UA91401C2 - 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(n,n-dimethylamino)-1-oxo-2-butene-1-yl]amino}-7-((s)-tetrahydrofurane-3-yloxy)-quinazoline maleate, production method and uses thereof - Google Patents

4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(n,n-dimethylamino)-1-oxo-2-butene-1-yl]amino}-7-((s)-tetrahydrofurane-3-yloxy)-quinazoline maleate, production method and uses thereof

Info

Publication number: UA91401C2
Authority: UA; Ukraine
Prior art keywords: amino; tetrahydrofurane; yloxy; fluorophenyl; butene
Prior art date: 2003-10-17

Application number

UAA200810609A

Other languages

English (en)

Inventor

Вернер Ралль

Райнер Зойка

Кристиан Кулинна

Юрген Шнаубельт

Петер Зигер

Original Assignee

Бёрингер Ингельхайм Интернациональ Гмбх

Priority date (The priority date 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 date listed.)

2003-10-17

Filing date

2004-10-12

Publication date

2010-07-26

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34428508&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=UA91401(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2004-10-12 Application filed by Бёрингер Ингельхайм Интернациональ Гмбх filed Critical Бёрингер Ингельхайм Интернациональ Гмбх

2010-07-26 Publication of UA91401C2 publication Critical patent/UA91401C2/ru

Classifications

- 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
- C07D405/12—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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Urology & Nephrology (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyrrole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

UAA200810609A 2003-10-17 2004-10-12 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(n,n-dimethylamino)-1-oxo-2-butene-1-yl]amino}-7-((s)-tetrahydrofurane-3-yloxy)-quinazoline maleate, production method and uses thereof UA91401C2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE10349113A DE10349113A1 (de)	2003-10-17	2003-10-17	Verfahren zur Herstellung von Aminocrotonylverbindungen

Publications (1)

Publication Number	Publication Date
UA91401C2 true UA91401C2 (en)	2010-07-26

Family

ID=34428508

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
UAA200810609A UA91401C2 (en)	2003-10-17	2004-10-12	4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(n,n-dimethylamino)-1-oxo-2-butene-1-yl]amino}-7-((s)-tetrahydrofurane-3-yloxy)-quinazoline maleate, production method and uses thereof
UAA200605327A UA91006C2 (ru)	2003-10-17	2004-10-12	Способ получения аминокротонильных соединений

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
UAA200605327A UA91006C2 (ru)	2003-10-17	2004-10-12	Способ получения аминокротонильных соединений

Country Status (34)

Country	Link
US (2)	US20050085495A1 (ru)
EP (2)	EP1678165B1 (ru)
JP (2)	JP4594317B2 (ru)
KR (2)	KR101180752B1 (ru)
CN (2)	CN101402631A (ru)
AR (1)	AR046118A1 (ru)
AU (2)	AU2004281938B2 (ru)
BR (2)	BR122013033343B8 (ru)
CA (2)	CA2541928C (ru)
CY (2)	CY1114866T1 (ru)
DE (1)	DE10349113A1 (ru)
DK (2)	DK1678165T3 (ru)
EA (1)	EA016624B1 (ru)
EC (1)	ECSP066509A (ru)
ES (2)	ES2563211T5 (ru)
HR (2)	HRP20131214T1 (ru)
HU (1)	HUE028254T2 (ru)
IL (2)	IL174951A (ru)
ME (1)	ME00341B (ru)
MX (2)	MX338920B (ru)
MY (2)	MY149921A (ru)
NO (2)	NO333971B1 (ru)
NZ (2)	NZ583049A (ru)
PE (2)	PE20100267A1 (ru)
PL (2)	PL2508521T5 (ru)
PT (2)	PT1678165E (ru)
RS (3)	RS60563B1 (ru)
SG (1)	SG139743A1 (ru)
SI (2)	SI2508521T2 (ru)
TW (2)	TWI373470B (ru)
UA (2)	UA91401C2 (ru)
UY (2)	UY28559A1 (ru)
WO (1)	WO2005037824A2 (ru)
ZA (1)	ZA200602234B (ru)

