JP4143413B2 - β２−アドレナリン受容体アゴニストとしてのホルムアニリド誘導体 - Google Patents
β２−アドレナリン受容体アゴニストとしてのホルムアニリド誘導体 Download PDFInfo
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- JP4143413B2 JP4143413B2 JP2002576195A JP2002576195A JP4143413B2 JP 4143413 B2 JP4143413 B2 JP 4143413B2 JP 2002576195 A JP2002576195 A JP 2002576195A JP 2002576195 A JP2002576195 A JP 2002576195A JP 4143413 B2 JP4143413 B2 JP 4143413B2
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- YUSMZDVTEOAHDL-NTMALXAHSA-N tert-butyl (3z)-3-(dimethylaminomethylidene)-4-oxopiperidine-1-carboxylate Chemical compound CN(C)\C=C1\CN(C(=O)OC(C)(C)C)CCC1=O YUSMZDVTEOAHDL-NTMALXAHSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
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- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
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- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- QDWJJTJNXAKQKD-UHFFFAOYSA-N trihexyphenidyl hydrochloride Chemical compound Cl.C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 QDWJJTJNXAKQKD-UHFFFAOYSA-N 0.000 description 1
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- 239000011701 zinc Substances 0.000 description 1
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- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
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- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- 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
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- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0107213A GB0107213D0 (en) | 2001-03-22 | 2001-03-22 | Chemical compounds |
| GB0126995A GB0126995D0 (en) | 2001-11-09 | 2001-11-09 | Chemical compounds |
| PCT/EP2002/003122 WO2002076933A1 (en) | 2001-03-22 | 2002-03-20 | Formailide derivatives as beta2-adrenoreceptor agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004538259A JP2004538259A (ja) | 2004-12-24 |
| JP2004538259A5 JP2004538259A5 (enExample) | 2005-12-22 |
| JP4143413B2 true JP4143413B2 (ja) | 2008-09-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002576195A Expired - Fee Related JP4143413B2 (ja) | 2001-03-22 | 2002-03-20 | β２−アドレナリン受容体アゴニストとしてのホルムアニリド誘導体 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7045658B2 (enExample) |
| EP (1) | EP1370521B1 (enExample) |
| JP (1) | JP4143413B2 (enExample) |
| AT (1) | ATE381537T1 (enExample) |
| DE (1) | DE60224172T2 (enExample) |
| ES (1) | ES2296923T3 (enExample) |
| WO (1) | WO2002076933A1 (enExample) |
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| AR028948A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| US6858596B2 (en) | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivative |
| US6750210B2 (en) | 2000-08-05 | 2004-06-15 | Smithkline Beecham Corporation | Formulation containing novel anti-inflammatory androstane derivative |
| US6858593B2 (en) | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
| CO5310534A1 (es) | 2000-08-05 | 2003-08-29 | Glaxo Group Ltd | Nuevos derivados de androstano anti-inflamatorios |
| US6777400B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
| US6777399B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
