CA2543858C - Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity - Google Patents
Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity Download PDFInfo
- Publication number
- CA2543858C CA2543858C CA2543858A CA2543858A CA2543858C CA 2543858 C CA2543858 C CA 2543858C CA 2543858 A CA2543858 A CA 2543858A CA 2543858 A CA2543858 A CA 2543858A CA 2543858 C CA2543858 C CA 2543858C
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- Prior art keywords
- ylene
- phen
- compound
- alkyl
- formula
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 490
- 230000000694 effects Effects 0.000 title claims description 34
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 title description 24
- 239000000048 adrenergic agonist Substances 0.000 title description 24
- 239000003149 muscarinic antagonist Substances 0.000 title description 21
- 229940126157 adrenergic receptor agonist Drugs 0.000 title description 20
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 title 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 94
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 53
- 239000012453 solvate Substances 0.000 claims abstract description 49
- 230000008569 process Effects 0.000 claims abstract description 27
- 239000000203 mixture Substances 0.000 claims description 139
- 125000000217 alkyl group Chemical group 0.000 claims description 119
- 239000001257 hydrogen Substances 0.000 claims description 95
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- -1 oxiran- 2,3-diyl Chemical group 0.000 claims description 82
- 238000006243 chemical reaction Methods 0.000 claims description 80
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 54
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 125000005843 halogen group Chemical group 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 108060003345 Adrenergic Receptor Proteins 0.000 claims description 35
- 102000017910 Adrenergic receptor Human genes 0.000 claims description 35
- 125000002947 alkylene group Chemical group 0.000 claims description 33
- 231100000491 EC50 Toxicity 0.000 claims description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims description 26
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 125000003386 piperidinyl group Chemical group 0.000 claims description 25
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- 125000000304 alkynyl group Chemical group 0.000 claims description 19
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- 125000004429 atom Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 125000005549 heteroarylene group Chemical group 0.000 claims description 17
- 125000006239 protecting group Chemical group 0.000 claims description 17
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- 125000004450 alkenylene group Chemical group 0.000 claims description 16
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
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- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical group BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 14
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
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- 229910052736 halogen Inorganic materials 0.000 claims description 6
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
- 230000008484 agonism Effects 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 claims description 2
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- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 claims 1
- RLKOVAYLKHPVRF-UHFFFAOYSA-N [1-[3-[4-[2-[2-(4-hydroxy-2-oxo-3h-1,3-benzothiazol-7-yl)ethylamino]ethyl]anilino]-3-oxopropyl]piperidin-4-yl] n-(2-phenylphenyl)carbamate Chemical compound C1=2SC(=O)NC=2C(O)=CC=C1CCNCCC(C=C1)=CC=C1NC(=O)CCN(CC1)CCC1OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 RLKOVAYLKHPVRF-UHFFFAOYSA-N 0.000 claims 1