Families Citing this family (84)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1194418A1 (de) *	1999-06-21	2002-04-10	Boehringer Ingelheim Pharma KG	Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
US7019012B2 (en)	2000-12-20	2006-03-28	Boehringer Ingelheim International Pharma Gmbh & Co. Kg	Quinazoline derivatives and pharmaceutical compositions containing them
DE10221018A1 (de) *	2002-05-11	2003-11-27	Boehringer Ingelheim Pharma	Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie
US20050043233A1 (en) *	2003-04-29	2005-02-24	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
DE10349113A1 (de) *	2003-10-17	2005-05-12	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von Aminocrotonylverbindungen
KR100832593B1 (ko) *	2005-11-08	2008-05-27	한미약품 주식회사	신호전달 저해제로서의 퀴나졸린 유도체 및 이의 제조방법
DK1948180T3 (da)	2005-11-11	2013-05-27	Boehringer Ingelheim Int	Kombinationsbehandling af cancer omfattende EGFR/HER2 inhibitorer
JP5688877B2 (ja) *	2005-11-11	2015-03-25	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	癌疾患の治療用キナゾリン誘導体
EP1981863B1 (en) *	2006-01-26	2012-10-10	Boehringer Ingelheim International GmbH	Process for preparing aminocrotonylamino-substituted quinazoline derivatives
MX2009002710A (es) *	2006-09-18	2009-03-25	Boehringer Ingelheim Int	Metodos para tratar canceres que portan mutaciones de egfr.
PE20100252A1 (es) *	2008-06-06	2010-04-12	Boehringer Ingelheim Int	Nuevas formulaciones farmaceuticas solidas que comprenden dimaleato de 4-[(3-cloro-4-fluorofenil) amino]-6-{[4-(n,n-dimetilamino)-1-oxo-2-buten-1-il] amino}-7-((s)-tetrahidrofuran-3-iloxi)-quinazolina
US20120157472A1 (en)	2009-01-14	2012-06-21	Boehringer Ingelheim International Gmbh	Method for treating colorectal cancer
KR20110130468A (ko)	2009-03-11	2011-12-05	오클랜드 유니서비시즈 리미티드	키나아제 억제제의 프로드럭 형태 및 치료법에서의 이들의 용도
EP2429520A1 (en)	2009-05-14	2012-03-21	Boehringer Ingelheim International GmbH	New combination therapy in treatment of oncological and fibrotic diseases
KR20120090025A (ko)	2009-07-02	2012-08-16	뉴젠 세러퓨틱스 인코포레이티드	인 함유 퀴나졸린 화합물 및 그것의 사용 방법
US9545381B2 (en)	2009-07-06	2017-01-17	Boehringer Ingelheim International Gmbh	Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient
WO2011069962A1 (en)	2009-12-07	2011-06-16	Boehringer Ingelheim International Gmbh	Bibw 2992 for use in the treatment of triple negative breast cancer
US20120107304A1 (en) *	2010-04-27	2012-05-03	Boehringer Ingelheim International Gmbh	Combination therapy in treatment of oncological and fibrotic diseases
RS56682B1 (sr)	2010-08-26	2018-03-30	Boehringer Ingelheim Int	Postupci primene egfr inhibitora
US9012464B2 (en)	2010-11-25	2015-04-21	Ratiopharm Gmbh	Salts and polymorphic forms of Afatinib
BR112013022552B1 (pt)	2011-03-04	2021-11-23	Newgen Therapeutics, Inc	Compostos de quinazolina substituídos com alcino, seu uso, composição farmacêutica, e kit
