CA2385871C - Ltb4 antagonist, processes for the preparation thereof and its use as a pharmaceutical composition - Google Patents
Ltb4 antagonist, processes for the preparation thereof and its use as a pharmaceutical composition Download PDFInfo
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- CA2385871C CA2385871C CA002385871A CA2385871A CA2385871C CA 2385871 C CA2385871 C CA 2385871C CA 002385871 A CA002385871 A CA 002385871A CA 2385871 A CA2385871 A CA 2385871A CA 2385871 C CA2385871 C CA 2385871C
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- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- 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
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- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- 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
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- 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
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- 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
- A61P11/14—Antitussive agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
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- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Nutrition Science (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
The present invention relates to a compound of formula (see formula I) processes for the preparation thereof and use of the compound and salts thereof as a LTB4 antagonist.
Description
L T B4 antagonist, processes for the preparation thereof and its use as a pharmaceuticai composition The present invention relates to a new LTB4 antagonist, processes for preparing it and its use as a pharmaceutical composition.
LTB4 antagonists are known from the prior art. Thus, International Patent Application WO 98/11062 discloses benzamidine derivatives having the lo abovementioned pharmacological activity.
Surprisingly, it has been found that the new LTB4 antagonist according to the invention has superior properties to the compounds known from the prior art.
In this context the exceptionally high in vitro and in vivo activity as well as the surprisingly high metabofic stability of the new LTB4 antagonist according to the invention should be mentioned.
The LTB4 antagonist according to the invention is the compound of formula (I) NH
HF2C O~~
O
Me (1) optionally in the form of the pharmacologically acceptable acid addition salts thereof.
As mentioned above, the compound of formula (i) can be converted into the salts thereof, particularly for pharmaceutical use into the physiologically and pharmacologically acceptable salts thereof with an inorganic or organic acid.
Suitable acids for this purpose include hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid. In addition, mixtures of the abovementioned acids can be used.
As has been found, the compound of formula I is characterised by its versatility of use in the therapeutic field. Particular emphasis should be laid on those applications for which the LTB4-receptor-antagonistic properties play a part.
- , r The following should be mentioned in particular: arthritis, asthma, chronic obstructive lung diseases such as chronic bronchitis, psoriasis, ulcerative colitis, gastro- or enteropathy induced by nonsteroidal antiphlogistics, cystic fibrosis, Alzheimer`s disease, shock, reperfusion damage/ischaemia, atherosclerosis, multiple sclerosis.
The new compounds may also be used to treat illnesses or conditions in which the passage of cells from the blood through the vascular endothelium into the tissues is of importance (such as metastasis) or illness and conditions in which the to combination of LTB4 or another molecule (such as 12-HETE) with the LTB4 receptor has an influence on cell proliferation (e.g. chronic myeloid leukaemia).
The new compound may also be used in conjunction with other active substances, e.g. those which are used for the same indications, or e.g. with antiallergic agents, secretolytics, 132-adrenergics, steroids taken by inhalation, antihistamines and/or PAF antagonists. They may be administered topically, orally, transdermally, nasally, parenterally or by inhalation.
The activity can be investigated pharmacologically and biochemically using tests as 2o disclosed for example in WO 93/16036, pp. 15 to 17; reference is hereby made to the contents of this publication.
The therapeutic or prophylactic dose depends - apart from the potency of the individual compounds and the patient's body weight - on the nature and gravity of the condition. For oral administration the dosage is between 10 and 500 mg, preferably between 20 and 250 mg. By inhalation the amount of active substance delivered to the patient is between about 0.5 and 25, preferably between about 2 and 20 mg.
Solutions for inhalation generally contain between about 0.5 and 5 % of active substance. The new compounds may be administered in conventional preparations, e.g. as plain or coated tablets, capsules, lozenges, powders, granules, solutions, emulsions, syrups, aerosols for inhalation, ointments and suppositories.