| GB0019172D0 (en) | 2000-08-05 | 2000-09-27 | Glaxo Group Ltd | Novel compounds |
| US6787532B2 (en) | 2000-08-05 | 2004-09-07 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivatives |
| US6759398B2 (en) | 2000-08-05 | 2004-07-06 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative |
| UA77656C2 (en) | 2001-04-07 | 2007-01-15 | Glaxo Group Ltd | S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent |
| ES2314052T3 (es) | 2001-04-30 | 2009-03-16 | Glaxo Group Limited | Derivados de ester de 17beta-carbotioato de androstano con un grupo ester ciclico en la posicion 17alfa. |
| EP1487417A4 (en) | 2001-09-17 | 2010-03-17 | Glaxo Group Ltd | DRY POWDER DRUG FORMULATIONS |
| US20030229058A1 (en) | 2001-11-13 | 2003-12-11 | Moran Edmund J. | Aryl aniline beta2 adrenergic receptor agonists |
| EP1471895B2 (en) * | 2002-02-04 | 2012-03-14 | Glaxo Group Limited | Formulation for inhalation comprising a glucocorticoid and a beta 2-adrenoreceptor agonist |
| JP2005527618A (ja) | 2002-05-28 | 2005-09-15 | セラヴァンス インコーポレーテッド | アルコキシアリールβ２アドレナリン作動性レセプターアゴニスト |
| GB2389530B (en) | 2002-06-14 | 2007-01-10 | Cipla Ltd | Pharmaceutical compositions |
| SI1567139T1 (sl) * | 2002-11-27 | 2008-12-31 | Nycomed Gmbh | Nova sinergistična kombinacija, ki obsega roflumilast in formoterol |
| PT1567140E (pt) * | 2002-11-27 | 2008-09-24 | Nycomed Gmbh | Combinação sinérgica compreendendo roflumilaste e (r,r)-formoterol |
| PE20040950A1 (es) | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| GB0303396D0 (en) | 2003-02-14 | 2003-03-19 | Glaxo Group Ltd | Medicinal compounds |
| EP1622875B1 (en) | 2003-05-08 | 2009-12-02 | Theravance, Inc. | Crystalline forms of an arylaniline beta-2 adrenergic receptor agonist |
| TW200510277A (en) | 2003-05-27 | 2005-03-16 | Theravance Inc | Crystalline form of β2-adrenergic receptor agonist |
| GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
| TW200526547A (en) * | 2003-09-22 | 2005-08-16 | Theravance Inc | Amino-substituted ethylamino β2 adrenergic receptor agonists |
| TW200531692A (en) * | 2004-01-12 | 2005-10-01 | Theravance Inc | Aryl aniline derivatives as β2 adrenergic receptor agonists |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| TWI341836B (en) | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| PE20060272A1 (es) | 2004-05-24 | 2006-05-22 | Glaxo Group Ltd | (2r,3r,4s,5r,2'r,3'r,4's,5's)-2,2'-{trans-1,4-ciclohexanodiilbis-[imino(2-{[2-(1-metil-1h-imidazol-4-il)etil]amino}-9h-purin-6,9-diil)]}bis[5-(2-etil-2h-tetrazol-5-il)tetrahidro-3,4-furanodiol] como agonista a2a |
| RU2006146042A (ru) * | 2004-06-03 | 2008-07-20 | Тереванс | Диаминные агонисты 2-адренергических рецепторов |
| TWI307630B (en) | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
| GB0418045D0 (en) | 2004-08-12 | 2004-09-15 | Glaxo Group Ltd | Compounds |
| WO2006023457A1 (en) * | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| WO2006023460A2 (en) | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| EP1786762A2 (en) * | 2004-09-10 | 2007-05-23 | Theravance, Inc. | Amidine substituted aryl aniline compounds |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| US7579335B2 (en) | 2005-01-10 | 2009-08-25 | Glaxo Group Limited | Androstane 17α-carbonate derivatives for use in the treatment of allergic and inflammatory conditions |