CN102731485B (zh) *	2011-04-02	2016-06-15	齐鲁制药有限公司	4-(取代苯氨基)喹唑啉衍生物及其制备方法、药物组合物和用途
US8828391B2 (en)	2011-05-17	2014-09-09	Boehringer Ingelheim International Gmbh	Method for EGFR directed combination treatment of non-small cell lung cancer
CN102918029B (zh) *	2011-05-17	2015-06-17	江苏康缘药业股份有限公司	4-苯胺-6-丁烯酰胺-7-烷醚喹唑啉衍生物及其制备方法和用途
CN102838590B (zh) *	2011-06-21	2014-07-09	苏州迈泰生物技术有限公司	氨基喹唑啉衍生物及其在制备抗恶性肿瘤药物中的用途
US20170079444A1 (en) *	2011-09-22	2017-03-23	Future Foam, Inc.	Enhanced washable mattress topper
EP2753616A1 (en)	2011-10-06	2014-07-16	Ratiopharm GmbH	Crystalline forms of afatinib di-maleate
CN103073539B (zh) *	2011-10-26	2016-05-11	齐鲁制药有限公司	4-(取代苯氨基)喹唑啉衍生物及其制备方法、药物组合物和用途
EP2875020B1 (en)	2012-07-19	2017-09-06	Boehringer Ingelheim International GmbH	Process for the preparation of a fumaric acid salt of 9-[4-(3-chloro-2-fluoro-phenylamino)-7-methoxy- chinazolin-6-yloxy]-1,4-diaza-spiro[5.5]undecan-5-one
JP2016511754A (ja)	2013-02-01	2016-04-21	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	放射性標識キナゾリン誘導体
CN103254156B (zh) *	2013-05-10	2015-08-26	苏州明锐医药科技有限公司	阿法替尼中间体的制备方法
WO2014180271A1 (zh) *	2013-05-10	2014-11-13	苏州明锐医药科技有限公司	阿法替尼及其中间体的制备方法
CN103242303B (zh) *	2013-05-16	2015-03-25	苏州明锐医药科技有限公司	阿法替尼的制备方法
CN103288808B (zh) *	2013-05-16	2015-11-11	苏州明锐医药科技有限公司	一种阿法替尼的制备方法
CN106279127B (zh) *	2013-07-16	2019-05-24	杭州普晒医药科技有限公司	阿法替尼酸加成盐及其晶型、其制备方法及药物组合物
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
CN104710413B (zh) *	2013-12-16	2019-05-03	江苏豪森药业集团有限公司	二马来酸阿法替尼的制备方法
CN104744445A (zh) *	2013-12-30	2015-07-01	广东东阳光药业有限公司	一种酪氨酸激酶抑制剂的晶型
US9242965B2 (en)	2013-12-31	2016-01-26	Boehringer Ingelheim International Gmbh	Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors
EP3089976B1 (en) *	2014-01-02	2019-08-14	Teva Pharmaceuticals International GmbH	Crystalline forms of afatinib dimaleate
CN104803992A (zh) *	2014-01-25	2015-07-29	广东东阳光药业有限公司	阿法替尼盐的晶型
WO2016001844A1 (en) *	2014-06-30	2016-01-07	Sun Pharmaceutical Industries Limited	Amorphous form of afatinib dimaleate
CN105315263B (zh) *	2014-07-30	2018-11-27	正大天晴药业集团股份有限公司	阿法替尼中间体的合成方法
WO2016027243A1 (en) *	2014-08-21	2016-02-25	Dr. Reddy’S Laboratories Limited	Novel solid state forms of afatinib dimaleate
EP3201190A4 (en) *	2014-10-01	2018-03-14	Sun Pharmaceutical Industries Ltd	Crystalline form of afatinib dimaleate
CN105534920B (zh) *	2014-10-29	2020-07-10	江苏豪森药业集团有限公司	一种药物组合物及其制备方法
CN104402872B (zh) *	2014-11-14	2016-08-24	广东东阳光药业有限公司	一种结晶除杂方法
CN104447713B (zh) *	2014-11-18	2019-03-29	江苏奥赛康药业股份有限公司	阿法替尼化合物的制备方法
EP3023421A1 (en) *	2014-11-21	2016-05-25	Sandoz Ag	Crystalline forms of afatinib dimaleate
CN104529800B (zh) *	2014-12-08	2017-01-25	重庆威鹏药业有限公司	反式‑4‑二甲基氨基巴豆酸及盐的制备方法
CN105801567A (zh) *	2014-12-31	2016-07-27	徐州万邦金桥制药有限公司	一种双马来酸阿法替尼的纯化方法
