IL264950B2 - Combined treatments for the treatment of malignant liver cell carcinoma - Google Patents
Combined treatments for the treatment of malignant liver cell carcinomaInfo
- Publication number
- IL264950B2 IL264950B2 IL264950A IL26495019A IL264950B2 IL 264950 B2 IL264950 B2 IL 264950B2 IL 264950 A IL264950 A IL 264950A IL 26495019 A IL26495019 A IL 26495019A IL 264950 B2 IL264950 B2 IL 264950B2
- Authority
- IL
- Israel
- Prior art keywords
- pharmaceutically acceptable
- pyrimidin
- acceptable salt
- amino
- ethylpiperazin
- Prior art date
Links
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Classifications
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
-
- 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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/495—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- 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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| US201662378455P | 2016-08-23 | 2016-08-23 | |
| PCT/US2017/048183 WO2018039324A1 (en) | 2016-08-23 | 2017-08-23 | Combination therapies for the treatment of hepatocellular carcinoma |
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| IL264950A IL264950A (en) | 2019-05-30 |
| IL264950B1 IL264950B1 (en) | 2023-09-01 |
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| EP (1) | EP3503923B1 (enExample) |
| JP (1) | JP7190425B2 (enExample) |
| KR (1) | KR102466192B1 (enExample) |
| CN (1) | CN109803684B (enExample) |
| AU (1) | AU2017315357B2 (enExample) |
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| CA (1) | CA3034875C (enExample) |
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| IL (1) | IL264950B2 (enExample) |
| MX (1) | MX2019002115A (enExample) |
| RU (1) | RU2769251C2 (enExample) |
| SG (1) | SG11201901472TA (enExample) |
| WO (1) | WO2018039324A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| SG11202005937QA (en) | 2018-01-08 | 2020-07-29 | G1 Therapeutics Inc | G1t38 superior dosage regimes |
| HUE064843T2 (hu) | 2018-05-14 | 2024-04-28 | Pfizer | Orális oldat kiszerelés |
| TW202128173A (zh) * | 2019-10-09 | 2021-08-01 | 美商G1治療公司 | 失調之纖維母細胞生長因子受體訊息傳遞的癌症之標靶性治療 |
| WO2021230886A1 (en) * | 2020-05-15 | 2021-11-18 | Eisai R&D Management Co., Ltd. | A method for treating cancer with an oral dosage form of an fgfr4 inhibitor |
| CN117479958A (zh) | 2022-05-30 | 2024-01-30 | 石药集团中奇制药技术（石家庄）有限公司 | 用于治疗癌症的药物组合和药物组合物 |
| CN120417928A (zh) * | 2023-11-30 | 2025-08-01 | 石药集团中奇制药技术（石家庄）有限公司 | 联合治疗肿瘤的药物 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011130232A1 (en) * | 2010-04-13 | 2011-10-20 | Novartis Ag | Combination comprising a cyclin dependent kinase 4 or cyclin dependent kinase (cdk4/6) inhibitor and an mtor inhibitor for treating cancer |
| WO2013006368A1 (en) * | 2011-07-01 | 2013-01-10 | Novartis Ag | Combination therapy |
| WO2015057938A1 (en) * | 2013-10-18 | 2015-04-23 | Eisai R&D Management Co., Ltd. | Pyrimidine fgfr4 inhibitors |
| WO2016025650A1 (en) * | 2014-08-13 | 2016-02-18 | Celgene Avilomics Research, Inc. | Combinations of an erk inhibitor and a cdk4/6 inhibitor and related methods |
| WO2016168331A1 (en) * | 2015-04-14 | 2016-10-20 | Eisai R&D Management Co., Ltd. | Crystalline fgfr4 inhibitor compound and uses thereof |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6399633B1 (en) | 1999-02-01 | 2002-06-04 | Aventis Pharmaceuticals Inc. | Use of 4-H-1-benzopryan-4-one derivatives as inhibitors of smooth muscle cell proliferation |
