EP0770058A1 - Novel chemical compound, its preparation and use as a drug - Google Patents
Novel chemical compound, its preparation and use as a drugInfo
- Publication number
- EP0770058A1 EP0770058A1 EP95922492A EP95922492A EP0770058A1 EP 0770058 A1 EP0770058 A1 EP 0770058A1 EP 95922492 A EP95922492 A EP 95922492A EP 95922492 A EP95922492 A EP 95922492A EP 0770058 A1 EP0770058 A1 EP 0770058A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- formula
- treatment
- diseases
- inflammatory
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the invention relates to the compound of the formula
- Chronic obstructive pulmonary diseases such as chronic bronchitis, psoriasis, colitis uicerosa, gastro- or enteropathy induced by non-steroidal anti-inflammatory drugs, Alzheimer's disease, shock, reperfusion damage / ischemia, atherosclerosis, multiple sclerosis.
- the new compound can also be used to treat diseases or conditions in which the passage of cells from the blood via the vascular endothelium into the tissue is important (for example metastasis) or diseases and conditions in which the combination of LTB4 or another molecule (for example 12-HETE) with the LTB4 receptor has an influence on cell proliferation (e.g. chronic myelocytic leukemia).
- diseases or conditions in which the passage of cells from the blood via the vascular endothelium into the tissue is important for example metastasis
- diseases and conditions in which the combination of LTB4 or another molecule (for example 12-HETE) with the LTB4 receptor has an influence on cell proliferation e.g. chronic myelocytic leukemia.
- the new compound can also be used in combination with other active ingredients, such as those used for the same indications, or e.g. with antiallergics, secretolytics, ß2-adrenergics, inhalable steroids, antihistamines and / or PAF antagonists.
- Administration can be topical, oral, transdermal, nasal, parenteral or inhalative.
- the therapeutic or prophylactic dose depends on the patient's body weight and the nature and seriousness of the disease. When used orally, the dose is between 10 and 500 mg, preferably between 20 and 250 mg. When used by inhalation, the patient is given between about 0.5 and 25, in particular between 2 and 20, mg of active ingredient.
- the new compounds can be administered in customary preparations, for example as tablets, dragées, capsules, wafers, powders, granules, solutions, emulsions, syrups, inhalation aerosols, ointments, suppositories.
- Active ingredient according to the invention 20 parts by weight
- the ingredients are processed in the usual way to tablets of 500 mg weight. If desired, the active substance content can be increased or decreased and the amount of glucose reduced or increased accordingly. Suppositories
- composition active ingredient according to the invention 100 parts by weight of lactose, powdered 45 parts by weight of cocoa butter 1555 parts by weight
- the ingredients are processed in the usual way to form suppositories weighing 1.7 g.
- Micronized active ingredient powder (compound of formula I; particle size approx. 0.5 to 7 ⁇ m) is filled into hard gelatin capsules in an amount of 5 mg, optionally with the addition of micronized lactose.
- the powder is extracted from conventional inhalation devices, e.g. according to DE-A 3 345 722, inhaled.
- the new compound shows a surprisingly superior activity compared to the known LTB4 antagonists. This is expressed, for example, in the test result for the LTB4-induced neutrophil accumulation on the mouse ear.
- the ED50 value of 0.05 mg / kg obtained is far lower than the values found for structurally similar compounds
- the new connection can be established using standard methods:
- reaction is conveniently carried out in a polar solvent such as
- Ethanol, glacial acetic acid or dimethylformamide at room temperature up to 60 ° C and at normal pressure up to 5 bar.
- Raney nickel or platinum are used as catalysts.
- the amidoxime used as the starting material is obtained, for example, by reacting the corresponding nitrile with hydroxylamine.
- Compound I can also be produced from partial structures with an amidine group already present.
- a compound of formula III is reacted with the phenol of formula IV or the phenol of formula V with a compound of formula VI:
- the alkyl radicals R2 are generally those radicals having up to 6 carbon atoms. Phenyl or tolyl is preferably used as the aryl.
- the methanol is distilled off, the residue is taken up in 2000 ml of ethyl acetate and extracted twice with 500 ml of water each time.
- the ethyl acetate is distilled off and the residue is recrystallized from 300 ml of ethanol.
