JP6704422B2 - キナゾリン誘導体の塩およびその製造方法 - Google Patents
キナゾリン誘導体の塩およびその製造方法 Download PDFInfo
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- JCUWUVFZWOZGTM-UHFFFAOYSA-N COc1cc2ncnc(Nc(cc3Cl)ccc3F)c2cc1NC1CCNCC1 Chemical compound COc1cc2ncnc(Nc(cc3Cl)ccc3F)c2cc1NC1CCNCC1 JCUWUVFZWOZGTM-UHFFFAOYSA-N 0.000 description 1
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- 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
- A61K31/495—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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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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
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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
- A61K31/535—Heterocyclic 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
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/13—Dicarboxylic acids
- C07C57/145—Maleic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
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- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
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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
Description
本願は2015年03月20日に中華人民共和国国家知的財産局に出願された出願番号が201510125962.4である中国特許出願に基づく優先権および利益を主張し、当該出願の全文を引用により本願に組み込む。
本発明は、医薬品化学分野に属し、より具体的には、キナゾリン誘導体の塩、その製造方法およびその医薬使用に関する。
ステップ1: 4−クロロ−7−フルオロ−6−ニトロキナゾリン
1H NMR (CDCl3): δ 9.18 (1H, s), 9.05 (1H, d, J = 7.6 Hz), 7.95 (1H, d, J = 10.4)。
1H NMR (CDCl3): δ 6.94−6.82 (4H, m), 6.63−6.61 (1H, m), 6.45−6.41 (1H, m), 4.18 (2H, s), 3.98 (1H, br), 3.87 (3H, s), 3.86 (3H, s)。
1H NMR (CDCl3): δ 8.85 (1H, s), 7.57 (1H, s), 7.35 (1H, s), 7.23−7.19 (2H, m), 7.00−6.96 (1H, m), 6.84−6.78 (2H, m), 5.35 (2H, s), 4.05 (3H, s), 3.88 (3H, s), 3.83 (3H, s)。
1H NMR (DMSO−d6): δ 9.24 (1H, s), 8.33 (1H, s), 8.09−8.08 (1H, m), 7.77−7.74 (1H, m), 7.42−7.40 (1H, m), 7.23 (1H, s), 7.06 (1H, s), 6.85−6.81 (1H, m), 6.10−6.06 (1H, m), 5.66−5.64 (1H, m), 5.32−5.29 (1H, m), 4.41−4.38 (1H, m), 4.09−4.06 (1H, m), 3.93 (3H, s), 3.79−3.78 (1H, m), 3.35−3.34 (1H, m), 2.87−2.84 (1H, m), 2.03−2.01 (2H, m), 1.44−1.41 (2H, m)。
研究方法:体重7.4〜9.4kgのビーグル犬15匹をランダムに5群に分け、5mg/kg体重の式Iで表される化合物およびそのマレイン酸塩、クエン酸塩、蓚酸塩、酢酸塩(式Iで表される化合物の量で換算)のCMC−Na(カルボキシメチルセルロースナトリウム)懸濁液をそれぞれ経口投与し、投与前と投与後(0.25、0.5、1、2、4、6、8、12、24、48時間の時点)に採血し、LC−MS法によって犬血漿サンプルにおける式Iで表される化合物の濃度をそれぞれ測定して生物学的利用能を計算した。
クロマトグラフィー条件は、移動相A:メタノール、移動相B:0.1%(v/v)のギ酸水溶液、アイソクラティック溶離方式: A:B=52:48、流速:0.2mL/min、カラム温度:35℃、クロマトグラフィーカラム:SHIMADZU Shim−pack VP−ODS C18(5.0μm、150mm×2.0mm I.D.島津社製)である。
1.インビトロ酵素学的検出方法
ヒト非小細胞肺癌細胞NCI−H1975、ヒト乳癌細胞系BT474を細胞インキュベータ(37℃、5%CO2)においてRPIM−1640、またはDMEM培地及び10%ウシ胎仔血清(FBS)で培養した。化合物の検出中、底層基質濃度を0.6%としており、細胞を0.3%の低融点寒天で再懸濁した後、1ウェルあたりに10,000個の細胞(100μL)を加えるように96ウェルプレートに播種した。化合物について10mMから始めて3倍段階希釈を行い、各濃度のもの2μLを取って培地98μLに加え、次に、得られた混合物5.3μLを取って細胞培養液(DMSO最終濃度0.1%、v/v)に加え、1週間(7日間)処理後、CellTiter−Blue(R)(Promega)試薬20μLを加えて、37℃で4時間インキュベートし、Envison(Perkin Elmer)において蛍光信号を読み取り、GraphPad Prism 5.0を用いて化合物による細胞増殖阻害のIC50を算出した。
