WO2004074263A1 - Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, ihre verwendung und verfahren zu ihrer herstellung - Google Patents
Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, ihre verwendung und verfahren zu ihrer herstellung Download PDFInfo
- Publication number
- WO2004074263A1 WO2004074263A1 PCT/EP2004/001398 EP2004001398W WO2004074263A1 WO 2004074263 A1 WO2004074263 A1 WO 2004074263A1 EP 2004001398 W EP2004001398 W EP 2004001398W WO 2004074263 A1 WO2004074263 A1 WO 2004074263A1
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- WIPO (PCT)
- Prior art keywords
- group
- yloxy
- alkyloxy
- substituted
- alkyl
- Prior art date
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- 0 CC*CC(C(C)=C1)=CC2/C1=C(/C)\*=C\C(C)CC2 Chemical compound CC*CC(C(C)=C1)=CC2/C1=C(/C)\*=C\C(C)CC2 0.000 description 2
- CRYZJMNLWOKBNV-UHFFFAOYSA-N CCC(C)(CC)CCN=O Chemical compound CCC(C)(CC)CCN=O CRYZJMNLWOKBNV-UHFFFAOYSA-N 0.000 description 1
- HIAHZEQOOZMTAR-UJXFUWLCSA-N O=C(/C=C/CN1CCOCCC1)Nc(c(O[C@@H]1COCC1)c1)cc2c1ncnc2Nc(cc1Cl)ccc1F Chemical compound O=C(/C=C/CN1CCOCCC1)Nc(c(O[C@@H]1COCC1)c1)cc2c1ncnc2Nc(cc1Cl)ccc1F HIAHZEQOOZMTAR-UJXFUWLCSA-N 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
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Definitions
- Bicyclic heterocycles medicaments containing these compounds, their use and processes for their preparation
- the present invention relates to bicyclic heterocycles of the general formula
- R b is a phenyl, benzyl or 1-phenylethyl group in which the phenyl nucleus in each case by the radicals R 1 to R 3 is substituted, wherein
- R 1 and R 2 which may be the same or different, each represents a hydrogen, fluorine, chlorine, bromine or iodine atom,
- R 3 is a hydrogen, fluorine, chlorine or bromine atom
- R ° is a hydrogen atom or a fluorine, chlorine or bromine atom
- R 4 is a hydroxy, d- 3 alkyloxy-, Gs ⁇ -Gycloalkyloxy-, Gs-e-Gycloalkyl- C ⁇ - 3 alkyloxy, amino, C ⁇ -3 alkylamino, di- (C ⁇ - 3 - alkyl) amino, bis- (2-C ⁇ -3 - alkyloxy-ethyl) -amino, bis- (3-C ⁇ -3 alkyloxy-propyl) amino, pyrrolidin-1-yl, pipe- ridin- 1-yl, homopiperidin-1-yl, morpholin-4-yl, Homomorpholin-4-yl, piperazine-yl, 1, 4- (G ⁇ -3 alkyl) -piperazin-1-yl, Represents homopiperazin-1-yl or 4- (G ⁇ 3 -alkyl) homopiperazine-1-yl group,
- R e and R d which may be identical or different, each represents a hydrogen atom or an alkyl group C ⁇ -3
- X is a methine group substituted by a cyano group or a nitrogen atom
- R a is a hydrogen atom
- R 1 is a hydrogen, fluorine, chlorine or bromine atom
- a pyridinyloxy or pyridinylmethoxy group wherein the pyridinyl moiety of the abovementioned groups is optionally substituted by a methyl or trifluoromethyl group,
- R 2 is a hydrogen, fluorine or chlorine atom
- R ° is a hydrogen atom
- R 4 is a hydroxy, C ⁇ -3 -alkyloxy-, amino, C ⁇ -3 alkylamino, di- (C ⁇ -3 alkyl) amino, bis- (2-methoxyethyl) -amino, pyrrolidin-1 yl, piperidin-1-yl, homopiperidin-1-yl, morpholin-4-yl, Homomorpholin-4-yl, piperazin-1-yl, 4- (C ⁇ -3 alkyl) -piperazine Represents 1-yl, homopiperazin-1-yl, or 4- (C 1-3 -alkyl) homopiperazin-1-yl group,
- R e and R d which may be the same or different, each represents a hydrogen atom or a methyl group
- alkyl groups may be straight-chain or branched
- R e and R d each represent a hydrogen atom
- X is a nitrogen atom
- R a is a hydrogen atom
- R b is a 3-chloro-4-fluoro-phenyl group
- R c is a tetrahydrofuran-3-yloxy group
- R e and R d each represent a hydrogen atom
- X is a nitrogen atom, their tautomers, their stereoisomers, their mixtures and their salts.