LTB4 antagonists are known from the prior art. Thus, International Patent Application WO 98/11062 discloses benzamidine derivatives having the lo abovementioned pharmacological activity.
Surprisingly, it has been found that the new LTB4 antagonist according to the invention has superior properties to the compounds known from the prior art.
In this context the exceptionally high in vitro and in vivo activity as well as the surprisingly high metabofic stability of the new LTB4 antagonist according to the invention should be mentioned.
The LTB4 antagonist according to the invention is the compound of formula (I) NH
HF2C O~~
O
Me (1) optionally in the form of the pharmacologically acceptable acid addition salts thereof.
As mentioned above, the compound of formula (i) can be converted into the salts thereof, particularly for pharmaceutical use into the physiologically and pharmacologically acceptable salts thereof with an inorganic or organic acid.
Suitable acids for this purpose include hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid. In addition, mixtures of the abovementioned acids can be used.
As has been found, the compound of formula I is characterised by its versatility of use in the therapeutic field. Particular emphasis should be laid on those applications for which the LTB4-receptor-antagonistic properties play a part.
- , r The following should be mentioned in particular: arthritis, asthma, chronic obstructive lung diseases such as chronic bronchitis, psoriasis, ulcerative colitis, gastro- or enteropathy induced by nonsteroidal antiphlogistics, cystic fibrosis, Alzheimer`s disease, shock, reperfusion damage/ischaemia, atherosclerosis, multiple sclerosis.
The new compounds may also be used to treat illnesses or conditions in which the passage of cells from the blood through the vascular endothelium into the tissues is of importance (such as metastasis) or illness and conditions in which the to combination of LTB4 or another molecule (such as 12-HETE) with the LTB4 receptor has an influence on cell proliferation (e.g. chronic myeloid leukaemia).
The new compound may also be used in conjunction with other active substances, e.g. those which are used for the same indications, or e.g. with antiallergic agents, secretolytics, 132-adrenergics, steroids taken by inhalation, antihistamines and/or PAF antagonists. They may be administered topically, orally, transdermally, nasally, parenterally or by inhalation.
The activity can be investigated pharmacologically and biochemically using tests as 2o disclosed for example in WO 93/16036, pp. 15 to 17; reference is hereby made to the contents of this publication.
The therapeutic or prophylactic dose depends - apart from the potency of the individual compounds and the patient's body weight - on the nature and gravity of the condition. For oral administration the dosage is between 10 and 500 mg, preferably between 20 and 250 mg. By inhalation the amount of active substance delivered to the patient is between about 0.5 and 25, preferably between about 2 and 20 mg.
Solutions for inhalation generally contain between about 0.5 and 5 % of active substance. The new compounds may be administered in conventional preparations, e.g. as plain or coated tablets, capsules, lozenges, powders, granules, solutions, emulsions, syrups, aerosols for inhalation, ointments and suppositories.
The following Examples show some possible ways of formulating the preparations:
1. Tablets Composition:
Active substance according to the invention 20 parts by weight Stearic acid 6 parts by weight Glucose 474 parts by weight The ingredients are processed in the usual way to form tablets weighing 500 mg. If desired, the active substance content may be increased or reduced and the quantity of glucose reduced or increased accordingly.
2. Suppositories Composition:
Active substance according to the invention 100 parts by weight Powdered lactose 45 parts by weight Cocoa butter 1 555 parts by weight The ingredients are processed in the usual way to form suppositories weighing 1.7 g.
3. Powder for inhalation Micronised powdered active substance (compound of formula I; particle size about 0.5 to 7 m) are packed into hard gelatine capsules in quantities of 5 mg, optionally with the addition of micronised lactose. The powder is inhaled from conventional inhalers, e.g. according to DE-A 33 45 722, to which reference is hereby made.
The new compound may be obtained analogously to methods of synthesis known from the prior art for preparing structurally comparable benzamidine derivatives. At this point reference is made particularly to the methods of preparation disclosed by Intemational Patent Application WO 98/11062, which describe, inter alia, the method of synthesising benzamidine derivatives by reducing the corresponding amidoximes, ` ;.
