WO2001056570A1 - Substances therapeutiques ou preventives pour insuffisance pulmonaire, contenant des derives de diaminotrifluoromethylpyridine - Google Patents
Substances therapeutiques ou preventives pour insuffisance pulmonaire, contenant des derives de diaminotrifluoromethylpyridine Download PDFInfo
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- WO2001056570A1 WO2001056570A1 PCT/JP2001/000616 JP0100616W WO0156570A1 WO 2001056570 A1 WO2001056570 A1 WO 2001056570A1 JP 0100616 W JP0100616 W JP 0100616W WO 0156570 A1 WO0156570 A1 WO 0156570A1
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- group
- optionally substituted
- substituted
- alkyl
- phenyl
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
Definitions
- the present invention relates to a therapeutic or preventive agent for lung failure comprising a diaminotrifluoromethylpyridine derivative or a salt thereof as a component.
- Japanese Patent No. 2762623 and US Patent No. 5,229,403 disclose a diaminotrifluoromethylpyridine derivative or a salt thereof containing phosphorino. Has Ichize A 2 inhibitory action, it has been placing himself useful as ⁇ ] component of the anti-inflammatory agent or flatter rate flame agent.
- phospholipase A 2 in platelets and inflammatory ⁇ in is secreted or activated by stimulation, contributing to the production of platelets active I production factor (PAF) and metabolites Arakidon acid
- the metabolites of arachidonic acid may have various pathologies, such as rheumatoid arthritis, deformity, 'I' arthritis, tendinitis, bursitis, psoriasis and other skin inflammations; Nasal inflammation, nose such as allergic monobronchial asthma; bronchial bronchial dysfunction; being closely related to immediate hypersensitivity, such as allergic monoconjunctivitis, etc.
- phospholipase A 2 such as splenitis, anti-inflammatory agents, bronchial It can be used as a therapeutic agent for asthma, an anti-allergic agent, a shelving agent, an anti-nephritis agent, an anti-multiple organ harmful agent, and so on.
- Acute distress () syndrome is a disease that is particularly problematic for difficulties I 'students in lung failure [Acute Re spiratory Distress Syndrome; fine S] and sphere occlusion ⁇ 4S city disease [Chronic Obstructive Pulm onary D i sease; COPD].
- Fine S occurs when an IJ invasion is added to a living body due to various underlying diseases.
- bases include viruses such as 'communitis, bacteria', infectious diseases, bacteremia, systemic inflammatory response syndrome (SIRS), shellfish disease, severe; Spontaneous shock, Hemorrhagic shock, Cardiogenic shock, Anaphylaxis, ⁇ ⁇ Multiple organ failure (M0F), Nail fil «dysfunction syndrome (M0DS), Sudden 141% inflammation, Dissemination (Extensive) 1 ' ⁇ Intraductal coagulation (DIC), direct writhing, head trauma, multiple I-bell trauma, fat embolism, amniotic fluid embolism, fetal death, oxygen poisoning, drug poisoning, etc. Weight.
- viruses such as 'communitis, bacteria', infectious diseases, bacteremia, systemic inflammatory response syndrome (SIRS), shellfish disease, severe; Spontaneous shock, Hemorrhagic shock, Cardiogenic shock, Anaphylaxis, ⁇
- non- ! patients have non- !: primary pulmonary edema, severe hypopharyngitis, decreased pulmonary covariance, severe gas impairment, acute and insufficiency symptoms such as diarrhea.
- PEEP end-expiratory positive pressure B and (PEEP) or AD with 1 ⁇ 2S-type ⁇ ⁇ and ⁇ ⁇ ⁇ ⁇ and ⁇ Many.
- some in vitro Wffi-assisted and inhaled S-oxygen therapy has been attempted.
- C0PD is a symptom of pulmonary disease in which forced expiratory flow is high, and includes, for example, 1 ⁇ 'bronchitis, lung weight, diffuse ⁇ bronchitis, airway obstruction, and the like.
- I and Ca ⁇ are the main causes of its onset, especially long-term 'heavy smokers' have high rates of wet coughing and other forms of death, and mortality rates are high.
- due to the recent exacerbation of fiber contamination the exposure to dust and chemical fumes has increased, the incidence of C0PD has increased, and the number of patients has been sharply increasing year by year.
- C0PD chronic obstructive pulmonary disease
- long-term oxygen therapy is used as a treatment.