| TWI389690B (zh) | 2005-03-25 | 2013-03-21 | Glaxo Group Ltd | 新穎化合物（一） |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
| US7994211B2 (en) | 2005-08-08 | 2011-08-09 | Argenta Discovery Limited | Bicyclo[2.2.1]hept-7-ylamine derivatives and their uses |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| TW200738658A (en) | 2005-08-09 | 2007-10-16 | Astrazeneca Ab | Novel compounds |
| CA2620281A1 (en) * | 2005-08-26 | 2007-03-01 | Astrazeneca Ab | A combination of compounds, which can be used in the treatment of respiratory diseases, especially chronic obstructive pulmonary disease (copd) and asthma |
| JP5006330B2 (ja) | 2005-10-21 | 2012-08-22 | ノバルティス アーゲー | Ｉｌ１３に対するヒト抗体および治療的使用 |
| TW200730498A (en) | 2005-12-20 | 2007-08-16 | Glaxo Group Ltd | Compounds |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| TW200745067A (en) | 2006-03-14 | 2007-12-16 | Astrazeneca Ab | Novel compounds |
| CA2649509A1 (en) | 2006-04-20 | 2007-11-01 | Glaxo Group Limited | Novel compounds |
| WO2007121920A2 (en) | 2006-04-21 | 2007-11-01 | Novartis Ag | Purine derivatives for use as adenosin a2a receptor agonists |
| TW200811105A (en) | 2006-04-25 | 2008-03-01 | Theravance Inc | Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| GB0611587D0 (en) | 2006-06-12 | 2006-07-19 | Glaxo Group Ltd | Novel compounds |
| TW200817006A (en) | 2006-06-23 | 2008-04-16 | Smithkline Beecham Corp | IL-8 receptor antagonist |
| US20090291976A1 (en) * | 2006-06-27 | 2009-11-26 | Peter Andrew Ferchmin | Neuronal circuit-dependent neuroprotection by interaction between nicotinic receptors |
| KR20090030347A (ko) | 2006-07-19 | 2009-03-24 | 아스트라제네카 아베 | 신규 트리시클릭 스피로피페리딘 화합물, 이들의 합성 및 이들의 케모킨 수용체 활성의 조절제로서의 용도 |
| US8003663B2 (en) | 2006-08-01 | 2011-08-23 | Glaxo Group Limited | Pyrazolo[3,4-b]pyridine compounds, and their use as PDE4 inhibitors |
| KR101378067B1 (ko) * | 2006-08-10 | 2014-04-10 | 더 거버먼트 오브 더 유나이티드 스테이츠 오브 아메리카 에즈 레프리젠티드 바이 더 세크러테리 오브 더 디파트먼트 오브 헬스 앤드 휴먼 서비시즈 | （ｒ,ｒ）―페노테롤 및 （ｒ,ｒ）―또는 （ｒ,ｓ）―페노테롤 유사체의 제조방법 및 이의 울혈성 심부전증 치료를 위한 용도 |
| WO2008041914A1 (en) * | 2006-10-06 | 2008-04-10 | Astrazeneca Ab | 5-(2-AMINO-L-HYDROXYETHYL)-8-HYDROXY-2-OXOQUINOLINE DERIVATIVES AND OTHER COMPOUNDS AS β2 -ADRENERGIC AGONISTS |
| TW200825084A (en) | 2006-11-14 | 2008-06-16 | Astrazeneca Ab | New compounds 521 |
| BRPI0721039A2 (pt) | 2006-12-19 | 2014-07-29 | Astrazeneca Ab | " derivados de quinuclidinol como antagonistas de receptores muscarínicos ". |
| TW200833670A (en) | 2006-12-20 | 2008-08-16 | Astrazeneca Ab | Novel compounds 569 |
| DK2104535T3 (da) | 2007-01-10 | 2011-04-04 | Irm Llc | Forbindelser og sammensætninger som kanalaktiverende proteaseinhibitorer |
| GB0702458D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | Salts 668 |
| CA2677485A1 (en) | 2007-02-09 | 2008-08-14 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| PE20081889A1 (es) | 2007-03-23 | 2009-03-05 | Smithkline Beecham Corp | Indol carboxamidas como inhibidores de ikk2 |
| CN101687851B (zh) | 2007-05-07 | 2013-02-27 | 诺瓦提斯公司 | 有机化合物 |
