TWI598341B - 苯達莫司汀衍生物及其使用方法 - Google Patents
苯達莫司汀衍生物及其使用方法 Download PDFInfo
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- TWI598341B TWI598341B TW102140964A TW102140964A TWI598341B TW I598341 B TWI598341 B TW I598341B TW 102140964 A TW102140964 A TW 102140964A TW 102140964 A TW102140964 A TW 102140964A TW I598341 B TWI598341 B TW I598341B
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- compound
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- alkyl
- bendamustine
- nanoparticle
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- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
- MGOHUKBFSWEKRL-UHFFFAOYSA-N methyl 4-(5-amino-1-methylbenzimidazol-2-yl)butanoate Chemical compound NC1=CC=C2N(C)C(CCCC(=O)OC)=NC2=C1 MGOHUKBFSWEKRL-UHFFFAOYSA-N 0.000 description 1
- CFNXGULFAQAFAB-UHFFFAOYSA-N methyl 4-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoate Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(=O)OC)=NC2=C1 CFNXGULFAQAFAB-UHFFFAOYSA-N 0.000 description 1
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- 239000007908 nanoemulsion Substances 0.000 description 1
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- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- FCBBRODPXVPZAH-UHFFFAOYSA-N nonan-5-ol Chemical compound CCCCC(O)CCCC FCBBRODPXVPZAH-UHFFFAOYSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000009116 palliative therapy Methods 0.000 description 1
- 201000002530 pancreatic endocrine carcinoma Diseases 0.000 description 1
- UHEFMWNMFFCHBE-UHFFFAOYSA-N pentadecyl 4-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoate Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(=O)OCCCCCCCCCCCCCCC)=NC2=C1 UHEFMWNMFFCHBE-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
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- 239000000902 placebo Substances 0.000 description 1
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- 150000003077 polyols Chemical class 0.000 description 1
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- 125000006308 propyl amino group Chemical group 0.000 description 1
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61K31/41—Heterocyclic 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
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| US201261725213P | 2012-11-12 | 2012-11-12 | |
| US201361776951P | 2013-03-12 | 2013-03-12 |
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| TW201439069A TW201439069A (zh) | 2014-10-16 |
| TWI598341B true TWI598341B (zh) | 2017-09-11 |
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| TW102140964A TWI598341B (zh) | 2012-11-12 | 2013-11-12 | 苯達莫司汀衍生物及其使用方法 |
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| JP (1) | JP6262246B2 (OSRAM) |
| KR (1) | KR20150086308A (OSRAM) |
| AR (1) | AR093457A1 (OSRAM) |
| AU (1) | AU2013342015B2 (OSRAM) |
| BR (1) | BR112015010501A2 (OSRAM) |
| CA (1) | CA2890462A1 (OSRAM) |
| CL (1) | CL2015001246A1 (OSRAM) |
| EA (1) | EA029706B1 (OSRAM) |
| HK (2) | HK1215701A1 (OSRAM) |
| IL (1) | IL238662A (OSRAM) |
| MX (1) | MX2015005805A (OSRAM) |
| PH (1) | PH12015501024A1 (OSRAM) |
| SG (1) | SG11201503560TA (OSRAM) |
| TW (1) | TWI598341B (OSRAM) |
| WO (1) | WO2014075035A1 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105693720B (zh) | 2010-05-20 | 2019-01-18 | 阵列生物制药公司 | 作为trk激酶抑制剂的大环化合物 |
| MX2015005805A (es) * | 2012-11-12 | 2016-04-15 | Ignyta Inc | Derivados de bendamustina y métodos para utilizarlos. |
| CA2904143A1 (en) * | 2013-03-12 | 2014-10-09 | Cephalon, Inc. | Nanoparticulate and macroparticulate formulations |
| EP3322706B1 (en) | 2015-07-16 | 2020-11-11 | Array Biopharma, Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as ret kinase inhibitors |