- symptomatic drug treatment / 32 ⁇ IJ such as metaph-oral monol, which promotes bronchodilation, and theophylline, which reduces the spasm of smooth muscle, are used to improve airway obstruction.
- anticholinergic drugs, steroid drugs, antibacterial drugs, etc. are also used as antiparasitic or multidrug combinations, but if systemic steroids are required, their side effects will be a problem. Therefore, development of more powerful treatment is desired. Disclosure of the invention
- the present inventors have conducted various studies on the pharmacological action of a diaminotrifluoromethylpyridine derivative or a salt thereof. As a result, the inventors have found that these compounds are extremely useful as a therapeutic agent for lung injury IJ or a preventive agent represented by ARDS or C0PD, and completed the present invention.
- the present invention provides a compound of the formula (I)
- X is —CW ′ R 1 group —COCOR 2 *.
- One CW′NHCOR two group —C (WW 2 R 3 group or one CW) N (R 4 ) R 5 group;
- R or R 6, R 9 is a group of (NH) m S 0 2 N (R n ) R 12 ;
- Single b7j-substituted multi-substituted poly is an optionally-substituted mono-it ⁇ ⁇ -substituted or optionally-substituted polycyclic-complex-substituted;
- R 2 and R 7 are each independently An optionally substituted alkyl group, an optionally substituted alkoxy group, an optionally substituted phenyl group or an optionally substituted phenoxy group;
- R 3 , R 8 and R 10 are each substituted with Optionally substituted alkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, optionally substituted cycloalkyl group
- R 4 , R 5 , R 11 and R 12 are each independently an alkyl group which may be substituted;
- W is a phenyl group which may be substituted or a
- X and Y is —COC F2 X 1 group
- X 1 is a hydrogen atom, a halogen atom, an alkyl group or a haloalkyl group
- the other is —COCF 2 X 2 group
- X 2 is a hydrogen atom A halogen atom, an alkyl group, an alkyl group or an alkylcarbonyl group) or one CO OX 3 group
- X 3 is an optionally substituted alkyl group or an optionally substituted phenyl group
- X 4 is an alkyl group, a haloalkyl group, an alkenyl group, an alkynyl group, a phenyl group, a furanyl group or a naphthyl group which may be substituted, excluding the case of the group ⁇ :
- Another object of the present invention is to provide a therapeutic or prophylactic agent for lung failure containing a methylpyridine derivative or a salt thereof as a
- examples of the above-mentioned amino group contained in R R, R 6 and R 9 include an alkyl group, an alkenyl group and an alkynyl group.
- examples of the ⁇ lt ⁇ bJ silicon group include a cycloalkyl cycloalkenylphenyl group and the like.
- examples of the poly group include a condensed poly-b group such as a naphthyl group and a tetrahydronaphthyl indanyl group, or a polycyclic group such as an adamantyl noradamantyl group and a norbornanyl norbornanonyl group.
- ⁇ ⁇ is a pyrrolyl group, furanyl phenyl pyrazolyl group, imidazolyl group, oxazolyl isooxosazolyl group thiazolyl group, isothiazolyl group thiadiazolyl pyrrolinyl pyrrolidinyl dihydrofuranyl group tetrahydrofuranyl group Lahydrochenil virazolinyl hydantoinyl group, oxazolidinyl isooxosazolinyl isoxazolidinyl thiazolinyl group thiazolidinyl group, dioxolanyl group, dithiolanyl pyridyl group pyridazinyl pyrimidinyl virazinyl group, dihydropyridyl group, dihydropyridyl group, dihydropyridyl group, dihydropyridyl group, dihydropyri
- the poly! ⁇ ⁇ cyclic group is a thienothenyl group dihydro Tacenyl group Indolyl group, benzofuranyl benzochenyl group, benzoxazolyl group, benzisoxazolyl benzothiazolyl group, benzimidazolyl group, tetrahydrobenzozoenyl dihydrobenzofuranyl group tetrahydrobenzodisoxazolyl benzodioxoxo Ril quinolinyl isoquinolinyl group Benzodioxanyl Condensed heterocyclic group such as quinoxalinyl group or bridged polycyclic compound such as quinuclidinyl group.
