CA2484395C - Heterocycles bicycliques, medicaments contenant ces composes, leur utilisation et leur procede de production - Google Patents
Heterocycles bicycliques, medicaments contenant ces composes, leur utilisation et leur procede de production Download PDFInfo
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- CA2484395C CA2484395C CA2484395A CA2484395A CA2484395C CA 2484395 C CA2484395 C CA 2484395C CA 2484395 A CA2484395 A CA 2484395A CA 2484395 A CA2484395 A CA 2484395A CA 2484395 C CA2484395 C CA 2484395C
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- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title claims abstract description 5
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- 238000000034 method Methods 0.000 title claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 96
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 80
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 9
- 210000004072 lung Anatomy 0.000 claims abstract description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
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- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims abstract description 3
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- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
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- 125000005002 aryl methyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 7
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 2
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- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 1
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims 1
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 1
- IAROKPFDVRCHKC-OALUTQOASA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]but-2-enamide Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 IAROKPFDVRCHKC-OALUTQOASA-N 0.000 claims 1
- ILWDXKDJZUXXIW-GUDVDZBRSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[(3r)-oxolan-3-yl]oxyquinazolin-6-yl]-4-[(1r,4r)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]but-2-enamide Chemical compound C([C@@]1(OC[C@@]2([H])C1)[H])N2CC=CC(=O)NC(C(=CC1=NC=N2)O[C@H]3COCC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 ILWDXKDJZUXXIW-GUDVDZBRSA-N 0.000 claims 1
- ILWDXKDJZUXXIW-OTWHNJEPSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[(3r)-oxolan-3-yl]oxyquinazolin-6-yl]-4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]but-2-enamide Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2CC=CC(=O)NC(C(=CC1=NC=N2)O[C@H]3COCC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 ILWDXKDJZUXXIW-OTWHNJEPSA-N 0.000 claims 1
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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
- C07D405/14—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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
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- Pulmonology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Otolaryngology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
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- Dermatology (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
Abstract
La présente invention concerne des hétérocycles bicycliques de la formule générale (I), où R?a¿, R?b¿, R?c¿, A, B, C, D, E et X ont la définition donnée dans la revendication 1, leurs tautomères, leurs stéréo-isomères, leurs mélanges et leurs sels, notamment leurs sels physiologiquement compatibles avec des acides inorganiques ou organiques ayant de précieuses caractéristiques pharmacologiques, notamment une action inhibitrice sur la transduction de signaux transmise par la tyrosine-kinase. L'invention concerne également leur utilisation pour le traitement de maladies, notamment de maladies tumorales et de l'hypertrophie de la prostate (BPH), de maladies des poumons et des voies respiratoires, ainsi que leur production.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10217689A DE10217689A1 (de) | 2002-04-19 | 2002-04-19 | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung |
| DE10217689.2 | 2002-04-19 | ||
| PCT/EP2003/003828 WO2003089439A1 (fr) | 2002-04-19 | 2003-04-14 | Heterocycles bicycliques, medicaments contenant ces composes, leur utilisation et leur procede de production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2484395A1 CA2484395A1 (fr) | 2003-10-30 |
| CA2484395C true CA2484395C (fr) | 2011-11-22 |
Family
ID=29224623
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2484395A Expired - Fee Related CA2484395C (fr) | 2002-04-19 | 2003-04-14 | Heterocycles bicycliques, medicaments contenant ces composes, leur utilisation et leur procede de production |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1499619A1 (fr) |
| JP (1) | JP4527406B2 (fr) |
| AR (1) | AR039571A1 (fr) |
| AU (1) | AU2003226806A1 (fr) |
| CA (1) | CA2484395C (fr) |
| DE (1) | DE10217689A1 (fr) |
| PE (1) | PE20040171A1 (fr) |
| TW (1) | TW200408643A (fr) |
| UY (1) | UY27767A1 (fr) |