CN105801568B (zh) *	2015-01-15	2019-07-30	杭州普晒医药科技有限公司	阿法替尼一马来酸盐晶型及其制备方法和药物组合物
JP6704422B2 (ja)	2015-03-20	2020-06-03	チアタイティエンチンファーマシューティカルグループカンパニーリミテッドChia Tai Tianqing Pharmaceutical Group Co., Ltd.	キナゾリン誘導体の塩およびその製造方法
AU2016248025B2 (en) *	2015-04-17	2020-12-24	Hetero Labs Ltd	Polymorphs of AFATINIB and its salts and process for the preparation of quinazolinyl derivatives
CN105859641B (zh) *	2015-05-05	2018-11-16	杭州华东医药集团新药研究院有限公司	喹唑啉巴豆基化合物二马来酸盐的晶体及其制备方法和用途
CN104892584B (zh) *	2015-05-27	2018-03-23	重庆泰濠制药有限公司	一种阿法替尼双马来酸盐无定型态及其制备方法、制剂
US10800763B2 (en)	2015-06-12	2020-10-13	Fresenius Kabi Oncology Ltd.	Polymorphic forms of Afatinib free base and Afatinib dimaleate
CN104926800A (zh) *	2015-06-26	2015-09-23	河北神威药业有限公司	一种阿法替尼二马来酸盐的结晶形式及其制备方法
CN105175331B (zh) *	2015-08-14	2019-04-26	江苏苏中药业集团股份有限公司	一种egfr类分子靶向抗肿瘤药物的制备方法
WO2017033107A1 (en)	2015-08-21	2017-03-02	Fresenius Kabi Oncology Ltd.	Pharmaceutical compositions comprising afatinib
WO2017093789A1 (en) *	2015-12-03	2017-06-08	Mylan Laboratories Ltd.	Polymorphic forms of afatinib dimaleate
CN106831733B (zh) *	2015-12-07	2021-05-11	海南先声药业有限公司	阿法替尼顺式异构体的制备方法与应用
CN106866641A (zh) *	2015-12-11	2017-06-20	河北神威药业有限公司	一种阿法替尼的精制方法
CN106916147A (zh) *	2015-12-25	2017-07-04	中美华世通生物医药科技（武汉）有限公司	化合物及其制备方法和用途
US10689359B2 (en)	2015-12-25	2020-06-23	Xuanzhu Pharma Co., Ltd.	Crystals of quinazoline derivative and preparation method therefor
CN105669658B (zh) *	2016-04-05	2018-06-29	北京民康百草医药科技有限公司	一种阿法替尼的精制方法
CN107488194B (zh) *	2016-06-10	2021-07-30	山东新时代药业有限公司	一种阿法替尼中间体及其制备方法
CN107488172B (zh) *	2016-06-10	2020-06-12	山东新时代药业有限公司	一种阿法替尼的制备方法
CN107488171B (zh) *	2016-06-10	2020-08-28	山东新时代药业有限公司	一种阿法替尼制备方法
CN107488153B (zh) *	2016-06-10	2020-06-23	山东新时代药业有限公司	一种阿法替尼中间体化合物
CN106243092B (zh) *	2016-07-28	2019-02-15	南京臣功制药股份有限公司	一种高选择性制备马来酸阿法替尼的方法
CN117599061A (zh)	2016-11-17	2024-02-27	得克萨斯州大学系统董事会	具有针对携带egfr或her2外显子20突变之癌细胞的抗肿瘤活性的化合物
TWI808958B (zh)	2017-01-25	2023-07-21	美商特普醫葯公司	涉及二芳基巨環化合物之組合療法
EP3606916A1 (en)	2017-04-06	2020-02-12	Johnson Matthey Public Limited Company	Novel forms of afatinib dimaleate
CN108358900A (zh) *	2018-03-30	2018-08-03	东北制药集团股份有限公司	一种阿法替尼及其马来酸盐的制备方法
KR20190141607A (ko)	2018-06-14	2019-12-24	주식회사 에이티파머	알로페론을 포함하는 췌장암 치료용 조성물 및 치료 보조제
KR102257913B1 (ko)	2018-07-17	2021-05-28	주식회사 에이티파머	알로페론을 포함하는 폐섬유증 치료용 조성물
CN109824657A (zh) *	2019-03-26	2019-05-31	石药集团中奇制药技术（石家庄）有限公司	一种二马来酸阿法替尼新晶型及其制备方法和应用
CN110590754A (zh) *	2019-09-21	2019-12-20	广东安诺药业股份有限公司	一种马来酸阿法替尼中间体的制备方法
CN110563710B (zh) *	2019-09-21	2020-05-19	广东安诺药业股份有限公司	一种马来酸阿法替尼的制备方法
CN113121512B (zh) *	2019-12-30	2022-11-04	江苏晶立信医药科技有限公司	一种喹唑啉基丁烯酰胺类化合物的制备方法
KR20210106158A (ko)	2020-02-20	2021-08-30	서울대학교산학협력단	알로페론을 포함하는 항암 치료 보조제
KR20210106157A (ko)	2020-02-20	2021-08-30	서울대학교산학협력단	알로페론을 포함하는 난소암 치료용 조성물 및 치료 보조제
CN114315808A (zh) *	2020-10-10	2022-04-12	西安新通药物研究有限公司	一种高收率马来酸阿法替尼的制备方法

