JP5478894B2 - キナゾリン誘導体、その調製法および使用法 - Google Patents
キナゾリン誘導体、その調製法および使用法 Download PDFInfo
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- JP5478894B2 JP5478894B2 JP2008550608A JP2008550608A JP5478894B2 JP 5478894 B2 JP5478894 B2 JP 5478894B2 JP 2008550608 A JP2008550608 A JP 2008550608A JP 2008550608 A JP2008550608 A JP 2008550608A JP 5478894 B2 JP5478894 B2 JP 5478894B2
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- fluorobenzyloxy
- phenylamino
- quinazoline
- give
- 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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- 238000002360 preparation method Methods 0.000 title claims description 5
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 35
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 4
- MVZGYPSXNDCANY-UHFFFAOYSA-N N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-quinazolinyl]-2-propenamide Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(NC(=O)C=C)=CC=C4N=CN=3)=CC=2)Cl)=C1 MVZGYPSXNDCANY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 2
- -1 4- (substituted phenylamino) -quinazoline Chemical class 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- 238000010992 reflux Methods 0.000 description 22
- 238000000034 method Methods 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- AYPFEYDGZDPAPE-UHFFFAOYSA-N 3-chloro-4-[(3-fluorophenyl)methoxy]aniline Chemical compound ClC1=CC(N)=CC=C1OCC1=CC=CC(F)=C1 AYPFEYDGZDPAPE-UHFFFAOYSA-N 0.000 description 8
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- 125000005843 halogen group Chemical group 0.000 description 8
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- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 125000004442 acylamino group Chemical group 0.000 description 5
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- 239000011541 reaction mixture Substances 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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- 125000000217 alkyl group Chemical group 0.000 description 4
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- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- 150000003246 quinazolines Chemical class 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
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- XRNZDKXOJFCXBI-UHFFFAOYSA-N 4-anilino-2h-phthalazin-1-one Chemical class C12=CC=CC=C2C(=O)NN=C1NC1=CC=CC=C1 XRNZDKXOJFCXBI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
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- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 3
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- NPFZKRFXQWDOCC-UHFFFAOYSA-N n-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 NPFZKRFXQWDOCC-UHFFFAOYSA-N 0.000 description 3
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- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 3
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- QBADLRDMMIGVMZ-UHFFFAOYSA-N 4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-ol Chemical compound C12=CC(O)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 QBADLRDMMIGVMZ-UHFFFAOYSA-N 0.000 description 2
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- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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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
- 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
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- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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| 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 |
| CN101245050A (zh) * | 2007-02-14 | 2008-08-20 | 上海艾力斯医药科技有限公司 | 4-苯胺喹唑啉衍生物的盐 |
| UY31137A1 (es) * | 2007-06-14 | 2009-01-05 | Smithkline Beecham Corp | Derivados de quinazolina como inhibidores de la pi3 quinasa |
| CN101347433B (zh) * | 2007-07-20 | 2012-05-02 | 江苏艾力斯生物医药有限公司 | 4-苯胺喹唑啉衍生物的制药用途 |
| CN101357905B (zh) * | 2007-08-01 | 2012-06-20 | 江苏艾力斯生物医药有限公司 | 4-[3-氯-4-(3-氟-苄氧基)-苯胺基]-6-取代胺基-喹唑啉衍生物的制备方法 |
| CN101544609A (zh) | 2008-03-25 | 2009-09-30 | 上海艾力斯医药科技有限公司 | 4-苯胺喹唑啉衍生物的结晶形式 |
| AU2013231084B2 (en) * | 2008-03-25 | 2015-06-18 | Shanghai Allist Pharmaceuticals Co., Ltd. | The polymorphs of 4-anilinoquinazoline derivatives, the preparation methods and uses thereof |
| CN101584696A (zh) | 2008-05-21 | 2009-11-25 | 上海艾力斯医药科技有限公司 | 包含喹唑啉衍生物的组合物及制备方法、用途 |
| BRPI1011505A2 (pt) | 2009-03-11 | 2016-03-22 | Auckland Uniservices Ltd | formas de pró-drogas de inibidores de quinase e sua aplicação em terapia |
| CN101899011B (zh) * | 2009-05-26 | 2013-01-16 | 北京大学 | 氨基二硫代甲酸酯类化合物、其制备方法和应用 |