- YNNXNAUDHNIODM-UHFFFAOYSA-N [1-[3-[4-[[2-(4-hydroxy-2-oxo-3h-1,3-benzothiazol-7-yl)ethylamino]methyl]anilino]-3-oxopropyl]piperidin-4-yl] n-(2-phenylphenyl)carbamate Chemical compound C1=2SC(=O)NC=2C(O)=CC=C1CCNCC(C=C1)=CC=C1NC(=O)CCN(CC1)CCC1OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 YNNXNAUDHNIODM-UHFFFAOYSA-N 0.000 claims 1
- KYUUSUOPYPJUCU-UHFFFAOYSA-N [1-[9-[2-(4-hydroxy-2-oxo-3h-1,3-benzothiazol-7-yl)ethylamino]nonyl]piperidin-4-yl] n-(2-phenylphenyl)carbamate Chemical compound C1=2SC(=O)NC=2C(O)=CC=C1CCNCCCCCCCCCN(CC1)CCC1OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 KYUUSUOPYPJUCU-UHFFFAOYSA-N 0.000 claims 1
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- HKTPUKNSTZKIHB-UHFFFAOYSA-N n-[4-[[2-(4-hydroxy-2-oxo-3h-1,3-benzothiazol-7-yl)ethylamino]methyl]phenyl]-3-[4-[(2-phenylphenyl)carbamoylamino]piperidin-1-yl]propanamide Chemical compound C1=2SC(=O)NC=2C(O)=CC=C1CCNCC(C=C1)=CC=C1NC(=O)CCN(CC1)CCC1NC(=O)NC1=CC=CC=C1C1=CC=CC=C1 HKTPUKNSTZKIHB-UHFFFAOYSA-N 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 19
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
-
- 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
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Document Processing Apparatus (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52423403P | 2003-11-21 | 2003-11-21 | |
| US60/524,234 | 2003-11-21 | ||
| PCT/US2004/038975 WO2005051946A2 (en) | 2003-11-21 | 2004-11-19 | Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2543858A1 CA2543858A1 (en) | 2005-06-09 |
| CA2543858C true CA2543858C (en) | 2014-04-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2543858A Expired - Fee Related CA2543858C (en) | 2003-11-21 | 2004-11-19 | Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
Country Status (9)
| Country | Link |
|---|---|
| US (4) | US7345060B2 (enExample) |
| EP (1) | EP1685118B1 (enExample) |
| JP (2) | JP4851937B2 (enExample) |
| CN (1) | CN100569760C (enExample) |
| AT (1) | ATE435855T1 (enExample) |
| CA (1) | CA2543858C (enExample) |
| DE (1) | DE602004021959D1 (enExample) |
| ES (1) | ES2329586T3 (enExample) |
| WO (1) | WO2005051946A2 (enExample) |
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|---|---|---|---|---|
| US6693202B1 (en) * | 1999-02-16 | 2004-02-17 | Theravance, Inc. | Muscarinic receptor antagonists |
| 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 |
| PE20050250A1 (es) * | 2003-07-17 | 2005-04-08 | Glaxo Group Ltd | Antagonistas de los receptores muscarinicos de la acetilcolina |
| AR048573A1 (es) * | 2003-07-17 | 2006-05-10 | Glaxo Group Ltd | Compuesto de 8-azoniabiciclo[3.2.1]octano sustituido en la posicion 3, composicion farmceutica que lo comprende y su uso para preparar esta ultima |
| PE20050327A1 (es) * | 2003-07-17 | 2005-06-08 | Glaxo Group Ltd | Derivados de 8-azoniabiciclo[3.2.1]octano como antagonistas de los receptores muscarinicos de la acetilcolina |
| JP2007508390A (ja) * | 2003-10-14 | 2007-04-05 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| AU2004281167A1 (en) * | 2003-10-17 | 2005-04-28 | Glaxo Group Limited | Muscarinic acetylcholine receptor antagonists field of the invention |
| PE20050489A1 (es) * | 2003-11-04 | 2005-09-02 | Glaxo Group Ltd | Antagonistas de receptores de acetilcolina muscarinicos |
| ES2329586T3 (es) * | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
| WO2005087736A1 (en) * | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2005087236A1 (en) * | 2004-03-11 | 2005-09-22 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
| TWI341836B (en) * | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2005087735A1 (en) | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| EP1723108A1 (en) * | 2004-03-11 | 2006-11-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200538095A (en) * | 2004-03-11 | 2005-12-01 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7524962B2 (en) * | 2004-03-11 | 2009-04-28 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| JP2007528410A (ja) * | 2004-03-11 | 2007-10-11 | セラヴァンス， インコーポレーテッド | ムスカリンレセプターアンタゴニストとしての有用なビフェニル化合物 |