- R a, R b, R ° and X are as hereinbefore defined and R 7 and R 8, which C ⁇ the same or may be different, -4 alkyl groups, with a compound of general formula
- the reaction is conveniently carried out in a solvent or solvent mixture such as tetrahydrofuran, tetrahydrofuran / water, acetonitrile, acetonitrile, dioxane, ethylene glycol dimethyl ether, isopropanol, methylene chloride, dimethylformamide or sulfolane, optionally in the presence of an inorganic or organic base, e.g. Sodium carbonate, potassium hydroxide or 1, 8-diazabicyclo [5.4.0] undec-7-ene and optionally in the presence of a lithium salt such as lithium chloride at temperatures between -50 and 150 ° C, but preferably at temperatures between -20 and 80 ° C.
- a lithium salt such as lithium chloride at temperatures between -50 and 150 ° C, but preferably at temperatures between -20 and 80 ° C.
- the reaction can also be carried out with a reactive derivative of the compound of the general formula III, for example the hydrate or a hemiacetal.
- R a , R b , R c and X are defined as mentioned above and Z 1 represents a leaving group such as a halogen atom or a substituted sulphonyloxy group such as a chlorine or bromine atom, a Methansulfonyloxy- or p-toluenesulfonyloxy group, with a compound of general formula
- reaction is conveniently carried out in a solvent such as isopropanol, butanol, tetrahydrofuran, dioxane, acetonitrile, dimethylformamide, sulfolane, toluene or methylene chloride or mixtures thereof, if appropriate in the presence of an inorganic or organic base, for example sodium carbonate, potassium carbonate, potassium hydroxide, triethylamine or N-ethyl diisopropylamine and optionally in the presence of a reaction accelerator such as an alkali metal iodide at temperatures between -20 and 150 ° C, but preferably at temperatures between 0 and 100 ° C carried out.
- a reaction accelerator such as an alkali metal iodide at temperatures between -20 and 150 ° C, but preferably at temperatures between 0 and 100 ° C carried out.
- the reaction can also be carried out without a solvent or in an excess of the compound of general formula V used.
- Suitable protecting groups for an amino, alkylamino or imino group are, for example, the formyl, acetyl, trifluoroacetyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dirnethoxybenzyl group ,
- the optional subsequent cleavage of a protective moiety used is carried out, for example, hydrolytically in an aqueous solvent, e.g. in water, isopropanol / water, acetic acid / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid or in the presence of an alkali metal base such as sodium hydroxide or potassium hydroxide or aprotic, e.g. in the presence of iodotrimethylsilane, at temperatures between 0 and 120 ° C, preferably at temperatures between 10 and 100 ° C.
- an aqueous solvent e.g. in water, isopropanol / water, acetic acid / water, tetrahydrofuran / water or dioxane / water
- an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid
- the cleavage of a benzyl, methoxybenzyl or benzyloxycarbonyl radical is carried out, for example, by hydrogenolysis, for example with hydrogen in the presence of a catalyst such as palladium / carbon in a suitable solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid, if appropriate with the addition of an acid such as hydrochloric acid at temperatures between 0 and 100 ° C, but preferably at room temperatures between 20 and 60 ° C, and at a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar.
- the cleavage of a 2,4-dimethoxy-benzyl radical is preferably carried out in trifluoroacetic acid in the presence of anisole.
- the compounds of general formula I obtained can be separated into their enantiomers and / or diastereomers.
- cis / trans mixtures can be separated into their cis and trans isomers, and compounds having at least one optically active carbon atom can be resolved into their enantiomers.
