AR101600A1 - COMPUESTOS DE SPIRO[3H-INDOL-3,2-PIRROLIDIN]-2(1H)-ONA Y DERIVADOS COMO INHIBIDORES DE MDM2-p53 - Google Patents

COMPUESTOS DE SPIRO[3H-INDOL-3,2-PIRROLIDIN]-2(1H)-ONA Y DERIVADOS COMO INHIBIDORES DE MDM2-p53

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AR101600A1
AR101600A1 ARP150102682A ARP150102682A AR101600A1 AR 101600 A1 AR101600 A1 AR 101600A1 AR P150102682 A ARP150102682 A AR P150102682A AR P150102682 A ARP150102682 A AR P150102682A AR 101600 A1 AR101600 A1 AR 101600A1
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alkyl
haloalkyl
independently selected
aryl
cycloalkenyl
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Weinstabl Harald
Toelle Nina
Henry Manuel
Gollner Andreas
Gille Annika
Broeker Joachim
Ramharter Juergen
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Boehringer Ingelheim Int
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    • 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
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    • 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
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    • 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
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    • 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
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    • 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
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    • 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
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    • 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
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    • 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
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    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • 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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  • 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)

Abstract

Su uso como inhibidores de la interacción MDM2-p53, composiciones farmacéuticas que contienen compuestos de esta clase, su uso como medicamentos, en especial como agentes para el tratamiento y/o prevención de las enfermedades oncológicas, e intermediarios sintéticos. Reivindicación 1: Un compuesto caracterizado porque tiene la fórmula (1), donde R¹ es un grupo, opcionalmente sustituido con uno o más, Rᵇ¹ y/o Rᶜ¹ idénticos o diferentes, seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᵇ¹ se selecciona de modo independiente de -ORᶜ¹, -NRᶜ¹Rᶜ¹, halógeno, -CN, -C(O)Rᶜ¹, -C(O)ORᶜ¹, -C(O)NRᶜ¹Rᶜ¹, -S(O)₂Rᶜ¹, -S(O)₂NRᶜ¹Rᶜ¹, -NHC(O)Rᶜ¹ y -N(alquilo C₁₋₄)C(O)Rᶜ¹; cada Rᶜ¹ de modo independiente entre sí indica hidrógeno o un grupo, opcionalmente sustituido con uno o más, Rᵈ¹ y/o Rᵉ¹ idénticos o diferentes, seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᵈ¹ se selecciona de modo independiente de -ORᵉ¹, -NRᵉ¹Rᵉ¹, halógeno, -CN, -C(O)Rᵉ¹, -C(O)ORᵉ¹, -C(O)NRᵉ¹Rᵉ¹, -S(O)₂Rᵉ¹, -S(O)₂NRᵉ¹Rᵉ¹, -NHC(O)Rᵉ¹ y -N(alquilo C₁₋₄)C(O)Rᵉ¹; cada Rᵉ¹ de modo independiente entre sí indica hidrógeno o un grupo, opcionalmente sustituido con uno o más, idénticos o diferentes Rᶠ¹ y/o Rᵍ¹, seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᶠ¹ se selecciona de modo independiente de -ORᵍ¹, -NRᵍ¹Rᵍ¹, halógeno, -CN, -C(O)Rᵍ¹, -C(O)ORᵍ¹, -C(O)NRᵍ¹Rᵍ¹, -S(O)₂Rᵍ¹, -S(O)₂NRᵍ¹Rᵍ¹, -NHC(O)Rᵍ¹ y -N(alquilo C₁₋₄)C(O)Rᵍ¹; cada