CN110678462B - Mdm2-p53相互作用的异吲哚啉酮抑制剂和其制造方法 - Google Patents

Mdm2-p53相互作用的异吲哚啉酮抑制剂和其制造方法 Download PDF

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Publication number
CN110678462B
CN110678462B CN201880022720.4A CN201880022720A CN110678462B CN 110678462 B CN110678462 B CN 110678462B CN 201880022720 A CN201880022720 A CN 201880022720A CN 110678462 B CN110678462 B CN 110678462B
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alkyl
heterocyclyl
formula
ring members
compound
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Chinese (zh)
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CN110678462A (zh
Inventor
S·霍华德
B·D·康斯
J·D·圣丹尼斯
C·M·格里菲斯-琼斯
S·D·西斯科克
R·S·霍维
A·R·伯恩斯
D·卡森
H·L·德克斯特
G·F·帕拉
J·P·沃茨
R·朱维尔
J·A·斯托克韦尔
K·L·赫斯特
I·A·勒马松
D·J·纳什
J·D·奥斯本
J·C·普列德
N·P·理查兹
A·M·杜马斯
B·C·毕舍普
D·帕瑞-琼斯
J·P·斯科特
M·S·肖恩穆安
P·R·穆伦斯
D·C·拉思伯里
D·J·迪克逊
M·J·冈特
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Cancer Research Technology Ltd
Astex Therapeutics Ltd
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Cancer Research Technology Ltd
Astex Therapeutics Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201880022720.4A 2017-03-28 2018-03-28 Mdm2-p53相互作用的异吲哚啉酮抑制剂和其制造方法 Active CN110678462B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1704965.1 2017-03-28
GBGB1704965.1A GB201704965D0 (en) 2017-03-28 2017-03-28 Pharmaceutical compounds
PCT/GB2018/050845 WO2018178691A1 (en) 2017-03-28 2018-03-28 Isoindolinone inhibitors of the mdm2-p53 interaction and process for making them

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CN110678462A CN110678462A (zh) 2020-01-10
CN110678462B true CN110678462B (zh) 2024-10-29

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US (3) US11603367B2 (https=)
EP (1) EP3601272A1 (https=)
JP (1) JP7495790B2 (https=)
KR (1) KR102673967B1 (https=)
CN (1) CN110678462B (https=)
GB (1) GB201704965D0 (https=)
WO (1) WO2018178691A1 (https=)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201517217D0 (en) 2015-09-29 2015-11-11 Astex Therapeutics Ltd And Cancer Res Technology Ltd Pharmaceutical compounds
GB201704966D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
GB201704965D0 (en) * 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
CN113453678A (zh) * 2018-11-26 2021-09-28 德彪药业国际股份公司 Hiv感染的联合治疗
CN109897069B (zh) * 2019-02-12 2021-08-20 华东师范大学 一种3，3-二取代吲哚啉酮及其衍生物及其合成方法和应用
CN110845288B (zh) * 2019-11-28 2022-07-19 浙江工业大学 一种手性β-氨基醛类化合物的不对称合成方法
GB201919219D0 (en) 2019-12-23 2020-02-05 Otsuka Pharma Co Ltd Cancer biomarkers
CN111057128B (zh) * 2019-12-25 2023-05-16 哈尔滨师范大学 一种含硫的异吲哚酮并环肽衍生物及其制备方法
CA3181715A1 (en) 2020-08-27 2022-03-03 Otsuka Pharmaceutical Co., Ltd. Biomarkers for cancer therapy using mdm2 antagonists
GB202103080D0 (en) * 2021-03-04 2021-04-21 Otsuka Pharma Co Ltd Cancer biomarkers
WO2025104679A1 (en) * 2023-11-16 2025-05-22 Otsuka Pharmaceutical Co., Ltd. Processes for making intermediates for isoindolinone inhibitors of the mdm2-p53 interaction having anticancer activity

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009156735A2 (en) * 2008-06-25 2009-12-30 Cancer Research Technology Limited New therapeutic agents
WO2018178691A1 (en) * 2017-03-28 2018-10-04 Astex Therapeutics Limited Isoindolinone inhibitors of the mdm2-p53 interaction and process for making them