- the cis- / trans mixtures obtained can be purified by chromatography into their cis and trans isomers, the compounds of general formula I which are obtained in racemates, by methods known per se (see Allinger NL and Eliel EL in " Topics in Stereochemistry ", Vol. 6, Wiley Interscience, 1971)) in their optical antipodes and compounds of general formula I having at least 2 asymmetric carbon atoms due to their physicochemical differences according to known methods, eg by chromatography and / or fractionated Crystallization, into their diastereomers, which, if they are obtained in racemic form, can then be separated into the enantiomers as mentioned above.
- the separation of enantiomers is preferably carried out by column separation on chiral phases or by recrystallization from an optically active solvent or by reacting with a, with the racemic compound salts or derivatives such as esters or amides forming optically active substance, in particular acids and their activated derivatives or alcohols, and Separation of the thus obtained diastereomeric salt mixture or derivative, for example due to different solubilities, wherein from the pure diastereomeric salts or derivatives, the free antipodes can be released by the action of suitable agents.
- optically active acids are, for example, the D and L forms of tartaric acid or dibenzoyltartaric acid, di-Op-toluoyl-tartaric acid, malic acid, mandelic acid, camphorsulfonic acid, glutamic acid, aspartic acid or quinic acid.
- optically active alcohols are (+) - or (-) - menthol and, for example, (+) - or (-) - menthyloxycarbonyl as the optically active acyl radical in amides.
- the compounds are also suitable for the treatment of diseases of the gastrointestinal tract and the bile ducts and bladder, which are associated with a disrupted activity of tyrosine kinases, such as those found in chronic inflammatory changes, such as cholecystitis, Crohn's disease, Ulcerative colitis, and ulcers in the gastrointestinal tract or as they occur in diseases of the gastrointestinal tract, which are associated with increased secretion, such as M. Menetrier, secreting adenomas and protein loss syndromes.
- tyrosine kinases such as those found in chronic inflammatory changes, such as cholecystitis, Crohn's disease, Ulcerative colitis, and ulcers in the gastrointestinal tract or as they occur in diseases of the gastrointestinal tract, which are associated with increased secretion, such as M. Menetrier, secreting adenomas and protein loss syndromes.
- these compounds may be used alone or in combination with other respiratory therapeutics, such as secretolytically (e.g., ambroxol, N-acetylcysteine), broncholytically (e.g., tiotropium or ipratropium or fenoterol, salmeterol, salbutamol) and / or anti-inflammatory (e.g., theophylline or glucocorticoids) substances.
- secretolytically e.g., ambroxol, N-acetylcysteine
- broncholytically e.g., tiotropium or ipratropium or fenoterol, salmeterol, salbutamol
- anti-inflammatory e.g., theophylline or glucocorticoids
- Homomorpholin-4-yl-acetaldehyde hydrochloride prepared by stirring (2.5 hours) 4- (2,2-dimethoxy-ethyl) homomorpholine with half-concentrated hydrochloric acid at 80 ° C. The resulting solution is reacted further directly under Ex.
- 1 drag core contains:
- the active substance is mixed with calcium phosphate, corn starch, polyvinylpyrrolidone, hydroxypropylmethylcellulose and half of the stated amount of magnesium stearate.
- a tableting machine compacts are produced with a diameter of about 13 mm, these are ground on a suitable machine through a sieve with 1.5 mm mesh size and mixed with the remaining amount of magnesium stearate. This granulate is pressed on a tabletting machine into tablets of the desired shape.
- 1 tablet contains:
- the granules dried at 45 ° C are again rubbed through the same sieve and mixed with the stated amount of magnesium stearate. From the mixture tablets are pressed.
- 1 capsule contains:
- Composition 1 suppository contains:
- 5 ml of suspension contain 50 mg of active ingredient.
- Active ingredient 10.0 mg 0.01 n hydrochloric acid s.q.
- the active ingredient is dissolved in the required amount 0.01 N HCl, made isotonic with sodium chloride, sterile filtered and filled into 2 ml ampoules.