| MY144753A (en) | 2004-04-27 | 2011-10-31 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| WO2005112644A2 (en) * | 2004-05-13 | 2005-12-01 | Glaxo Group Limited | Muscarinic acetylcholine receptor antagonists |
| JP2008510015A (ja) * | 2004-08-16 | 2008-04-03 | セラヴァンス， インコーポレーテッド | β２アドレナリン作用性レセプターアゴニスト活性およびムスカリン性レセプターアンタゴニスト活性を有する化合物 |
| WO2006023457A1 (en) * | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| JP2008533028A (ja) * | 2005-03-10 | 2008-08-21 | セラヴァンス， インコーポレーテッド | ムスカリン性受容体アンタゴニストとして有用なビフェニル化合物 |
| US7659403B2 (en) * | 2005-03-10 | 2010-02-09 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200714587A (en) * | 2005-03-10 | 2007-04-16 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2006099031A1 (en) * | 2005-03-10 | 2006-09-21 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7642355B2 (en) * | 2005-03-10 | 2010-01-05 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| JP2008546695A (ja) | 2005-06-13 | 2008-12-25 | セラヴァンス， インコーポレーテッド | ムスカリン受容体アンタゴニストとして有用なビフェニル化合物 |
| US8429052B2 (en) * | 2005-07-19 | 2013-04-23 | Lincoln National Life Insurance Company | Method and system for providing employer-sponsored retirement plan |
| JP2009503099A (ja) * | 2005-08-02 | 2009-01-29 | グラクソ グループ リミテッド | Ｍ３ムスカリン性アセチルコリン受容体アンタゴニスト |
| EP1937230A4 (en) * | 2005-08-02 | 2009-08-26 | Glaxo Group Ltd | M3-MUSCARIN ACETYLCHOLIN RECEPTOR ANTAGONISTS |
| JP2009504768A (ja) * | 2005-08-18 | 2009-02-05 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| GB0602778D0 (en) * | 2006-02-10 | 2006-03-22 | Glaxo Group Ltd | Novel compound |
| TW200811105A (en) | 2006-04-25 | 2008-03-01 | Theravance Inc | Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| TW200811104A (en) * | 2006-04-25 | 2008-03-01 | Theravance Inc | Crystalline forms of a dimethylphenyl compound |
| TW201036957A (en) | 2009-02-20 | 2010-10-16 | Astrazeneca Ab | Novel salt 628 |
| US8519138B2 (en) * | 2009-04-14 | 2013-08-27 | Glaxo Group Limited | Process for the preparation of a biphenyl-2-yl carbamic acid ester |
| PT3111927T (pt) | 2009-05-29 | 2020-03-03 | Pearl Therapeutics Inc | Composições para administração respiratória de agentes ativos e métodos e sistemas associados |
| GB0913342D0 (en) * | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | Compounds - 801 |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| WO2011081937A1 (en) | 2009-12-15 | 2011-07-07 | Gilead Sciences, Inc. | Corticosteroid-beta-agonist-muscarinic antagonist compounds for use in therapy |
| RS54201B1 (sr) * | 2010-07-13 | 2015-12-31 | Theravance Biopharma R&D Ip, Llc | Postupak za pripremu bifenil-2-ilkarbaminske kiseline |
| WO2012032546A2 (en) * | 2010-09-08 | 2012-03-15 | Cadila Healthcare Limited | Process for the preparation of salmeterol and its intermediates |
| GB201016912D0 (en) | 2010-10-07 | 2010-11-24 | Astrazeneca Ab | Novel combination |
| CN105106200A (zh) * | 2011-05-17 | 2015-12-02 | 珍珠治疗公司 | 用于呼吸递送两种或多种活性剂的组合物、方法和系统 |
| RS54365B1 (sr) | 2011-06-10 | 2016-04-28 | Chiesi Farmaceutici S.P.A. | Jedinjenja koja imaju aktivnost antagonista muskarinskih receptora i agonist beta2 adrenergičnog receptora |
| RU2606121C2 (ru) | 2011-06-10 | 2017-01-10 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Соединения, обладающие антагонистической активностью в отношении мускариновых рецепторов и агонистической активностью в отношении бета2-адренорецепторов |
| JO3192B1 (ar) | 2011-09-06 | 2018-03-08 | Novartis Ag | مركب بنزوثيازولون |
| CN104854105B (zh) | 2012-12-06 | 2017-05-17 | 奇斯药制品公司 | 具有毒蕈碱受体拮抗剂和β2肾上腺素能受体激动剂活性的化合物 |
| HRP20180915T1 (hr) | 2012-12-06 | 2018-07-27 | Chiesi Farmaceutici S.P.A. | Spojevi koji imaju aktivnost kao antagonist muskarinskog receptora i kao agonist beta2 adrenergijskog receptora |
| TWI703138B (zh) | 2015-02-12 | 2020-09-01 | 義大利商吉斯藥品公司 | 具有蕈毒鹼受體拮抗劑及β２腎上腺素受體促效劑活性之化合物 |
| CN107074816B (zh) * | 2015-03-27 | 2020-07-17 | 四川海思科制药有限公司 | 一种杂环衍生物及其制备方法和在医药上的用途 |
