-04 Merck Sharp & Dohme Corp. Modulateurs allostériques positifs du récepteur m1 de benzoisoquinoline
WO2019192533A1 (fr) * 2018-04-04 2019-10-10 深圳福沃药业有限公司 Agent de dégradation du récepteur des œstrogènes pour le traitement du cancer du sein

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015086496A1 (fr) * 2013-12-09 2015-06-18 Ucb Biopharma Sprl Dérivés de triazolopyridine comme modulateurs de l'activité du tnf
WO2015191506A2 (fr) * 2014-06-13 2015-12-17 Merck Sharp & Dohme Corp. Pyrrolo[2,3-c]pyridines utilisables en tant qu'agents d'imagerie pour les enchevêtrements neurofibrillaires

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021139756A1 (fr) * 2020-01-10 2021-07-15 江苏恒瑞医药股份有限公司 Dérivé tétrahydroisoquinoline tricyclique, son procédé de préparation et son application en médecine
CN114746424A (zh) * 2020-01-10 2022-07-12 江苏恒瑞医药股份有限公司 三环四氢异喹啉类衍生物、其制备方法及其在医药上的应用
CN114746424B (zh) * 2020-01-10 2023-06-16 江苏恒瑞医药股份有限公司 三环四氢异喹啉类衍生物、其制备方法及其在医药上的应用
CN116731064A (zh) * 2020-01-10 2023-09-12 江苏恒瑞医药股份有限公司 三环四氢异喹啉类衍生物、其制备方法及其在医药上的应用
US12428428B2 (en) 2020-01-10 2025-09-30 Jiangsu Hengrui Medicine Co., Ltd. Tricyclic tetrahydroisoquinoline derivative, preparation method therefor and application thereof in medicine
WO2022194096A1 (fr) * 2021-03-15 2022-09-22 深圳福沃药业有限公司 Antagoniste du récepteur des oestrogènes
JP2024511044A (ja) * 2021-03-15 2024-03-12 深▲せん▼福沃薬業有限公司 エストロゲン受容体モジュレーター
JP7605536B2 (ja) 2021-03-15 2024-12-24 深▲せん▼福沃薬業有限公司 エストロゲン受容体モジュレーター
JP2025023300A (ja) * 2021-03-15 2025-02-14 深▲せん▼福沃薬業有限公司 エストロゲン受容体モジュレーター

Also Published As

Publication number Publication date
CN111770924B (zh) 2023-05-09
CN110343101A (zh) 2019-10-18
CN111770924A (zh) 2020-10-13
CN110343101B (zh) 2022-07-12

Similar Documents

Publication Publication Date Title
CN108366996B (zh) 四氢-1H-吡啶[3,4-b]吲哚类抗雌激素药物
EP3455204B1 (fr) Composés cyclopropyl-amide comme inhibiteurs doubles lsd1/hdac
CN108884079B (zh) 作为雌激素受体调节剂的6，7-二氢-5h-苯并[7]轮烯衍生物
EP3378861B1 (fr) Dérivé de l'acide acrylique, son procédé de préparation et son utilisation en médecine
TWI617546B (zh) 咪唑啉類衍生物、其製備方法及其在醫藥上的應用
KR20210146984A (ko) 에스트로겐 수용체 분해 protac
TW201427963A (zh) 化合物及其使用方法
TWI839738B (zh) 含氮雜環化合物、其製備方法及應用
TW201925204A (zh) 稠合三環化合物
TW202016084A (zh) 選擇性雌激素受體下調劑和其用途
JP2017508779A5 (fr)
CN111770924B (zh) 用于治疗乳腺癌的雌激素受体降解剂
CN113710668A (zh) 用于ep300或cbp调节及其适应症的缩合吖嗪
WO2022135610A1 (fr) Composé tétracyclique, composition pharmaceutique et utilisation associées
TWI858082B (zh) 吲唑類衍生物、其製備方法及其在醫藥上的應用
JP2020502188A (ja) Ａｒ−ｖ７インヒビター
CN117956996A (zh) 用于yap/tead调节的化合物和方法及其适应证
TW202525792A (zh) 經取代之側氧異吲哚啉基哌啶－２，６－二酮化合物
CN116514891B (zh) 甾类化合物、其制备方法和应用
JP2022507559A (ja) Ａｍ２受容体阻害剤としての複素環スピロ化合物
JP2022507561A (ja) Ａｍ２受容体阻害剤としての複素環スピロ化合物
CN112334462A (zh) Oga抑制剂化合物
CN118922421A (zh) 双环酞嗪-1(2h)-酮衍生物和相关用途
KR20210129119A (ko) 파르네소이드 x 수용체 조정제로서 유용한 치환된 아미드 화합물
HK40056233A (en) Tetrahydro-1h-pyrido[3,4-b]indole anti-estrogenic drugs

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19780690

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 12/02/2021)

122 Ep: pct application non-entry in european phase

Ref document number: 19780690

Country of ref document: EP

Kind code of ref document: A1