| EA017919B1 (ru) | 2007-12-10 | 2013-04-30 | Новартис Аг | Производные пиразин-2-карбоксамида для лечения заболеваний, которые поддаются лечению путем блокирования эпителиальных натриевых каналов |
| CN101910153B (zh) | 2008-01-11 | 2014-01-22 | 诺华股份有限公司 | 作为激酶抑制剂的嘧啶类 |
| EP2300464A1 (en) | 2008-05-13 | 2011-03-30 | AstraZeneca AB | Quinuclidine derivatives as muscarinic m3 receptor antagonists |
| JP5791500B2 (ja) | 2008-05-23 | 2015-10-07 | パンミラ ファーマシューティカルズ，エルエルシー． | ５−リポキシゲナーゼ活性化タンパク質阻害剤 |
| MX2010012492A (es) | 2008-05-27 | 2010-12-21 | Astrazeneca Ab | Derivados de fenoxipiridinilamida y su uso en el tratamiento de estados de enfermedad mediados por fosfodiesterasa 4. |
| JP5502858B2 (ja) | 2008-06-05 | 2014-05-28 | グラクソ グループ リミテッド | Ｐｉ３キナーゼの阻害剤として有用な４−カルボキサミドインダゾール誘導体 |
| EA201001848A1 (ru) | 2008-06-10 | 2011-08-30 | Новартис Аг | Производные пиразина в качестве блокаторов эпителиальных натриевых каналов |
| WO2009154557A1 (en) | 2008-06-18 | 2009-12-23 | Astrazeneca Ab | Benzoxazinone derivatives acting as beta2-adrenoreceptor agonist for the treatment of respiratory disorders |
| US8236786B2 (en) | 2008-08-07 | 2012-08-07 | Pulmagen Therapeutics (Inflammation) Limited | Respiratory disease treatment |
| WO2010067102A1 (en) | 2008-12-09 | 2010-06-17 | Astrazeneca Ab | Diazaspiro [5.5] undecane derivatives and related compounds as muscarinic-receptor antagonists and beta-adrenoreceptor agonists for the treatment of pulmonary disorders |
| SI2379507T1 (sl) | 2008-12-30 | 2014-02-28 | Pulmagen Therapeutics (Inflammation) Limited | Spojine sulfonamida za zdravljenje respiratornih motenj |
| WO2010094643A1 (en) | 2009-02-17 | 2010-08-26 | Glaxo Group Limited | Quinoline derivatives and their uses for rhinitis and urticaria |
| WO2010102958A1 (en) | 2009-03-09 | 2010-09-16 | Glaxo Group Limited | 4-oxadiazol-2 -yl- indazoles as inhibitors of p13 kinases |
| WO2010102968A1 (en) | 2009-03-10 | 2010-09-16 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| US20120058984A1 (en) | 2009-03-17 | 2012-03-08 | Catherine Mary Alder | Pyrimidine derivatives used as itk inhibitors |
| US20120016011A1 (en) | 2009-03-19 | 2012-01-19 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Connective Tissue Growth Factor (CTGF) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| JP2012520686A (ja) | 2009-03-19 | 2012-09-10 | メルク・シャープ・エンド・ドーム・コーポレイション | 低分子干渉核酸（ｓｉＮＡ）を用いたシグナル伝達性転写因子６（ＳＴＡＴ６）遺伝子発現のＲＮＡ干渉媒介性阻害 |
| JP2012520685A (ja) | 2009-03-19 | 2012-09-10 | メルク・シャープ・エンド・ドーム・コーポレイション | 低分子干渉核酸（ｓｉＮＡ）を用いたＧＡＴＡ結合タンパク質３（ＧＡＴＡ３）遺伝子発現のＲＮＡ干渉媒介性阻害 |
| AU2010226604A1 (en) | 2009-03-19 | 2011-10-13 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of BTB and CNC homology 1, basic leucine zipper transcription factor 1 (Bach 1) gene expression using short interfering nucleic acid (siNA) sequence listing |
| US20120004281A1 (en) | 2009-03-27 | 2012-01-05 | Merck Sharp & Dohme Corp | RNA Interference Mediated Inhibition of the Nerve Growth Factor Beta Chain (NGFB) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| WO2010111464A1 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| CA2756069A1 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | Rna interference mediated inhibition of the intercellular adhesion molecule 1 (icam-1)gene expression using short interfering nucleic acid (sina) |
| WO2010111490A2 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE THYMIC STROMAL LYMPHOPOIETIN (TSLP) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP2411019A2 (en) | 2009-03-27 | 2012-02-01 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1 (STAT1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP2421834A1 (en) | 2009-04-24 | 2012-02-29 | Glaxo Group Limited | Pyrazole and triazole carboxamides as crac channel inhibitors |
| US8399436B2 (en) | 2009-04-24 | 2013-03-19 | Glaxo Group Limited | N-pyrazolyl carboxamides as CRAC channel inhibitors |
| CA2759476C (en) | 2009-04-30 | 2018-10-09 | Julie Nicole Hamblin | Novel compounds |
| WO2010150014A1 (en) | 2009-06-24 | 2010-12-29 | Pulmagen Therapeutics (Inflammation) Limited | 5r- 5 -deuterated glitazones for respiratory disease treatment |
| PL2453894T3 (pl) | 2009-07-15 | 2016-04-29 | Theravance Biopharma R&D Ip Llc | Postać krystaliczna wolnej zasady związku bifenylowego |
| JP2013508414A (ja) | 2009-10-22 | 2013-03-07 | バーテックス ファーマシューティカルズ インコーポレイテッド | 嚢胞性線維症および他の慢性疾患の治療のための組成物 |
| GB0918924D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Azaindole derivatives |
| GB0918923D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminothiazole derivatives |
| GB0918922D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| WO2011067366A1 (en) | 2009-12-03 | 2011-06-09 | Glaxo Group Limited | Indazole derivatives as pi 3 - kinase inhibitors |
| EP2507226A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Novel compounds |
| EP2507223A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Benzpyrazole derivatives as inhibitors of p13 kinases |
| WO2011084316A2 (en) | 2009-12-16 | 2011-07-14 | 3M Innovative Properties Company | Formulations and methods for controlling mdi particle size delivery |
| WO2011098746A1 (en) | 2010-02-09 | 2011-08-18 | Pulmagen Therapeutics (Inflammation) Limited | Crystalline acid addition salts of ( 5r) -enanti0mer of pioglitazone |
| GB201002224D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
| GB201002243D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
| EP2544676B1 (en) | 2010-03-10 | 2018-09-19 | The United States of America, as represented by The Secretary, Department of Health and Human Services | The use of fenoterol and fenoterol analogues in the treatment of glioblastomas and astrocytomas |
| WO2011110575A1 (en) | 2010-03-11 | 2011-09-15 | Glaxo Group Limited | Derivatives of 2-[2-(benzo- or pyrido-) thiazolylamino]-6-aminopyridine, useful in the treatment of respiratoric, allergic or inflammatory diseases |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| GB201007203D0 (en) | 2010-04-29 | 2010-06-16 | Glaxo Group Ltd | Novel compounds |
| ES2548036T3 (es) | 2010-09-08 | 2015-10-13 | Glaxosmithkline Intellectual Property Development Limited | Polimorfos y sales de N-[5-[4-(5-{[(2R,6S)-2,6-dimetil-4-morfolinil]metil}-1,3-oxazol-2-il)-1H-indazol-6-il]-2-(metiloxi)-3-piridinil]metanosulfonamida |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| WO2012035055A1 (en) | 2010-09-17 | 2012-03-22 | Glaxo Group Limited | Novel compounds |
| GB201016912D0 (en) | 2010-10-07 | 2010-11-24 | Astrazeneca Ab | Novel combination |
| ES2532213T3 (es) | 2010-10-21 | 2015-03-25 | Glaxo Group Limited | Compuestos de pirazol que actúan contra afecciones alérgicas, inmunitarias e inflamatorias |
| JP2013544794A (ja) | 2010-10-21 | 2013-12-19 | グラクソ グループ リミテッド | アレルギー性障害、炎症性障害及び免疫障害に作用するピラゾール化合物 |
| GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
| SG192795A1 (en) | 2011-02-25 | 2013-09-30 | Irm Llc | Compounds and compositions as trk inhibitors |
| US20140005188A1 (en) | 2011-03-11 | 2014-01-02 | Glaxo Group Limited | Pyrido[3,4-b]pyrazine derivatives as syk inhibitors |
| GB201104153D0 (en) | 2011-03-11 | 2011-04-27 | Glaxo Group Ltd | Novel compounds |
| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| US9056867B2 (en) | 2011-09-16 | 2015-06-16 | Novartis Ag | N-substituted heterocyclyl carboxamides |
| CN103946221B (zh) | 2011-09-16 | 2016-08-03 | 诺华股份有限公司 | 用于治疗囊性纤维化的杂环化合物 |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| RS57075B1 (sr) | 2013-03-15 | 2018-06-29 | Verona Pharma Plc | Kombinacija leka |
| AU2014336250A1 (en) | 2013-10-17 | 2016-04-14 | Glaxosmithkline Intellectual Property Development Limited | PI3K inhibitor for treatment of respiratory disease |
| JP6475707B2 (ja) | 2013-10-17 | 2019-02-27 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | 呼吸器疾患の治療のためのｐｉ３ｋ阻害剤 |
| BR112016024533A8 (pt) | 2014-04-24 | 2021-03-30 | Novartis Ag | derivados de amino pirazina como inibidores de fosfatidilinositol 3-cinase ou sal, seu uso, e composição e combinação farmacêuticas |
| WO2015162461A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| KR20160145780A (ko) | 2014-04-24 | 2016-12-20 | 노파르티스 아게 | 포스파티딜이노시톨 3-키나제 억제제로서의 아미노 피리딘 유도체 |
| US20170100385A1 (en) | 2014-05-12 | 2017-04-13 | Glaxosmithkline Intellectual Property (No. 2) Limited | Pharmaceutical compositions comprising danirixin for treating infectious diseases |
| GB201602527D0 (en) | 2016-02-12 | 2016-03-30 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| EP3497100A1 (en) | 2016-08-08 | 2019-06-19 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds |
| GB201706102D0 (en) | 2017-04-18 | 2017-05-31 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| GB201712081D0 (en) | 2017-07-27 | 2017-09-13 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| BR112021024668A2 (pt) | 2019-06-10 | 2022-05-31 | Novartis Ag | Derivado de piridina e pirazina para o tratamento de fc, dpoc e bronquiectasia |
| KR20220052934A (ko) | 2019-08-28 | 2022-04-28 | 노파르티스 아게 | 치환 1,3-페닐 헤테로아릴 유도체 및 질환 치료에서의 이의 용도 |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3994974A (en) * | 1972-02-05 | 1976-11-30 | Yamanouchi Pharmaceutical Co., Ltd. | α-Aminomethylbenzyl alcohol derivatives |
| CY1308A (en) | 1979-12-06 | 1985-12-06 | Glaxo Group Ltd | Device for dispensing medicaments |
| EP0069715B1 (en) | 1981-07-08 | 1986-11-05 | Aktiebolaget Draco | Powder inhalator |
| AT396333B (de) | 1982-10-08 | 1993-08-25 | Glaxo Group Ltd | Vorrichtung zur verabreichung von medikamenten an patienten, einrichtung mit mehreren solchen vorrichtungen und traeger mit medikamentbehaeltern hiefuer |
| GB2169265B (en) | 1982-10-08 | 1987-08-12 | Glaxo Group Ltd | Pack for medicament |
| ZW6584A1 (en) * | 1983-04-18 | 1985-04-17 | Glaxo Group Ltd | Phenethanolamine derivatives |
| US4853381A (en) * | 1984-04-17 | 1989-08-01 | Glaxo Group Limited | Ethanolamine compounds |
| DE3571808D1 (en) | 1984-04-17 | 1989-08-31 | Glaxo Group Ltd | Ethanolamine compounds |
| FR2562889B1 (fr) * | 1984-04-17 | 1988-10-28 | Glaxo Group Ltd | Composes de phenethanolamine. procede pour leur preparation et compositions pharmaceutiques les comprenant |
| GB8426200D0 (en) * | 1984-10-17 | 1984-11-21 | Glaxo Holdings Ltd | Chemical compounds |
| IL75794A (en) | 1984-07-13 | 1989-01-31 | Glaxo Group Ltd | 2-hydroxy-5-(1-hydroxy-2-(aralkyloxyalkylamino)ethyl)aniline derivatives,their preparation and pharmaceutical compositions containing them |
| DK163640C (da) | 1985-07-30 | 1992-08-17 | Glaxo Group Ltd | Apparat til administrering af medikamenter |
| EP0223410A3 (en) | 1985-10-16 | 1987-11-19 | Glaxo Group Limited | Ethanolamine derivatives |
| GB8525483D0 (en) | 1985-10-16 | 1985-11-20 | Glaxo Group Ltd | Chemical compounds |
| EP0220054A3 (en) | 1985-10-16 | 1987-12-02 | Glaxo Group Limited | Ethanolamine derivatives |
| JPS6485964A (en) * | 1987-03-12 | 1989-03-30 | Glaxo Group Ltd | Compound |
| GB8718940D0 (en) * | 1987-08-11 | 1987-09-16 | Glaxo Group Ltd | Chemical compounds |
| JPH0228141A (ja) * | 1987-11-13 | 1990-01-30 | Glaxo Group Ltd | フェネタノールアミン誘導体 |
| GB8909273D0 (en) * | 1989-04-24 | 1989-06-07 | Glaxo Group Ltd | Chemical compounds |
| IL95590A (en) | 1989-09-08 | 1996-06-18 | Glaxo Group Ltd | Medicinal preparations containing Salmetrol and Pluticasone Propionate |
| GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| WO1993019749A1 (en) * | 1992-04-02 | 1993-10-14 | Smithkline Beecham Corporation | Compounds useful for treating allergic and inflammatory diseases |
| GB9313574D0 (en) | 1993-07-01 | 1993-08-18 | Glaxo Group Ltd | Medicaments |
| WO1999016766A1 (en) | 1997-10-01 | 1999-04-08 | Kyowa Hakko Kogyo Co., Ltd. | Benzodioxole derivatives |
| SI1070056T1 (en) | 1998-03-14 | 2004-12-31 | Altana Pharma Ag | Phthalazinone pde iii/iv inhibitors |
| SI1212089T1 (sl) | 1999-08-21 | 2006-08-31 | Altana Pharma Ag | Sinergisticna kombinacija roflumilasta in salmeterola |
-
2002
- 2002-03-20 ES ES02730035T patent/ES2296923T3/es not_active Expired - Lifetime
- 2002-03-20 JP JP2002576195A patent/JP4143413B2/ja not_active Expired - Fee Related
- 2002-03-20 AT AT02730035T patent/ATE381537T1/de not_active IP Right Cessation
- 2002-03-20 WO PCT/EP2002/003122 patent/WO2002076933A1/en not_active Ceased
- 2002-03-20 US US10/472,343 patent/US7045658B2/en not_active Expired - Fee Related
- 2002-03-20 EP EP02730035A patent/EP1370521B1/en not_active Expired - Lifetime
- 2002-03-20 DE DE60224172T patent/DE60224172T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20040157830A1 (en) | 2004-08-12 |
| DE60224172T2 (de) | 2008-12-04 |
| US7045658B2 (en) | 2006-05-16 |
| ES2296923T3 (es) | 2008-05-01 |
| EP1370521A1 (en) | 2003-12-17 |
| JP2004538259A (ja) | 2004-12-24 |
| EP1370521B1 (en) | 2007-12-19 |
| WO2002076933A1 (en) | 2002-10-03 |
| ATE381537T1 (de) | 2008-01-15 |
| DE60224172D1 (de) | 2008-01-31 |
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