TWI849043B - B-raf激酶二聚體抑制劑之穩定固體分散體、製備方法及其用途 - Google Patents

B-raf激酶二聚體抑制劑之穩定固體分散體、製備方法及其用途 Download PDF

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TWI849043B
TWI849043B TW109102401A TW109102401A TWI849043B TW I849043 B TWI849043 B TW I849043B TW 109102401 A TW109102401 A TW 109102401A TW 109102401 A TW109102401 A TW 109102401A TW I849043 B TWI849043 B TW I849043B
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compound
hpmcas
solid dispersion
amorphous solid
stable amorphous
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TW109102401A
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TW202043225A (zh
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張國良
昌友 周
孫熀彬
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英屬開曼群島商百濟神州有限公司
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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
    • A61K31/435—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
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs
    • 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
    • C07D471/02—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 two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Dispersion Chemistry (AREA)
TW109102401A 2019-01-25 2020-01-22 B-raf激酶二聚體抑制劑之穩定固體分散體、製備方法及其用途 TWI849043B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN2019073254 2019-01-25
WOPCT/CN2019/073254 2019-01-25
CN2019095227 2019-07-09
WOPCT/CN2019/095227 2019-07-09

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TW202043225A TW202043225A (zh) 2020-12-01
TWI849043B true TWI849043B (zh) 2024-07-21

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TW113123511A TWI909513B (zh) 2019-01-25 2020-01-22 作為ｂ-ｒａｆ激酶二聚體抑制劑之化合物及其製備方法

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US (1) US12582604B2 (enExample)
EP (1) EP3914591A4 (enExample)
JP (2) JP7591504B2 (enExample)
KR (1) KR20210120039A (enExample)
CN (1) CN113330011A (enExample)
AU (1) AU2020211000B2 (enExample)
BR (1) BR112021014563A2 (enExample)
CA (1) CA3123476A1 (enExample)
IL (1) IL284636A (enExample)
MX (1) MX2021008884A (enExample)
SG (1) SG11202107849RA (enExample)
TW (2) TWI849043B (enExample)
WO (1) WO2020151756A1 (enExample)
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Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111484490B (zh) * 2019-01-25 2024-07-09 百济神州有限公司 适合大规模生产b-raf激酶二聚体抑制剂的方法
TWI849043B (zh) 2019-01-25 2024-07-21 英屬開曼群島商百濟神州有限公司 B-raf激酶二聚體抑制劑之穩定固體分散體、製備方法及其用途
AU2021412688B2 (en) * 2020-12-29 2025-06-12 Txinno Bioscience Inc. Novel naphthyridinone derivative having inhibitory activity against ectonucleotide pyrophosphatase-phosphodiesterase and use thereof
KR102889693B1 (ko) 2021-09-08 2025-11-20 주식회사 엘지에너지솔루션 배터리 진단 장치, 배터리 관리 시스템, 배터리 팩, 전기 차량 및 배터리 진단 방법
CN114366717B (zh) * 2022-01-11 2023-06-09 四川农业大学 一种基于egcg纳米粒的肠溶固体分散体颗粒、制备方法及其应用
JP2025519981A (ja) * 2022-06-08 2025-06-30 マップキュア，エルエルシー Ｂ－ｒａｆ阻害剤によるがんの治療方法
JP2025532826A (ja) * 2022-09-26 2025-10-03 マップキュア，エルエルシー がんの処置のためのｂ－ｒａｆ阻害剤と、抗ｅｇｆｒ抗体との組み合わせ
JP2026507361A (ja) * 2023-03-10 2026-03-02 エスティー ファーム カンパニー リミテッド 新規固体分散体およびその製造方法
TW202515875A (zh) 2023-10-12 2025-04-16 瑞士商百濟神州瑞士有限責任公司 包含b-raf激酶二聚體抑制劑之固體形式、其製備方法及用途
WO2025252204A1 (en) * 2024-06-07 2025-12-11 Beigene (Suzhou) Co., Ltd. Amorphous solid dispersions of a braf inhibitor

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011025947A1 (en) * 2009-08-28 2011-03-03 Array Biopharma Inc. Raf inhibitor compounds and methods of use thereof
WO2014206344A1 (en) * 2013-06-28 2014-12-31 Beigene, Ltd. Fused tricyclic amide compounds as multiple kinase inhibitors
WO2014206343A1 (en) * 2013-06-28 2014-12-31 Beigene, Ltd. Fused tricyclic urea compounds as raf kinase and/or raf kinase dimer inhibitors