- the optionally substituted chain contained in RR 6 and R 9 is a prime group, the optionally substituted alkyl group and the optionally substituted alkoxy group R 3 and R 8 contained in R 2 and R 7 and an optionally substituted alkyl group contained in R 1 0, are substituted are included in the optionally substituted alkynyl groups as well as be also an alkenyl group and substituted R 4, R 5, R] 1 and R] 2
- the substituent of the alkyl group and the alkyl group which may be substituted in X 3 include a halogen atom, an alkoxy group, a haloalkoxy alkylthio cycloalkyl cycloalkoxy cycloalkenyl cycloalkenyloxy alkoxycarbonyl group, and an alkylcarbonyl group.
- the substituted ⁇ lt ⁇ contained in RR 6 and R 9 may be substituted with an elementary group, or may be substituted with a number of ⁇ complex complex and may be substituted.
- Examples of the substituent of the phenyl group which may be substituted and the benzyl group which may be substituted and the phenyl group which may be substituted and contained in X 3 include a halogen atom, an alkylhaloalkyl group, an alkoxy group, a haloalkoxy group and an alkylthiocycloalkyl group Cycloalkoxy group cycloalkenyl group, cycloalkenyloxy group, alkoxycarbonyl alkylcarbonyl alkylcarbonyloxy group, aryl group ary
- the alkyl group and the alkyl moiety contained in X and Y include those having 1 to 18 carbon atoms, for example, methyl group, ethyl propyl group, butyl pentyl group, hexyl group, heptyl octyl group, decyl group, and nonadecyl.
- the alkenyl group and alkenyl moiety contained in X and Y include those having 2 to 18 carbon atoms, for example, vinyl propyl group butenyl group pentenyl group hexenyl group decenyl nonadecenyl group, and the like. They are straight-chain: X also includes those of structural isomerism of branched fatty chains. Examples of the alkynyl group and the alkynyl moiety contained in X and Y include those having 2 to 18 carbon atoms, such as ethynyl group propynyl group butynyl group penthyl group, hexynyl group, decynyl group, and nonadecynyl group.
- X includes those having structural isomers of branched fatty chains.
- the cycloalkyl group and the cycloalkyl moiety contained in X and Y include those having 3 to 8 carbon atoms, such as cyclopropyl cyclobutyl group, cyclopentyl cyclohexyl group, and cyclooctyl group.
- Examples of the cycloalkenyl group and the cycloalkenyl group contained in X and Y include those having 5 to 8 carbon atoms, such as a cyclopentenyl group and a cyclohexenyl cyclooctenyl group.
- examples of the halogen atom contained in X and Y include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
- R 1 and R 6 is a substituted Alkyl which may be substituted alkenyl group which may be substituted, cycloalkyl group which may be substituted, cycloalkenyl group which may be substituted, phenyl group which may be substituted, tetrahydronaphthyl group which may be substituted, A substituted or unsubstituted furanyl group or a substituted phenyl group; an alkyl group, a haloalkyl group, an alkoxycarbonylalkyl group, an alkenyl group, a haloalkenyl group, a cycloalkyl group, or a halogen atom; Cycloalkyl group, phenyl phenyl group substituted with halogen atom, phenyl group substituted with alkyl group or haloalkyl group, alcohol A phenyl group substituted with an xy group or a
- R 2 and R 7 are preferably an optionally substituted alkoxy group or an optionally substituted phenyl group; and more preferably an alkoxy group, a haloalkoxy group, a phenyl group or a phenyl group substituted with a halogen atom.
- RR 8 and R 10 are preferably an alkyl group which may be substituted; and more preferably an alkyl group or a haloalkyl group.
- R 9 is preferably an optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl & optionally substituted cycloalkenyl group or optionally substituted phenyl group; alkyl haloalkyl group phenyl A phenyl group substituted with a halogen atom, a phenyl group substituted with an alkyl group or a haloalkyl group, or a phenyl group substituted with an alkoxy group or a haloalkoxy group is more desirable.
- X is an alkoxyl carbonyl group substituted with an alkenylcarbonyl group or an alkenylcarbonyl group.
- a benzoyl group which may be substituted with a dithiophenecarbonyl group, a tetrahydronaphthylcarbonyl group or a halogen atom or a haloalkyl group, and a compound in which Y is an aralkylsulfonyl group.
- X is a cycloalkylcarbonylalkenylcarbonyl group, a thiophenecarbonyl group or a benzoyl group which may be substituted with a halogen atom
- Y is an alkylsulfonyl group.
