CN112041320A - 一种可用作肿瘤抑制剂的化合物及其制备方法与应用 - Google Patents

一种可用作肿瘤抑制剂的化合物及其制备方法与应用 Download PDF

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CN112041320A
CN112041320A CN201880082128.3A CN201880082128A CN112041320A CN 112041320 A CN112041320 A CN 112041320A CN 201880082128 A CN201880082128 A CN 201880082128A CN 112041320 A CN112041320 A CN 112041320A
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alkyl
chloro
isopropyl
imidazole
pyrrolo
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CN112041320B (zh
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尹磊
姚郑林
李恒
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Gan and Lee Pharmaceuticals Co Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/20—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
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    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
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  • Immunology (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

一种可用作肿瘤抑制剂的化合物及其制备方法与应用，所述化合物具有如通式I所示结构，包括其立体异构体、对映异构体、外消旋体、顺反异构体、互变异构体、同位素变体。所述化合物可单独或与其他药物组合用于治疗肿瘤或炎症疾病，或者用于治疗MDM2和/或MDM4活性介导的其他障碍或疾病，显示出突出的治疗活性。

Description

PCT国内申请，说明书已公开。

Claims (17)

  1. PCT国内申请，权利要求书已公开。
CN201880082128.3A 2017-12-29 2018-12-21 一种可用作肿瘤抑制剂的化合物及其制备方法与应用 Active CN112041320B (zh)

Applications Claiming Priority (3)

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CN2017114842808 2017-12-29
CN201711484280 2017-12-29
PCT/CN2018/122796 WO2019128877A1 (zh) 2017-12-29 2018-12-21 一种可用作肿瘤抑制剂的化合物及其制备方法与应用

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CN112041320A true CN112041320A (zh) 2020-12-04
CN112041320B CN112041320B (zh) 2023-05-23

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US (1) US11339171B2 (zh)
EP (1) EP3733676A4 (zh)
JP (1) JP2021508727A (zh)
KR (1) KR20200105837A (zh)
CN (1) CN112041320B (zh)
AU (1) AU2018398881A1 (zh)
BR (1) BR112020013069A2 (zh)
CA (1) CA3087110A1 (zh)
CL (1) CL2020001685A1 (zh)
CO (1) CO2020009271A2 (zh)
EA (1) EA202091583A1 (zh)
IL (1) IL275667A (zh)
MX (1) MX2020006816A (zh)
PE (1) PE20211908A1 (zh)
SG (1) SG11202006262TA (zh)
WO (1) WO2019128877A1 (zh)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104080787A (zh) * 2011-11-29 2014-10-01 诺华股份有限公司 吡唑并吡咯烷化合物
CN104203952A (zh) * 2012-01-26 2014-12-10 诺华股份有限公司 咪唑并吡咯烷酮化合物
WO2015155332A1 (en) * 2014-04-11 2015-10-15 Boehringer Ingelheim International Gmbh Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors
WO2016001376A1 (en) * 2014-07-03 2016-01-07 Boehringer Ingelheim International Gmbh New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors
WO2017060431A1 (en) * 2015-10-09 2017-04-13 Boehringer Ingelheim International Gmbh Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors
CN106794171A (zh) * 2014-04-17 2017-05-31 密执安大学评议会 Mdm2抑制剂和使用其的治疗方法
CN106795168A (zh) * 2014-06-12 2017-05-31 阿达梅德公司 作为p53‑mdm2蛋白质‑蛋白质相互作用的抑制剂的包含1,1’,2,5’‑四氢螺[吲哚‑3,2’‑吡咯]‑2,5’‑二酮系统的化合物

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ611866A (en) * 2010-11-12 2015-04-24 Univ Michigan Spiro-oxindole mdm2 antagonists
CN104321325B (zh) * 2012-05-24 2016-11-16 诺华股份有限公司 吡咯并吡咯烷酮化合物

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104080787A (zh) * 2011-11-29 2014-10-01 诺华股份有限公司 吡唑并吡咯烷化合物
CN104203952A (zh) * 2012-01-26 2014-12-10 诺华股份有限公司 咪唑并吡咯烷酮化合物
WO2015155332A1 (en) * 2014-04-11 2015-10-15 Boehringer Ingelheim International Gmbh Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors
CN106794171A (zh) * 2014-04-17 2017-05-31 密执安大学评议会 Mdm2抑制剂和使用其的治疗方法
CN106795168A (zh) * 2014-06-12 2017-05-31 阿达梅德公司 作为p53‑mdm2蛋白质‑蛋白质相互作用的抑制剂的包含1,1’,2,5’‑四氢螺[吲哚‑3,2’‑吡咯]‑2,5’‑二酮系统的化合物
WO2016001376A1 (en) * 2014-07-03 2016-01-07 Boehringer Ingelheim International Gmbh New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors
WO2017060431A1 (en) * 2015-10-09 2017-04-13 Boehringer Ingelheim International Gmbh Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors

Also Published As

Publication number Publication date
CA3087110A1 (en) 2019-07-04
AU2018398881A1 (en) 2020-08-06
CL2020001685A1 (es) 2020-09-25
EP3733676A4 (en) 2021-09-01
KR20200105837A (ko) 2020-09-09
WO2019128877A1 (zh) 2019-07-04
IL275667A (en) 2020-08-31
PE20211908A1 (es) 2021-09-28
MX2020006816A (es) 2020-09-03
EA202091583A1 (ru) 2020-10-08
CN112041320B (zh) 2023-05-23
US11339171B2 (en) 2022-05-24
EP3733676A1 (en) 2020-11-04
US20210079007A1 (en) 2021-03-18
SG11202006262TA (en) 2020-07-29
CO2020009271A2 (es) 2020-08-10
JP2021508727A (ja) 2021-03-11
BR112020013069A2 (pt) 2020-12-01

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