- o 1 capsule contains:
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE502004008024T DE502004008024D1 (de) | 2003-02-20 | 2004-02-14 | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, ihre verwendung und verfahren zu ihrer herstellung |
NZ542402A NZ542402A (en) | 2003-02-20 | 2004-02-14 | Bicyclic heterocycles, medicaments containing said compounds, use thereof, and method for the production thereof |
CA002516426A CA2516426A1 (en) | 2003-02-20 | 2004-02-14 | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
JP2005518423A JP4468305B2 (ja) | 2003-02-20 | 2004-02-14 | 二環式複素環、これらの化合物を含む医薬組成物、それらの使用及びそれらの製造方法 |
MXPA05008780A MXPA05008780A (es) | 2003-02-20 | 2004-02-14 | Heterociclos biciclicos, medicamentos que contienen estos compuestos, su utilizacion y preocedimientos para su preparacion. |
BRPI0407709-1A BRPI0407709A (pt) | 2003-02-20 | 2004-02-14 | heterociclos bicìclicos, composições farmacêuticas contendo esses compostos, seu uso e processos para o preparo dos mesmos |
EP04711303A EP1597240B1 (de) | 2003-02-20 | 2004-02-14 | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, ihre verwendung und verfahren zu ihrer herstellung |
AU2004213129A AU2004213129A1 (en) | 2003-02-20 | 2004-02-14 | Bicyclic heterocycles, medicaments containing said compounds, use thereof, and method for the production thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10307165.2 | 2003-02-20 | ||
DE10307165A DE10307165A1 (de) | 2003-02-20 | 2003-02-20 | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004074263A1 true WO2004074263A1 (de) | 2004-09-02 |
Family
ID=32797568
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2004/001398 WO2004074263A1 (de) | 2003-02-20 | 2004-02-14 | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, ihre verwendung und verfahren zu ihrer herstellung |
Country Status (20)
Country | Link |
---|---|
EP (1) | EP1597240B1 (de) |
JP (1) | JP4468305B2 (de) |
KR (1) | KR20050103230A (de) |
CN (1) | CN1751033A (de) |
AR (1) | AR043249A1 (de) |
AT (1) | ATE407929T1 (de) |
AU (1) | AU2004213129A1 (de) |
BR (1) | BRPI0407709A (de) |
CA (1) | CA2516426A1 (de) |
CL (1) | CL2004000284A1 (de) |
DE (2) | DE10307165A1 (de) |
ES (1) | ES2314374T3 (de) |
MX (1) | MXPA05008780A (de) |
NZ (1) | NZ542402A (de) |
PE (1) | PE20040953A1 (de) |
RU (1) | RU2005128826A (de) |
TW (1) | TW200505912A (de) |
UY (1) | UY28191A1 (de) |
WO (1) | WO2004074263A1 (de) |
ZA (1) | ZA200506121B (de) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007054551A1 (en) | 2005-11-11 | 2007-05-18 | Boehringer Ingelheim International Gmbh | Combination treatment of cancer comprising egfr/her2 inhibitors |
WO2007054550A1 (en) * | 2005-11-11 | 2007-05-18 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
WO2007085638A1 (en) * | 2006-01-26 | 2007-08-02 | Boehringer Ingelheim International Gmbh | Process for preparing aminocrotonylamino-substituted quinazoline derivatives |
WO2012027445A1 (en) | 2010-08-26 | 2012-03-01 | Boehringer Ingelheim International Gmbh | Methods of administering an egfr inhibitor |
USRE43431E1 (en) | 2000-12-20 | 2012-05-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
WO2012156437A1 (en) | 2011-05-17 | 2012-11-22 | Boehringer Ingelheim International Gmbh | Method for egfr directed combination treatment of cancer |
WO2013053206A1 (en) | 2011-10-12 | 2013-04-18 | Teligene Ltd | Quinazoline derivatives as kinases inhibitors and methods of use thereof |
US8722694B2 (en) | 1999-06-21 | 2014-05-13 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
WO2014118197A1 (en) | 2013-02-01 | 2014-08-07 | Boehringer Ingelheim International Gmbh | Radiolabeled quinazoline derivatives |
US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
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 |