- Y is - S 0 2 R 9 group (R 9 are as defined above) may form a salt, as the salts thereof, are pharmaceutically acceptable Organic salts such as potassium salts, alkali metal salts such as sodium salts, alkaline earth metal salts such as calcium salts, triethanolamine salts, and tris (hydroxymethyl) aminomethane salts. And the like. Some of these salts have water of crystallization.
- the compound represented by the formula (I) can be obtained by the method described in, for example, Japanese Patent No. 2762032.
- these diastereomers have geometrically different isomers depending on the type of the tansan group.
- each isomer cis isomer, trans isomer
- isomerism are included.
- the present invention represented by the above-mentioned (I) is included in the present invention.
- It is useful as a force component of ri.
- various pulmonary failures it is particularly useful as a component of ARDS treatment. It can be expected to be more powerful when used in combination with other drugs.
- compositions suitable for oral or parenteral administration by mixing with a physiologically acceptable carrier, etc. for example, tablets, powder wrappers, capsules, granules, sizing agents, ointments, inhalants It is administered in the form of preparations, suppositories and the like.
- Solid compositions such as tablets, capsules, powders, granules, troches and the like, binders such as valley cellulose, gum arabic, gum tragacanth, gelatin, polyvinylpyrrolidone;
- Disintegrators such as alginic acid, cornstarch, and carboxylmethylcellulose; lubricants such as magnesium stearate, light non- ⁇ -silicic acid, colloidal silicon dioxide; and sucrose. Flavoring agents such as peppermint and methyl salicylate; and the like.
- Liquids such as syrups and suspensions are made of sorbitol, gelatin, methylcellulose, carboxymethylcellulose, vegetable oils such as peanut oil, emulsifiers such as lecithin, and, if necessary, sweeteners, preservatives, It can contain coloring agents and flavoring agents, which can also be used as dry preparations. These preparations preferably contain 1 to 95% by weight of the ingredient.
- Preparations suitable for parenteral administration include, for example, sizing agents and the like.
- the sizing agent may be, for example, a salt which can be dissolved in ordinary sizing water or the like, or a suspension or emulsion (in a mixture of a medically acceptable oil or liquid).
- This sizing agent contains 0.1
- That force Masui including to 8 wt 0/0.
- Formulations suitable for topical or convenient use include, for example, inhalants, ointments, remedies, suppositories and the like.
- inhalant it can be dissolved in an aerosol or a nebulizer solution together with the inert carrier of the present invention or a pharmaceutically acceptable carrier, or can be administered as a fine powder for inhalation to a peripheral organ.
- the particles In the case of fine powder for inhalation, the particles have a size of less than 50 microns, preferably less than 10 microns.
- these drugs when used as an inhalant, they can be used in combination with other anti-asthmatics or bronchodilator D if necessary.
- Ointments are prepared by conventional methods, with the addition of reversible coagulants.
- Ointment is a Wei ingredient Spoon ⁇ f
- forces preferable comprise 30 weight 0/0.
- Suppositories may contain pharmaceutical carriers well known in the art, for example, polyethylene glycol, lanolin, cocoa luster, fatty acid triglyceride, etc. Suppositories may contain 1 to 95 weight parts of the active ingredient 0/0 be a force 5 Masui, including.
- Formulations suitable for topical, parenteral, topical or topical administration should be administered to patients in a known manner, with a sustained release such that the activity is rapidly released. It can be formulated to be released at a later time or to be released later.
- the dose of the present invention may vary depending on the nature of the drug, the method of administration, the condition of the patient or the subject, and the appropriate amount and the number of doses under certain conditions are determined by a specialist. Usually, about 0.1 mg to about 10 g, preferably about 1 mg to about 1 g, is administered per adult day. In addition, the dose of the present invention per one dose in the inhalation method is preferably about 0.01 mg to about 1 g.
- the above components (1) to (4) are made into one tablet and molded into tablets.
- the above (1) to (4) are mixed to obtain a fine powder or granule by powder and further granulation. or, These can be encapsulated in capsules to make capsules.
- Tris (hydroxymethyl) aminomethane 16 mg or more Tris buffer containing the components (1) to (3) is frozen and dried to obtain a size.
- Formulation Example 6 Thigh formulation by preparing the components (1) to (8) by a general ointment preparation method to obtain an external ointment for skin
- Disperse or dissolve (1) in (2) fill in a suitable size plastic container as a suppository, seal, cool and solidify to obtain a suppository.