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8618846D0 (en)	1986-08-01	1986-09-10	Smithkline Beckman Corp	Chemical process
JPS6442472A (en)	1987-08-10	1989-02-14	Kanebo Ltd	Quinazoline derivative, production thereof and brain function disorder improving agent containing said derivative as active ingredient
GB9005014D0 (en) *	1990-03-06	1990-05-02	Janssen Pharmaceutica Nv	N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives
RU2043352C1 (ru) *	1991-07-01	1995-09-10	Пермский фармацевтический институт	2-пропил-3- (5-нитрофурфулиден)амино- 4(3н)-хиназолинон, проявляющий противостафилококковую и анальгетическую активность
AU661533B2 (en)	1992-01-20	1995-07-27	Astrazeneca Ab	Quinazoline derivatives
GB9401182D0 (en)	1994-01-21	1994-03-16	Inst Of Cancer The Research	Antibodies to EGF receptor and their antitumour effect
ES2161290T3 (es)	1995-03-30	2001-12-01	Pfizer	Derivados de quinazolina.
GB9508538D0 (en)	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
US6140332A (en)	1995-07-06	2000-10-31	Novartis Ag	Pyrrolopyrimidines and processes for the preparation thereof
CN100503580C (zh)	1996-04-12	2009-06-24	沃尼尔·朗伯公司	酪氨酸激酶的不可逆抑制剂
UA73073C2 (ru)	1997-04-03	2005-06-15	Уайт Холдінгз Корпорейшн	Замещенные 3-циан хинолины
ZA986729B (en)	1997-07-29	1999-02-02	Warner Lambert Co	Irreversible inhibitors of tyrosine kinases
ZA986732B (en)	1997-07-29	1999-02-02	Warner Lambert Co	Irreversible inhibitiors of tyrosine kinases
TW436485B (en)	1997-08-01	2001-05-28	American Cyanamid Co	Substituted quinazoline derivatives
GB9800569D0 (en)	1998-01-12	1998-03-11	Glaxo Group Ltd	Heterocyclic compounds
US6297258B1 (en)	1998-09-29	2001-10-02	American Cyanamid Company	Substituted 3-cyanoquinolines
US6262088B1 (en)	1998-11-19	2001-07-17	Berlex Laboratories, Inc.	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
US6972288B1 (en) *	1999-02-27	2005-12-06	Boehringer Ingelheim Pharma Kg	4-amino-quinazoline and quinoline derivatives having an inhibitory effect on signal transduction mediated by tyrosine kinases
DE19911366A1 (de)	1999-03-15	2000-09-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE19911509A1 (de)	1999-03-15	2000-09-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
EP1194418A1 (de)	1999-06-21	2002-04-10	Boehringer Ingelheim Pharma KG	Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
US6627634B2 (en)	2000-04-08	2003-09-30	Boehringer Ingelheim Pharma Kg	Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them
US20030158196A1 (en)	2002-02-16	2003-08-21	Boehringer Ingelheim Pharma Gmbh Co. Kg	Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors
US7019012B2 (en)	2000-12-20	2006-03-28	Boehringer Ingelheim International Pharma Gmbh & Co. Kg	Quinazoline derivatives and pharmaceutical compositions containing them
DE10063435A1 (de)	2000-12-20	2002-07-04	Boehringer Ingelheim Pharma	Chinazolinderviate,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE10204462A1 (de)	2002-02-05	2003-08-07	Boehringer Ingelheim Pharma	Verwendung von Tyrosinkinase-Inhibitoren zur Behandlung inflammatorischer Prozesse
US20030225079A1 (en)	2002-05-11	2003-12-04	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy
DE10221018A1 (de)	2002-05-11	2003-11-27	Boehringer Ingelheim Pharma	Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie
PE20040945A1 (es)	2003-02-05	2004-12-14	Warner Lambert Co	Preparacion de quinazolinas substituidas
US20050043233A1 (en)	2003-04-29	2005-02-24	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
DE10349113A1 (de)	2003-10-17	2005-05-12	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von Aminocrotonylverbindungen
US20060058311A1 (en)	2004-08-14	2006-03-16	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation
JP5688877B2 (ja)	2005-11-11	2015-03-25	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	癌疾患の治療用キナゾリン誘導体
DK1948180T3 (da)	2005-11-11	2013-05-27	Boehringer Ingelheim Int	Kombinationsbehandling af cancer omfattende EGFR/HER2 inhibitorer
EP1981863B1 (en)	2006-01-26	2012-10-10	Boehringer Ingelheim International GmbH	Process for preparing aminocrotonylamino-substituted quinazoline derivatives
MX2009002710A (es)	2006-09-18	2009-03-25	Boehringer Ingelheim Int	Metodos para tratar canceres que portan mutaciones de egfr.
US8022216B2 (en)	2007-10-17	2011-09-20	Wyeth Llc	Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof
PE20100252A1 (es)	2008-06-06	2010-04-12	Boehringer Ingelheim Int	Nuevas formulaciones farmaceuticas solidas que comprenden dimaleato de 4-[(3-cloro-4-fluorofenil) amino]-6-{[4-(n,n-dimetilamino)-1-oxo-2-buten-1-il] amino}-7-((s)-tetrahidrofuran-3-iloxi)-quinazolina
US20120157472A1 (en)	2009-01-14	2012-06-21	Boehringer Ingelheim International Gmbh	Method for treating colorectal cancer
US9545381B2 (en)	2009-07-06	2017-01-17	Boehringer Ingelheim International Gmbh	Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient
WO2011069962A1 (en)	2009-12-07	2011-06-16	Boehringer Ingelheim International Gmbh	Bibw 2992 for use in the treatment of triple negative breast cancer
US9012464B2 (en)	2010-11-25	2015-04-21	Ratiopharm Gmbh	Salts and polymorphic forms of Afatinib
EP2753616A1 (en)	2011-10-06	2014-07-16	Ratiopharm GmbH	Crystalline forms of afatinib di-maleate
CN106279127B (zh)	2013-07-16	2019-05-24	杭州普晒医药科技有限公司	阿法替尼酸加成盐及其晶型、其制备方法及药物组合物
WO2016027243A1 (en)	2014-08-21	2016-02-25	Dr. Reddy’S Laboratories Limited	Novel solid state forms of afatinib dimaleate
CN104892584B (zh)	2015-05-27	2018-03-23	重庆泰濠制药有限公司	一种阿法替尼双马来酸盐无定型态及其制备方法、制剂
CN104926800A (zh)	2015-06-26	2015-09-23	河北神威药业有限公司	一种阿法替尼二马来酸盐的结晶形式及其制备方法

