CN109219604B - 四氢异喹啉雌激素受体调节剂及其用途 - Google Patents

四氢异喹啉雌激素受体调节剂及其用途 Download PDF

Info

Publication number
CN109219604B
CN109219604B CN201780034424.1A CN201780034424A CN109219604B CN 109219604 B CN109219604 B CN 109219604B CN 201780034424 A CN201780034424 A CN 201780034424A CN 109219604 B CN109219604 B CN 109219604B
Authority
CN
China
Prior art keywords
phenyl
fluoromethyl
methyl
ethoxy
azetidin
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.)
Active
Application number
CN201780034424.1A
Other languages
English (en)
Chinese (zh)
Other versions
CN109219604A (zh
Inventor
S·拉巴迪
J·梁
D·F·奥特文
X·王
B·张
J·佐比格
M·维诺格拉多瓦
T·王
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.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
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 F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of CN109219604A publication Critical patent/CN109219604A/zh
Application granted granted Critical
Publication of CN109219604B publication Critical patent/CN109219604B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201780034424.1A 2016-04-08 2017-04-07 四氢异喹啉雌激素受体调节剂及其用途 Active CN109219604B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CNPCT/CN2016/078807 2016-04-08
CNPCT/CN2016/078807 2016-04-08
PCT/EP2017/058313 WO2017174757A1 (en) 2016-04-08 2017-04-07 Tetrahydroisoquinoline estrogen receptor modulators and uses thereof

Publications (2)

Publication Number Publication Date
CN109219604A CN109219604A (zh) 2019-01-15
CN109219604B true CN109219604B (zh) 2021-09-24

Family

ID=58489690

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780034424.1A Active CN109219604B (zh) 2016-04-08 2017-04-07 四氢异喹啉雌激素受体调节剂及其用途

Country Status (5)

Country Link
US (1) US9969732B2 (https=)
EP (1) EP3440067B1 (https=)
JP (1) JP7241542B2 (https=)
CN (1) CN109219604B (https=)
WO (1) WO2017174757A1 (https=)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10125135B2 (en) 2016-04-20 2018-11-13 Astrazeneca Ab Chemical compounds
WO2018019793A1 (en) 2016-07-25 2018-02-01 Astrazeneca Ab N-(2-(4-((1r,3r)-3-methyl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)propan-1-amine derivatives and related compounds as selective down-regulators of the estrogen receptor for treating cancer
TWI735681B (zh) * 2016-10-24 2021-08-11 瑞典商阿斯特捷利康公司 化合物
EA037533B9 (ru) * 2016-12-16 2021-05-27 Астразенека Аб 6,7,8,9-ТЕТРАГИДРО-3H-ПИРАЗОЛО[4,3-f]ИЗОХИНОЛИНОВЫЕ ПРОИЗВОДНЫЕ, ПРИМЕНИМЫЕ В ЛЕЧЕНИИ РАКА
PT3494116T (pt) 2017-01-30 2020-01-28 Astrazeneca Ab Moduladores de recetores de estrogénio
WO2019002442A1 (en) * 2017-06-29 2019-01-03 Astrazeneca Ab CHEMICAL COMPOUNDS
WO2019002441A1 (en) * 2017-06-29 2019-01-03 Astrazeneca Ab CHEMICAL COMPOUNDS
US11236088B2 (en) 2017-11-14 2022-02-01 Kind Pharmaceutical Heterocyclic compounds and their application in medicine
CN111315378A (zh) * 2017-11-16 2020-06-19 诺华股份有限公司 包含lsz102和瑞博西尼的药物组合
MD3820874T2 (ro) * 2018-07-12 2023-05-31 Lilly Co Eli Degradanți selectivi ai receptorului estrogen
CN111499614A (zh) * 2019-01-31 2020-08-07 江苏恒瑞医药股份有限公司 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
WO2021213358A1 (zh) * 2020-04-21 2021-10-28 江苏先声药业有限公司 含硼化合物及其应用
WO2021214253A1 (en) 2020-04-24 2021-10-28 Astrazeneca Ab Dosage regimen for the treatment of cancer
PE20221838A1 (es) 2020-04-24 2022-11-29 Astrazeneca Ab Formulaciones farmaceuticas
CN111825613B (zh) * 2020-08-17 2022-02-15 上海勋和医药科技有限公司 作为选择性雌激素受体下调剂的四氢异喹啉类化合物、合成方法及用途
CN114105977B (zh) * 2020-08-28 2023-09-01 先声再明医药有限公司 雌激素受体调节剂化合物及其用途
CN116669729A (zh) * 2021-02-08 2023-08-29 贝达药业股份有限公司 杂芳基并哌啶类衍生物及其药物组合物和应用
WO2022178139A1 (en) * 2021-02-19 2022-08-25 The University Of Chicago Estrogen receptor alpha antagonists and uses thereof
CN113024460B (zh) * 2021-03-10 2022-11-08 中国药科大学 作为雌激素受体与组蛋白去乙酰化酶双靶点化合物的四氢异喹啉类化合物、合成方法及用途
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
WO2023280309A1 (zh) * 2021-07-09 2023-01-12 江苏恒瑞医药股份有限公司 一种三环四氢异喹啉类衍生物的盐型
CN117813288A (zh) * 2021-07-15 2024-04-02 西藏海思科制药有限公司 芳氨基衍生物雌激素受体调节剂及其用途
JP2025529875A (ja) * 2022-08-25 2025-09-09 サノフイ 新規の置換テトラヒドロイソキノリン－６－カルボン酸誘導体、この誘導体を調製する方法、及びこの誘導体の治療的使用
CN115252606B (zh) * 2022-09-29 2023-02-03 北京市神经外科研究所 化合物在制备用于治疗肿瘤的药物中的应用
TW202547495A (zh) * 2024-04-01 2025-12-16 大陸商山東盛迪醫藥有限公司 一種選擇性雌激素受體降解劑的製備方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1441785A (zh) * 2000-05-11 2003-09-10 布里斯托尔-迈尔斯斯奎布公司 可用作生长激素促分泌素的四氢异喹啉类似物
CN102875466A (zh) * 2012-04-23 2013-01-16 中国药科大学 异喹啉酮衍生物,其制备方法及其医药用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5552412A (en) * 1995-01-09 1996-09-03 Pfizer Inc 5-substitued-6-cyclic-5,6,7,8-tetrahydronaphthalen2-ol compounds which are useful for treating osteoporosis
US5981521A (en) * 1998-11-13 1999-11-09 Abbott Laboratories Tetrahydroisoquinoline derivatives as LHRH antagonists
AU766648B2 (en) * 1999-03-17 2003-10-23 Axys Pharmaceuticals, Inc. Compounds and methods for modulation of estrogen receptors
GB0000313D0 (en) 2000-01-10 2000-03-01 Astrazeneca Uk Ltd Formulation
WO2002046164A1 (en) * 2000-12-07 2002-06-13 Astrazeneca Ab Therapeutic compounds
CA2819299A1 (en) 2010-12-24 2012-06-28 Merck Sharp & Dohme B.V. N-substituted azetidine derivatives
WO2015092634A1 (en) 2013-12-16 2015-06-25 Novartis Ag 1,2,3,4-tetrahydroisoquinoline compounds and compositions as selective estrogen receptor antagonists and degraders
CN107406424B (zh) 2014-12-18 2020-08-25 豪夫迈·罗氏有限公司 雌激素受体调节剂及其用途
US10125135B2 (en) 2016-04-20 2018-11-13 Astrazeneca Ab Chemical compounds
TWI735681B (zh) 2016-10-24 2021-08-11 瑞典商阿斯特捷利康公司 化合物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1441785A (zh) * 2000-05-11 2003-09-10 布里斯托尔-迈尔斯斯奎布公司 可用作生长激素促分泌素的四氢异喹啉类似物
CN102875466A (zh) * 2012-04-23 2013-01-16 中国药科大学 异喹啉酮衍生物,其制备方法及其医药用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Selective Estrogen Receptor Modulators with Conformationally Restricted Side Chains. Synthesis and Structure-Activity Relationship of ERr-Selective Tetrahydroisoquinoline Ligands;Johanne Renaud 等;《J. Med. Chem.》;20050101;第48卷(第2期);第369页表1 *