- Test Example 1 Sensitivity to lipopolysaccharide (LPS) -induced rat ARDS model: N- (2-ethylsulfonylamino-1-5-trifluorotrifluoromethyl-3-pyridyl) cyclohexanecarboxamide against LPS-induced rat ARDS model The effects of treating sodium salt and monohydrate (hereinafter referred to as Compound 1) were examined.
- LPS lipopolysaccharide
- Compound 1 N- (2-ethylsulfonylamino-1-5-trifluorotrifluoromethyl-3-pyridyl) cyclohexanecarboxamide against LPS-induced rat ARDS model
- Scores are:- ⁇ nosignir icant lesion), ⁇ (siight), +, mild), ++ (moderate) +++, mark ed) After 5 stages of Hffi, 0, 0.5, 1, 2, Group average value was calculated as 3 points
- Glucose administration group In the non-treated group (5 /. Glucose administration group), exudative and degenerative changes in the lungs and trachea were associated with increased lung wet weight. Hemoconcentration was also observed due to an increase in red blood cell line items, and the overall pathology of ARDS was recognized.
- the i-drug of course, one administration group alleviated severe changes in bronchial alveolar wall, lung 3 ⁇ 4 ⁇ oma and hemorrhage, and precipitation of Itoizogen in the alveoli, which were serious changes in this trial. However, a remarkable inhibitory effect on the disease state of ARDS;
- Test Example 2 Effect on cigarette smoke inhalation rat ⁇ 'live occlusion 1' city disease (C0PD) model: cigarette smoke inhalation rat C0PD model ⁇ — (2-ethylsulfonylamino-1-5-fluoromethyl)
- C0PD city disease
- C0PD Cri: CD (SD) IGS, a 6-week-old male rat (Nippon Chars River Co., Ltd.) for 2 months (8 weeks) with a cigarette smoke exposure device (INH06-CIGR01)
- IPS, Inc. a commercial non-filter cigarette is exposed to the head 10 times a day for 5 days a week. The normal group is exposed to fresh air to the same drug.
- Chemical group 1 was prepared by diluting Chemical 1 with 5% glucose. (Used in Test Example 1) is administered subcutaneously by a pressure pump from the start of induction to Komi-ji Temple so that the amount of ⁇ % ⁇ of course becomes 0.03 nig / kghr in terms of anhydride.
- 5% glucose used as a vehicle is administered in the same manner.
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- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002398992A CA2398992C (en) | 2000-02-01 | 2001-01-30 | Therapeutic or preventive agent for pulmonary insufficiency containing a diaminotrifluoromethylpyridine derivative |
DE60122111T DE60122111T8 (de) | 2000-02-01 | 2001-01-30 | Diaminotrifluormethylpyridinderivat enthaltendes therapeutisches oder prophylaktisches mittel für pulmonalinsuffizienz |
AU30528/01A AU774479B2 (en) | 2000-02-01 | 2001-01-30 | Remedies or preventives for pulmonary insufficiency containing diaminotrifluoromethylpyridine derivatives |
NZ520376A NZ520376A (en) | 2000-02-01 | 2001-01-30 | Therapeutic or preventive agent for pulmonary insufficiency containing a diaminotrifluoromethylpyridine derivative |
EP01902668A EP1252889B1 (en) | 2000-02-01 | 2001-01-30 | Remedies or preventives for pulmonary insufficiency containing diaminotrifluoromethylpyridine derivatives |
IL15100901A IL151009A0 (en) | 2000-02-01 | 2001-01-30 | Therapeutic or preventive agent for pulmonary insufficiency containing a diaminotrifluoromethylpyridine derivative |
US10/181,431 US6635665B2 (en) | 2000-02-01 | 2001-01-30 | Remedies or preventives for pulmonary insufficiency containing diaminotrifluoromethylpyridine derivatives |