- the product is dissolved hot in 200 ml of ethanol and slowly cooled to room temperature overnight.
- the crystals are filtered off, washed with 50 ml of cold ethanol and dried. Yield: 69 g; Melting point 160 ° C.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Neue chemische Verbindung, ihre Herstellung und ihre Verwendung als ArzneistoffNew chemical compound, its production and its use as a drug
Die Erfindung betrifft die Verbindung der FormelThe invention relates to the compound of the formula
Verwandte Verbindungen sind aus der WO 93/16036 bekannt. Sie werden als LTB4-Antagonisten beschrieben und eignen sich zur therapeutischen Anwendung in den entsprechenden Indikationen.Related compounds are known from WO 93/16036. They are described as LTB4 antagonists and are suitable for therapeutic use in the corresponding indications.
Wie gefunden wurde, zeichnet sich die Verbindung der Formel I durch vielfältige Anwendungsmöglichkeiten auf therapeutischem Gebiet aus. Hervorzuheben sind solche Anwendungsmöglichkeiten, für welche die LTB4-rezeptorantagonistischen Eigenschaften eine Rolle spielen. Hier sind insbesondere zu nennen:It has been found that the compound of the formula I is distinguished by a wide range of uses in the therapeutic field. Emphasis should be placed on those applications for which the LTB4 receptor antagonistic properties play a role. The following are particularly worth mentioning:
Arthritis, Asthma, chronische obstruktive Lungenerkrankungen, etwa chronische Bronchitis, Psoriasis, Colitis uicerosa, durch nichtsteroidale Antiphlogistika induzierte Gastro- oder Enteropathie, Alzheimer- Krankheit, Schock, Reperfusionsschäden/Ischämien, Atherosklerose, Multiple Sklerose.Arthritis, asthma, chronic obstructive pulmonary diseases, such as chronic bronchitis, psoriasis, colitis uicerosa, gastro- or enteropathy induced by non-steroidal anti-inflammatory drugs, Alzheimer's disease, shock, reperfusion damage / ischemia, atherosclerosis, multiple sclerosis.
Auch lassen sich mit der neuen Verbindung Krankheiten oder Zustände behandeln, bei denen die Passage von Zellen aus dem Blut über das vaskuläre Endothelium in das Gewebe von Bedeutung ist (etwa Metastasis) oder Krankheiten und Zustände, bei denen die Kombination des LTB4 oder eines anderen Moleküls (beispielsweise 12-HETE) mit dem LTB4-Rezeptor einen Einfluß auf die Zell-Proliferation hat (etwa chronische myelozytische Leukämie).The new compound can also be used to treat diseases or conditions in which the passage of cells from the blood via the vascular endothelium into the tissue is important (for example metastasis) or diseases and conditions in which the combination of LTB4 or another molecule (for example 12-HETE) with the LTB4 receptor has an influence on cell proliferation (e.g. chronic myelocytic leukemia).
Die neue Verbindung kann auch in Kombination mit anderen Wirkstoffen angewendet werden, etwa solchen, die für dieselben Indikationen Verwendung finden, oder z.B. mit Antiallergika, Sekretolytika, ß2- Adrenergika, inhalativ anwendbaren Steroiden, Antihistaminika und/oder PAF-Antagonisten. Die Verabreichung kann topisch, oral, transdermal, nasal, parenteral oder inhalativ erfolgen.The new compound can also be used in combination with other active ingredients, such as those used for the same indications, or e.g. with antiallergics, secretolytics, ß2-adrenergics, inhalable steroids, antihistamines and / or PAF antagonists. Administration can be topical, oral, transdermal, nasal, parenteral or inhalative.
