NO329438B1 - Ny fremgangsmate for syntesen av 1,3-dihydro-2H-3-benzazepin-2-onforbindelser, og anvendelse i syntesen av ivabradin og addisjonssalter derav med en farmasoytisk akseptabel syre - Google Patents
Ny fremgangsmate for syntesen av 1,3-dihydro-2H-3-benzazepin-2-onforbindelser, og anvendelse i syntesen av ivabradin og addisjonssalter derav med en farmasoytisk akseptabel syre Download PDFInfo
- Publication number
- NO329438B1 NO329438B1 NO20050885A NO20050885A NO329438B1 NO 329438 B1 NO329438 B1 NO 329438B1 NO 20050885 A NO20050885 A NO 20050885A NO 20050885 A NO20050885 A NO 20050885A NO 329438 B1 NO329438 B1 NO 329438B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- synthesis method
- synthesis
- dioxane
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 13
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 13
- WUYVQJOTPXVUIS-UHFFFAOYSA-N 1,3-dihydro-3-benzazepin-2-one Chemical class C1=CNC(=O)CC2=CC=CC=C21 WUYVQJOTPXVUIS-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960003825 ivabradine Drugs 0.000 claims abstract description 10
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 150000004677 hydrates Chemical class 0.000 claims abstract description 3
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical compound C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 ACRHBAYQBXXRTO-OAQYLSRUSA-N 0.000 claims abstract 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims 9
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- HLUKNZUABFFNQS-ZMBIFBSDSA-N ivabradine hydrochloride Chemical compound Cl.C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 HLUKNZUABFFNQS-ZMBIFBSDSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000005595 deprotonation Effects 0.000 description 3
- 238000010537 deprotonation reaction Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- -1 1,3-dihydro-2H-3-benzazepin-2-one compound Chemical class 0.000 description 1
- NPAQKATYYLLTKM-UHFFFAOYSA-N 3-[2-(1,3-dioxolan-2-yl)ethyl]-7,8-dimethoxy-1h-3-benzazepin-2-one Chemical compound C1=CC=2C=C(OC)C(OC)=CC=2CC(=O)N1CCC1OCCO1 NPAQKATYYLLTKM-UHFFFAOYSA-N 0.000 description 1
- FFDNRFMIOVQZMT-UHFFFAOYSA-N 3-chloropropanal Chemical compound ClCCC=O FFDNRFMIOVQZMT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- ZETHHMPKDUSZQQ-UHFFFAOYSA-N Betulafolienepentol Natural products C1C=C(C)CCC(C(C)CCC=C(C)C)C2C(OC)OC(OC)C2=C1 ZETHHMPKDUSZQQ-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- PCSMJKASWLYICJ-UHFFFAOYSA-N Succinic aldehyde Chemical compound O=CCCC=O PCSMJKASWLYICJ-UHFFFAOYSA-N 0.000 description 1
- 206010042600 Supraventricular arrhythmias Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000000059 bradycardiac effect Effects 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical class [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- HEOKFDGOFROELJ-UHFFFAOYSA-N diacetal Natural products COc1ccc(C=C/c2cc(O)cc(OC3OC(COC(=O)c4cc(O)c(O)c(O)c4)C(O)C(O)C3O)c2)cc1O HEOKFDGOFROELJ-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960000504 ivabradine hydrochloride Drugs 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0403829A FR2868776B1 (fr) | 2004-04-13 | 2004-04-13 | Nouveau procede de synthese de derives de la 1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20050885D0 NO20050885D0 (no) | 2005-02-18 |
| NO20050885L NO20050885L (no) | 2005-10-14 |
| NO329438B1 true NO329438B1 (no) | 2010-10-18 |
Family
ID=34941960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20050885A NO329438B1 (no) | 2004-04-13 | 2005-02-18 | Ny fremgangsmate for syntesen av 1,3-dihydro-2H-3-benzazepin-2-onforbindelser, og anvendelse i syntesen av ivabradin og addisjonssalter derav med en farmasoytisk akseptabel syre |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US7074920B2 (ja) |
| EP (1) | EP1589014B1 (ja) |
| JP (2) | JP4511970B2 (ja) |
| KR (1) | KR100636500B1 (ja) |
| CN (1) | CN1332951C (ja) |
| AR (1) | AR047686A1 (ja) |
| AT (1) | ATE375339T1 (ja) |
| AU (1) | AU2005200860B2 (ja) |
| BR (1) | BRPI0500478B8 (ja) |
| CA (1) | CA2496721C (ja) |
| CY (1) | CY1107101T1 (ja) |
| DE (1) | DE602005002776T2 (ja) |
| DK (1) | DK1589014T3 (ja) |
| EA (1) | EA007744B1 (ja) |
| ES (1) | ES2294652T3 (ja) |
| FR (1) | FR2868776B1 (ja) |
| GE (1) | GEP20074137B (ja) |
| HK (1) | HK1079776A1 (ja) |
| HR (1) | HRP20070503T3 (ja) |
| MA (1) | MA27599A1 (ja) |
| ME (1) | ME01402B (ja) |
| MX (1) | MXPA05003695A (ja) |
| MY (1) | MY141223A (ja) |
| NO (1) | NO329438B1 (ja) |
| NZ (1) | NZ538327A (ja) |
| PL (1) | PL1589014T3 (ja) |
| PT (1) | PT1589014E (ja) |
| RS (1) | RS50546B (ja) |
| SG (1) | SG116573A1 (ja) |
| SI (1) | SI1589014T1 (ja) |
| UA (1) | UA81772C2 (ja) |
| WO (1) | WO2005111026A1 (ja) |