| AR104828A1 (es) | 2015-06-01 | 2017-08-16 | Chiesi Farm Spa | COMPUESTOS CON ACTIVIDAD ANTAGONISTA DE LOS RECEPTORES MUSCARÍNICOS Y ACTIVIDAD AGONISTA DEL RECEPTOR b2 ADRENÉRGICO |
| WO2017093208A1 (en) | 2015-12-03 | 2017-06-08 | Chiesi Farmaceutici S.P.A. | Compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| CN107849035B (zh) * | 2015-12-29 | 2021-12-10 | 四川海思科制药有限公司 | 一种苯基杂环衍生物及其在医药上的用途 |
| KR20180100106A (ko) * | 2016-01-22 | 2018-09-07 | 스촨 하이스코 파마수티컬 씨오., 엘티디 | 질소함유 헤테로 고리 아미드 유도체 및 그 제조방법과 약학적 용도 |
| WO2018011090A1 (en) | 2016-07-13 | 2018-01-18 | Chiesi Farmaceutici S.P.A. | Hydroxyquinolinone compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| ES2836113T3 (es) | 2016-12-14 | 2021-06-24 | Beijing Showby Pharmaceutical Co Ltd | Clase de compuestos bifuncionales con estructura de sal de amonio cuaternario |
| CN106632257B (zh) * | 2016-12-15 | 2019-02-12 | 上海市奉贤区中心医院 | Gsk961081及其中间体的合成方法 |
| WO2019015639A1 (zh) * | 2017-07-21 | 2019-01-24 | 四川海思科制药有限公司 | 一种氮杂环酰胺衍生物组合物及其制备 |
| WO2019015640A1 (zh) * | 2017-07-21 | 2019-01-24 | 四川海思科制药有限公司 | 一种氮杂环酰胺衍生物的盐、其晶型及其制备方法和用途 |
| CN111423434A (zh) * | 2019-01-09 | 2020-07-17 | 四川海思科制药有限公司 | 一种碳酰胺衍生物及其制备方法 |
| CN115093365B (zh) * | 2022-07-25 | 2023-07-25 | 沈阳药科大学 | 一种雷芬那辛的合成方法 |
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| SE9900693D0 (sv) | 1999-02-26 | 1999-02-26 | Astra Pharma Prod | Novel process |
| DE19921693A1 (de) * | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
| SE9902936D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| SE9902938D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| SE9902937D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| SE9902935D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| UA73543C2 (uk) | 1999-12-07 | 2005-08-15 | Тераванс, Інк. | Похідні сечовини, фармацевтична композиція та застосування похідного при приготуванні лікарського засобу для лікування захворювання, яке опосередковується мускариновим рецептором |
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-
2004
- 2004-11-19 ES ES04811663T patent/ES2329586T3/es not_active Expired - Lifetime
- 2004-11-19 WO PCT/US2004/038975 patent/WO2005051946A2/en not_active Ceased
- 2004-11-19 DE DE602004021959T patent/DE602004021959D1/de not_active Expired - Lifetime
- 2004-11-19 CA CA2543858A patent/CA2543858C/en not_active Expired - Fee Related
- 2004-11-19 AT AT04811663T patent/ATE435855T1/de not_active IP Right Cessation
- 2004-11-19 CN CNB2004800342018A patent/CN100569760C/zh not_active Expired - Fee Related
- 2004-11-19 EP EP04811663A patent/EP1685118B1/en not_active Expired - Lifetime
- 2004-11-19 US US10/992,927 patent/US7345060B2/en not_active Expired - Fee Related
- 2004-11-19 JP JP2006541552A patent/JP4851937B2/ja not_active Expired - Fee Related
-
2007
- 2007-12-11 US US12/001,363 patent/US7838535B2/en not_active Expired - Fee Related
- 2007-12-11 US US12/001,362 patent/US7842704B2/en not_active Expired - Fee Related
-
2010
- 2010-10-13 US US12/903,365 patent/US8247564B2/en not_active Expired - Fee Related
-
2011
- 2011-05-30 JP JP2011121065A patent/JP2011190271A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005051946A2 (en) | 2005-06-09 |
| ES2329586T3 (es) | 2009-11-27 |
| US7345060B2 (en) | 2008-03-18 |
| US8247564B2 (en) | 2012-08-21 |
| CN1882556A (zh) | 2006-12-20 |
| DE602004021959D1 (de) | 2009-08-20 |
| EP1685118A2 (en) | 2006-08-02 |
| US20080096911A1 (en) | 2008-04-24 |
| US20050113417A1 (en) | 2005-05-26 |
| JP2011190271A (ja) | 2011-09-29 |
| CA2543858A1 (en) | 2005-06-09 |
| CN100569760C (zh) | 2009-12-16 |
| US7838535B2 (en) | 2010-11-23 |
| WO2005051946A3 (en) | 2005-07-14 |
| JP2007514662A (ja) | 2007-06-07 |
| EP1685118B1 (en) | 2009-07-08 |
| US20080097105A1 (en) | 2008-04-24 |
| JP4851937B2 (ja) | 2012-01-11 |
| US7842704B2 (en) | 2010-11-30 |
| US20110034694A1 (en) | 2011-02-10 |
| ATE435855T1 (de) | 2009-07-15 |
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