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6350786B1 (en) 1998-09-22 2002-02-26 Hoffmann-La Roche Inc. Stable complexes of poorly soluble compounds in ionic polymers
EP1027885B1 (en) 1999-02-09 2008-07-09 Pfizer Products Inc. Basic drug compositions with enhanced bioavailability
SE0100733D0 (sv) 2001-03-05 2001-03-05 Medivir Ab Non-nucleoside reverse transcriptase inhibitors
KR20050033663A (ko) 2002-09-05 2005-04-12 메디비르 아베 비-뉴클레오시드 역전사효소 억제제
JP5138938B2 (ja) 2003-12-19 2013-02-06 プレキシコン インコーポレーテッド Ｒｅｔ調節剤の開発のための化合物および方法
EP1833829A2 (en) 2004-12-23 2007-09-19 F. Hoffmann-Roche AG Benzamide substituted imidazo- and pyrrolo-pyridines as protein kinase inhibitors
WO2007067444A1 (en) 2005-12-08 2007-06-14 Millennium Pharmaceuticals, Inc. Bicyclic compounds with kinase inhibitory activity
AU2007254325B2 (en) 2006-05-15 2012-05-10 Merck Sharp & Dohme Corp. Antidiabetic bicyclic compounds
BRPI0716477A2 (pt) 2006-09-06 2014-03-18 Hoffmann La Roche Derivados heteroarila como inibidores de quinase protéica
PE20121126A1 (es) 2006-12-21 2012-08-24 Plexxikon Inc Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa
WO2008079909A1 (en) 2006-12-21 2008-07-03 Plexxikon, Inc. Pyrrolo [2,3-b] pyridines as kinase modulators
JP2010526848A (ja) 2007-05-11 2010-08-05 エフ．ホフマン−ラ ロシュ アーゲー 難溶性薬物用の医薬組成物
JP2010533729A (ja) 2007-07-17 2010-10-28 プレキシコン，インコーポレーテッド キナーゼ調節のための化合物と方法、及びそのための適応
AU2009226136B2 (en) * 2008-03-17 2013-08-15 Ambit Biosciences Corporation Quinazoline derivatives as RAF kinase modulators and methods of use thereof
JO3101B1 (ar) 2008-12-02 2017-09-20 Takeda Pharmaceuticals Co مشتقات بنزوثيازول كعوامل مضادة للسرطان
US20100197924A1 (en) 2008-12-22 2010-08-05 Millennium Pharmaceuticals, Inc. Preparation of aminotetralin compounds
CA2738573C (en) * 2009-04-03 2013-02-19 F. Hoffmann-La Roche Ag Compositions of propane-1 sulfonic acid {3-[5-(4-chloro-phenyl)-1h-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide and uses thereof
AU2011209234B2 (en) 2010-01-27 2015-05-07 Nerviano Medical Sciences S.R.L. Sulfonamido derivatives of 3,4-diarylpyrazoles as protein kinase inhibitors
WO2011115069A1 (ja) 2010-03-19 2011-09-22 第一三共株式会社 結晶の網羅的探索
PE20141360A1 (es) * 2011-02-07 2014-10-13 Plexxikon Inc Compuestos y metodos para la modulacion de quinasas e indicaciones para los mismos.
DK2797888T3 (en) 2011-12-31 2016-09-19 Beigene Ltd Fused tricyclic compounds as RAF kinase inhibitors
IN2015DN00450A (enExample) * 2012-08-07 2015-06-26 Novartis Ag
NZ708272A (en) 2013-01-22 2020-07-31 Hoffmann La Roche Pharmaceutical composition with improved bioavailability
JP2014189462A (ja) 2013-03-27 2014-10-06 Osaka Univ 結晶製造方法、準安定形結晶、医薬の製造方法および医薬
WO2015152433A1 (en) * 2014-03-31 2015-10-08 Hanmi Pharm. Co., Ltd. Amorphous solid dispersion comprising paclitaxel, tablet comprising the same, and method for preparing the same
TWI849043B (zh) 2019-01-25 2024-07-21 英屬開曼群島商百濟神州有限公司 B-raf激酶二聚體抑制劑之穩定固體分散體、製備方法及其用途

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011025947A1 (en) * 2009-08-28 2011-03-03 Array Biopharma Inc. Raf inhibitor compounds and methods of use thereof
WO2014206344A1 (en) * 2013-06-28 2014-12-31 Beigene, Ltd. Fused tricyclic amide compounds as multiple kinase inhibitors
WO2014206343A1 (en) * 2013-06-28 2014-12-31 Beigene, Ltd. Fused tricyclic urea compounds as raf kinase and/or raf kinase dimer inhibitors

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EP3914591A1 (en) 2021-12-01
AU2020211000A1 (en) 2021-08-12
TW202444718A (zh) 2024-11-16
AU2020211000B2 (en) 2025-11-06
JP2025017374A (ja) 2025-02-05
CA3123476A1 (en) 2020-07-30
US20220105033A1 (en) 2022-04-07
KR20210120039A (ko) 2021-10-06
TW202043225A (zh) 2020-12-01
WO2020151756A1 (en) 2020-07-30
CN113330011A (zh) 2021-08-31
EP3914591A4 (en) 2022-11-09
SG11202107849RA (en) 2021-08-30
ZA202104032B (en) 2022-08-31
TWI909513B (zh) 2025-12-21
JP2022517675A (ja) 2022-03-09
BR112021014563A2 (pt) 2021-10-05
JP7591504B2 (ja) 2024-11-28
IL284636A (en) 2021-08-31
MX2021008884A (es) 2021-08-19
US12582604B2 (en) 2026-03-24

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