2003
- 2003-10-17 DE DE10349113A patent/DE10349113A1/de not_active Withdrawn
2004
- 2004-09-15 US US10/941,116 patent/US20050085495A1/en not_active Abandoned
- 2004-10-12 NZ NZ583049A patent/NZ583049A/en not_active IP Right Cessation
- 2004-10-12 MX MX2011004537A patent/MX338920B/es unknown
- 2004-10-12 SI SI200432301T patent/SI2508521T2/sl unknown
- 2004-10-12 CA CA2541928A patent/CA2541928C/en not_active Expired - Lifetime
- 2004-10-12 CA CA2759063A patent/CA2759063C/en not_active Expired - Lifetime
- 2004-10-12 NZ NZ547154A patent/NZ547154A/en not_active IP Right Cessation
- 2004-10-12 SG SG200800279-2A patent/SG139743A1/en unknown
- 2004-10-12 EP EP04765927.1A patent/EP1678165B1/de not_active Expired - Lifetime
- 2004-10-12 ES ES12155662T patent/ES2563211T5/es not_active Expired - Lifetime
- 2004-10-12 HR HRP20131214TT patent/HRP20131214T1/hr unknown
- 2004-10-12 ES ES04765927.1T patent/ES2440466T3/es not_active Expired - Lifetime
- 2004-10-12 UA UAA200810609A patent/UA91401C2/ru unknown
- 2004-10-12 WO PCT/EP2004/011378 patent/WO2005037824A2/de not_active Ceased
- 2004-10-12 PT PT47659271T patent/PT1678165E/pt unknown
- 2004-10-12 RS RS20130524A patent/RS60563B1/sr unknown
- 2004-10-12 RS RS20060260A patent/RS53398B/sr unknown
- 2004-10-12 JP JP2006534662A patent/JP4594317B2/ja not_active Expired - Lifetime
- 2004-10-12 HU HUE12155662A patent/HUE028254T2/en unknown
- 2004-10-12 AU AU2004281938A patent/AU2004281938B2/en not_active Expired
- 2004-10-12 DK DK04765927.1T patent/DK1678165T3/da active
- 2004-10-12 KR KR1020067009605A patent/KR101180752B1/ko not_active Expired - Lifetime
- 2004-10-12 ME MEP-2008-508A patent/ME00341B/me unknown
- 2004-10-12 EA EA200600604A patent/EA016624B1/ru active Protection Beyond IP Right Term
- 2004-10-12 BR BR122013033343A patent/BR122013033343B8/pt active IP Right Grant
- 2004-10-12 MX MXPA06004076A patent/MXPA06004076A/es active IP Right Grant
- 2004-10-12 PL PL12155662.5T patent/PL2508521T5/pl unknown
- 2004-10-12 RS YUP-2006/0260A patent/RS20060260A/sr unknown
- 2004-10-12 EP EP12155662.5A patent/EP2508521B2/de not_active Expired - Lifetime
- 2004-10-12 UA UAA200605327A patent/UA91006C2/ru unknown
- 2004-10-12 PL PL04765927T patent/PL1678165T3/pl unknown
- 2004-10-12 SI SI200432099T patent/SI1678165T1/sl unknown
- 2004-10-12 DK DK12155662.5T patent/DK2508521T4/da active
- 2004-10-12 PT PT121556625T patent/PT2508521E/pt unknown
- 2004-10-12 CN CNA2008101664841A patent/CN101402631A/zh active Pending
- 2004-10-12 HR HRP20160246TT patent/HRP20160246T4/hr unknown
- 2004-10-12 BR BRPI0415424A patent/BRPI0415424B8/pt active IP Right Grant
- 2004-10-12 KR KR1020127003787A patent/KR101282812B1/ko not_active Expired - Lifetime
- 2004-10-12 CN CN2004800305555A patent/CN1867564B/zh not_active Expired - Lifetime
- 2004-10-14 MY MYPI20044237A patent/MY149921A/en unknown
- 2004-10-14 MY MYPI2010002645A patent/MY155425A/en unknown
- 2004-10-14 UY UY28559A patent/UY28559A1/es not_active IP Right Cessation
- 2004-10-15 PE PE2010000135A patent/PE20100267A1/es not_active Application Discontinuation
- 2004-10-15 AR ARP040103754A patent/AR046118A1/es not_active Application Discontinuation
- 2004-10-15 TW TW099147116A patent/TWI373470B/zh not_active IP Right Cessation
- 2004-10-15 TW TW093131395A patent/TWI348468B/zh not_active IP Right Cessation
- 2004-10-15 PE PE2004001000A patent/PE20050965A1/es active IP Right Grant
2006
- 2006-03-16 ZA ZA200602234A patent/ZA200602234B/en unknown
- 2006-04-11 IL IL174951A patent/IL174951A/en active IP Right Grant
- 2006-04-17 EC EC2006006509A patent/ECSP066509A/es unknown
- 2006-05-15 NO NO20062181A patent/NO333971B1/no unknown
- 2006-07-14 US US11/457,622 patent/US8426586B2/en active Active
2010
- 2010-06-21 JP JP2010140697A patent/JP5264830B2/ja not_active Expired - Lifetime
2011
- 2011-03-16 AU AU2011201171A patent/AU2011201171B2/en active Active
- 2011-11-10 IL IL216249A patent/IL216249A/en active IP Right Grant
2013
- 2013-05-10 NO NO20130663A patent/NO335103B1/no unknown
- 2013-12-09 CY CY20131101112T patent/CY1114866T1/el unknown
2015
- 2015-02-04 UY UY0001035979A patent/UY35979A/es not_active IP Right Cessation
2016
- 2016-03-11 CY CY20161100212T patent/CY1117279T1/el unknown