Die therapeutische oder prophylaktische Dosis ist von dem Körper¬ gewicht des Patienten sowie von der Beschaffenheit und Ernsthaftigkeit des Krankheitszustandes abhängig. Bei oraler Anwendung liegt die Dosis zwischen 10 und 500 mg, vorzugsweise zwischen 20 und 250 mg. Bei inhalativer Anwendung werden dem Patienten zwischen etwa 0,5 und 25, insbesondere zwischen 2 und 20 mg Wirkstoff zugeführt. Die neuen Verbindungen können in üblichen Zubereitungen verabreicht werden, etwa als Tabletten, Dragees, Kapseln, Oblaten, Pulver, Granulate, Lösungen, Emulsionen, Sirupe, Inhalationsaerosole, Salben, Suppositorien.The therapeutic or prophylactic dose depends on the patient's body weight and the nature and seriousness of the disease. When used orally, the dose is between 10 and 500 mg, preferably between 20 and 250 mg. When used by inhalation, the patient is given between about 0.5 and 25, in particular between 2 and 20, mg of active ingredient. The new compounds can be administered in customary preparations, for example as tablets, dragées, capsules, wafers, powders, granules, solutions, emulsions, syrups, inhalation aerosols, ointments, suppositories.
Die nachsteh den Beispiele zeigen einige Möglichkeiten für αie Formulierung der Darreichungsformen.The examples below show some possibilities for the formulation of the dosage forms.
FormulierunqsbeispieleFormulation examples
1. Tabletten1. tablets
Zusammensetzung:Composition:
Wirkstoff gemäß der Erfindung 20 Gew. -TeileActive ingredient according to the invention 20 parts by weight
Stearinsäure 6 Gew. -TeileStearic acid 6 parts by weight
Traubenzucker 474 Gew.-TeileDextrose 474 parts by weight
Die Bestandteile werden in üblicher Weise zu Tabletten von 500 mg Gewicht verarbeitet. Gewünschtenfalls kann der Wirkstoffgehalt erhöht oder vermindert und die Traubenzuckermenge entsprechend vermindert oder erhöht werden. SuppositorienThe ingredients are processed in the usual way to tablets of 500 mg weight. If desired, the active substance content can be increased or decreased and the amount of glucose reduced or increased accordingly. Suppositories
Zusammensetzung: Wirkstoff gemäß der Erfindung 100 Gew. -Teile Laktose, gepulvert 45 Gew.-Teile Kakao-Butter 1555 Gew.-TeileComposition: active ingredient according to the invention 100 parts by weight of lactose, powdered 45 parts by weight of cocoa butter 1555 parts by weight
Die Bestandteile werden in üblicher Weise zu Suppositorien von 1 ,7 g Gewicht verarbeitet.The ingredients are processed in the usual way to form suppositories weighing 1.7 g.
3. Inhalationspulver3. Inhalation powder
Mikronisiertes Wirkstoffpulver (Verbindung der Formel I; Teilchengröße ca. 0,5 bis 7 μm) werden in einer Menge von 5 mg gegebenenfalls unter Zusatz mikronisierter Lactose in Hartgelatinekapseln abgefüllt. Das Pulver wird aus üblichen Inhalationsgeräten, z.B. gemäß DE-A 3 345 722, inhaliert.Micronized active ingredient powder (compound of formula I; particle size approx. 0.5 to 7 μm) is filled into hard gelatin capsules in an amount of 5 mg, optionally with the addition of micronized lactose. The powder is extracted from conventional inhalation devices, e.g. according to DE-A 3 345 722, inhaled.
Die neue Verbindung zeigt im Vergleich zu den bekannten LTB4- Antagonisten eine überraschend überlegene Wirksamkeit. Dies kommt beispielsweise im Untersuchungsergebnis bei der LTB4-induzierten Neutrophilen-Akkumulation am Mäuseohr zum Ausdruck. Der erhaltene ED50-Wert von 0,05 mg/kg ist weitaus niedriger als die für strukturell ähnliche Verbindungen gefundenen WerteThe new compound shows a surprisingly superior activity compared to the known LTB4 antagonists. This is expressed, for example, in the test result for the LTB4-induced neutrophil accumulation on the mouse ear. The ED50 value of 0.05 mg / kg obtained is far lower than the values found for structurally similar compounds
Die neue Verbindung kann üblichen Methoden hergestellt werden:The new connection can be established using standard methods:
Verfahren 1Procedure 1
Das AmidoximThe amidoxime
wird katalytisch hydriert. is catalytically hydrogenated.