Also Published As

Publication number Publication date
EP3440067B1 (en) 2021-05-26
US9969732B2 (en) 2018-05-15
US20170320871A1 (en) 2017-11-09
JP2019510799A (ja) 2019-04-18
JP7241542B2 (ja) 2023-03-17
CN109219604A (zh) 2019-01-15
EP3440067A1 (en) 2019-02-13
WO2017174757A1 (en) 2017-10-12

Similar Documents

Publication Publication Date Title
CN109219604B (zh) 四氢异喹啉雌激素受体调节剂及其用途
JP7792942B2 (ja) テトラヒドロ－ピリド［３，４－ｂ］インドールエストロゲン受容体モジュレーター及びその使用
CN109311876B (zh) 杂芳基雌激素受体调节剂及其用途
CN108349952A (zh) 四氢萘雌激素受体调节剂及其用途
HK40003208A (en) Tetrahydroisoquinoline estrogen receptor modulators and uses thereof
HK40003208B (zh) 四氢异喹啉雌激素受体调节剂及其用途
HK40109078A (zh) 四氢-吡啶并[3，4-b]吲哚雌激素受体调节剂及其用途
HK40107389A (zh) 四氢-吡啶并[3，4-b]吲哚雌激素受体调节剂及其用途
JP2026067858A (ja) テトラヒドロ－ピリド［３，４－ｂ］インドールエストロゲン受容体モジュレーター及びその使用
HK40041466A (en) Tetrahydro-pyrido[3,4-b]indole estrogen receptor modulators and uses thereof
HK40041467A (en) Tetrahydro-pyrido[3,4-b]indole estrogen receptor modulators and uses thereof
HK40041467B (zh) 四氢-吡啶并[3，4-b]吲哚雌激素受体调节剂及其用途
HK40003989A (en) Heteroaryl estrogen receptor modulators and uses thereof
HK1243074B (zh) 四氢-吡啶并[3,4-b]吲哚雌激素受体调节剂及其用途

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
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40003208

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant