EA022909B1 - Соединение бензотиазолона - Google Patents
Соединение бензотиазолона Download PDFInfo
- Publication number
- EA022909B1 EA022909B1 EA201490573A EA201490573A EA022909B1 EA 022909 B1 EA022909 B1 EA 022909B1 EA 201490573 A EA201490573 A EA 201490573A EA 201490573 A EA201490573 A EA 201490573A EA 022909 B1 EA022909 B1 EA 022909B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- pharmaceutically acceptable
- formula
- butoxyphenyl
- acceptable salt
- Prior art date
Links
- -1 Benzothiazolone compound Chemical class 0.000 title claims description 104
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- CZWWCTHQXBMHDA-UHFFFAOYSA-N 3h-1,3-thiazol-2-one Chemical compound OC1=NC=CS1 CZWWCTHQXBMHDA-UHFFFAOYSA-N 0.000 claims description 40
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- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
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Classifications
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/08—Acetic acid
- C07C53/10—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicinal Preparation (AREA)
- Emergency Medicine (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011079379 | 2011-09-06 | ||
| PCT/IB2012/054580 WO2013035047A1 (en) | 2011-09-06 | 2012-09-05 | Benzothiazolone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201490573A1 EA201490573A1 (ru) | 2014-06-30 |
| EA022909B1 true EA022909B1 (ru) | 2016-03-31 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201490573A EA022909B1 (ru) | 2011-09-06 | 2012-09-05 | Соединение бензотиазолона |
Country Status (39)
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| JO3192B1 (ar) | 2011-09-06 | 2018-03-08 | Novartis Ag | مركب بنزوثيازولون |
| UA117092C2 (uk) | 2011-09-06 | 2018-06-25 | Байєр Інтеллектуал Проперті Гмбх | Амінозаміщені імідазопіридазини |
| ES2642003T3 (es) * | 2012-08-30 | 2017-11-14 | Novartis Ag | Sales de un compuesto de benzotiazolona como agonistas del adreno-receptor beta-2 |
| ES2646916T3 (es) | 2012-11-19 | 2017-12-18 | Bayer Pharma Aktiengesellschaft | Aminoimidazopiridazinas como inhibidores de MKNK1 cinasa |
| MA38354B1 (fr) * | 2013-02-28 | 2016-09-30 | Novartis Ag | Préparation contenant un composé de benzothiazolone |
| US10967119B1 (en) | 2019-04-01 | 2021-04-06 | Azizi Bilal | Wearable medication injecting device |
Family Cites Families (46)
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| EP0662324A1 (en) * | 1987-09-15 | 1995-07-12 | The Rowett Research Institute | Use of beta-adrenergic agonists for treating loss of function of striated muscles |
| US20070082918A1 (en) * | 1993-11-02 | 2007-04-12 | Naftchi N E | Neurologically active compounds and compounds with multiple activities |
| GB9405019D0 (en) | 1994-03-15 | 1994-04-27 | Smithkline Beecham Plc | Novel compounds |
| ZA967892B (en) | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
| WO1999009018A1 (en) | 1997-08-14 | 1999-02-25 | Kirin Beer Kabushiki Kaisha | BENZOTHIAZOLONE DERIVATIVES HAVING SELECTIVE β2 RECEPTOR AGONIST ACTIVITY |
| CA2349616A1 (en) | 1998-12-04 | 2000-06-15 | Neurosearch A/S | New benzimidazolone-, benzoxazolone-, or benzothiazolone derivatives as ion channel modulating agents |
| US6566372B1 (en) | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
| US6872723B2 (en) * | 2002-01-28 | 2005-03-29 | Wyeth | Stabilized difloxacin injectable solution |
| US6743797B2 (en) * | 2002-02-22 | 2004-06-01 | Chantest, Inc. | Methods for treating cardiac arrhythmia |
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| EP1631260A2 (en) | 2003-02-28 | 2006-03-08 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| WO2004085058A1 (en) * | 2003-03-26 | 2004-10-07 | Pharmacia & Upjohn Company Llc | Process to produce enantiomerically enriched alcohols and amines |