Family Cites Families (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH374071A (de) 1959-04-30 1963-12-31 Geigy Ag J R Verfahren zur Herstellung von neuen Isoindolinderivaten
US3466298A (en) 1967-03-14 1969-09-09 American Home Prod Process for the preparation of 2-(2-aminoethyl)isoindolines
US3763178A (en) 1968-09-05 1973-10-02 American Home Prod Imidazolinyl phenyl carbonyl acid addition salts and related compounds
GB1325065A (en) 1970-02-12 1973-08-01 American Home Prod Imidazoline derivatives
AR203991A1 (es) 1972-03-16 1975-11-12 Rhone Poulenc Sa Procedimiento para preparar derivados de(hidroxi-2-amino-3-propoxi)-3-isoindolinona-1
FR2217000B1 (https=) 1973-02-08 1976-04-09 Rhone Poulenc Ind
GB1601701A (en) 1977-07-22 1981-11-04 Delmar Chem Production of heterocyclic benzamide compounds
US4200759A (en) 1978-07-20 1980-04-29 Delmar Chemicals, Limited Preparation of imidazo[2,1-a]isoindole compounds
US4244966A (en) 1979-09-24 1981-01-13 American Home Products Corporation 1,3-Dihydro-3-(2-hydroxy-, 2-bromo- or 2-chloroethyl)-2H-isoindol-1-one derivatives
US4331600A (en) 1980-10-31 1982-05-25 Usv Pharmaceutical Corporation Intermediates for the synthesis of phthalimidines
US4312809A (en) 1980-10-31 1982-01-26 E. R. Squibb & Sons, Inc. Lactam derivatives of mercaptoacylamino acids
FR2533563A1 (fr) 1982-09-23 1984-03-30 Adir Nouveaux derives de la sulfonyluree, leurs procedes de preparation et les compositions pharmaceutiques les renfermant
HU212435B (en) 1990-06-07 1996-06-28 Sandoz Ag Herbicidal compositions containing substituted phthalides and heterocyclic phthalides as active ingredient and process for preparation of their active ingredients.
TW448172B (en) 1996-03-08 2001-08-01 Pharmacia & Upjohn Co Llc Novel hydroxamic acid derivatives useful for the treatment of diseases related to connective tissue degradation
DE19807423A1 (de) 1998-02-21 1999-08-26 Hoechst Marion Roussel De Gmbh Subustituierte Isoindolone, ihre Herstellung und ihre Verwendung in Arzneimitteln
US6958333B1 (en) 1999-07-26 2005-10-25 Banyu Pharmaceutical Co., Ltd. Biarylurea derivatives
WO2001032928A2 (en) 1999-11-05 2001-05-10 Phase-1 Molecular Toxicology Methods of determining individual hypersensitivity to an agent
DE10134482A1 (de) 2001-07-16 2003-01-30 Bayer Ag Substituierte Isoindole und ihre Verwendung
BR0215157A (pt) 2001-12-18 2004-10-19 Hoffmann La Roche Cis-2,4,5-trifenil-imidazolinas e seu uso no tratamento de tumores
FR2840302B1 (fr) 2002-06-03 2004-07-16 Aventis Pharma Sa Derives d'isoindolones, procede de preparation et intermediaire de ce procede a titre de medicaments et compositions pharmaceutiques les renfermant
EP1566378B1 (en) 2002-11-26 2012-08-15 Maruishi Pharmaceutical Co., Ltd. Isoindoline derivative
JP2004217591A (ja) 2003-01-16 2004-08-05 Dai Ichi Seiyaku Co Ltd シス選択的フルオロシクロプロパン誘導体の製造方法
US7320992B2 (en) 2003-08-25 2008-01-22 Amgen Inc. Substituted 2,3-dihydro-1h-isoindol-1-one derivatives and methods of use
JP2005255660A (ja) 2004-03-10 2005-09-22 Katsuhiko Tomooka 多官能基を有するラクタム類とその製法
JPWO2005095341A1 (ja) 2004-03-30 2007-08-16 協和醗酵工業株式会社 含窒素複素環化合物
TW200613272A (en) 2004-08-13 2006-05-01 Astrazeneca Ab Isoindolone compounds and their use as metabotropic glutamate receptor potentiators
GB0419481D0 (en) 2004-09-02 2004-10-06 Cancer Rec Tech Ltd Isoindolin-1-one derivatives
KR100944301B1 (ko) 2005-02-22 2010-02-24 더 리젠츠 오브 더 유니버시티 오브 미시간 Ｍｄｍ２의 소분자 억제제 및 이의 용도
US7705021B2 (en) * 2005-05-02 2010-04-27 Fox Chase Cancer Center Isoindolone compounds, compositions containing the same, and methods of use thereof for the treatment of viral infections related to the etiology of cancer
CN101309905A (zh) 2005-08-12 2008-11-19 阿斯利康(瑞典)有限公司 取代的异吲哚酮及其作为代谢型谷氨酸受体增效剂的用途
US7727978B2 (en) 2006-08-24 2010-06-01 Bristol-Myers Squibb Company Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors
JPWO2008047831A1 (ja) 2006-10-17 2010-02-25 協和発酵キリン株式会社 Ｊａｋ阻害剤
GB0706072D0 (en) 2007-03-28 2007-05-09 Sterix Ltd Compound
SG185285A1 (en) 2007-06-03 2012-11-29 Univ Vanderbilt Benzamide mglur5 positive allosteric modulators and methods of making and using same