Die Reaktion wird zweckmäßig in einem polaren Lösungsmittel wieThe reaction is conveniently carried out in a polar solvent such as
Ethanol, Eisessig oder Dimethylformamid bei Raumtemperatur bis 60°C und bei Normaldruck bis 5 bar durchgeführt.Ethanol, glacial acetic acid or dimethylformamide at room temperature up to 60 ° C and at normal pressure up to 5 bar.
Als Katalysatoren werden Raney-Nickel oder Platin verwendet.Raney nickel or platinum are used as catalysts.
Das als Ausgangsstoff benutzte Amidoxim wird beispielsweise durch Umsetzung des entsprechenden Nitrils mit Hydroxylamin erhalten.The amidoxime used as the starting material is obtained, for example, by reacting the corresponding nitrile with hydroxylamine.
Verfahren 2Procedure 2
Die Verbindung I kann auch aus Partialstrukturen mit schon vorhandener Amidingruppe hergestellt werden.Compound I can also be produced from partial structures with an amidine group already present.
Eine Verbindung der Formel III wird mit dem Phenol der Formel IV umgesetzt oder das Phenol der Formel V mit einer Verbindung der Formel VI:A compound of formula III is reacted with the phenol of formula IV or the phenol of formula V with a compound of formula VI:
(Y = Halogen, bevorzugt Chlor, Brom; -O-SO2-R2; F 2 = Alkv|. Arv|) Die Umsetzung erfolgt in polaren Lösungsmitteln wie Acetonitril, Dimethylformamid und Ethanol bei Temperaturen von 60 bis 120°C in Gegenwart einer Base wie beispielsweise Natriummethylat oder Kaliumcarbonat.(Y = halogen, preferably chlorine, bromine; -O-SO2-R2; F 2 = Alkv | . Arv | ) The reaction takes place in polar solvents such as acetonitrile, dimethylformamide and ethanol at temperatures from 60 to 120 ° C in Presence of a base such as sodium methylate or potassium carbonate.
Die Alkylreste R2 sind in der Regel solche Reste mit bis zu 6 C-Atomen Als Aryl wird bevorzugt Phenyl oder Tolyl verwendet.The alkyl radicals R2 are generally those radicals having up to 6 carbon atoms. Phenyl or tolyl is preferably used as the aryl.
Nachstehend wird die Herstellung der neuen Verbindung näher beschrieben. VerfahrensbeispielThe preparation of the new compound is described in more detail below. Process example
Beispiel 1example 1
1 10,0 g (4-{3-[4-(1 -Methyl-1 -phenylethyl)-phenoxymethyl]-benzyloxy}- phenyl)-carbaldoxim-hydrochlorid, herstellbar aus (4-{3-[4-(1 -Methyl-1 - phenylethyl)-phenoxymethyl]-benzyloxy}-phenyl)-carbonitril mit Hydroxylaminhydrochlorid und Natriumcarbonat in siedendem Wasser- Ethanol-Gemisch (1 :7), wird mit 2100 ml Methanol in Gegenwart von 1 Eßlöffel Raney-Nickel bei Raumtemperatur in etwa drei Stunden hydriert. Der Katalysator wird abgesaugt und die Lösung über Kieselgur filtriert. Das Methanol wird abdestilliert, der Rückstand in 2000 ml Essigester aufgenommen und zweimal mit je 500 ml Wasser extrahiert. Der Essigester wird abdestilliert und der Rückstand aus 300 ml Ethanol umkristallisiert. Das Produkt wird in 200 ml Ethanol heiß gelöst und über Nacht langsam auf Raumtemperatur abgekühlt. Die Kristalle werden abgesaugt, mit 50 ml kaltem Ethanol nachgewaschen und getrocknet. Ausbeute: 69 g; Schmelzpunkt 160°C. 1 10.0 g (4- {3- [4- (1-methyl-1-phenylethyl) phenoxymethyl] benzyloxy} phenyl) carbaldoxime hydrochloride, obtainable from (4- {3- [4- (1st -Methyl-1 - phenylethyl) -phenoxymethyl] -benzyloxy} -phenyl) -carbonitrile with hydroxylamine hydrochloride and sodium carbonate in boiling water-ethanol mixture (1: 7), is mixed with 2100 ml of methanol in the presence of 1 tablespoon of Raney nickel at room temperature hydrogenated in about three hours. The catalyst is suctioned off and the solution is filtered through diatomaceous earth. The methanol is distilled off, the residue is taken up in 2000 ml of ethyl acetate and extracted twice with 500 ml of water each time. The ethyl acetate is distilled off and the residue is recrystallized from 300 ml of ethanol. The product is dissolved hot in 200 ml of ethanol and slowly cooled to room temperature overnight. The crystals are filtered off, washed with 50 ml of cold ethanol and dried. Yield: 69 g; Melting point 160 ° C.