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 |
WO2018140554A1 (en) | 2017-01-25 | 2018-08-02 | Tp Therapeutics, Inc. | Combination therapy involving diaryl macrocyclic compounds |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2006288716A1 (en) | 2005-09-06 | 2007-03-15 | T.K. Signal Ltd. | Polyalkylene glycol derivatives of 4- (phenylamino)quinazolines useful as irreversible inhibitors of epidermal growth factor receptor tyrosine kinase |
MX2012000166A (es) * | 2009-07-02 | 2012-04-02 | Newgen Therapeutics Inc | Compuestos de quinazolina que contienen fosforo y metodos de uso de los mismos. |
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 |
CN102675287A (zh) * | 2011-03-11 | 2012-09-19 | 江苏恒瑞医药股份有限公司 | (e)-n-[4-[[3-氯-4-(2-吡啶基甲氧基)苯基]氨基]-3-氰基-7-乙氧基-6-喹啉基]-3-[(2r)-1-甲基吡咯烷-2-基]丙-2-烯酰胺的可药用的盐、其制备方法及其在医药上的应用 |
WO2013135176A1 (zh) * | 2012-03-16 | 2013-09-19 | 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 |
US10710968B2 (en) | 2016-01-13 | 2020-07-14 | Hadasit Medical Research Services And Development Ltd. | Radiolabeled erlotinib analogs and uses thereof |
TWI820414B (zh) * | 2020-04-17 | 2023-11-01 | 大陸商北京賽特明強醫藥科技有限公司 | 喹唑啉類化合物、製備方法及其應用 |
CN115806548A (zh) * | 2021-09-15 | 2023-03-17 | 甫康(上海)健康科技有限责任公司 | 含有egfr抑制剂的药物组合物及其制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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DE10042060A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
WO2002050043A1 (de) * | 2000-12-20 | 2002-06-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Chinazolinderivate, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
US20020177601A1 (en) * | 1999-03-15 | 2002-11-28 | Frank Himmelsbach | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
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2003
- 2003-02-20 DE DE10307165A patent/DE10307165A1/de not_active Withdrawn
-
2004
- 2004-02-14 AU AU2004213129A patent/AU2004213129A1/en not_active Abandoned
- 2004-02-14 AT AT04711303T patent/ATE407929T1/de active
- 2004-02-14 ES ES04711303T patent/ES2314374T3/es not_active Expired - Lifetime
- 2004-02-14 CN CNA2004800047746A patent/CN1751033A/zh active Pending
- 2004-02-14 KR KR1020057015218A patent/KR20050103230A/ko not_active Application Discontinuation
- 2004-02-14 CA CA002516426A patent/CA2516426A1/en not_active Abandoned
- 2004-02-14 BR BRPI0407709-1A patent/BRPI0407709A/pt not_active IP Right Cessation
- 2004-02-14 EP EP04711303A patent/EP1597240B1/de not_active Expired - Lifetime
- 2004-02-14 WO PCT/EP2004/001398 patent/WO2004074263A1/de active IP Right Grant
- 2004-02-14 MX MXPA05008780A patent/MXPA05008780A/es not_active Application Discontinuation
- 2004-02-14 RU RU2005128826/04A patent/RU2005128826A/ru not_active Application Discontinuation
- 2004-02-14 NZ NZ542402A patent/NZ542402A/en unknown
- 2004-02-14 JP JP2005518423A patent/JP4468305B2/ja not_active Expired - Fee Related
- 2004-02-14 DE DE502004008024T patent/DE502004008024D1/de not_active Expired - Lifetime
- 2004-02-18 PE PE2004000166A patent/PE20040953A1/es not_active Application Discontinuation
- 2004-02-18 CL CL200400284A patent/CL2004000284A1/es unknown
- 2004-02-18 UY UY28191A patent/UY28191A1/es not_active Application Discontinuation
- 2004-02-18 TW TW093103966A patent/TW200505912A/zh unknown
- 2004-02-20 AR ARP040100540A patent/AR043249A1/es unknown
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2005
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DE10042060A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
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Cited By (25)
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US8722694B2 (en) | 1999-06-21 | 2014-05-13 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