Rᵍ¹ se selecciona de modo independiente de hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; R² y R³, cada uno se selecciona de modo independiente de hidrógeno, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros, donde este arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros está opcionalmente sustituido con uno o más, idénticos o diferentes Rᵇ² y/o Rᶜ²; cada Rᵇ² se selecciona de modo independiente de -ORᶜ², -NRᶜ²Rᶜ², halógeno, -CN, -C(O)Rᶜ², -C(O)ORᶜ², -C(O)NRᶜ²Rᶜ², -S(O)₂Rᶜ², -S(O)₂NRᶜ²Rᶜ², -NHC(O)Rᶜ² y -N(alquilo C₁₋₄)C(O)Rᶜ²; cada Rᶜ² de modo independiente entre sí indica hidrógeno o un grupo, opcionalmente sustituido con uno o más, idénticos o diferentes Rᵈ² y/o Rᵉ², seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₆, cicloalquenilo C₄₋₆, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᵈ² se selecciona de modo independiente de -ORᵉ², -NRᵉ²Rᵉ², halógeno, -CN, -C(O)Rᵉ², -C(O)ORᵉ², -C(O)NRᵉ²Rᵉ², -S(O)₂Rᵉ², -S(O)₂NRᵉ²Rᵉ², -NHC(O)Rᵉ² y -N(alquilo C₁₋₄)C(O)Rᵉ²; cada Rᵉ² de modo independiente entre sí indica hidrógeno o un grupo seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₆, cicloalquenilo C₄₋₆, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; A se selecciona de fenilo y heteroarilo de 5 - 6 miembros; cada R⁴ se selecciona de modo independiente de Rᵃ⁴ y Rᵇ⁴; cada Rᵃ⁴ de modo independiente entre sí es un grupo, opcionalmente sustituido con uno o más, idénticos o diferentes Rᵇ⁴ y/o Rᶜ⁴, seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₄₋₆, cicloalquilo C₃₋₆, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᵇ⁴ se selecciona de modo independiente de -ORᶜ⁴, -NRᶜ⁴Rᶜ⁴, halógeno, -CN, -C(O)Rᶜ⁴, -C(O)ORᶜ⁴, -C(O)NRᶜ⁴Rᶜ⁴, -C(O)NRᵍ⁴ORᶜ⁴, -S(O)₂Rᶜ⁴, -S(O)₂NRᶜ⁴Rᶜ⁴, -NHSO₂Rᶜ⁴, -N(alquilo C₁₋₄)SO₂Rᶜ⁴, -NHC(O)Rᶜ⁴ y -N(alquilo C₁₋₄)C(O)Rᶜ⁴; cada Rᶜ⁴ de modo independiente entre sí indica hidrógeno o un grupo, opcionalmente sustituido con uno o más, idénticos o diferentes Rᵈ⁴ y/o Rᵉ⁴, seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᵈ⁴ se selecciona de modo independiente de -ORᵉ⁴, -NRᵉ⁴Rᵉ⁴, halógeno, -CN, -C(O)Rᵉ⁴, -C(O)ORᵉ⁴, -C(O)NRᵉ⁴Rᵉ⁴, -C(O)NRᵍ⁴ORᵉ⁴, -S(O)₂Rᵉ⁴, -S(O)₂NRᵉ⁴Rᵉ⁴, -NHC(O)Rᵉ⁴ y -N(alquilo C₁₋₄)C(O)Rᵉ⁴; cada Rᵉ⁴ de modo independiente entre sí indica hidrógeno o un grupo, opcionalmente sustituido con uno o más, idénticos o diferentes Rᶠ⁴ y/o Rᵍ⁴, seleccionadas de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; cada Rᶠ⁴ se selecciona de modo independiente de -ORᵍ⁴, -NRᵍ⁴Rᵍ⁴, halógeno, -CN, -C(O)Rᵍ⁴, -C(O)ORᵍ⁴, -C(O)NRᵍ⁴Rᵍ⁴, -C(O)NRᵍ⁴ORᵍ⁴, -S(O)₂Rᵍ⁴, -S(O)₂NRᵍ⁴Rᵍ⁴, -NHC(O)Rᵍ⁴ y -N(alquilo C₁₋₄)C(O)Rᵍ⁴; cada Rᵍ⁴ se selecciona de modo independiente de hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 10 miembros; r indica el número 0, 1, 2 ó 3; R⁵ y R⁶, cada uno se selecciona de modo independiente de hidrógeno, alquilo C₁₋₄ y haloalquilo C₁₋₄; n indica el número 0 ó 1; cada R⁷ se selecciona de modo independiente de halógeno, alquilo C₁₋₄, -CN, haloalquilo C₁₋₄, -O alquilo C₁₋₄ y -O haloalquilo C₁₋₄; q indica el número 0, 1, 2 ó 3; W, X e Y cada uno se selecciona de modo independiente de -N= y -CH= con la condición de que el hidrógeno en cada -CH= se puede reemplazar con un sustituyente R⁷ si está presente y que un máximo de dos de W, X e Y puede ser -N=; V es oxígeno o azufre; o una de sus sales.
ARP150102682A 2014-08-21 2015-08-20 COMPUESTOS DE SPIRO[3H-INDOL-3,2-PIRROLIDIN]-2(1H)-ONA Y DERIVADOS COMO INHIBIDORES DE MDM2-p53 AR101600A1 (es)