| ZA (1) | ZA200501467B (ja) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2868777B1 (fr) * | 2004-04-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2868776B1 (fr) * | 2004-04-13 | 2008-04-18 | Servier Lab | Nouveau procede de synthese de derives de la 1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| EP2162438A4 (en) | 2007-05-30 | 2011-07-06 | Ind Swift Lab Ltd | PROCESS FOR THE PREPARATION OF IVABRADINE HYDROCHLORIDE AND CORRESPONDING POLYMORPHIDE |
| ES2402765T3 (es) | 2008-12-22 | 2013-05-08 | Krka, D.D., Novo Mesto | Procedimiento de preparación de ivabradina |
| EA201290772A1 (ru) | 2010-02-12 | 2013-02-28 | КРКА, д.д., НОВО МЕСТО | Новые формы ивабрадина гидрохлорида |
| FR2956401B1 (fr) * | 2010-02-17 | 2012-02-03 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2984320B1 (fr) * | 2011-12-20 | 2013-11-29 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4490369A (en) * | 1981-05-19 | 1984-12-25 | Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung | Benzazepine derivatives, their pharmaceutical compositions and method of use |
| DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3242599A1 (de) * | 1982-11-18 | 1984-05-24 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| DE3418270A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue aminotetralinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| EP0204349A3 (de) * | 1985-06-01 | 1990-01-03 | Dr. Karl Thomae GmbH | Neue heteroaromatische Aminderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE3519735A1 (de) * | 1985-06-01 | 1986-12-04 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue heteroaromatische aminderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3717561A1 (de) * | 1987-05-25 | 1988-12-08 | Thomae Gmbh Dr K | Indol-, isochinolin- und benzazepinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| JP2568416B2 (ja) * | 1986-11-04 | 1997-01-08 | 大塚製薬株式会社 | ヒドロフルオレン誘導体 |
| JPH0495078A (ja) * | 1990-08-08 | 1992-03-27 | Nippon Shoji Kk | ピリミドン誘導体の製造法、そのための中間体 |
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| TW279860B (ja) * | 1993-11-12 | 1996-07-01 | Ciba Geigy Ag | |
| FR2868776B1 (fr) * | 2004-04-13 | 2008-04-18 | Servier Lab | Nouveau procede de synthese de derives de la 1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2868777B1 (fr) * | 2004-04-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
-
2004
- 2004-04-13 FR FR0403829A patent/FR2868776B1/fr not_active Expired - Fee Related
-
2005
- 2005-02-07 CA CA2496721A patent/CA2496721C/fr active Active
- 2005-02-14 US US11/057,491 patent/US7074920B2/en active Active
- 2005-02-15 SG SG200500769A patent/SG116573A1/en unknown
- 2005-02-17 BR BRPI0500478A patent/BRPI0500478B8/pt active IP Right Grant
- 2005-02-18 GE GEAP8648A patent/GEP20074137B/en unknown
- 2005-02-18 MY MYPI20050622A patent/MY141223A/en unknown
- 2005-02-18 NZ NZ538327A patent/NZ538327A/en unknown
- 2005-02-18 NO NO20050885A patent/NO329438B1/no unknown
- 2005-02-18 AU AU2005200860A patent/AU2005200860B2/en active Active
- 2005-02-18 CN CNB2005100542097A patent/CN1332951C/zh active Active
- 2005-02-18 UA UAA200501523A patent/UA81772C2/uk unknown
- 2005-02-18 AR ARP050100587A patent/AR047686A1/es active IP Right Grant
- 2005-02-18 ZA ZA2005/01467A patent/ZA200501467B/en unknown
- 2005-02-18 JP JP2005041811A patent/JP4511970B2/ja active Active
- 2005-02-18 MA MA28113A patent/MA27599A1/fr unknown
- 2005-02-19 KR KR1020050013871A patent/KR100636500B1/ko active IP Right Grant
- 2005-02-21 EP EP05290382A patent/EP1589014B1/fr active Active
- 2005-02-21 AT AT05290382T patent/ATE375339T1/de active
- 2005-02-21 WO PCT/FR2005/000395 patent/WO2005111026A1/fr active Application Filing
- 2005-02-21 RS RSP-2007/0493A patent/RS50546B/sr unknown
- 2005-02-21 SI SI200530088T patent/SI1589014T1/sl unknown
- 2005-02-21 ME MEP-2007-493A patent/ME01402B/me unknown
- 2005-02-21 DE DE602005002776T patent/DE602005002776T2/de active Active
- 2005-02-21 ES ES05290382T patent/ES2294652T3/es active Active
- 2005-02-21 PL PL05290382T patent/PL1589014T3/pl unknown
- 2005-02-21 PT PT05290382T patent/PT1589014E/pt unknown
- 2005-02-21 DK DK05290382T patent/DK1589014T3/da active
- 2005-02-21 EA EA200500237A patent/EA007744B1/ru unknown
- 2005-04-07 MX MXPA05003695A patent/MXPA05003695A/es active IP Right Grant
- 2005-12-22 HK HK05111842A patent/HK1079776A1/xx unknown
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2007
- 2007-10-29 HR HR20070503T patent/HRP20070503T3/xx unknown
- 2007-12-19 CY CY20071101612T patent/CY1107101T1/el unknown
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2009
- 2009-09-25 JP JP2009220282A patent/JP2010043096A/ja active Pending
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