DE102008031517A1 (de) * 2008-07-03 2010-01-07 Merck Patent Gmbh Pyrrolopyridinyl-pyrimidin-2-yl-amin-derivate
AU2009294673B2 (en) 2008-09-18 2014-08-14 F. Hoffmann-La Roche Ag Substituted pyrrolidine-2-carboxamides
US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
KR20120099462A (ko) 2009-11-12 2012-09-10 더 리젠츠 오브 더 유니버시티 오브 미시건 스피로-옥신돌 ｍｄｍ2 길항제
US8440693B2 (en) 2009-12-22 2013-05-14 Novartis Ag Substituted isoquinolinones and quinazolinones
JO2998B1 (ar) 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
AU2012226890B2 (en) 2011-03-10 2016-10-06 Daiichi Sankyo Company, Limited Dispiropyrrolidine derivative
EP2721007B1 (en) 2011-06-20 2015-04-29 Novartis AG Cyclohexyl isoquinolinone compounds
WO2012175520A1 (en) 2011-06-20 2012-12-27 Novartis Ag Hydroxy substituted isoquinolinone derivatives
EP2750768B1 (en) 2011-08-30 2018-10-03 Astex Pharmaceuticals, Inc. Decitabine derivative formulations
US8815926B2 (en) 2012-01-26 2014-08-26 Novartis Ag Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
KR101401705B1 (ko) 2012-01-31 2014-06-27 울산대학교 산학협력단 로듐 촉매를 이용한 이소인돌린 유도체의 합성방법
US9365512B2 (en) 2012-02-13 2016-06-14 AbbVie Deutschland GmbH & Co. KG Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy
PT2914254T (pt) 2012-10-30 2020-04-02 Mei Pharma Inc Terapias de combinação para tratar cancros quimiorresistentes
SI2961388T1 (sl) 2013-03-01 2019-10-30 Astex Pharmaceuticals Inc Kombinacije zdravil
BR112015031542A2 (pt) 2013-07-03 2017-07-25 Hoffmann La Roche métodos de previsão de reação de pacientes com câncer, método de tratamento de câncer, kit de previsão da reação ao tratamento e processos, métodos e usos inovadores
US20160333419A1 (en) 2014-01-14 2016-11-17 Daiichi Sankyo Company, Limited Gene signatures associated with sensitivity to mdm2 inhibitors
ES2712973T3 (es) 2014-04-17 2019-05-17 Univ Michigan Regents Inhibidores de MDM2 y métodos terapéuticos que usan los mismos
JP2017532959A (ja) 2014-10-09 2017-11-09 第一三共株式会社 Ｍｄｍ２阻害剤に対する感受性の遺伝子シグネチャーに基づく予測因子に関するアルゴリズム
WO2016059241A2 (en) 2014-10-17 2016-04-21 Biomirna Holdings Ltd. Lung cancer diagnostics and therapeutics with mir-660
AU2016287585B2 (en) 2015-07-02 2020-12-17 Otsuka Pharmaceutical Co., Ltd. Lyophilized pharmaceutical compositions
GB201517217D0 (en) 2015-09-29 2015-11-11 Astex Therapeutics Ltd And Cancer Res Technology Ltd Pharmaceutical compounds
GB201517216D0 (en) 2015-09-29 2015-11-11 Cancer Res Technology Ltd And Astex Therapeutics Ltd Pharmaceutical compounds
EP3365334B1 (en) 2015-10-21 2024-07-17 Otsuka Pharmaceutical Co., Ltd. Benzolactam compounds as protein kinase inhibitors
TWI734715B (zh) 2015-11-19 2021-08-01 美商卡默森屈有限公司 趨化因子受體調節劑
GB201704966D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
CA3050645A1 (en) 2018-07-27 2020-01-27 Ottawa Hospital Research Institute Treatment of acute myeloid leukemia
TWI772753B (zh) 2019-02-24 2022-08-01 大陸商蘇州亞盛藥業有限公司 Mdm2抑制劑的治療方法和生物標記物
GB201919219D0 (en) 2019-12-23 2020-02-05 Otsuka Pharma Co Ltd Cancer biomarkers
CA3181715A1 (en) 2020-08-27 2022-03-03 Otsuka Pharmaceutical Co., Ltd. Biomarkers for cancer therapy using mdm2 antagonists
GB202103080D0 (en) 2021-03-04 2021-04-21 Otsuka Pharma Co Ltd Cancer biomarkers

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009156735A2 (en) * 2008-06-25 2009-12-30 Cancer Research Technology Limited New therapeutic agents
WO2018178691A1 (en) * 2017-03-28 2018-10-04 Astex Therapeutics Limited Isoindolinone inhibitors of the mdm2-p53 interaction and process for making them

Also Published As

Publication number Publication date
US12077526B2 (en) 2024-09-03
JP2020515546A (ja) 2020-05-28
CN110678462A (zh) 2020-01-10
KR102673967B1 (ko) 2024-06-12
US11603367B2 (en) 2023-03-14
WO2018178691A1 (en) 2018-10-04
JP7495790B2 (ja) 2024-06-05
US20210101887A1 (en) 2021-04-08
EP3601272A1 (en) 2020-02-05
KR20190133190A (ko) 2019-12-02
GB201704965D0 (en) 2017-05-10
US20250074900A1 (en) 2025-03-06
US20230278989A1 (en) 2023-09-07

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