| WO (1) | WO2003089439A1 (fr) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU90901A (sh) | 1999-06-21 | 2004-07-15 | Boehringer Ingelheim Pharma Gmbh. & Co.Kg. | Biciklični heterocikli, lekovi koji sadrže ta jedinjenja, njihova primena i postupci za njihovo pripremanje |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| US20040044014A1 (en) | 2002-04-19 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
| ES2400339T3 (es) | 2002-07-15 | 2013-04-09 | Symphony Evolution, Inc. | Compuestos, composiciones farmacéuticas de los mismos y su uso en el tratamiento del cáncer |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| WO2006074147A2 (fr) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Composes et utilisation therapeutique associee |
| WO2005003100A2 (fr) | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | Composes et leur utilisation therapeutique |
| DK1667991T3 (da) | 2003-09-16 | 2008-08-18 | Astrazeneca Ab | Quinazolinderivater som tyrosinkinaseinhibitorer |
| CA2744997A1 (fr) | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | Modulateurs de c-met et procede d'utilisation |
| AP2204A (en) * | 2004-05-06 | 2011-02-07 | Warner Lambert Co | 4-phenylamino-quinazolin-6-yl-amides. |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| KR100832594B1 (ko) | 2005-11-08 | 2008-05-27 | 한미약품 주식회사 | 다중저해제로서의 퀴나졸린 유도체 및 이의 제조방법 |
| EP1948179A1 (fr) | 2005-11-11 | 2008-07-30 | Boehringer Ingelheim International GmbH | Derives de quinazoline pour le traitement des affections cancereuses |
| BRPI0717586A2 (pt) | 2006-09-18 | 2013-10-29 | Boehringer Ingelheim Int | Método para tratar câncer apresentando mutações do egfr |
| EA038195B1 (ru) | 2009-01-16 | 2021-07-22 | Экселиксис, Инк. | Малатная соль n-(4-{[6,7-бис-(метилокси)хинолин-4-ил]окси}фенил)-n'-(4-фторфенил)циклопропан-1,1-дикарбоксамида и ее применение для лечения рака почек и печени |
| JP5721709B2 (ja) * | 2009-07-02 | 2015-05-20 | ニューゲン セラピューティクス， インコーポレイテッド | リンを含むキナゾリン化合物および使用方法 |
| PL2451445T3 (pl) | 2009-07-06 | 2019-09-30 | Boehringer Ingelheim International Gmbh | Sposób suszenia BIBW2992, jego soli i stałych preparatów farmaceutycznych zawierających tę substancję czynną |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| CN102020639A (zh) | 2009-09-14 | 2011-04-20 | 上海恒瑞医药有限公司 | 6-氨基喹唑啉或3-氰基喹啉类衍生物、其制备方法及其在医药上的应用 |
| JP5859118B2 (ja) * | 2011-05-26 | 2016-02-10 | 山東軒竹医薬科技有限公司 | チロシンキナーゼ阻害剤としてのキナゾリン誘導体、その調製方法及びその使用 |
| CN103874696B (zh) * | 2011-10-12 | 2015-06-03 | 苏州韬略生物科技有限公司 | 作为激酶抑制剂的喹唑啉衍生物及其使用方法 |
| 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 |
| KR20210137422A (ko) | 2018-09-25 | 2021-11-17 | 블랙 다이아몬드 테라퓨틱스, 인코포레이티드 | 티로신 키나아제 억제제로서의 퀴나졸린 유도체, 조성물, 이들의 제조 방법 및 이들의 용도 |
| CN119390683A (zh) | 2019-08-15 | 2025-02-07 | 黑钻治疗公司 | 炔基喹唑啉化合物 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3370340B2 (ja) * | 1996-04-12 | 2003-01-27 | ワーナー―ランバート・コンパニー | チロシンキナーゼの不可逆的阻害剤 |
| TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| AU6159499A (en) * | 1998-09-29 | 2000-04-17 | Wyeth Holdings Corporation | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
| DE19908567A1 (de) * | 1999-02-27 | 2000-08-31 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| SK12112001A3 (sk) * | 1999-02-27 | 2001-12-03 | Boehringer Ingelheim Pharma Kg | 4-amino-chinazolínové a chinolínové deriváty, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie |
| YU90901A (sh) * | 1999-06-21 | 2004-07-15 | Boehringer Ingelheim Pharma Gmbh. & Co.Kg. | Biciklični heterocikli, lekovi koji sadrže ta jedinjenja, njihova primena i postupci za njihovo pripremanje |
| DE10017539A1 (de) * | 2000-04-08 | 2001-10-11 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbingungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| CA2403152C (fr) * | 2000-04-08 | 2008-10-28 | Boehringer Ingelheim Pharma Kg | Heterocycles bicycliques, compositions pharmaceutiques contenant ces composes, leur utilisation et leur procede de preparation |
| DE10042062A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Hertellung |
| DE10042061A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
-
2002
- 2002-04-19 DE DE10217689A patent/DE10217689A1/de not_active Withdrawn
-
2003
- 2003-04-14 EP EP03746824A patent/EP1499619A1/fr not_active Withdrawn
- 2003-04-14 JP JP2003586159A patent/JP4527406B2/ja not_active Expired - Fee Related
- 2003-04-14 CA CA2484395A patent/CA2484395C/fr not_active Expired - Fee Related
- 2003-04-14 AU AU2003226806A patent/AU2003226806A1/en not_active Abandoned
- 2003-04-14 WO PCT/EP2003/003828 patent/WO2003089439A1/fr not_active Ceased
- 2003-04-15 PE PE2003000384A patent/PE20040171A1/es not_active Application Discontinuation
- 2003-04-16 UY UY27767A patent/UY27767A1/es not_active Application Discontinuation
- 2003-04-16 AR ARP030101330A patent/AR039571A1/es not_active Application Discontinuation
- 2003-04-16 TW TW092108807A patent/TW200408643A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1499619A1 (fr) | 2005-01-26 |
| JP2005526837A (ja) | 2005-09-08 |
| DE10217689A1 (de) | 2003-11-13 |
| AR039571A1 (es) | 2005-02-23 |
| WO2003089439A1 (fr) | 2003-10-30 |
| JP4527406B2 (ja) | 2010-08-18 |
| TW200408643A (en) | 2004-06-01 |
| UY27767A1 (es) | 2003-11-28 |
| AU2003226806A1 (en) | 2003-11-03 |
| CA2484395A1 (fr) | 2003-10-30 |
| PE20040171A1 (es) | 2004-06-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130415 |