EA007745B1 - Способ получения ивабрадина - Google Patents
Способ получения ивабрадина Download PDFInfo
- Publication number
- EA007745B1 EA007745B1 EA200500238A EA200500238A EA007745B1 EA 007745 B1 EA007745 B1 EA 007745B1 EA 200500238 A EA200500238 A EA 200500238A EA 200500238 A EA200500238 A EA 200500238A EA 007745 B1 EA007745 B1 EA 007745B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- formula
- accordance
- compound
- synthesis method
- compounds
- Prior art date
Links
- 229960003825 ivabradine Drugs 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 title claims description 9
- 238000003786 synthesis reaction Methods 0.000 title claims description 9
- 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 title 1
- 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 claims abstract description 32
- 229960000504 ivabradine hydrochloride Drugs 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 5
- 150000004677 hydrates Chemical class 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 50
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000001308 synthesis method Methods 0.000 claims description 12
- 238000005984 hydrogenation reaction Methods 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000033764 rhythmic process Effects 0.000 claims description 6
- CZLMRJZAHXYRIX-UHFFFAOYSA-N 1,3-dioxepane Chemical group C1CCOCOC1 CZLMRJZAHXYRIX-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 230000000059 bradycardiac effect Effects 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 208000031225 myocardial ischemia Diseases 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 230000007170 pathology Effects 0.000 claims description 2
- HGGNZMUHOHGHBJ-UHFFFAOYSA-N dioxepane Chemical group C1CCOOCC1 HGGNZMUHOHGHBJ-UHFFFAOYSA-N 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000007809 chemical reaction catalyst Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 229910002651 NO3 Inorganic materials 0.000 description 6
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000005913 hydroamination reaction Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- -1 malic Chemical compound 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000003245 coal Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 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
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- RXKTVGMZJMDNLF-UHFFFAOYSA-N 7,8-dimethoxy-1,2,3,5-tetrahydro-3-benzazepin-4-one Chemical compound C1CNC(=O)CC2=C1C=C(OC)C(OC)=C2 RXKTVGMZJMDNLF-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 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
-
- E—FIXED CONSTRUCTIONS
- E01—CONSTRUCTION OF ROADS, RAILWAYS, OR BRIDGES
- E01C—CONSTRUCTION OF, OR SURFACES FOR, ROADS, SPORTS GROUNDS, OR THE LIKE; MACHINES OR AUXILIARY TOOLS FOR CONSTRUCTION OR REPAIR
- E01C11/00—Details of pavings
- E01C11/16—Reinforcements
- E01C11/165—Reinforcements particularly for bituminous or rubber- or plastic-bound pavings
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Architecture (AREA)
- Civil Engineering (AREA)
- Structural Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0403830A FR2868777B1 (fr) | 2004-04-13 | 2004-04-13 | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200500238A1 EA200500238A1 (ru) | 2005-10-27 |
| EA007745B1 true EA007745B1 (ru) | 2006-12-29 |
Family
ID=34941959
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200500238A EA007745B1 (ru) | 2004-04-13 | 2005-02-21 | Способ получения ивабрадина |
Country Status (43)
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2473544C2 (ru) * | 2007-05-30 | 2013-01-27 | Инд-Свифт Лабораториз Лимитед | Способ получения ивабрадина гидрохлорида и его полиморфных модификаций |
| EA020735B1 (ru) * | 2011-02-14 | 2015-01-30 | Ле Лаборатуар Сервье | Новый способ синтеза ивабрадина и его фармацевтически приемлемых кислотно-аддитивных солей |
| EA021713B1 (ru) * | 2011-12-20 | 2015-08-31 | Ле Лаборатуар Сервье | Новый способ синтеза ивабрадина и его фармацевтически приемлемых кислотно-аддитивных солей |
| EA022774B1 (ru) * | 2012-03-27 | 2016-02-29 | Ле Лаборатуар Сервье | Способ синтеза ивабрадина и его аддитивных солей с фармацевтически приемлемой кислотой |
| EA026510B1 (ru) * | 2011-12-20 | 2017-04-28 | Ле Лаборатуар Сервье | Новый способ синтеза ивабрадина и его фармацевтически приемлемых кислотно-аддитивных солей |