IL151009A IL151009A (en) | 2000-02-01 | 2002-07-31 | Medicinal or prophylactic drug for pulmonary insufficiency containing a history of diaminotrifluoromethylpyridine |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000024349 | 2000-02-01 | ||
JP2000-24349 | 2000-02-01 |
Publications (1)
Publication Number | Publication Date |
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WO2001056570A1 true WO2001056570A1 (fr) | 2001-08-09 |
Family
ID=18550353
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2001/000616 WO2001056570A1 (fr) | 2000-02-01 | 2001-01-30 | Substances therapeutiques ou preventives pour insuffisance pulmonaire, contenant des derives de diaminotrifluoromethylpyridine |
Country Status (15)
Country | Link |
---|---|
US (1) | US6635665B2 (ja) |
EP (1) | EP1252889B1 (ja) |
JP (1) | JP4848092B2 (ja) |
KR (1) | KR100706725B1 (ja) |
CN (1) | CN1230170C (ja) |
AU (1) | AU774479B2 (ja) |
CA (1) | CA2398992C (ja) |
DE (1) | DE60122111T8 (ja) |
ES (1) | ES2269343T3 (ja) |
IL (2) | IL151009A0 (ja) |
NZ (1) | NZ520376A (ja) |
RU (1) | RU2253450C2 (ja) |
TW (1) | TWI293029B (ja) |
WO (1) | WO2001056570A1 (ja) |
ZA (1) | ZA200206038B (ja) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004040302A1 (ja) * | 2002-10-30 | 2004-05-13 | Ishihara Sangyo Kaisha, Ltd. | RAPL・Rap1相互作用制御 |
WO2019088214A1 (ja) | 2017-11-02 | 2019-05-09 | 石原産業株式会社 | 徐放性医薬組成物 |
WO2019167979A1 (ja) | 2018-03-01 | 2019-09-06 | 石原産業株式会社 | 保存安定性に優れた医薬組成物 |
WO2020230876A1 (ja) | 2019-05-15 | 2020-11-19 | 石原産業株式会社 | N-(2-エチルスルホニルアミノ-5-トリフルオロメチル-3-ピリジル)シクロヘキサンカルボキサミド・一ナトリウム塩の無水和物結晶体 |
KR20230084205A (ko) | 2020-09-29 | 2023-06-12 | 이시하라 산교 가부시끼가이샤 | 우수한 보존 효력을 나타내는 액상 의약 조성물 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA200800251B (en) * | 2005-06-24 | 2009-04-29 | Drugrecure Aps | Airway administration of tissue factor pathway inhibitor in inflammatory conditions affecting the respiratory track |
WO2008136378A1 (ja) * | 2007-04-27 | 2008-11-13 | Toyama Chemical Co., Ltd. | 新規なスルホンアミド誘導体またはその塩 |
JP5584518B2 (ja) * | 2009-05-28 | 2014-09-03 | 石原産業株式会社 | ジアミノトリフルオロメチルピリジン誘導体を含有する抗ショック剤 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US5229403A (en) * | 1990-07-10 | 1993-07-20 | Ishihara Sangyo Kaisha Ltd. | Diaminotrifluoromethylpyridine derivatives and phospholipase A2 inhibitor containing them |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0465913T3 (da) * | 1990-07-10 | 1997-10-20 | Ishihara Sangyo Kaisha | Diaminotrifluormethylpyridinderivater, fremgangsmåder til fremstilling deraf og phospholipase-A2-inhibitor indeholdende samme |
TW415843B (en) * | 1997-02-28 | 2000-12-21 | Ishihara Sangyo Kaisha | Anti-cancer pharmaceutical compositions comprising a diaminotrifluoromethylpyridine derivatives or the pharmaceutically acceptable salts thereof |
-
2001
- 2001-01-29 JP JP2001020057A patent/JP4848092B2/ja not_active Expired - Lifetime
- 2001-01-30 EP EP01902668A patent/EP1252889B1/en not_active Expired - Lifetime
- 2001-01-30 NZ NZ520376A patent/NZ520376A/en not_active IP Right Cessation
- 2001-01-30 AU AU30528/01A patent/AU774479B2/en not_active Ceased
- 2001-01-30 CA CA002398992A patent/CA2398992C/en not_active Expired - Lifetime
- 2001-01-30 IL IL15100901A patent/IL151009A0/xx active IP Right Grant
- 2001-01-30 ES ES01902668T patent/ES2269343T3/es not_active Expired - Lifetime