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US10138251B2 (en) 2014-04-11 2018-11-27 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors
US10576064B2 (en) 2014-07-03 2020-03-03 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors
KR102627097B1 (ko) 2014-08-21 2024-01-18 베링거 인겔하임 인터내셔날 게엠베하 Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체
NO2721710T3 (es) 2014-08-21 2018-03-31
EA036013B1 (ru) 2015-10-09 2020-09-14 Бёрингер Ингельхайм Интернациональ Гмбх Новые спиро[3h-индол-3,2'-пирролидин]-2(1h)-оновые соединения и производные в качестве ингибиторов mdm2-p53
CN113788818A (zh) 2016-04-06 2021-12-14 密执安大学评议会 Mdm2蛋白质降解剂
EP3458101B1 (en) 2016-05-20 2020-12-30 H. Hoffnabb-La Roche Ag Protac antibody conjugates and methods of use
JP2020516604A (ja) 2017-04-05 2020-06-11 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 抗がん併用療法
CN107290543A (zh) * 2017-05-02 2017-10-24 南方医科大学 一种检测细胞内与p53转录激活域相互作用蛋白的方法
EP3511334A1 (en) * 2018-01-16 2019-07-17 Adamed sp. z o.o. 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53
JP2020193181A (ja) * 2019-05-30 2020-12-03 東ソー株式会社 芳香族ニトリル化合物の製造方法
CN114072140A (zh) * 2019-07-17 2022-02-18 讷克斯药物有限公司 使用异黄酮类化合物的免疫肿瘤治疗
EP4157836A1 (en) 2020-06-02 2023-04-05 Boehringer Ingelheim International GmbH Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
CN112375086A (zh) * 2020-12-11 2021-02-19 浙江工业大学 一种手性螺[呋喃-3,3′-假吲哚]-2-酮类化合物的制备方法
RU2770902C1 (ru) * 2021-05-24 2022-04-25 Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) 3-Арил-6H-спиро[бензо[b]фуро[3',4':2,3]пирроло[1,2-d][1,4]оксазин 5,3'-индолин]-1,2,2',6-тетраоны, обладающие противовоспалительной активностью, и способ их получения
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
TW202337431A (zh) 2021-12-01 2023-10-01 德商百靈佳殷格翰國際股份有限公司 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物
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
WO2023099620A1 (en) 2021-12-01 2023-06-08 Boehringer Ingelheim International Gmbh Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes
WO2023099608A1 (en) 2021-12-01 2023-06-08 Boehringer Ingelheim International Gmbh Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
WO2023099623A1 (en) 2021-12-01 2023-06-08 Boehringer Ingelheim International Gmbh Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
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
US11944604B1 (en) 2023-03-10 2024-04-02 King Saud University Nanoformulation of spriooxindole and methods for treating hepatocellular carcinoma

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU9307098A (en) 1997-09-08 1999-03-29 Arqule, Inc. Spiro{pyrrolidine-2,3'-oxindole} compounds and methods of use
JP2006234861A (ja) 2005-02-22 2006-09-07 Fujinon Sano Kk 光学ガラスの製造方法，偏光変換素子の製造方法及び偏光変換素子
EA019566B1 (ru) * 2005-02-22 2014-04-30 Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган Низкомолекулярные ингибиторы mdm2
CA2598956A1 (en) 2005-02-24 2006-08-31 Pfizer Products Inc. Bicyclic heteroaromatic derivatives useful as anticancer agents
AR073578A1 (es) 2008-09-15 2010-11-17 Priaxon Ag Pirrolidin-2-onas
US8076482B2 (en) * 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
JO2998B1 (ar) 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
US20120071499A1 (en) * 2010-09-20 2012-03-22 Xin-Jie Chu Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones
US20130053410A1 (en) * 2011-03-03 2013-02-28 David Joseph Bartkovitz Substituted heteroaryl 2',3',7',7a'-tetrahydrospiro[pyrrole-3,6'-pyrrolo[1,2-c]imidazole]-1',2(1h,5'h)-dione
CN102443004A (zh) 2011-11-01 2012-05-09 南京工业大学 有机发光材料6,7,14,15-四氢-5,13-二取代苯并[1,2-c:4,5-c’]二吖啶类化合物、合成方法及应用
CN103910746B (zh) * 2014-02-28 2016-08-03 中山大学 一类海洋真菌来源的Berkeleyones化合物及其制备方法和应用
US10138251B2 (en) 2014-04-11 2018-11-27 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors
US10576064B2 (en) 2014-07-03 2020-03-03 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors
KR102627097B1 (ko) 2014-08-21 2024-01-18 베링거 인겔하임 인터내셔날 게엠베하 Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체
NO2721710T3 (es) 2014-08-21 2018-03-31
EA036013B1 (ru) 2015-10-09 2020-09-14 Бёрингер Ингельхайм Интернациональ Гмбх Новые спиро[3h-индол-3,2'-пирролидин]-2(1h)-оновые соединения и производные в качестве ингибиторов mdm2-p53

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