Claims (13)
- 前記式Iで表される化合物とマレイン酸とのモル比が1:0.5〜4である、請求項1に記載の式Iで表される化合物のマレイン酸塩。
- 前記式Iで表される化合物とマレイン酸とのモル比が1:1または1:2である、請求項2に記載の式Iで表される化合物のマレイン酸塩。
- 前記式Iで表される化合物とマレイン酸とのモル比が1:1である、請求項2に記載の式Iで表される化合物のマレイン酸塩。
- 請求項1〜4のいずれかに記載の式Iで表される化合物のマレイン酸塩の製造方法であって、
式Iで表される化合物の溶液を製造するステップ(1)と、
ステップ(1)で得られた前記式Iで表される化合物の溶液とマレイン酸とを混合するステップ(2)と、
ステップ(2)で得られた反応混合物を噴霧乾燥させて、前記式Iで表される化合物のマレイン酸塩を得るステップ(3)とを含む、
式Iで表される化合物のマレイン酸塩の製造方法。 - 前記式Iで表される化合物とマレイン酸との使用量のモル比は1:1〜20である、請求項5に記載の製造方法。
- 前記ステップ(1)において、前記式Iで表される化合物を有機溶剤に溶解して前記式Iで表される化合物の溶液を製造する、請求項5または6に記載の製造方法。
- 前記有機溶剤はDMFである、請求項7に記載の製造方法。
- 噴霧乾燥前に、前記有機溶剤と相溶する溶剤を加える、請求項7または8に記載の製造方法。
- 前記有機溶剤と相溶する溶剤は水である、請求項9に記載の製造方法。
- 請求項1〜4のいずれかに記載の式Iで表される化合物のマレイン酸塩と、薬学的に許容される担体、賦形剤、希釈剤および/または媒体とを含む、医薬組成物。
- 請求項1〜4のいずれかに記載の式Iで表される化合物のマレイン酸塩を含む、腫瘍を治療するための医薬組成物。
- 前記腫瘍は非小細胞肺癌または乳癌である、請求項12に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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CN201510125962 | 2015-03-20 | ||
CN201510125962.4 | 2015-03-20 | ||
PCT/CN2016/076693 WO2016150340A1 (zh) | 2015-03-20 | 2016-03-18 | 喹唑啉衍生物的盐及其制备方法 |
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JP2018508583A JP2018508583A (ja) | 2018-03-29 |
JP6704422B2 true JP6704422B2 (ja) | 2020-06-03 |
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JP2017567522A Active JP6704422B2 (ja) | 2015-03-20 | 2016-03-18 | キナゾリン誘導体の塩およびその製造方法 |
Country Status (8)
Country | Link |
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US (1) | US10231973B2 (ja) |
EP (1) | EP3272746B1 (ja) |
JP (1) | JP6704422B2 (ja) |
CN (1) | CN107406430B (ja) |
ES (1) | ES2775614T3 (ja) |
HK (1) | HK1244278B (ja) |
RU (1) | RU2720810C2 (ja) |
WO (1) | WO2016150340A1 (ja) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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EP3505516B1 (en) * | 2016-08-25 | 2021-10-06 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Crystal of salt of quinazoline derivative |
CN108069946B (zh) * | 2016-11-08 | 2020-06-05 | 威尚(上海)生物医药有限公司 | 具有穿过血脑屏障能力的取代的喹唑啉化合物 |
US20220242851A1 (en) * | 2019-06-19 | 2022-08-04 | Shenzhen Jinrui Foundation Biotech Co., Ltd | Crystal form and salt of quinazoline compound and preparation method thereof |
CN114401957B (zh) * | 2019-09-04 | 2023-11-21 | 正大天晴药业集团股份有限公司 | 一种喹唑啉衍生物的制备方法及其结晶 |
CN110627731A (zh) * | 2019-10-09 | 2019-12-31 | 贵州大学 | 一类4-氨基喹唑啉接丙烯酰胺类化合物及其制备方法和应用 |
US20220395505A1 (en) * | 2019-11-01 | 2022-12-15 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Pharmaceutical Composition Comprising Quinazoline Derivative or Salt Thereof |
WO2021083347A1 (zh) * | 2019-11-01 | 2021-05-06 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物或其盐、或其药物组合物的用途 |