| DE19959546A1 (de) | 1999-12-09 | 2001-06-21 | Rhone Poulenc Rorer Gmbh | Pharmazeutische Zubereitung zur Behandlung von Tumorerkrankungen |
| JP2003520798A (ja) | 2000-01-18 | 2003-07-08 | アベンテイス・フアーマシユーチカルズ・インコーポレーテツド | （−）−シス−２−（２−クロロフェニル）−５，７−ジヒドロキシ−８［４ｒ−（３ｓ−ヒドロキシ−１−メチル）ピペリジニル］−４ｈ−１−ベンゾピラン−４−オンのエタノール溶媒化合物 |
| EA005247B1 (ru) | 2000-01-18 | 2004-12-30 | Авентис Фармасьютикалз Инк. | Псевдополиморф (-)-цис-2-(2-хлорфенил)-5,7-дигидрокси-8[4r-(3s-гидрокси-1-метил)пиперидинил]-4h-1-бензопиран-4-она |
| WO2002022133A1 (en) | 2000-09-12 | 2002-03-21 | Virginia Commonwealth University | Promotion of adoptosis in cancer cells by co-administration of cyclin dependent kinase inhibitors and cellular differentiation agents |
| ATE314370T1 (de) | 2002-01-22 | 2006-01-15 | Warner Lambert Co | 2-(pyridin-2-ylamino)-pyrido(2,3-d)pyrimidin-7- one |
| WO2005012256A1 (en) | 2003-07-22 | 2005-02-10 | Astex Therapeutics Limited | 3, 4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US20080161355A1 (en) | 2005-01-21 | 2008-07-03 | Astex Therapeutics Limited | Combinations of Pyrazole Kinase Inhibitors and Further Antitumor Agents |
| CA2594477C (en) | 2005-01-21 | 2016-07-12 | Astex Therapeutics Limited | Pharmaceutical compounds |
| US20080161251A1 (en) | 2005-01-21 | 2008-07-03 | Astex Therapeutics Limited | Pharmaceutical Compounds |
| JP2008255008A (ja) | 2005-07-19 | 2008-10-23 | Tokyo Medical & Dental Univ | 滑膜細胞増殖抑制剤 |
| JO3235B1 (ar) | 2006-05-26 | 2018-03-08 | Astex Therapeutics Ltd | مركبات بيررولوبيريميدين و استعمالاتها |
| US20110159111A1 (en) | 2006-06-29 | 2011-06-30 | Astex Therapeutics Limited | Pharmaceutical combinations |
| US20090263398A1 (en) | 2006-07-14 | 2009-10-22 | Astex Therapeutics Limited | Pharmaceutical combinations |
| US20100021420A1 (en) | 2006-07-14 | 2010-01-28 | Astex Therapeutics Limited | Combinations of pyrazole derivatives for the inhibition of cdks and gsk's |
| US20090318430A1 (en) | 2006-07-21 | 2009-12-24 | Astex Therapeutics Limited | Medical use of cyclin dependent kinases inhibitors |
| EP1918376A1 (en) * | 2006-11-03 | 2008-05-07 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | FGFR4 promotes cancer cell resistance in response to chemotherapeutic drugs |
| US7902147B2 (en) | 2007-11-05 | 2011-03-08 | Duke University | Chronic lymphocytic leukemia prognosis and treatment |
| JP5351254B2 (ja) * | 2008-05-23 | 2013-11-27 | ノバルティス アーゲー | キノキサリン−およびキノリン−カルボキシアミド誘導体 |
| EA019094B1 (ru) | 2008-08-22 | 2014-01-30 | Новартис Аг | Пирролопиримидины и их применение |
| PA8852901A1 (es) | 2008-12-22 | 2010-07-27 | Lilly Co Eli | Inhibidores de proteina cinasa |
| AR079257A1 (es) * | 2009-12-07 | 2012-01-04 | Novartis Ag | Formas cristalinas de 3-(2,6-dicloro-3-5-dimetoxi-fenil)-1-{6-[4-(4-etil-piperazin-1-il)-fenil-amino]-pirimidin-4-il}-1-metil-urea y sales de las mismas |
| UY33226A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina deuterada como inhibidores de la cdk4/6 |
| CN103429243B (zh) | 2010-10-25 | 2016-06-08 | G1治疗公司 | Cdk抑制剂 |
| US20120115878A1 (en) | 2010-11-10 | 2012-05-10 | John Vincent Calienni | Salt(s) of 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide and processes of making thereof |
| DK2937349T3 (en) | 2011-03-23 | 2017-02-20 | Amgen Inc | CONDENSED TRICYCLIC DUAL INHIBITORS OF CDK 4/6 AND FLT3 |
| AR091876A1 (es) * | 2012-07-26 | 2015-03-04 | Novartis Ag | Combinaciones farmaceuticas para el tratamiento de enfermedades proliferativas |
| WO2014097125A1 (en) * | 2012-12-20 | 2014-06-26 | Novartis Ag | Pharmaceutical combination comprising binimetinib |