Also Published As

Publication number	Publication date
TWI373470B (en)	2012-10-01
RS20060260A (sr)	2008-06-05
CN101402631A (zh)	2009-04-08
HRP20160246T4 (hr)	2022-11-11
ECSP066509A (es)	2006-10-10
PL2508521T5 (pl)	2023-03-27
EA200600604A1 (ru)	2006-10-27
JP5264830B2 (ja)	2013-08-14
NO335103B1 (no)	2014-09-15
WO2005037824A2 (de)	2005-04-28
CA2759063A1 (en)	2005-04-28
US20050085495A1 (en)	2005-04-21
MY149921A (en)	2013-10-31
KR20060120121A (ko)	2006-11-24
EP2508521B2 (de)	2022-09-07
TW201118086A (en)	2011-06-01
CY1114866T1 (el)	2016-12-14
RS53398B (sr)	2014-10-31
BR122013033343B1 (pt)	2020-10-13
AU2011201171A1 (en)	2011-04-07
KR101282812B1 (ko)	2013-07-05
KR101180752B1 (ko)	2012-09-10
NO20130663L (no)	2006-05-15
CA2541928C (en)	2012-12-11
AU2004281938B2 (en)	2011-04-14
NO333971B1 (no)	2013-11-04
SI2508521T1 (sl)	2016-03-31
HRP20131214T1 (hr)	2014-01-31
EP1678165A2 (de)	2006-07-12
RS20130524A3 (en)	2015-08-31
BRPI0415424B1 (pt)	2019-01-22
SI1678165T1 (sl)	2013-12-31
MX338920B (es)	2016-05-06
TW200526644A (en)	2005-08-16
PE20100267A1 (es)	2010-04-21
UY35979A (es)	2016-09-30
BRPI0415424A (pt)	2006-12-05
BRPI0415424B8 (pt)	2021-05-25
CN1867564B (zh)	2011-06-08
AR046118A1 (es)	2005-11-23
NZ583049A (en)	2011-08-26
MY155425A (en)	2015-10-15
SG139743A1 (en)	2008-02-29
IL174951A0 (en)	2006-08-20
US20070027170A1 (en)	2007-02-01
BR122013033343B8 (pt)	2021-05-25
CN1867564A (zh)	2006-11-22
IL174951A (en)	2012-03-29
HK1095817A1 (en)	2007-05-18
ZA200602234B (en)	2007-09-26
CY1117279T1 (el)	2017-04-26
AU2011201171B2 (en)	2012-02-09
KR20120037987A (ko)	2012-04-20
MEP50808A (en)	2011-02-10
NO20062181L (no)	2006-05-15
JP2007510624A (ja)	2007-04-26
DE10349113A1 (de)	2005-05-12
ME00341B (me)	2011-05-10
RS60563B1 (sr)	2020-08-31
PT2508521E (pt)	2016-03-31
CA2759063C (en)	2012-04-17
JP2010202668A (ja)	2010-09-16
CA2541928A1 (en)	2005-04-28
NZ547154A (en)	2010-02-26
PL1678165T3 (pl)	2014-03-31
EA016624B1 (ru)	2012-06-29
EP2508521A2 (de)	2012-10-10
DK1678165T3 (da)	2013-12-09
UY28559A1 (es)	2005-05-31
PT1678165E (pt)	2013-11-07
JP4594317B2 (ja)	2010-12-08
IL216249A (en)	2015-05-31
MXPA06004076A (es)	2006-06-27
PL2508521T3 (pl)	2016-06-30
SI2508521T2 (sl)	2022-11-30
PE20050965A1 (es)	2005-12-19
US8426586B2 (en)	2013-04-23
UA91006C2 (ru)	2010-06-25
EP1678165B1 (de)	2013-09-25
IL216249A0 (en)	2011-12-29
ES2563211T3 (es)	2016-03-11
AU2004281938A1 (en)	2005-04-28
ES2440466T3 (es)	2014-01-29
ES2563211T5 (es)	2022-12-27
RS20130524A2 (sr)	2014-06-30
WO2005037824A3 (de)	2005-07-21
DK2508521T4 (da)	2022-10-03
TWI348468B (en)	2011-09-11
EP2508521B1 (de)	2015-12-30
HUE028254T2 (en)	2016-12-28
EP2508521A3 (de)	2013-01-23
DK2508521T3 (en)	2016-03-29
HRP20160246T1 (hr)	2016-04-08

