AU2016314082B2 - Mdm2 inhibitors and combinations thereof - Google Patents

Mdm2 inhibitors and combinations thereof Download PDF

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Publication number
AU2016314082B2
AU2016314082B2 AU2016314082A AU2016314082A AU2016314082B2 AU 2016314082 B2 AU2016314082 B2 AU 2016314082B2 AU 2016314082 A AU2016314082 A AU 2016314082A AU 2016314082 A AU2016314082 A AU 2016314082A AU 2016314082 B2 AU2016314082 B2 AU 2016314082B2
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AU
Australia
Prior art keywords
compound
combination
inhibitor
methyl
cell
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Ceased
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AU2016314082A
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AU2016314082A1 (en
Inventor
Giordano Caponigro
Ensar HALILOVIC
Thomas HORN-SPIROHN
Joseph Lehar
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Novartis AG
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Novartis AG
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Application filed by Novartis AG filed Critical Novartis AG
Publication of AU2016314082A1 publication Critical patent/AU2016314082A1/en
Priority to AU2019204938A priority Critical patent/AU2019204938B2/en
Application granted granted Critical
Publication of AU2016314082B2 publication Critical patent/AU2016314082B2/en
Ceased legal-status Critical Current
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4412Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/63Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
AU2016314082A 2015-08-28 2016-08-24 Mdm2 inhibitors and combinations thereof Ceased AU2016314082B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2019204938A AU2019204938B2 (en) 2015-08-28 2019-07-09 Mdm2 inhibitors and combinations thereof

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201562211080P 2015-08-28 2015-08-28
US62/211,080 2015-08-28
US201562243337P 2015-10-19 2015-10-19
US62/243,337 2015-10-19
US201562250574P 2015-11-04 2015-11-04
US62/250,574 2015-11-04
PCT/IB2016/055050 WO2017037579A1 (en) 2015-08-28 2016-08-24 Mdm2 inhibitors and combinations thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2019204938A Division AU2019204938B2 (en) 2015-08-28 2019-07-09 Mdm2 inhibitors and combinations thereof

Publications (2)

Publication Number Publication Date
AU2016314082A1 AU2016314082A1 (en) 2018-02-08
AU2016314082B2 true AU2016314082B2 (en) 2019-07-25

Family

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AU2016314082A Ceased AU2016314082B2 (en) 2015-08-28 2016-08-24 Mdm2 inhibitors and combinations thereof
AU2019204938A Ceased AU2019204938B2 (en) 2015-08-28 2019-07-09 Mdm2 inhibitors and combinations thereof

Family Applications After (1)

Application Number Title Priority Date Filing Date
AU2019204938A Ceased AU2019204938B2 (en) 2015-08-28 2019-07-09 Mdm2 inhibitors and combinations thereof

Country Status (11)

Country Link
US (3) US20190060309A1 (cg-RX-API-DMAC7.html)
EP (2) EP4241850A3 (cg-RX-API-DMAC7.html)
JP (2) JP2018528206A (cg-RX-API-DMAC7.html)
KR (1) KR20180041677A (cg-RX-API-DMAC7.html)
CN (2) CN111821306A (cg-RX-API-DMAC7.html)
AU (2) AU2016314082B2 (cg-RX-API-DMAC7.html)
CA (1) CA2992221C (cg-RX-API-DMAC7.html)
ES (1) ES2962460T3 (cg-RX-API-DMAC7.html)
IL (2) IL257015B (cg-RX-API-DMAC7.html)
RU (2) RU2020142739A (cg-RX-API-DMAC7.html)
WO (1) WO2017037579A1 (cg-RX-API-DMAC7.html)

