HRP20120955T1 - Novi postupak za sintetiziranje ivabradina i njegovih adicijskih soli - Google Patents
Novi postupak za sintetiziranje ivabradina i njegovih adicijskih soli Download PDFInfo
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- HRP20120955T1 HRP20120955T1 HRP20120955AT HRP20120955T HRP20120955T1 HR P20120955 T1 HRP20120955 T1 HR P20120955T1 HR P20120955A T HRP20120955A T HR P20120955AT HR P20120955 T HRP20120955 T HR P20120955T HR P20120955 T1 HRP20120955 T1 HR P20120955T1
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- Prior art keywords
- formula
- compound
- acids
- reaction
- synthesis process
- Prior art date
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- 238000000034 method Methods 0.000 title claims 10
- 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 claims 3
- 229960003825 ivabradine Drugs 0.000 title claims 3
- 150000003839 salts Chemical class 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims 17
- 230000015572 biosynthetic process Effects 0.000 claims 9
- 238000003786 synthesis reaction Methods 0.000 claims 9
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims 8
- 238000006243 chemical reaction Methods 0.000 claims 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- 238000007363 ring formation reaction Methods 0.000 claims 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- 238000006722 reduction reaction Methods 0.000 claims 2
- 150000003573 thiols Chemical class 0.000 claims 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 claims 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- 150000000996 L-ascorbic acids Chemical class 0.000 claims 1
- 239000002841 Lewis acid Substances 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims 1
- 229910000564 Raney nickel Inorganic materials 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- COPNMDQMKUUBRE-UHFFFAOYSA-N [I+].[Sm+2] Chemical compound [I+].[Sm+2] COPNMDQMKUUBRE-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 1
- 235000011087 fumaric acid Nutrition 0.000 claims 1
- 150000002238 fumaric acids Chemical class 0.000 claims 1
- 150000002311 glutaric acids Chemical class 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 1
- 150000007517 lewis acids Chemical class 0.000 claims 1
- 235000011090 malic acid Nutrition 0.000 claims 1
- 150000002691 malonic acids Chemical class 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- 150000002913 oxalic acids Chemical class 0.000 claims 1
- 150000004717 pyruvic acids Chemical class 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 235000011044 succinic acid Nutrition 0.000 claims 1
- 150000003444 succinic acids Chemical class 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 claims 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
Classifications
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- 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
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/06—One of the condensed rings being a six-membered aromatic ring the other ring being four-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (12)
1. Postupak sinteze ivabradina formule (I):
[image]
naznačen time, daje spoj formule (VI):
[image]
izložen djelovanju tiola u organskom otapalu kako bi se dobio hemitioacetal formule (VII):
[image]
pri čemu R predstavlja supstituiranu ili nesupstituiranu, po izboru perfluoriniranu, ravnu ili razgrananu alkilnu skupinu, supstituiranu ili nesupstituiranu arilnu skupinu, supstituiranu ili nesupstituirani benzilnu skupinu ili skupinu CH2CO2Et, koja je izložena reakciji ciklizacije kako bi se dobio spoj formule (VIII):
[image]
pri čemu je R ranije gore definiran,
koji je izložen redukcijskoj reakciji kako bi se dobio ivabradin formule (I), koji po izboru može biti konvertiran u njihove adicijske soli s farmaceutski prihvatljivom kiselinom odabranom od klorovodične kiseline, bromovodične kiseline, sumporne kiseline, fosforne kiseline, octene kiseline, trifluoroctene kiseline, mliječne kiseline, piruvinske kiseline, malonske kiseline, sukcinske kiseline, glutarne kiseline, fumarne kiseline, tartarne kiseline, jabučne kiseline, limunske kiseline, askorbinske kiseline, oksalne kiseline, metanesulfonske kiseline, benzenesulfonske kiseline i kamforne kiseline i u njihove hidrate.
2. Postupak sinteze u skladu s patentnim zahtjevom 1, naznačene time, da je organsko otapalo koje je korišteno u reakciji za formiranje hemitioacetala formule (VII) diklormetan.
3. Postupak sinteze u skladu s patentnim zahtjevom bilo 1 ili 2, naznačen time, da tiol koji je reagirao sa spojem formule (VI) je tiofenol.
4. Postupak sinteze u skladu s jednim od patentnih zahtjeva 1 do 3, naznačen time, da je otapalo koje je korišteno u reakciji za ciklizaciju spoja formule (VII) kako bi se dobio spoj formule (VIII) diklormetan.
5. Postupak sinteze u skladu s jednim od patentnih zahtjeva 1 do 4, naznačen time, da reakcija za ciklizaciju spoja formule (VII) kako bi se dobio spoj formule (VIII) se izvodi u nazočnosti reagensa odabranog od octenog anhidrida, trifluoroctenog anhidrida i trimetilsilil trifluorometanesulfonata.
6. Postupak sinteze u skladu s patentnim zahtjevom 5, naznačen time, da se reakcija za ciklizaciju spoja formule (VII) kako bi se dobio spoj formule (VIII) izvodi u nazočnosti trifluoroctenog anhidrida.
7. Postupak sinteze u skladu s patentnim zahtjevom 6, naznačen time, da se reakcija za ciklizaciju spoja formule (VII) kako bi se dobio spoj formule (VIII) izvodi u nazočnosti trifluoroctenog anhidrida i Lewis-ove kiseline odabrane od BF3OEt2, Sc(OTf)3 i Yb(OTf)3.
8. Postupak sinteze u skladu s patentnim zahtjevom 7, naznačen time, da se reakcija za ciklizaciju spoja formule (VII) kako bi se dobio spoj formule (VIII) izvodi u nazočnosti trifluoroctenog anhidrida i BF3.OEt2.