Publication	Publication Date	Title
UA91401C2 (en)	2010-07-26	4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(n,n-dimethylamino)-1-oxo-2-butene-1-yl]amino}-7-((s)-tetrahydrofurane-3-yloxy)-quinazoline maleate, production method and uses thereof
WO2003084539A3 (en)	2004-09-02	New pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors
MX2007007458A (es)	2007-08-15	Derivados de quinazolina para inhibir crecimiento de celulas cancerigenas y metodo para la preparacion de los mismos.
EP1485381B8 (en)	2010-05-12	Azolylaminoazine as inhibitors of protein kinases
PT1687305E (pt)	2008-10-17	Derivados de 1h-imidazoquinolina como inibidores de proteína quinase
AU2003220299A1 (en)	2003-09-29	Azinylaminoazoles as inhibitors of protein kinases
AU2003218215A1 (en)	2003-09-29	Azolylaminoazines as inhibitors of protein kinases
AU2003220300A1 (en)	2003-09-29	Compositions useful as inhibitors of protein kinases
HUS1600060I1 (hu)	2017-01-30	4[[4-[[4-(2-cianoetenil)-2,6-dimetilfenil]-2-pirimidinil]amino]benzonitril
WO2005037798A3 (en)	2005-06-16	Amide or thiomide derivatives and their use in the treatment of pain
PL374443A1 (en)	2005-10-17	Novel pyrimidineamide derivatives and the use thereof
UA90518C2 (ru)	2010-05-11	Фармацевтическая композиция в форме таблетки, которая имеет улучшеное всасывание при трансбукальном введение, которая содержит наркотический активный ингредиент и амин
MXPA03010054A (es)	2004-04-02	Composiciones que comprenden lopinavir y metodos para aumentar la biodisponibilidad de agentes farmaceuticos.
WO2004002491A8 (en)	2005-02-17	Morpholine and tetrahydropyran drivatives and their use as cathepsin inhibitors
EP1262197A3 (en)	2002-12-18	Combination treatment for sleep disorders including sleep apnea
IL179206A0 (en)	2007-03-08	Pyrrolylpyrimidine derivatives and pharmaceutical compositions containing the same
CA2505500A1 (en)	2004-05-27	Method of stimulating hair growth using benzopyrans
WO2004004725A3 (en)	2004-05-27	Pharmaceutical compositions of anticholinergics and p38 kinase inhibitors in the treatment of respiratory diseases
EA200801614A1 (ru)	2008-10-30	Фармацевтическая композиция, содержащая монтелукаст
WO2002069944A3 (de)	2003-10-02	Neue arzneimittelkompositionen auf der basis von anticholinergika und nk1-rezeptor-antagonisten
MXPA05007253A (es)	2005-12-14	Sales novedosas de derivados anticonvulsivantes.
UA92469C2 (en)	2010-11-10	Fumarate of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl amino benzonitrile
SI1789139T1 (sl)	2012-08-31	Fumarat 4-((4-((4-(2-cianoetenil)-2,6-dimetifenil amino-2-pirimidinil amino benzonitrila
EE200400069A (et)	2004-08-16	Tsitalopraami kasutamine ravimkoostiste valmistamiseks kõrgenenud vererõhu raviks
MXPA05003633A (es)	2005-12-14	2"-oxo-voruscharina y derivados de la misma.