Claims
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4424714A DE4424714A1 (en) | 1994-07-13 | 1994-07-13 | New chemical compound, its production and its use as an arsenic |
| DE4424714 | 1994-07-13 | ||
| PCT/EP1995/002113 WO1996002496A1 (en) | 1994-07-13 | 1995-06-03 | Novel chemical compound, its preparation and use as a drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0770058A1 true EP0770058A1 (en) | 1997-05-02 |
Family
ID=6523048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP95922492A Withdrawn EP0770058A1 (en) | 1994-07-13 | 1995-06-03 | Novel chemical compound, its preparation and use as a drug |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US5686496A (en) |
| EP (1) | EP0770058A1 (en) |
| JP (1) | JPH10502646A (en) |
| KR (1) | KR970704674A (en) |
| CN (1) | CN1152303A (en) |
| AU (1) | AU2736895A (en) |
| BG (1) | BG101104A (en) |
| BR (1) | BR9508395A (en) |
| CA (1) | CA2194886A1 (en) |
| CO (1) | CO4410185A1 (en) |
| CZ (1) | CZ8297A3 (en) |
| DE (1) | DE4424714A1 (en) |
| EE (1) | EE9700065A (en) |
| FI (1) | FI970095A0 (en) |
| HR (1) | HRP950363A2 (en) |
| HU (1) | HUT76827A (en) |
| IL (1) | IL114572A0 (en) |
| MX (1) | MX9700245A (en) |
| NO (1) | NO970123L (en) |
| PE (1) | PE35196A1 (en) |
| PL (1) | PL318114A1 (en) |
| SK (1) | SK1897A3 (en) |
| WO (1) | WO1996002496A1 (en) |
| YU (1) | YU45395A (en) |
| ZA (1) | ZA955781B (en) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6486181B1 (en) | 1992-08-28 | 2002-11-26 | City Of Hope | Human leukocutye 12-lipoxygenase and its role in the pathogenesis of disease states |
| US6191169B1 (en) | 1992-08-28 | 2001-02-20 | City Of Hope | Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states |
| WO1996036347A1 (en) * | 1995-05-17 | 1996-11-21 | Eli Lilly And Company | Use of leukotriene antagonists for alzheimer's disease |
| DE19546452A1 (en) * | 1995-12-13 | 1997-06-19 | Boehringer Ingelheim Kg | New phenylamidine derivatives, process for their preparation and their use as medicaments |
| DE19636689A1 (en) * | 1996-09-10 | 1998-03-12 | Boehringer Ingelheim Kg | New benzamidine derivatives |
| DE19718334A1 (en) | 1997-04-30 | 1998-11-05 | Boehringer Ingelheim Pharma | Novel benzylamine derivatives and phenylethylamine derivatives, process for their preparation and their use as pharmaceuticals |
| ID24720A (en) | 1997-12-12 | 2000-08-03 | Novartis Ag | COMPOUNDED AMIDINO COMPOUNDS IN TREATMENT OF CHRONIC LUNGS DISEASE |
| DE19834713A1 (en) * | 1998-07-31 | 2000-02-03 | Boehringer Ingelheim Pharma | New phenylethylamine derivatives, processes for their preparation and their use as pharmaceuticals |
| US6528491B2 (en) * | 2000-10-24 | 2003-03-04 | Boehringer Ingelheim Pharma Kg | Pyranoside derivatives |
| CA2433451A1 (en) * | 2001-01-16 | 2002-07-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of an ltb4 antagonist for the treatment and/or prevention of diseases caused by increased expression of mucin genes |
| JP2005504053A (en) * | 2001-08-31 | 2005-02-10 | ニューロケム （インターナショナル） リミテッド | Amidine derivatives for the treatment of amyloidosis |
| WO2004099783A2 (en) * | 2003-05-06 | 2004-11-18 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with g-protein-coupled receptor ltb4 (ltb4) |