| RU2658824C2 (ru) * | 2014-01-06 | 2018-06-25 | Бейджинг Лунарсан Фармасьютикал Ко., Лтд. | S-кристаллическая форма хлористоводородного ивабрадина, способ ее получения и фармацевтическая композиция на основе этой формы |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| FR2868775B1 (fr) * | 2004-04-13 | 2008-04-11 | Servier Lab | Nouveau procede de synthese de derives de la 1,3,4,5- tetrahydro-2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2882556B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2882553B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline beta du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2882554B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2882555B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2891826B1 (fr) * | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline 6 du chlorhydrate de l'ivabradine, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
| FR2891827B1 (fr) * | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline deltad du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2894826B1 (fr) * | 2005-12-21 | 2010-10-22 | Servier Lab | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur calcique et les compositions pharmaceutiques qui la contiennent |
| WO2008065681A2 (en) * | 2006-11-30 | 2008-06-05 | Cadila Healthcare Limited | Process for preparation of ivabradine hydrochloride |
| WO2008125006A1 (fr) * | 2007-04-12 | 2008-10-23 | Utopharm (Shanghai) Co., Ltd | Procédés de préparation du chlorhydrate d'ivabradine et de sa forme cristalline stable |
| SI22750A (sl) * | 2008-04-07 | 2009-10-31 | Krka D.D. | Ivabradin hidrobromid |
| FR2932800B1 (fr) * | 2008-06-20 | 2015-02-20 | Servier Lab | Nouveau procede de synthese de la 7,8-dimethoxy-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 |
| FR2933975B1 (fr) | 2008-07-17 | 2011-02-18 | Servier Lab | Nouveau procede de preparation de benzocyclobutenes fonctionnalises,et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable. |
| FR2935381B1 (fr) * | 2008-08-29 | 2010-12-17 | Servier Lab | Nouveau procede de resolution des enantiomerees du (3,4-dimethoxy-bicyclo°4.2.0!octa-1,3,5-trien-7-yl)nitrile et application a la synthese de l'ivabradine |
| CN101723897B (zh) * | 2008-10-31 | 2011-11-16 | 齐鲁制药有限公司 | 伊伐布雷定的合成方法 |
| WO2010072409A1 (en) | 2008-12-22 | 2010-07-01 | Krka, D. D., Novo Mesto | Process for preparation of ivabradine |
| FR2940287B1 (fr) * | 2008-12-24 | 2010-12-24 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable. |
| CN101768117B (zh) * | 2008-12-29 | 2014-05-07 | 北京德众万全药物技术开发有限公司 | 一种盐酸伊伐布雷定晶型及其制备方法 |
| CN101768116B (zh) * | 2008-12-29 | 2014-06-18 | 北京德众万全药物技术开发有限公司 | 一种伊伐布雷定的制备方法 |
| FR2941695B1 (fr) * | 2009-02-04 | 2011-02-18 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| ME00987B (me) * | 2009-03-31 | 2012-06-20 | Servier Lab | Novi postupak sinteze ivabradina i njegovih soli sa farmaceutski prihvatljivom kiselinom |
| FR2943668B1 (fr) * | 2009-03-31 | 2011-05-06 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable. |
| WO2010128525A2 (en) | 2009-05-04 | 2010-11-11 | Dinesh Shantilal Patel | A formulation of ivabradine for treating the cardiovascular disease |
| PL2902384T3 (pl) | 2010-02-12 | 2018-04-30 | Krka, D.D., Novo Mesto | Postać chlorowodorku iwabradyny |
| 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 |
| WO2011104723A2 (en) * | 2010-02-23 | 2011-09-01 | Ind-Swift Laboratories Limited | Acid addition salts of ivabradine and preparation thereof |
| HUP1000245A2 (en) | 2010-05-07 | 2011-11-28 | Richter Gedeon Nyrt | Industrial process for the production ivabradin salts |
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| RU2473544C2 (ru) * | 2007-05-30 | 2013-01-27 | Инд-Свифт Лабораториз Лимитед | Способ получения ивабрадина гидрохлорида и его полиморфных модификаций |
| EA020735B1 (ru) * | 2011-02-14 | 2015-01-30 | Ле Лаборатуар Сервье | Новый способ синтеза ивабрадина и его фармацевтически приемлемых кислотно-аддитивных солей |
| EA021713B1 (ru) * | 2011-12-20 | 2015-08-31 | Ле Лаборатуар Сервье | Новый способ синтеза ивабрадина и его фармацевтически приемлемых кислотно-аддитивных солей |
| EA026510B1 (ru) * | 2011-12-20 | 2017-04-28 | Ле Лаборатуар Сервье | Новый способ синтеза ивабрадина и его фармацевтически приемлемых кислотно-аддитивных солей |
| EA022774B1 (ru) * | 2012-03-27 | 2016-02-29 | Ле Лаборатуар Сервье | Способ синтеза ивабрадина и его аддитивных солей с фармацевтически приемлемой кислотой |
| RU2658824C2 (ru) * | 2014-01-06 | 2018-06-25 | Бейджинг Лунарсан Фармасьютикал Ко., Лтд. | S-кристаллическая форма хлористоводородного ивабрадина, способ ее получения и фармацевтическая композиция на основе этой формы |
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