1. Tablets Composition:
Active substance according to the invention 20 parts by weight Stearic acid 6 parts by weight Glucose 474 parts by weight The ingredients are processed in the usual way to form tablets weighing 500 mg. If desired, the active substance content may be increased or reduced and the quantity of glucose reduced or increased accordingly.
2. Suppositories Composition:
Active substance according to the invention 100 parts by weight Powdered lactose 45 parts by weight Cocoa butter 1 555 parts by weight The ingredients are processed in the usual way to form suppositories weighing 1.7 g.
3. Powder for inhalation Micronised powdered active substance (compound of formula I; particle size about 0.5 to 7 m) are packed into hard gelatine capsules in quantities of 5 mg, optionally with the addition of micronised lactose. The powder is inhaled from conventional inhalers, e.g. according to DE-A 33 45 722, to which reference is hereby made.
The new compound may be obtained analogously to methods of synthesis known from the prior art for preparing structurally comparable benzamidine derivatives. At this point reference is made particularly to the methods of preparation disclosed by Intemational Patent Application WO 98/11062, which describe, inter alia, the method of synthesising benzamidine derivatives by reducing the corresponding amidoximes, ` ;.
by aminolysis of the corresponding imino ester and by reacting suitably substituted phenols with aryloxyalkyls substituted by a nucleofugic leaving group in the manner of a Williamson ether synthesis.
Altematively, the compound of formula (I) according to the invention may be obtained, for example, by reacting the nitrile of formula (II) CN
HF2C O"/'O
~
Me (II) with Li-hexamethyldisilazane. For the reaction it is appropriate to use non-polar and polar aprotic solvents such as toluene, ether, tetrahydrofuran at temperatures from io -80 Cto 120 C. To cleave the silyl groups, inorganic and organic acids are used such as HCI, HBr, H2SO4, sulphonic acids such as p-toluenesulphonic acid, benzenesulphonic acid or methanesulphonic acid and carboxylic acids such as formic acid, acetic acid or trifluoroacetic acid at temperatures from 0 C to 100 C.
The compound according to the invention may be prepared, starting from compounds known from the prior art, inter alia using the process described in the following synthesis example. Various other embodiments of the process will be apparent to anyone skilled in the art from the present specification and from the abovementioned Intemational Patent Application WO 98/11062; reference is hereby made to the contents of this pubication. It is specifically pointed out that the following synthesis example is provided solely as an illustration and not as a restriction to the invention.
Synthesis Example:
CN
HF2C \ O~~O \
I (III) 1 g of the nitrile (III) were placed in 20 mi of ethanol and a solution of 700 mg of hydroxylamine hydrochloride, 590 mg of Na2CO3 in 3 mi of H20 was slowly added dropwise while refluxing. The mixture was then boiled for 4 h and after cooling the crystals precipitated were suction filtered and washed with H20. After neutralisation with 260 mg of inethanesulphonic acid in 5 mi of ethanol, precipitation was carried out with diethylether and the precipitate was suction filtered. The substance was hydrogenated in 50 ml of methanol with the addition of 200 mg of Pd/C (5%) at normal pressure. After the catalyst had been suction filtered, Raney Ni was added and hydrogenation was carried out again. The catalyst was suction filtered, the io solvent was distilled off, the residue was dissolved in a little ethanol and precipitated with diethylether. Yield: 830 mg. Mp.: 204-205 C (as the methanesulphonate).
Altematively, the compound of formula (I) according to the invention may be obtained, for example, by reacting the nitrile of formula (II) CN
HF2C O"/'O
~
Me (II) with Li-hexamethyldisilazane. For the reaction it is appropriate to use non-polar and polar aprotic solvents such as toluene, ether, tetrahydrofuran at temperatures from io -80 Cto 120 C. To cleave the silyl groups, inorganic and organic acids are used such as HCI, HBr, H2SO4, sulphonic acids such as p-toluenesulphonic acid, benzenesulphonic acid or methanesulphonic acid and carboxylic acids such as formic acid, acetic acid or trifluoroacetic acid at temperatures from 0 C to 100 C.
