JP2019505509A - ゲフィチニブの結晶形aを製造する方法 - Google Patents
ゲフィチニブの結晶形aを製造する方法 Download PDFInfo
- Publication number
- JP2019505509A JP2019505509A JP2018534677A JP2018534677A JP2019505509A JP 2019505509 A JP2019505509 A JP 2019505509A JP 2018534677 A JP2018534677 A JP 2018534677A JP 2018534677 A JP2018534677 A JP 2018534677A JP 2019505509 A JP2019505509 A JP 2019505509A
- Authority
- JP
- Japan
- Prior art keywords
- gefitinib
- volume
- crystalline form
- water
- alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 239000005411 L01XE02 - Gefitinib Substances 0.000 title claims abstract description 57
- 229960002584 gefitinib Drugs 0.000 title claims abstract description 57
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 239000013078 crystal Substances 0.000 title claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 29
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000011877 solvent mixture Substances 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 6
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 12
- 230000005855 radiation Effects 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- -1 or chemically Chemical compound 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940002501 gefitinib 250 mg Drugs 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
【化1】
1.ゲフィチニブを、水とエタノールおよびブタノールから選択されるアルコールとを含む溶媒混合物中に溶解するステップであって、水とアルコールの比が1:16〜1:25(体積:体積)であるステップと、2.ゲフィチニブの結晶形1を単離するステップとを含む方法に関する。
Description
2.ゲフィチニブの結晶形1を単離するステップ
を含む、方法である。
2.ゲフィチニブの結晶形1を単離するステップと
を含む。
ゲフィチニブ(10g、22.29mmol)を含む2−ブタノール(85.3ml)および水(4.7ml)の懸濁液を、撹拌しながら94℃(還流)に加熱して、透明な溶液を得た。その溶液を撹拌しながら75℃に冷却した。それにゲフィチニブの結晶形1の結晶種を入れ、得られた懸濁液を75℃で1時間撹拌した。次いで、それを2時間以上かけて23℃に冷却し、さらに12時間撹拌し、ろ過し、2−ブタノール(10ml)で洗浄し、乾燥して、ゲフィチニブの結晶形1を収率87%で得た。
ゲフィチニブ(10g、22.29mmol)を含む2−ブタノール(88ml)および水(4.4ml)の懸濁液を、撹拌しながら94℃(還流)に加熱して、透明な溶液を得た。その溶液を撹拌しながら75℃に冷却した。それにゲフィチニブの結晶形1の結晶種を入れ、得られた懸濁液を75℃で1時間撹拌した。次いで、それを2時間以上かけて23℃に冷却し、さらに12時間撹拌し、ろ過し、2−ブタノール(10ml)で洗浄し、乾燥して、ゲフィチニブの結晶形1を収率85%で得た。
ゲフィチニブ(10g、22.29mmol)を含むエタノール(88ml)および水(4.4ml)の懸濁液を、撹拌しながら加熱還流して、透明な溶液を得た。その溶液を撹拌しながら75℃に冷却した。それにゲフィチニブの結晶形1の結晶種を入れ、得られた懸濁液を75℃で1時間撹拌した。次いで、それを2時間以上かけて23℃に冷却し、さらに13時間撹拌し、ろ過し、エタノール(10ml)で洗浄し、乾燥して、ゲフィチニブの結晶形1を収率86%で得た。
Claims (4)
- CuKα1放射線(λ=1.54060Å)で測定し、約7.14、11.26、14.25、15.86、24.33、および26.40°2θ(±0.2°2θ)のピークを含むXRPD粉末回折パターンを特徴とする式(1)
1.ゲフィチニブを、水とエタノールおよびブタノールから選択されるアルコールとを含む溶媒混合物中に溶解するステップであって、水とアルコールの比が1:16〜1:25(体積:体積)であるステップと、
2.ゲフィチニブの結晶形1を単離するステップと
を含む方法。 - 前記水とアルコールの比が、1:18〜1:20(体積:体積)である請求項1に記載の方法。
- 前記水とアルコールの比が、1:20(体積:体積)である請求項1または2に記載の方法。
- 前記混合物中のゲフィチニブの濃度が、0.08g/ml〜0.15g/mlである請求項1から3のいずれか1項に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15203106.8 | 2015-12-30 | ||
EP15203106 | 2015-12-30 | ||
PCT/EP2016/082322 WO2017114735A1 (en) | 2015-12-30 | 2016-12-22 | Process for making crystalline form a of gefitinib |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019505509A true JP2019505509A (ja) | 2019-02-28 |
JP6871255B2 JP6871255B2 (ja) | 2021-05-12 |
Family
ID=55027578
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Application Number | Title | Priority Date | Filing Date |
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JP2018534677A Active JP6871255B2 (ja) | 2015-12-30 | 2016-12-22 | ゲフィチニブの結晶形aを製造する方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US10259805B2 (ja) |