| US7262223B2 (en) * | 2004-01-23 | 2007-08-28 | Neurochem (International) Limited | Amidine derivatives for treating amyloidosis |
| AU2005260328B2 (en) * | 2004-07-05 | 2009-10-01 | Dong Wha Pharmaceutical Co., Ltd. | Composition for the prevention and treatment of allergic inflammatory disease |
| JP3983272B2 (en) * | 2004-07-14 | 2007-09-26 | 有限会社 炎症研究所 | Method for inhibiting tumor metastasis |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0518818A3 (en) * | 1991-06-11 | 1993-04-28 | Ciba-Geigy Ag | Arylethers, their manufacture and use as medicament |
| EP0625138B1 (en) * | 1992-02-05 | 1999-06-02 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Novel amidine derivatives, their preparation and their use as medicaments with ltb4 antagonistic effect |
-
1994
- 1994-07-13 DE DE4424714A patent/DE4424714A1/en not_active Withdrawn
-
1995
- 1995-06-03 MX MX9700245A patent/MX9700245A/en unknown
- 1995-06-03 CA CA002194886A patent/CA2194886A1/en not_active Abandoned
- 1995-06-03 AU AU27368/95A patent/AU2736895A/en not_active Abandoned
- 1995-06-03 JP JP8504619A patent/JPH10502646A/en active Pending
- 1995-06-03 EP EP95922492A patent/EP0770058A1/en not_active Withdrawn
- 1995-06-03 KR KR1019970700123A patent/KR970704674A/en not_active Withdrawn
- 1995-06-03 PL PL95318114A patent/PL318114A1/en unknown
- 1995-06-03 CZ CZ9782A patent/CZ8297A3/en unknown
- 1995-06-03 US US08/765,527 patent/US5686496A/en not_active Expired - Fee Related
- 1995-06-03 EE EE9700065A patent/EE9700065A/en unknown
- 1995-06-03 BR BR9508395A patent/BR9508395A/en unknown
- 1995-06-03 CN CN95194047A patent/CN1152303A/en active Pending
- 1995-06-03 HU HU9700060A patent/HUT76827A/en unknown
- 1995-06-03 SK SK18-97A patent/SK1897A3/en unknown
- 1995-06-03 FI FI970095A patent/FI970095A0/en not_active Application Discontinuation
- 1995-06-03 WO PCT/EP1995/002113 patent/WO1996002496A1/en not_active Ceased
- 1995-06-27 HR HRP4424714.1A patent/HRP950363A2/en not_active Application Discontinuation
- 1995-07-06 YU YU45395A patent/YU45395A/en unknown
- 1995-07-11 PE PE1995273520A patent/PE35196A1/en not_active Application Discontinuation
- 1995-07-12 CO CO95030620A patent/CO4410185A1/en unknown
- 1995-07-12 ZA ZA955781A patent/ZA955781B/en unknown
- 1995-07-12 IL IL11457295A patent/IL114572A0/en unknown
-
1997
- 1997-01-04 BG BG101104A patent/BG101104A/en unknown
- 1997-01-10 NO NO970123A patent/NO970123L/en unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9602496A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| DE4424714A1 (en) | 1996-01-18 |
| ZA955781B (en) | 1996-02-22 |
| FI970095A7 (en) | 1997-01-10 |
| MX9700245A (en) | 1997-05-31 |
| US5686496A (en) | 1997-11-11 |
| WO1996002496A1 (en) | 1996-02-01 |
| BR9508395A (en) | 1997-12-23 |
| CA2194886A1 (en) | 1996-02-01 |
| NO970123D0 (en) | 1997-01-10 |
| SK1897A3 (en) | 1997-08-06 |
| HUT76827A (en) | 1997-11-28 |
| HRP950363A2 (en) | 1997-08-31 |
| JPH10502646A (en) | 1998-03-10 |
| CO4410185A1 (en) | 1997-01-09 |
| EE9700065A (en) | 1997-08-15 |
| PL318114A1 (en) | 1997-05-12 |
| IL114572A0 (en) | 1995-11-27 |
| AU2736895A (en) | 1996-02-16 |
| HU9700060D0 (en) | 1997-02-28 |
| FI970095L (en) | 1997-01-10 |
| CZ8297A3 (en) | 1997-09-17 |
| NO970123L (en) | 1997-01-10 |
| KR970704674A (en) | 1997-09-06 |
| PE35196A1 (en) | 1996-09-05 |