| WO2018013783A1 (en) * | 2016-07-13 | 2018-01-18 | Cephalon, Inc. | Pharmaceutical prodrugs and methods of their preparation and use |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| CN110267960B (zh) | 2017-01-18 | 2022-04-26 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[1,5-a]吡嗪化合物 |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TW201938169A (zh) | 2018-01-18 | 2019-10-01 | 美商亞雷生物製藥股份有限公司 | 作為RET激酶抑制劑之經取代吡唑并[3,4-d]嘧啶化合物 |
| WO2019143994A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| CN111971286B (zh) | 2018-01-18 | 2023-04-14 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡咯并[2,3-d]嘧啶化合物 |
| KR102653681B1 (ko) | 2018-07-31 | 2024-04-03 | 록쏘 온콜로지, 인코포레이티드 | (s)-5-아미노-3-(4-((5-플루오로-2-메톡시벤즈아미도)메틸)페닐)-1-(1,1,1-트리플루오로프로판-2-일)-1h-피라졸-4-카르복스아미드의분무-건조된 분산물 및 제제 |
| ES2922314T3 (es) | 2018-09-10 | 2022-09-13 | Array Biopharma Inc | Compuestos heterocíclicos condensados como inhibidores de cinasa RET |
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| US7089218B1 (en) | 2004-01-06 | 2006-08-08 | Neuric Technologies, Llc | Method for inclusion of psychological temperament in an electronic emulation of the human brain |
| US8853260B2 (en) | 1997-06-27 | 2014-10-07 | Abraxis Bioscience, Llc | Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
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-
2013
- 2013-11-12 MX MX2015005805A patent/MX2015005805A/es unknown
- 2013-11-12 KR KR1020157015682A patent/KR20150086308A/ko not_active Withdrawn
- 2013-11-12 SG SG11201503560TA patent/SG11201503560TA/en unknown
- 2013-11-12 US US14/442,088 patent/US9452988B2/en not_active Expired - Fee Related
- 2013-11-12 EA EA201590925A patent/EA029706B1/ru not_active IP Right Cessation
- 2013-11-12 WO PCT/US2013/069550 patent/WO2014075035A1/en not_active Ceased
- 2013-11-12 HK HK16100090.1A patent/HK1215701A1/zh unknown
- 2013-11-12 EP EP13795940.9A patent/EP2917183A1/en not_active Withdrawn
- 2013-11-12 BR BR112015010501A patent/BR112015010501A2/pt not_active IP Right Cessation
- 2013-11-12 JP JP2015541995A patent/JP6262246B2/ja not_active Expired - Fee Related
- 2013-11-12 CA CA2890462A patent/CA2890462A1/en not_active Abandoned
- 2013-11-12 TW TW102140964A patent/TWI598341B/zh not_active IP Right Cessation
- 2013-11-12 AU AU2013342015A patent/AU2013342015B2/en not_active Ceased
- 2013-11-12 AR ARP130104160A patent/AR093457A1/es unknown
- 2013-11-12 HK HK16100891.2A patent/HK1212977A1/zh unknown
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2015
- 2015-04-29 US US14/699,965 patent/US9150517B2/en not_active Expired - Fee Related
- 2015-05-06 IL IL238662A patent/IL238662A/en not_active IP Right Cessation
- 2015-05-07 PH PH12015501024A patent/PH12015501024A1/en unknown
- 2015-05-08 CL CL2015001246A patent/CL2015001246A1/es unknown
- 2015-05-13 US US14/711,747 patent/US9149464B2/en not_active Expired - Fee Related
- 2015-09-28 US US14/868,278 patent/US20160016912A1/en not_active Abandoned
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2016
- 2016-06-16 US US15/184,968 patent/US9630926B2/en not_active Expired - Fee Related
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2017
- 2017-03-10 US US15/456,439 patent/US9913827B2/en not_active Expired - Fee Related
-
2018
- 2018-01-24 US US15/879,130 patent/US20180147186A1/en not_active Abandoned
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| US20100111984A1 (en) * | 2008-09-29 | 2010-05-06 | The Corporation Of Mercer University | Nanospheres encapsulating bioactive material and method for formulation of nanospheres |
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