EP (1) | EP3397618B1 (ja) |
JP (1) | JP6871255B2 (ja) |
ES (1) | ES2851499T3 (ja) |
WO (1) | WO2017114735A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110101668B (zh) * | 2019-05-29 | 2021-09-07 | 华东理工大学 | 一种吉非替尼复合微粒的制备方法 |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
KR20040086452A (ko) * | 2002-02-26 | 2004-10-08 | 아스트라제네카 아베 | 항암 화합물 zd1839의 신규한 결정질 형태 |
WO2006090413A1 (en) | 2005-02-23 | 2006-08-31 | Natco Pharma Limited | Novel crystalline form of gefitinib and a process for its preparation |
US8198281B2 (en) * | 2007-04-25 | 2012-06-12 | Merck Sharp & Dohme Corp. | Crystalline forms of dihydropyrazolopyrimidinone |
CN101973944B (zh) * | 2010-10-14 | 2012-07-04 | 江苏先声药物研究有限公司 | 一种Gefitinib Form 1 晶型的制备方法 |
CN103030599B (zh) * | 2011-10-09 | 2014-12-10 | 齐鲁制药有限公司 | 吉非替尼中间体及其制备方法 |
CN103319422B (zh) * | 2012-03-21 | 2016-05-04 | 石药集团中奇制药技术(石家庄)有限公司 | 一种吉非替尼晶型及其制备方法 |
CN103896862B (zh) * | 2012-12-25 | 2017-05-10 | 江苏天士力帝益药业有限公司 | 一种吉非替尼Form 1晶型的制备方法 |
CN103896863B (zh) * | 2012-12-26 | 2017-06-13 | 亚宝药业集团股份有限公司 | 抗癌化合物zd1839的晶型及其制备方法 |
CN103910690A (zh) * | 2013-01-06 | 2014-07-09 | 上海科胜药物研发有限公司 | 一种吉非替尼新晶型及其制备方法 |
CN103102316A (zh) | 2013-01-17 | 2013-05-15 | 李彦 | ZD1839Form 1晶型的制备方法 |
CN103360326B (zh) * | 2013-04-19 | 2016-03-30 | 南京优科生物医药研究有限公司 | 吉非替尼晶型i的精制方法 |
KR20150001936A (ko) * | 2013-06-28 | 2015-01-07 | 제일약품주식회사 | 게피티닙의 신규한 결정형 및 이의 제조방법 |
WO2015170345A1 (en) * | 2014-05-09 | 2015-11-12 | Council Of Scientific & Industrial Research | Pharmaceutical cocrystals of gefitinib |
RU2577518C2 (ru) * | 2014-06-02 | 2016-03-20 | Олег Ростиславович Михайлов | КРИСТАЛЛИЧЕСКАЯ БЕЗВОДНАЯ γ-МОДИФИКАЦИЯ 4-(3'-ХЛОР-4'-ФТОРАНИЛИНО)-7-МЕТОКСИ-6-(3-МОРФОЛИНОПРОПОКСИ)ХИНАЗОЛИНА, СПОСОБ ЕЕ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ЕЕ ОСНОВЕ |
CN104277005A (zh) * | 2014-09-19 | 2015-01-14 | 成都新恒创药业有限公司 | 一种吉非替尼Form 1晶型的制备方法 |
CN104693127B (zh) * | 2015-02-14 | 2016-06-15 | 齐鲁制药有限公司 | 吉非替尼乙二醇溶剂合物及其制备方法和用途 |
ES2841600T3 (es) * | 2015-10-19 | 2021-07-08 | Sunshine Lake Pharma Co Ltd | Sal de di(ácido metanosulfónico) de (3-cloro-4-fluoro-fenil)-(6-((4aR,7aS)-3-(hexahidro-(1,4)dioxino(2,3-c)pirrol-6-il)- propoxi)-7-metoxi-quinazolin-4-il)-amina y forma cristalina del monohidrato (un inhibidor de EGFR) |
EP3373932B1 (en) * | 2015-11-14 | 2022-03-30 | Sunshine Lake Pharma Co., Ltd. | Crystalline form of a substituted quinoline compound and pharmaceutical compositions thereof |
CN105294715B (zh) * | 2015-11-18 | 2017-12-22 | 乳源瑶族自治县大众药品贸易有限公司 | 一种氨基喹唑啉类衍生物的富马酸盐及其晶型 |
CN106083739B (zh) * | 2016-05-31 | 2019-05-14 | 华南理工大学 | 吉非替尼新晶型及其基于超临界反溶剂技术的制备方法 |
-
2016
- 2016-12-22 JP JP2018534677A patent/JP6871255B2/ja active Active
- 2016-12-22 ES ES16820268T patent/ES2851499T3/es active Active
- 2016-12-22 WO PCT/EP2016/082322 patent/WO2017114735A1/en unknown
- 2016-12-22 EP EP16820268.7A patent/EP3397618B1/en active Active
- 2016-12-22 US US16/067,330 patent/US10259805B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
ES2851499T3 (es) | 2021-09-07 |
EP3397618B1 (en) | 2020-11-18 |
EP3397618A1 (en) | 2018-11-07 |
JP6871255B2 (ja) | 2021-05-12 |
US20190010147A1 (en) | 2019-01-10 |
WO2017114735A1 (en) | 2017-07-06 |
US10259805B2 (en) | 2019-04-16 |
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