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DK3183254T3 - Nye spiro[3h-indol-3,2 ?-pyrrolidin]-2(1h)-one forbindelser og derivater som mdm2-p53 inhibitorer - Google Patents

Nye spiro[3h-indol-3,2 ?-pyrrolidin]-2(1h)-one forbindelser og derivater som mdm2-p53 inhibitorer Download PDF

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Publication number
DK3183254T3
DK3183254T3 DK15751029.8T DK15751029T DK3183254T3 DK 3183254 T3 DK3183254 T3 DK 3183254T3 DK 15751029 T DK15751029 T DK 15751029T DK 3183254 T3 DK3183254 T3 DK 3183254T3
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DK
Denmark
Prior art keywords
mdm2
indol
pyrrolidine
inhibitors
derivatives
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DK15751029.8T
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English (en)
Inventor
Juergen Ramharter
Joachim Broeker
Annika Gille
Andreas Gollner
Manuel Henry
Nina Toelle
Harald Weinstabl
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Boehringer Ingelheim Int
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Publication of DK3183254T3 publication Critical patent/DK3183254T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/20—Spiro-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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring 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
    • A61K31/535—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
    • A61K31/5365—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 ortho- or peri-condensed with heterocyclic ring 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
    • A61K31/535—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
    • A61K31/537—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 spiro-condensed or forming part of bridged ring 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • 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
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/20—Spiro-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
    • C07D471/22—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 systems contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D487/02—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 two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Oncology (AREA)
  • Polymers & Plastics (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
DK15751029.8T 2014-08-21 2015-08-20 Nye spiro[3h-indol-3,2 ?-pyrrolidin]-2(1h)-one forbindelser og derivater som mdm2-p53 inhibitorer DK3183254T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14181746 2014-08-21
PCT/EP2015/069174 WO2016026937A1 (en) 2014-08-21 2015-08-20 New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors

Publications (1)

Publication Number Publication Date
DK3183254T3 true DK3183254T3 (da) 2019-08-19

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DK15751029.8T DK3183254T3 (da) 2014-08-21 2015-08-20 Nye spiro[3h-indol-3,2 ?-pyrrolidin]-2(1h)-one forbindelser og derivater som mdm2-p53 inhibitorer

Country Status (26)

Country Link
US (5) US10246467B2 (da)
EP (1) EP3183254B1 (da)
JP (1) JP6591532B2 (da)
KR (2) KR102627097B1 (da)
CN (1) CN107001385B (da)
AR (1) AR101600A1 (da)
AU (1) AU2015306128B2 (da)
BR (1) BR112017002942B1 (da)
CA (1) CA2956129C (da)
CL (1) CL2017000381A1 (da)
CY (1) CY1122127T1 (da)
DK (1) DK3183254T3 (da)
EA (1) EA038071B1 (da)
ES (1) ES2739697T3 (da)
HR (1) HRP20191414T1 (da)
HU (1) HUE046057T2 (da)
IL (1) IL250280B (da)
LT (1) LT3183254T (da)
MX (1) MX2017002260A (da)
PH (1) PH12017500252A1 (da)
PL (1) PL3183254T3 (da)
PT (1) PT3183254T (da)
RS (1) RS59111B1 (da)
SI (1) SI3183254T1 (da)
TW (1) TW201625617A (da)
WO (1) WO2016026937A1 (da)

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US10246467B2 (en) 2014-08-21 2019-04-02 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-p53 inhibitors
NO2721710T3 (da) 2014-08-21 2018-03-31
CN108137590B (zh) 2015-10-09 2021-04-09 勃林格殷格翰国际有限公司 作为mdm2-p53抑制剂的新的螺(3h-吲哚-3,2′-吡咯烷)-2(1h)-酮化合物及其衍生物
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BR112019021032A2 (pt) 2017-04-05 2020-05-05 Boehringer Ingelheim Int terapia combinada anticâncer
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WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
WO2023099592A1 (en) 2021-12-01 2023-06-08 Boehringer Ingelheim International Gmbh Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
CN118574836A (zh) 2021-12-01 2024-08-30 勃林格殷格翰国际有限公司 用于治疗癌症的环状2-胺基-3-氰基噻吩及衍生物
EP4441056A1 (en) 2021-12-01 2024-10-09 Boehringer Ingelheim International GmbH Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
PE20241356A1 (es) 2021-12-01 2024-07-03 Boehringer Ingelheim Int Tiofenos 2-amino-3-ciano anulados y derivados para el tratamiento del cancer
JP2024542692A (ja) 2021-12-01 2024-11-15 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 環化２－アミノ－３－シアノチオフェンを含むｋｒａ分解化合物
CN114831991B (zh) * 2022-06-10 2024-02-06 陕西科技大学 Gsk2334470用于制备抗真菌药物及其增效剂的应用
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US10246467B2 (en) * 2014-08-21 2019-04-02 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-p53 inhibitors
NO2721710T3 (da) 2014-08-21 2018-03-31
CN108137590B (zh) 2015-10-09 2021-04-09 勃林格殷格翰国际有限公司 作为mdm2-p53抑制剂的新的螺(3h-吲哚-3,2′-吡咯烷)-2(1h)-酮化合物及其衍生物

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MX2017002260A (es) 2017-05-03
AU2015306128A1 (en) 2017-02-23
SI3183254T1 (sl) 2019-08-30
US20170247394A1 (en) 2017-08-31
NZ728685A (en) 2024-01-26
CA2956129C (en) 2022-10-25
EP3183254B1 (en) 2019-05-22
US10246467B2 (en) 2019-04-02
BR112017002942B1 (pt) 2022-10-18
KR102627097B1 (ko) 2024-01-18
IL250280B (en) 2021-02-28
CL2017000381A1 (es) 2017-10-30
JP2017524025A (ja) 2017-08-24
RS59111B1 (sr) 2019-09-30
HUE046057T2 (hu) 2020-02-28
PH12017500252B1 (en) 2017-07-10
CN107001385B (zh) 2020-03-13
PH12017500252A1 (en) 2017-07-10
AU2015306128B2 (en) 2020-03-26
PT3183254T (pt) 2019-08-29
WO2016026937A1 (en) 2016-02-25
EP3183254A1 (en) 2017-06-28
US20190169209A1 (en) 2019-06-06
LT3183254T (lt) 2019-08-26
EA038071B1 (ru) 2021-07-01
HRP20191414T1 (hr) 2019-11-01
IL250280A0 (en) 2017-03-30
CA2956129A1 (en) 2016-02-25
PL3183254T3 (pl) 2019-10-31
KR20230098695A (ko) 2023-07-04
JP6591532B2 (ja) 2019-10-16
CY1122127T1 (el) 2020-11-25
CN107001385A (zh) 2017-08-01
AR101600A1 (es) 2016-12-28
US20240109913A1 (en) 2024-04-04
US20210101912A1 (en) 2021-04-08
US10919913B2 (en) 2021-02-16
BR112017002942A2 (pt) 2017-12-05
EA201790425A1 (ru) 2017-07-31
TW201625617A (zh) 2016-07-16
US20160052938A1 (en) 2016-02-25
ES2739697T3 (es) 2020-02-03
KR20170042779A (ko) 2017-04-19

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