9. Postupak sinteze u skladu s jednim od patentnih zahtjeva 1 to 8, naznačen time, da se reakcija za redukciju spoja formule (VI) izvodi u nazočnosti Raney-ovog nikla u etanolu ili nazočnosti samarij(II) joda u tetrahidrofuranu.
10. Spoj formule (VI):
[image]
11. Spoj formule (VII):
[image]
pri čemu R predstavlja supstituiranu ili nesupstituiranu, po izboru perfluoriranu, ravnu ili razgrananu alkilnu skupinu, supstituiranu ili nesupstituiranu arilnu skupinu, supstituiranu ili nesupstituiranu benzilnu skupinu ili skupinu CH2CO2Et.
12. Spoj formule (VIII):
[image]
pri čemu je R definiran u patentnom zahtjevu 11.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1000657A FR2956401B1 (fr) | 2010-02-17 | 2010-02-17 | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20120955T1 true HRP20120955T1 (hr) | 2012-12-31 |
Family
ID=42133409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20120955AT HRP20120955T1 (hr) | 2010-02-17 | 2012-11-21 | Novi postupak za sintetiziranje ivabradina i njegovih adicijskih soli |
Country Status (36)
| Country | Link |
|---|---|
| US (1) | US8278440B2 (hr) |
| EP (1) | EP2364972B1 (hr) |
| JP (1) | JP5306387B2 (hr) |
| KR (1) | KR101310683B1 (hr) |
| CN (3) | CN102161642B (hr) |
| AR (1) | AR080178A1 (hr) |
| AU (1) | AU2011200403B2 (hr) |
| BR (1) | BRPI1100169A2 (hr) |
| CA (1) | CA2731315C (hr) |
| CL (1) | CL2011000297A1 (hr) |
| CY (1) | CY1113338T1 (hr) |
| DK (1) | DK2364972T3 (hr) |
| EA (1) | EA019373B1 (hr) |
| ES (1) | ES2396042T3 (hr) |
| FR (1) | FR2956401B1 (hr) |
| GE (1) | GEP20135737B (hr) |
| HK (3) | HK1162021A1 (hr) |
| HR (1) | HRP20120955T1 (hr) |
| JO (1) | JO2854B1 (hr) |
| MA (1) | MA32681B1 (hr) |
| ME (1) | ME01464B (hr) |
| MX (1) | MX2011001465A (hr) |
| MY (1) | MY147697A (hr) |
| NZ (1) | NZ590883A (hr) |
| PE (1) | PE20120576A1 (hr) |
| PL (1) | PL2364972T3 (hr) |
| PT (1) | PT2364972E (hr) |
| RS (1) | RS52529B (hr) |
| SA (1) | SA111320199B1 (hr) |
| SG (1) | SG173961A1 (hr) |
| SI (1) | SI2364972T1 (hr) |
| TW (1) | TWI395738B (hr) |
| UA (1) | UA106208C2 (hr) |
| UY (1) | UY33211A (hr) |
| WO (1) | WO2011101558A1 (hr) |
| ZA (1) | ZA201100964B (hr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2950343B1 (fr) * | 2009-09-18 | 2011-11-18 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| CN102566619B (zh) * | 2012-02-07 | 2013-12-25 | 宁波市镇海华泰电器厂 | 噪声式水温控制装置 |
| FR2988720B1 (fr) * | 2012-03-27 | 2014-03-14 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| CN103848789B (zh) * | 2012-11-29 | 2016-05-18 | 江苏恒瑞医药股份有限公司 | 一种伊伐布雷定的制备方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| WO2002051232A2 (en) | 2000-12-27 | 2002-07-04 | Actelion Pharmaceuticals Ltd. | Novel benzazepines and related heterocyclic derivatives |
| AU2003239508A1 (en) * | 2002-05-21 | 2003-12-12 | Bristol-Myers Squibb Company | Indole compounds useful as impdh inhibitors |
| 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 |
| 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 |
| TW200817334A (en) * | 2005-02-07 | 2008-04-16 | Servier Lab | New process for the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid |
| EP2097383B1 (en) * | 2006-11-30 | 2012-02-08 | Cadila Healthcare Limited | Process for preparation of ivabradine hydrochloride |
| CN101284813B (zh) * | 2007-04-12 | 2012-08-15 | 上海优拓医药科技有限公司 | 伊伐布雷定的制备方法 |
| JP5632279B2 (ja) * | 2007-05-30 | 2014-11-26 | アイエヌディー−スイフト ラボラトリーズ リミテッド | 塩酸イバブラジンの調製方法及びポリモルフ |
| CN101544605A (zh) * | 2008-03-24 | 2009-09-30 | 北京深蓝海生物医药科技有限公司 | 伊伐布雷定及其药学上可接受的加成盐的制备方法 |
| 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 |
| WO2010072409A1 (en) | 2008-12-22 | 2010-07-01 | Krka, D. D., Novo Mesto | Process for preparation of ivabradine |
-
2010
- 2010-02-17 FR FR1000657A patent/FR2956401B1/fr not_active Expired - Fee Related
-
2011
- 2011-01-30 JO JO201130A patent/JO2854B1/en active
- 2011-01-31 UY UY33211A patent/UY33211A/es unknown
- 2011-01-31 SG SG2011006848A patent/SG173961A1/en unknown
- 2011-01-31 PE PE2011000106A patent/PE20120576A1/es active IP Right Grant
- 2011-01-31 MY MYPI2011000487A patent/MY147697A/en unknown
- 2011-01-31 AU AU2011200403A patent/AU2011200403B2/en not_active Ceased
- 2011-02-02 NZ NZ590883A patent/NZ590883A/en not_active IP Right Cessation
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