| CN102574846B (zh) | 2009-09-02 | 2014-12-03 | 奥克兰联合服务有限公司 | 激酶抑制剂、其前药形式及它们在治疗中的用途 |
| CN102146059A (zh) * | 2010-02-08 | 2011-08-10 | 上海艾力斯医药科技有限公司 | 喹唑啉衍生物、制备方法及其应用 |
| CN102153544B (zh) * | 2010-02-12 | 2015-04-29 | 上海阳帆医药科技有限公司 | 一类酪氨酸激酶抑制剂的制备及用途 |
| CN101857617A (zh) * | 2010-04-28 | 2010-10-13 | 中国海洋大学 | 喹唑啉类糖衍生物及其制备方法和应用 |
| CN101857618B (zh) * | 2010-06-13 | 2015-11-25 | 中国海洋大学 | 作为蛋白酪氨酸激酶抑制剂的一系列喹唑啉糖衍生物,其制备方法和应用 |
| JP6437820B2 (ja) | 2011-07-27 | 2018-12-12 | シャンハイ ファーマシューティカルズ ホールディング カンパニー,リミティド | キナゾリン誘導体、その製造方法、中間体、組成物及びその適用 |
| CN103304572A (zh) * | 2012-03-09 | 2013-09-18 | 上海医药集团股份有限公司 | 一类3-氰基喹啉类化合物及其药用组合物和应用 |
| CN102659764A (zh) * | 2012-04-16 | 2012-09-12 | 中国科学院广州生物医药与健康研究院 | 酪氨酸激酶不可逆抑制剂及其制备方法和用途 |
| CN102702116B (zh) * | 2012-06-13 | 2014-12-31 | 华南理工大学 | 4-(3-氯-4-甲氧基苯胺基)-6-(3-胺基苯基)喹唑啉类化合物或其药学上可接受的盐和制备方法与应用 |
| CN102924387B (zh) * | 2012-06-13 | 2015-07-01 | 黄唯燕 | 4-(3-氯-4-甲氧基苯胺基)-6-(3,4-取代苯基)喹唑啉及盐和制法与应用 |
| CN104119350B (zh) | 2013-04-28 | 2017-04-12 | 广东东阳光药业有限公司 | 氨基喹唑啉类衍生物及其盐和使用方法 |
| 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 |
| KR20200091954A (ko) * | 2014-12-15 | 2020-07-31 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Egfr 및 pi3k의 소분자 억제제 |
| EP3272746B1 (en) | 2015-03-20 | 2019-12-25 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Salts of quinazoline derivative and method for preparing same |
| CN105384745A (zh) * | 2015-07-27 | 2016-03-09 | 北京师范大学 | 冠醚环状的喹唑啉类化合物及其制备方法和在制备肿瘤治疗与显像药物中的应用 |
| CN109952290B (zh) * | 2016-11-17 | 2022-05-03 | 广东众生药业股份有限公司 | Fgfr4抑制剂及其制备方法和应用 |
| EP4194443A4 (en) * | 2020-08-10 | 2024-10-09 | Abbisko Therapeutics Co., Ltd. | Efgr inhibitor, preparation method therefor, and application thereof |
| US20240239764A1 (en) | 2020-12-22 | 2024-07-18 | Mekanistic Therapeutics | Substituted aminobenzyl heteroaryl compounds as egfr and/or pi3k inhibitors |
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| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (enExample) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| EP0817775B1 (en) | 1995-03-30 | 2001-09-12 | Pfizer Inc. | Quinazoline derivatives |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| EP0892789B2 (en) | 1996-04-12 | 2009-11-18 | Warner-Lambert Company LLC | Irreversible inhibitors of tyrosine kinases |
| ZA986732B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
| RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| GB9800575D0 (en) * | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| AU5391099A (en) * | 1998-07-30 | 2000-02-21 | American Home Products Corporation | Substituted quinazoline derivatives |
| AU5783300A (en) | 1999-07-09 | 2001-01-30 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| CZ20021009A3 (cs) * | 1999-09-21 | 2002-06-12 | Astrazeneca Ab | Deriváty chinazolinu, způsob jejich přípravy a jejich pouľití jako léčiv |
| BR0014133A (pt) * | 1999-09-21 | 2002-06-11 | Astrazeneca Ab | Uso de um composto, composto, métodos de preparação de um composto, e para inibir aurora 2 quinase em um animal de sangue quente, e, composição farmacêutica |
| GB9925958D0 (en) * | 1999-11-02 | 1999-12-29 | Bundred Nigel J | Therapeutic use |
| US20070123537A1 (en) * | 2003-10-06 | 2007-05-31 | Gpc Biotech Ag | Quinazoline derivatives for the treatment of herpesviral infections |
| JP2007510667A (ja) * | 2003-11-07 | 2007-04-26 | スミスクライン ビーチャム (コーク) リミテッド | 癌の治療法 |
| WO2005097134A2 (en) * | 2004-03-31 | 2005-10-20 | The Scripps Research Institute | Quinazoline based protein kinase inhibitors |
| KR100735639B1 (ko) * | 2004-12-29 | 2007-07-04 | 한미약품 주식회사 | 암세포 성장 억제 효과를 갖는 퀴나졸린 유도체 및 이의제조방법 |
| WO2006090717A1 (ja) * | 2005-02-23 | 2006-08-31 | Shionogi & Co., Ltd. | チロシンキナーゼ阻害作用を有するキナゾリン誘導体 |
| 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 |
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- 2006-10-20 JP JP2008550608A patent/JP5478894B2/ja active Active
- 2006-10-20 WO PCT/CN2006/002786 patent/WO2007082434A1/zh not_active Ceased
- 2006-10-20 EP EP10172688.3A patent/EP2248806B1/en active Active
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| EP2248806A2 (en) | 2010-11-10 |
| JP2012214502A (ja) | 2012-11-08 |
| EP2248806B1 (en) | 2013-04-24 |
| CN101003514A (zh) | 2007-07-25 |
| CN101103005B (zh) | 2011-05-04 |
| US20080300248A1 (en) | 2008-12-04 |
| EP1990337A1 (en) | 2008-11-12 |
| US8044063B2 (en) | 2011-10-25 |
| US20110245246A1 (en) | 2011-10-06 |
| CN101103005A (zh) | 2008-01-09 |
| EP1990337B1 (en) | 2013-05-08 |
| WO2007082434A1 (en) | 2007-07-26 |
| EP2248806A3 (en) | 2011-02-23 |
| US8309563B2 (en) | 2012-11-13 |
| JP2009525956A (ja) | 2009-07-16 |
| EP1990337A4 (en) | 2009-07-22 |
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