- 2001-01-30 DE DE60122111T patent/DE60122111T8/de active Active
- 2001-01-30 WO PCT/JP2001/000616 patent/WO2001056570A1/ja active IP Right Grant
- 2001-01-30 US US10/181,431 patent/US6635665B2/en not_active Expired - Lifetime
- 2001-01-30 RU RU2002123372/15A patent/RU2253450C2/ru not_active IP Right Cessation
- 2001-01-30 CN CNB018042538A patent/CN1230170C/zh not_active Expired - Fee Related
- 2001-01-30 KR KR1020027009852A patent/KR100706725B1/ko not_active IP Right Cessation
- 2001-02-01 TW TW090102077A patent/TWI293029B/zh not_active IP Right Cessation
-
2002
- 2002-07-29 ZA ZA200206038A patent/ZA200206038B/en unknown
- 2002-07-31 IL IL151009A patent/IL151009A/en not_active IP Right Cessation
Patent Citations (1)
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US5229403A (en) * | 1990-07-10 | 1993-07-20 | Ishihara Sangyo Kaisha Ltd. | Diaminotrifluoromethylpyridine derivatives and phospholipase A2 inhibitor containing them |
Non-Patent Citations (4)
Title |
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ARBIBE L. ET AL.: "Generation of lyso-phospholipids from surfactant in acute lung injury is mediated by type-II phospholipase A2 and inhibited by direct surfactant protein A-phospholipase A2 protein interaction", J. CLIN. INVEST., vol. 102, no. 6, 1998, pages 1152 - 1160, XP002938910 * |
BOWTON D.L. ET AL.: "Phospholipase A2 and arachidonate increase in bronchoalveolar lavage fluid after inhaled antigen challenge in athmatics", AM. J. RTESIP. CRIT. CARE MED., vol. 155, 1997, pages 421 - 425, XP002938909 * |
See also references of EP1252889A4 * |
TOUQUI L., ARBIBE L.: "A role for pholpholipase A2 in ARDS pathogenesis", MOL. MED. TODAY, vol. 5, 1999, pages 244 - 249, XP002938908 * |
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WO2004040302A1 (ja) * | 2002-10-30 | 2004-05-13 | Ishihara Sangyo Kaisha, Ltd. | RAPL・Rap1相互作用制御 |
WO2019088214A1 (ja) | 2017-11-02 | 2019-05-09 | 石原産業株式会社 | 徐放性医薬組成物 |
WO2019167979A1 (ja) | 2018-03-01 | 2019-09-06 | 石原産業株式会社 | 保存安定性に優れた医薬組成物 |
JPWO2019167979A1 (ja) * | 2018-03-01 | 2021-02-12 | 石原産業株式会社 | 保存安定性に優れた医薬組成物 |
JP7421770B2 (ja) | 2018-03-01 | 2024-01-25 | 石原産業株式会社 | 保存安定性に優れた医薬組成物 |
WO2020230876A1 (ja) | 2019-05-15 | 2020-11-19 | 石原産業株式会社 | N-(2-エチルスルホニルアミノ-5-トリフルオロメチル-3-ピリジル)シクロヘキサンカルボキサミド・一ナトリウム塩の無水和物結晶体 |
KR20230084205A (ko) | 2020-09-29 | 2023-06-12 | 이시하라 산교 가부시끼가이샤 | 우수한 보존 효력을 나타내는 액상 의약 조성물 |
Also Published As
Publication number | Publication date |
---|---|
CA2398992A1 (en) | 2001-08-09 |
DE60122111D1 (de) | 2006-09-21 |
JP4848092B2 (ja) | 2011-12-28 |
AU3052801A (en) | 2001-08-14 |
TWI293029B (en) | 2008-02-01 |
EP1252889B1 (en) | 2006-08-09 |
RU2253450C2 (ru) | 2005-06-10 |
IL151009A (en) | 2008-04-13 |
AU774479B2 (en) | 2004-07-01 |
DE60122111T2 (de) | 2006-12-07 |
US6635665B2 (en) | 2003-10-21 |
EP1252889A1 (en) | 2002-10-30 |
CN1396827A (zh) | 2003-02-12 |
DE60122111T8 (de) | 2007-04-05 |
IL151009A0 (en) | 2003-02-12 |
ES2269343T3 (es) | 2007-04-01 |
NZ520376A (en) | 2005-02-25 |
CA2398992C (en) | 2009-11-17 |
KR100706725B1 (ko) | 2007-04-12 |
KR20020072576A (ko) | 2002-09-16 |
ZA200206038B (en) | 2003-08-18 |
CN1230170C (zh) | 2005-12-07 |
EP1252889A4 (en) | 2004-12-15 |
US20030109551A1 (en) | 2003-06-12 |
JP2001288088A (ja) | 2001-10-16 |
RU2002123372A (ru) | 2004-03-10 |
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