US8586608B2 (en) | 2000-12-20 | 2013-11-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
USRE43431E1 (en) | 2000-12-20 | 2012-05-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
US9089571B2 (en) | 2005-11-11 | 2015-07-28 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
WO2007054550A1 (en) * | 2005-11-11 | 2007-05-18 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
US9539258B2 (en) | 2005-11-11 | 2017-01-10 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
EP2340837A1 (de) | 2005-11-11 | 2011-07-06 | Boehringer Ingelheim International GmbH | Kombinationsbehandlung gegen Krebs mit EGFR/HER2-Hemmern |
WO2007054551A1 (en) | 2005-11-11 | 2007-05-18 | Boehringer Ingelheim International Gmbh | Combination treatment of cancer comprising egfr/her2 inhibitors |
EP3173084A1 (de) * | 2005-11-11 | 2017-05-31 | Boehringer Ingelheim International GmbH | Chinazolinderivate zur behandlung von krebserkrankungen |
US8404697B2 (en) | 2005-11-11 | 2013-03-26 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
US7960546B2 (en) | 2006-01-26 | 2011-06-14 | Boehringer Ingelheim International Gmbh | Process for preparing aminocrotonylamino-substituted quinazoline derivatives |
US8188274B2 (en) | 2006-01-26 | 2012-05-29 | Boehringer Ingelheim International Gmbh | Process for preparing aminocrotonylamino-substituted quinazoline derivatives |
US8067593B2 (en) | 2006-01-26 | 2011-11-29 | Boehringer Ingelheim International Gmbh | Process for preparing aminocrotonylamino-substituted quinazoline derivatives |
JP2009528981A (ja) * | 2006-01-26 | 2009-08-13 | 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 | アミノクロトニルアミノ置換キナゾリン誘導体の合成方法 |
WO2007085638A1 (en) * | 2006-01-26 | 2007-08-02 | Boehringer Ingelheim International Gmbh | Process for preparing aminocrotonylamino-substituted quinazoline derivatives |
US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
US10004743B2 (en) | 2009-07-06 | 2018-06-26 | Boehringer Ingelheim International Gmbh | Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
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 |
WO2012027445A1 (en) | 2010-08-26 | 2012-03-01 | Boehringer Ingelheim International Gmbh | Methods of administering an egfr inhibitor |
WO2012156437A1 (en) | 2011-05-17 | 2012-11-22 | Boehringer Ingelheim International Gmbh | Method for egfr directed combination treatment of cancer |
WO2013053206A1 (en) | 2011-10-12 | 2013-04-18 | Teligene Ltd | Quinazoline derivatives as kinases inhibitors and methods of use thereof |
US9388160B2 (en) | 2011-10-12 | 2016-07-12 | Teligene Ltd | Quinazoline derivatives as kinases inhibitors and methods of use thereof |
WO2014118197A1 (en) | 2013-02-01 | 2014-08-07 | Boehringer Ingelheim International Gmbh | Radiolabeled quinazoline derivatives |
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 |
WO2018140554A1 (en) | 2017-01-25 | 2018-08-02 | Tp Therapeutics, Inc. | Combination therapy involving diaryl macrocyclic compounds |
Also Published As
Publication number | Publication date |
---|---|
NZ542402A (en) | 2008-09-26 |
AU2004213129A1 (en) | 2004-09-02 |
CA2516426A1 (en) | 2004-09-02 |
JP2006515005A (ja) | 2006-05-18 |
ATE407929T1 (de) | 2008-09-15 |
MXPA05008780A (es) | 2005-10-18 |
PE20040953A1 (es) | 2005-01-20 |
KR20050103230A (ko) | 2005-10-27 |
DE502004008024D1 (de) | 2008-10-23 |
AR043249A1 (es) | 2005-07-20 |
DE10307165A1 (de) | 2004-09-02 |
UY28191A1 (es) | 2004-09-30 |
EP1597240A1 (de) | 2005-11-23 |
CL2004000284A1 (es) | 2005-01-14 |
RU2005128826A (ru) | 2006-08-27 |
EP1597240B1 (de) | 2008-09-10 |
ES2314374T3 (es) | 2009-03-16 |
CN1751033A (zh) | 2006-03-22 |
BRPI0407709A (pt) | 2006-02-14 |
ZA200506121B (en) | 2006-11-29 |
TW200505912A (en) | 2005-02-16 |
JP4468305B2 (ja) | 2010-05-26 |
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