The compound according to the invention may be prepared, starting from compounds known from the prior art, inter alia using the process described in the following synthesis example. Various other embodiments of the process will be apparent to anyone skilled in the art from the present specification and from the abovementioned Intemational Patent Application WO 98/11062; reference is hereby made to the contents of this pubication. It is specifically pointed out that the following synthesis example is provided solely as an illustration and not as a restriction to the invention.
Synthesis Example:
CN
HF2C \ O~~O \
I (III) 1 g of the nitrile (III) were placed in 20 mi of ethanol and a solution of 700 mg of hydroxylamine hydrochloride, 590 mg of Na2CO3 in 3 mi of H20 was slowly added dropwise while refluxing. The mixture was then boiled for 4 h and after cooling the crystals precipitated were suction filtered and washed with H20. After neutralisation with 260 mg of inethanesulphonic acid in 5 mi of ethanol, precipitation was carried out with diethylether and the precipitate was suction filtered. The substance was hydrogenated in 50 ml of methanol with the addition of 200 mg of Pd/C (5%) at normal pressure. After the catalyst had been suction filtered, Raney Ni was added and hydrogenation was carried out again. The catalyst was suction filtered, the io solvent was distilled off, the residue was dissolved in a little ethanol and precipitated with diethylether. Yield: 830 mg. Mp.: 204-205 C (as the methanesulphonate).
Claims (16)
1. A compound of formula (I) or a pharmacologically acceptable acid addition salt thereof.
2. A process for preparing the compound of formula (I) as defined in claim 1, wherein a nitrile of formula (II) is converted into the compound of formula (I).
3. A process for preparing the compound of formula (I) as defined in claim 1, wherein a nitrile of formula (III) is converted into the compound of formula (I).
4. A pharmaceutical composition comprising the compound or salt as defined in claim 1 and a pharmaceutically acceptable carrier or diluent.
5. The pharmaceutical composition of claim 4 with an LTB4-antagonistic activity.
6. The pharmaceutical composition of claim 4 for therapeutic treatment of arthritis, asthma, a chronic obstructive lung disease, psoriasis, ulcerative colitis, enteropathy induced by a nonsteroidal antiphlogistic, gastropathy induced by a nonsteroidal antiphlogistic, cystic fibrosis, Alzheimer's disease, shock, reperfusion damage/ischaemia, atherosclerosis or multiple sclerosis.
7. The pharmaceutical composition of claim 6, wherein the chronic obstructive lung disease is chronic bronchitis.
8. A use of the compound or salt as defined in claim 1 in preparation of a pharmaceutical composition with an LTB4-antagonistic activity.
9. A use of the compound or salt as defined in claim 1 in preparation of a pharmaceutical composition for the therapeutic treatment of arthritis, asthma, a chronic obstructive lung disease, psoriasis, ulcerative colitis, enteropathy induced by a nonsteroidal antiphlogistic, gastropathy induced by a nonsteroidal antiphlogistic, cystic fibrosis, Alzheimer's disease, shock, reperfusion damage/ischaemia, atherosclerosis or multiple sclerosis.
10. The use of claim 9, wherein the chronic obstructive lung disease is chronic bronchitis.
11. Use of the compound or salt as defined in claim 1 as an LTB4 antagonist.
12. A use of the compound or salt as defined in claim 1 for the therapeutic treatment of arthritis, asthma, a chronic obstructive lung disease, psoriasis, ulcerative colitis, enteropathy induced by a nonsteroidal antiphiogistic, gastropathy induced by a nonsteroidal antiphlogistic, cystic fibrosis, Alzheimer's disease, shock, reperfusion damage/ischaemia, atherosclerosis or multiple sclerosis.