| BG101104A (en) | 1998-04-30 |
| YU45395A (en) | 1997-12-05 |
| FI970095A0 (en) | 1997-01-10 |
| CN1152303A (en) | 1997-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1203764B1 (en) | Benzamidine derivatives with LTB4-antagonistic activity | |
| DE60006280T2 (en) | BETA 2 ADRENERGIC RECEPTOR AGONISTS | |
| AT363096B (en) | METHOD FOR PRODUCING NEW PHTHALAZINE DERIVATIVES AND THEIR SALTS | |
| DE2833140C2 (en) | ||
| EP0222191B1 (en) | 4-benzyl-1-2(h)-phthalazinone derivatives | |
| DE2558501C2 (en) | ||
| EP0770058A1 (en) | Novel chemical compound, its preparation and use as a drug | |
| EP0770059B1 (en) | Substituted benzamidines, their production and their use as medicaments | |
| EP0014951A2 (en) | Heterocyclic oxypropanolamine derivatives, process for their preparation and medicines containing these compounds | |
| EP1015421B1 (en) | New phenylamidine derivatives, a process for preparing the same and their use as medicaments | |
| EP0888313B1 (en) | 2,3-benzodiazepine derivatives and their use as ampa-receptor inhibitors | |
| WO2008061456A1 (en) | The folacin-metformin compound and its manufacture | |
| DE2713389A1 (en) | INNOVATIVE XANTHINE COMPOUNDS AND PHARMACEUTICAL PREPARATION CONTAINING THE SAME | |
| DE69424183T2 (en) | 6- (2-IMIDAZOLINYLAMINO) QUINOLINE COMPOUNDS AS ALPHA-2 ADRENOCEPTOR ANTAGONISTS | |
| DE60005517T2 (en) | POTASS CHANNEL BLOCKING AGENTS | |
| EP0171645A1 (en) | 2H-1-benzopyran-2-on derivatives, process for their preparation and medicines containing these compounds | |
| WO2002034715A1 (en) | Benzamidine derivatives comprising a sulfate group serving as ltb4 antagonists | |
| EP0000693B1 (en) | Aminophenoxymethyl-2-morpholine derivatives, the preparation thereof and pharmaceuticals containing them | |
| EP0980351B1 (en) | Benzylamine and phenylethylamine derivatives, processes for preparing the same and their use as medicaments | |
| EP1222162B1 (en) | Novel ltb4-antagonist, method for the production thereof and its use as a medicament | |
| CH633962A5 (en) | Pharmaceutical preparations which contain pteridine compounds | |
| DD210266A5 (en) | PROCESS FOR PREPARING 3- (UREIDOCYCLOHEXYLAMINO) PROPANE-1,2-DIOLDERIVATE | |
| EP0590558B1 (en) | Pharmaceutical composition containing 1,5,6,7-tetrahydro-4H-indazol-4-ones,new 1,5,6,7-tetrahydro-4H-indazol-4-ones and process for their manufacture | |
| EP0557877A1 (en) | Soluble salts of 4-amino-2-(4,4-dimethyl-imidazolidin-2-on-1-yl)-pyrimidin-5-carboxylic acid N-methyl-N-(3-trifluoromethyl-phenyl)-amide, process for their preparation, their use as medicine and initial products | |
| DE2827454A1 (en) | 4-HOMOISOTWISTAN DERIVATIVES, METHOD FOR MANUFACTURING THEM, USE OF THE SAME AND MEDICINAL PRODUCTS CONTAINING THEM |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19970213 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
|
| AX | Request for extension of the european patent |
Free format text: LT PAYMENT 970213;LV PAYMENT 970213;SI PAYMENT 970213 |
|
| 17Q | First examination report despatched |
Effective date: 19971204 |
|
| GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
| GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BOEHRINGER INGELHEIM PHARMA KG |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19980728 |