| DK2945628T3 (da) * | 2013-01-15 | 2020-05-04 | Aragon Pharmaceuticals Inc | Androgen receptormodulator i kombination med abirateronacetat og prednison til behandling af prostatacancer |
| CA2906166C (en) | 2013-03-15 | 2023-03-14 | G1 Therapeutics, Inc. | Hspc-sparing treatments for rb-positive abnormal cellular proliferation |
| SI3033086T1 (sl) * | 2013-08-14 | 2022-01-31 | Novartis Ag | Kombinirana terapija za zdravljenje raka |
| WO2016040848A1 (en) | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Treatment of rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors |
| CN104529904B (zh) | 2015-01-09 | 2016-08-31 | 苏州明锐医药科技有限公司 | 玻玛西尼的制备方法 |
| WO2016126889A1 (en) | 2015-02-03 | 2016-08-11 | G1 Therapeutics, Inc. | Cdk4/6 inhibitor dosage formulations for the protection of hematopoietic stem and progenitor cells during chemotherapy |
-
2017
- 2017-08-23 US US16/324,643 patent/US20190175598A1/en not_active Abandoned
- 2017-08-23 BR BR112019003722A patent/BR112019003722A2/pt not_active Application Discontinuation
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- 2017-08-23 JP JP2019511500A patent/JP7190425B2/ja active Active
- 2017-08-23 CN CN201780062334.3A patent/CN109803684B/zh active Active
- 2017-08-23 AU AU2017315357A patent/AU2017315357B2/en active Active
- 2017-08-23 KR KR1020197008327A patent/KR102466192B1/ko active Active
- 2017-08-23 EP EP17761701.6A patent/EP3503923B1/en active Active
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- 2017-08-23 MX MX2019002115A patent/MX2019002115A/es unknown
- 2017-08-23 WO PCT/US2017/048183 patent/WO2018039324A1/en not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011130232A1 (en) * | 2010-04-13 | 2011-10-20 | Novartis Ag | Combination comprising a cyclin dependent kinase 4 or cyclin dependent kinase (cdk4/6) inhibitor and an mtor inhibitor for treating cancer |
| WO2013006368A1 (en) * | 2011-07-01 | 2013-01-10 | Novartis Ag | Combination therapy |
| WO2015057938A1 (en) * | 2013-10-18 | 2015-04-23 | Eisai R&D Management Co., Ltd. | Pyrimidine fgfr4 inhibitors |
| WO2016025650A1 (en) * | 2014-08-13 | 2016-02-18 | Celgene Avilomics Research, Inc. | Combinations of an erk inhibitor and a cdk4/6 inhibitor and related methods |
| WO2016168331A1 (en) * | 2015-04-14 | 2016-10-20 | Eisai R&D Management Co., Ltd. | Crystalline fgfr4 inhibitor compound and uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| RIVADENEIRA D B ET AL,, PROLIFERATIVE SUPPRESSION BY CDK4/6 INHIBITION: COMPLEX FUNCTION OF THE RETINOBLASTOMA PATHWAY IN LIVER TISSUE AND HEPATOMA CELLS, 25 January 2010 (2010-01-25) * |
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| MX2019002115A (es) | 2019-07-08 |
| AU2017315357A1 (en) | 2019-02-28 |
| CA3034875C (en) | 2024-05-28 |
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| ES2966469T3 (es) | 2024-04-22 |
| EP3503923A1 (en) | 2019-07-03 |
| RU2769251C2 (ru) | 2022-03-29 |
| CN109803684B (zh) | 2022-08-23 |
| JP2019528302A (ja) | 2019-10-10 |
| EP3503923B1 (en) | 2023-10-04 |
| CA3034875A1 (en) | 2018-03-01 |
| RU2019108259A3 (enExample) | 2020-11-24 |
| IL264950A (en) | 2019-05-30 |
| IL264950B1 (en) | 2023-09-01 |
| KR20190040996A (ko) | 2019-04-19 |
| BR112019003722A2 (pt) | 2019-05-28 |
| SG11201901472TA (en) | 2019-03-28 |
| AU2017315357B2 (en) | 2022-12-01 |
| WO2018039324A1 (en) | 2018-03-01 |
| US20190175598A1 (en) | 2019-06-13 |
| CN109803684A (zh) | 2019-05-24 |
| JP7190425B2 (ja) | 2022-12-15 |
| RU2019108259A (ru) | 2020-09-25 |
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