WO2021104319A1 (zh) * | 2019-11-25 | 2021-06-03 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物或其盐的联用药物组合物及其用途 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
EA003786B1 (ru) | 1998-11-19 | 2003-10-30 | Варнер Ламберт Компани | N-[4-(3-хлор-4-фторфениламино)-7-(3-морфолин-4-илпропокси)хиназолин-6-ил]акриламид - необратимый ингибитор тирозинкиназ |
DE10063435A1 (de) | 2000-12-20 | 2002-07-04 | Boehringer Ingelheim Pharma | Chinazolinderviate,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
NZ545913A (en) | 2003-09-19 | 2009-01-31 | Astrazeneca Ab | Quinazoline derivatives |
DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
WO2007055513A1 (en) | 2005-11-08 | 2007-05-18 | Hanmi Pharm. Co., Ltd. | Quinazoline derivatives as a signal transduction inhibitor and method for the preparation thereof |
CN101003514A (zh) | 2006-01-20 | 2007-07-25 | 上海艾力斯医药科技有限公司 | 喹唑啉衍生物、其制备方法及用途 |
WO2008002039A1 (en) | 2006-06-28 | 2008-01-03 | Hanmi Pharm. Co., Ltd. | Quinazoline derivatives for inhibiting the growth of cancer cell |
TWI377944B (en) | 2007-06-05 | 2012-12-01 | Hanmi Holdings Co Ltd | Novel amide derivative for inhibiting the growth of cancer cells |
MX2010004625A (es) * | 2007-10-29 | 2010-05-20 | Natco Pharma Ltd | Nuevos derivados de 4(tetrazol-5-il)-quinazolina como agentes anticancerosos. |
SG2014014450A (en) | 2011-09-22 | 2014-09-26 | Pfizer | Pyrrolopyrimidine and purine derivatives |
KR101272613B1 (ko) | 2011-10-05 | 2013-06-10 | 한미사이언스 주식회사 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온 염산염의 제조 방법 및 이에 사용되는 중간체 |
CN104513229A (zh) | 2013-09-28 | 2015-04-15 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物及其制备方法 |
CN103948689A (zh) | 2014-04-15 | 2014-07-30 | 西北农林科技大学 | 用于治疗非小细胞肺癌的药物组合物及其应用 |
-
2016
- 2016-03-18 US US15/560,099 patent/US10231973B2/en active Active
- 2016-03-18 CN CN201680015924.6A patent/CN107406430B/zh active Active
- 2016-03-18 JP JP2017567522A patent/JP6704422B2/ja active Active
- 2016-03-18 WO PCT/CN2016/076693 patent/WO2016150340A1/zh active Application Filing
- 2016-03-18 ES ES16767717T patent/ES2775614T3/es active Active
- 2016-03-18 RU RU2017132330A patent/RU2720810C2/ru active
- 2016-03-18 EP EP16767717.8A patent/EP3272746B1/en active Active
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RU2017132330A (ru) | 2019-04-22 |
JP2018508583A (ja) | 2018-03-29 |
EP3272746A4 (en) | 2018-11-07 |
ES2775614T3 (es) | 2020-07-27 |
RU2017132330A3 (ja) | 2019-07-24 |
EP3272746B1 (en) | 2019-12-25 |
US20180085369A1 (en) | 2018-03-29 |
CN107406430A (zh) | 2017-11-28 |
CN107406430B (zh) | 2019-04-26 |
RU2720810C2 (ru) | 2020-05-13 |
US10231973B2 (en) | 2019-03-19 |
EP3272746A1 (en) | 2018-01-24 |
WO2016150340A1 (zh) | 2016-09-29 |
HK1244278B (zh) | 2020-04-17 |
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