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TW201613576A (en) 2014-06-26 2016-04-16 Novartis Ag Intermittent dosing of MDM2 inhibitor
US11672801B2 (en) 2016-10-19 2023-06-13 United States Government As Represented By The Department Of Veterans Affairs Compositions and methods for treating cancer
US11040027B2 (en) 2017-01-17 2021-06-22 Heparegenix Gmbh Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death
US11285154B2 (en) 2017-03-29 2022-03-29 United States Government As Represented By The Department Of Veterans Affairs Methods and compositions for treating cancer
WO2018178925A1 (en) * 2017-03-31 2018-10-04 Novartis Ag Dose and regimen for an hdm2-p53 interaction inhibitor in hematological tumors
WO2019040511A1 (en) * 2017-08-22 2019-02-28 University Of Maryland Batimore DOUBLE INHIBITORS OF BCL-2 AND HDM2 FAMILIES BY CO-MIMETTISM OF ALPHA BH3 AND P53 PROPELLERS
CN111868039A (zh) * 2017-09-26 2020-10-30 加利福尼亚大学董事会 用于治疗癌症的组合物和方法
EP3694518A1 (en) * 2017-10-12 2020-08-19 Novartis AG Combinations of mdm2 inhibitors with inhibitors of erk for treating cancers
US12053454B2 (en) * 2017-12-31 2024-08-06 Evergreen Biosciences Compositions for cryopreservation and methods of use thereof
US11639355B2 (en) 2018-03-12 2023-05-02 Luoxin Pharmaceutical (Shanghai) Co., Ltd. Substituted pyrrolo[3,4-d]imidazoles as MDM2-p53 inhibitors
CA3092307A1 (en) * 2018-03-20 2019-09-26 Novartis Ag Pharmaceutical combinations
CN110772521A (zh) 2018-07-31 2020-02-11 苏州亚盛药业有限公司 Bcl-2抑制剂或Bcl-2/Bcl-xL抑制剂与BTK抑制剂的组合产品及其用途
AU2019314819A1 (en) 2018-07-31 2020-10-22 Ascentage Pharma (Suzhou) Co., Ltd. Combination product of Bcl-2 inhibitor and chemotherapeutic agent and use thereof in the prevention and/or treatment of diseases
CA3092753C (en) 2018-07-31 2023-10-17 Ascentage Pharma (Suzhou) Co., Ltd. Synergistic antitumor effect of bcl-2 inhibitor combined with rituximab
UA126098C2 (uk) * 2018-07-31 2022-08-10 Есентейдж Фарма (Сучжоу) Ко., Лтд. КОМБІНОВАНИЙ ПРОДУКТ НА ОСНОВІ ІНГІБІТОРА Bcl-2 ТА ІНГІБІТОРА MDM2 ТА ЙОГО ЗАСТОСУВАННЯ В ПОПЕРЕДЖЕННІ ТА/АБО ЛІКУВАННІ ЗАХВОРЮВАНЬ
MX2021007391A (es) * 2018-12-20 2021-09-23 Novartis Ag Regimenes de baja dosis extendida para inhibidores de mdm2.
WO2021018032A1 (en) * 2019-07-26 2021-02-04 Ascentage Pharma (Suzhou) Co., Ltd. Pharmaceutical composition of mdm2 inhibitor and use thereof for preventing and/or treating disease
TWI772992B (zh) * 2019-12-03 2022-08-01 大陸商蘇州亞盛藥業有限公司 作為bcl-2抑制劑的n-(苯基磺醯基)苯甲醯胺及相關化合物
TW202200147A (zh) * 2020-05-26 2022-01-01 韓商韓美藥品股份有限公司 Belvarafenib用於癌症治療
CN115124533A (zh) * 2021-03-26 2022-09-30 浙江海正药业股份有限公司 四环类衍生物、其制备方法和其医药上的用途
JP2024157057A (ja) * 2021-06-29 2024-11-07 国立大学法人 東京大学 バレット食道の治療用組成物
CN117562907B (zh) * 2023-11-17 2025-08-22 广州医科大学 一种提升抗癌效果的可口服吉非替尼复合物及其制备方法与应用

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US20130281473A1 (en) * 2009-12-22 2013-10-24 Novartis Ag Substituted isoquinolinones and quinazolinones
EP2752191A1 (en) * 2013-01-07 2014-07-09 Sanofi Compositions and methods using hdm2 antagonist and mek inhibitor
WO2015070224A2 (en) * 2013-11-11 2015-05-14 Amgen Inc. Combination therapy including an mdm2 inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers
WO2015084804A1 (en) * 2013-12-03 2015-06-11 Novartis Ag Combination of mdm2 inhibitor and braf inhibitor and their use

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US20130281473A1 (en) * 2009-12-22 2013-10-24 Novartis Ag Substituted isoquinolinones and quinazolinones
EP2752191A1 (en) * 2013-01-07 2014-07-09 Sanofi Compositions and methods using hdm2 antagonist and mek inhibitor
WO2015070224A2 (en) * 2013-11-11 2015-05-14 Amgen Inc. Combination therapy including an mdm2 inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers
WO2015084804A1 (en) * 2013-12-03 2015-06-11 Novartis Ag Combination of mdm2 inhibitor and braf inhibitor and their use

Also Published As

Publication number Publication date
AU2019204938B2 (en) 2020-07-16
EP3340989B1 (en) 2023-08-16
RU2018110770A3 (cg-RX-API-DMAC7.html) 2020-01-15
RU2020142739A (ru) 2021-01-15
US20230398115A1 (en) 2023-12-14
US20210260059A1 (en) 2021-08-26
EP3340989A1 (en) 2018-07-04
JP2021042222A (ja) 2021-03-18
CA2992221C (en) 2023-06-27
CN111821306A (zh) 2020-10-27
EP4241850A2 (en) 2023-09-13
RU2018110770A (ru) 2019-09-30
AU2016314082A1 (en) 2018-02-08
US20190060309A1 (en) 2019-02-28
AU2019204938A1 (en) 2019-07-25
ES2962460T3 (es) 2024-03-19
KR20180041677A (ko) 2018-04-24
RU2020142739A3 (cg-RX-API-DMAC7.html) 2021-05-20
IL257015A (en) 2018-03-29
IL257015B (en) 2022-02-01
CA2992221A1 (en) 2017-03-09
CN108348520A (zh) 2018-07-31
RU2740091C2 (ru) 2021-01-11
JP2018528206A (ja) 2018-09-27
EP4241850A3 (en) 2023-11-08
IL277239B (en) 2022-04-01
WO2017037579A1 (en) 2017-03-09
IL277239A (en) 2020-10-29

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