| AU2004226824B2 (en) * | 2003-04-04 | 2008-05-01 | Novartis Ag | Quinoline-2-one-derivatives for the treatment of airways diseases |
| JP2007503472A (ja) * | 2003-06-10 | 2007-02-22 | カリプシス・インコーポレーテッド | 病気治療用のヒストン脱アセチル化酵素阻害剤としてのカルボニル化合物 |
| WO2004110418A2 (en) | 2003-06-10 | 2004-12-23 | Kalypsys, Inc. | Carbonyl compounds as inhibitors of histone deacetylase for the treatment of disease |
| EP1646370A1 (en) | 2003-07-11 | 2006-04-19 | Glaxo Group Limited | Pharmaceutical formulations |
| JP2009513531A (ja) | 2003-07-11 | 2009-04-02 | グラクソ グループ リミテッド | 糖エステルを含む吸入可能医薬製剤 |
| US7345060B2 (en) | 2003-11-21 | 2008-03-18 | Theravance, Inc. | Compounds having β2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| GB0328490D0 (en) | 2003-12-09 | 2004-01-14 | Glaxo Group Ltd | Medicinal compounds |
| JP2005187357A (ja) | 2003-12-25 | 2005-07-14 | Nippon Suisan Kaisha Ltd | 選択的なβ２受容体アゴニスト活性を有するベンゾチアゾロン誘導体の製造方法 |
| GB0402797D0 (en) * | 2004-02-09 | 2004-03-10 | Novartis Ag | Organic compounds |
| JP2007537187A (ja) | 2004-05-13 | 2007-12-20 | 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 | 呼吸器疾患の治療においてβアゴニストとして使用するためのヒドロキシ置換ベンゾ縮合ヘテロ環化合物 |
| EP1595873A1 (de) | 2004-05-13 | 2005-11-16 | Boehringer Ingelheim Pharma GmbH & Co.KG | Substituierte Cycloalkylderivate zur Behandlung von Atemswegerkrankungen |
| JP2008507532A (ja) | 2004-07-21 | 2008-03-13 | セラヴァンス， インコーポレーテッド | ジアリールエーテルβ２アドレナリン作用性レセプターアゴニスト |
| DE102004045648A1 (de) | 2004-09-21 | 2006-03-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Betamimetika zur Behandlung von Atemwegserkrankungen |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| DE102005007654A1 (de) | 2005-02-19 | 2006-08-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue langwirksame Betamimetika zur Behandlung von Atemwegserkrankungen |
| TW200738659A (en) | 2005-08-29 | 2007-10-16 | Astrazeneca Ab | Novel compounds |
| TW200740781A (en) | 2005-08-29 | 2007-11-01 | Astrazeneca Ab | Novel compounds |
| WO2007086078A2 (en) | 2006-01-30 | 2007-08-02 | Panacea Biotec Ltd. | Novel pharmaceutical compositions and process of preparation thereof |
| CA2641880C (en) | 2006-02-10 | 2014-09-09 | Summit Corporation Plc | Treatment of duchenne muscular dystrophy |
| TW200745084A (en) | 2006-03-08 | 2007-12-16 | Astrazeneca Ab | Novel compounds |
| GB0613154D0 (en) | 2006-06-30 | 2006-08-09 | Novartis Ag | Organic Compounds |
| BRPI0716495A2 (pt) * | 2006-08-10 | 2014-03-04 | Us Gov Health & Human Serv | (r,r)-fenoterol e análogos de (r,r)- ou (r,s)-fenoterol, uso dos mesmos na preparação de composição farmacêutica e composição farmacêutica compreendendo o referidos compostos. |
| TW200833670A (en) | 2006-12-20 | 2008-08-16 | Astrazeneca Ab | Novel compounds 569 |
| TW200911237A (en) | 2007-08-03 | 2009-03-16 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
| WO2010015792A1 (en) | 2008-08-06 | 2010-02-11 | Argenta Discovery Limited | Nitrogen containing heterocyclic compounds useful as bifunctional modulators of m3 receptors and beta-2 receptors |
| GB0814728D0 (en) | 2008-08-12 | 2008-09-17 | Argenta Discovery Ltd | New combination |
| GB0823140D0 (en) | 2008-12-18 | 2009-01-28 | Astrazeneca Ab | New combination |
| GB201009801D0 (en) | 2010-06-11 | 2010-07-21 | Astrazeneca Ab | Compounds 950 |
| GB201107985D0 (en) | 2011-05-13 | 2011-06-29 | Astrazeneca Ab | Process |
| JO3192B1 (ar) | 2011-09-06 | 2018-03-08 | Novartis Ag | مركب بنزوثيازولون |
| ES2642003T3 (es) * | 2012-08-30 | 2017-11-14 | Novartis Ag | Sales de un compuesto de benzotiazolona como agonistas del adreno-receptor beta-2 |
| MA38354B1 (fr) | 2013-02-28 | 2016-09-30 | Novartis Ag | Préparation contenant un composé de benzothiazolone |
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