13. The use of claim 12, wherein the chronic obstructive lung disease is chronic bronchitis.
14. The compound or salt as defined in claim 1 for therapeutic treatment of a disease or condition responsive to an LTB4 antagonist.
15. The compound or salt as defined in claim 1 for the therapeutic treatment of arthritis, asthma, a chronic obstructive lung disease, psoriasis, ulcerative colitis, enteropathy induced by a nonsteroidal antiphlogistic, gastropathy induced by a nonsteroidal antiphlogistic, cystic fibrosis, Alzheimer's disease, shock, reperfusion damage/ischaemia, atherosclerosis or multiple sclerosis.
16. The compound or salt of claim 15, wherein the chronic obstructive lung disease is chronic bronchitis.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19948428A DE19948428A1 (en) | 1999-10-07 | 1999-10-07 | New LTB¶4¶ antagonist, process for its preparation and its use as a medicament |
| DE19948428.7 | 1999-10-07 | ||
| PCT/EP2000/009793 WO2001025186A1 (en) | 1999-10-07 | 2000-10-06 | Novel ltb4 antagonist, method for the production thereof and its use as a medicament |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2385871A1 CA2385871A1 (en) | 2001-04-12 |
| CA2385871C true CA2385871C (en) | 2008-12-09 |
Family
ID=7924884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002385871A Expired - Fee Related CA2385871C (en) | 1999-10-07 | 2000-10-06 | Ltb4 antagonist, processes for the preparation thereof and its use as a pharmaceutical composition |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1222162B1 (en) |
| JP (1) | JP4428900B2 (en) |
| AT (1) | ATE265999T1 (en) |
| AU (1) | AU1022201A (en) |
| CA (1) | CA2385871C (en) |
| DE (2) | DE19948428A1 (en) |
| MX (1) | MXPA02002739A (en) |
| WO (1) | WO2001025186A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1298316C (en) * | 2001-07-14 | 2007-02-07 | 贝林格尔英格海姆法玛两合公司 | Pharma ceutical formulation containing and LTB4 antagonist |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ287209B6 (en) * | 1992-02-05 | 2000-10-11 | Boehringer Ingelheim Kg | Amidine derivatives, process of their preparation and pharmaceutical preparations containing thereof |
| DE19636689A1 (en) * | 1996-09-10 | 1998-03-12 | Boehringer Ingelheim Kg | New benzamidine derivatives |
-
1999
- 1999-10-07 DE DE19948428A patent/DE19948428A1/en not_active Withdrawn
-
2000
- 2000-10-06 WO PCT/EP2000/009793 patent/WO2001025186A1/en active IP Right Grant
- 2000-10-06 AT AT00971328T patent/ATE265999T1/en not_active IP Right Cessation
- 2000-10-06 AU AU10222/01A patent/AU1022201A/en not_active Abandoned
- 2000-10-06 CA CA002385871A patent/CA2385871C/en not_active Expired - Fee Related
- 2000-10-06 DE DE50006351T patent/DE50006351D1/en not_active Expired - Lifetime
- 2000-10-06 MX MXPA02002739A patent/MXPA02002739A/en active IP Right Grant
- 2000-10-06 JP JP2001528134A patent/JP4428900B2/en not_active Expired - Fee Related
- 2000-10-06 EP EP00971328A patent/EP1222162B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ATE265999T1 (en) | 2004-05-15 |
| JP4428900B2 (en) | 2010-03-10 |
| MXPA02002739A (en) | 2002-10-23 |
| AU1022201A (en) | 2001-05-10 |
| EP1222162A1 (en) | 2002-07-17 |
| DE19948428A1 (en) | 2001-04-12 |
| CA2385871A1 (en) | 2001-04-12 |
| DE50006351D1 (en) | 2004-06-09 |
| WO2001025186A1 (en) | 2001-04-12 |
| JP2003511361A (en) | 2003-03-25 |
| EP1222162B1 (en) | 2004-05-06 |
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