HRP20100679T1 - Novi postupak za resoluciju enantiomera (3,4-dimetoksi-biciklo[4.2.0]okta-1,3,5-trien-7-il)nitrila i njegova primjena u sintezi ivabradina - Google Patents
Novi postupak za resoluciju enantiomera (3,4-dimetoksi-biciklo[4.2.0]okta-1,3,5-trien-7-il)nitrila i njegova primjena u sintezi ivabradina Download PDFInfo
- Publication number
- HRP20100679T1 HRP20100679T1 HR20100679T HRP20100679T HRP20100679T1 HR P20100679 T1 HRP20100679 T1 HR P20100679T1 HR 20100679 T HR20100679 T HR 20100679T HR P20100679 T HRP20100679 T HR P20100679T HR P20100679 T1 HRP20100679 T1 HR P20100679T1
- Authority
- HR
- Croatia
- Prior art keywords
- acid
- formula
- compound
- octa
- dimethoxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 26
- 150000002825 nitriles Chemical class 0.000 title claims abstract 13
- -1 3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl Chemical group 0.000 title claims abstract 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 title claims abstract 3
- 230000015572 biosynthetic process Effects 0.000 title claims 4
- 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 4
- 238000003786 synthesis reaction Methods 0.000 title claims 4
- 229960003825 ivabradine Drugs 0.000 title claims 3
- 150000001875 compounds Chemical class 0.000 claims abstract 17
- 239000000203 mixture Substances 0.000 claims abstract 9
- 238000003821 enantio-separation Methods 0.000 claims abstract 7
- 230000003287 optical effect Effects 0.000 claims abstract 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 4
- 239000003960 organic solvent Substances 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- 230000005526 G1 to G0 transition Effects 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- 239000007983 Tris buffer Substances 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 150000004677 hydrates Chemical class 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- 238000006722 reduction reaction Methods 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- SBTVLCPCSXMWIQ-UHFFFAOYSA-N (3,5-dimethylphenyl) carbamate Chemical compound CC1=CC(C)=CC(OC(N)=O)=C1 SBTVLCPCSXMWIQ-UHFFFAOYSA-N 0.000 claims 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-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
- 229920000856 Amylose Polymers 0.000 claims 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 229960005070 ascorbic acid Drugs 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 claims 1
- 239000001913 cellulose Substances 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 150000004676 glycans Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- LPNBBFKOUUSUDB-UHFFFAOYSA-M p-toluate Chemical compound CC1=CC=C(C([O-])=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-M 0.000 claims 1
- 229920001282 polysaccharide Polymers 0.000 claims 1
- 239000005017 polysaccharide Substances 0.000 claims 1
- 229940107700 pyruvic acid Drugs 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 239000000741 silica gel Substances 0.000 claims 1
- 229910002027 silica gel Inorganic materials 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
Classifications
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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
- A61P9/10—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
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/44—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers
- C07C209/48—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/47—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of rings being part of condensed ring systems
-
- 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
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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 to ring carbon atoms
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Vascular Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0804755A FR2935381B1 (fr) | 2008-08-29 | 2008-08-29 | 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20100679T1 true HRP20100679T1 (hr) | 2011-01-31 |
Family
ID=40431490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20100679T HRP20100679T1 (hr) | 2008-08-29 | 2010-12-07 | Novi postupak za resoluciju enantiomera (3,4-dimetoksi-biciklo[4.2.0]okta-1,3,5-trien-7-il)nitrila i njegova primjena u sintezi ivabradina |
Country Status (39)
| Country | Link |
|---|---|
| US (3) | US8536365B2 (ar) |
| EP (1) | EP2166004B1 (ar) |
| JP (2) | JP5663154B2 (ar) |
| KR (1) | KR101119309B1 (ar) |
| CN (1) | CN101659631B (ar) |
| AR (1) | AR073147A1 (ar) |
| AT (1) | ATE483688T1 (ar) |
| AU (1) | AU2009208068B2 (ar) |
| BR (1) | BRPI0903051A2 (ar) |
| CA (1) | CA2676712C (ar) |
| CL (1) | CL2009001758A1 (ar) |
| CY (1) | CY1110943T1 (ar) |
| DE (1) | DE602009000256D1 (ar) |
| DK (1) | DK2166004T3 (ar) |
| EA (1) | EA015777B1 (ar) |
| ES (1) | ES2353251T3 (ar) |
| FR (1) | FR2935381B1 (ar) |
| GE (1) | GEP20125409B (ar) |
| HK (1) | HK1141511A1 (ar) |
| HR (1) | HRP20100679T1 (ar) |
| JO (1) | JO2786B1 (ar) |
| MA (1) | MA31228B1 (ar) |
| ME (1) | ME00835B (ar) |
| MX (1) | MX2009008443A (ar) |
| MY (1) | MY145992A (ar) |
| NZ (1) | NZ579270A (ar) |
| PA (1) | PA8840901A1 (ar) |
| PE (1) | PE20100234A1 (ar) |
| PL (1) | PL2166004T3 (ar) |
| PT (1) | PT2166004E (ar) |
| RS (1) | RS51554B (ar) |
| SA (1) | SA109300533B1 (ar) |
| SG (1) | SG159454A1 (ar) |
| SI (1) | SI2166004T1 (ar) |
| TW (1) | TWI404705B (ar) |
| UA (1) | UA105890C2 (ar) |
| UY (1) | UY32034A (ar) |
| WO (1) | WO2010023383A1 (ar) |
| ZA (1) | ZA200905566B (ar) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| CN101774969B (zh) * | 2009-01-13 | 2012-07-04 | 江苏恒瑞医药股份有限公司 | 硫酸伊伐布雷定及其i型结晶的制备方法 |
| HUP1000245A2 (en) * | 2010-05-07 | 2011-11-28 | Richter Gedeon Nyrt | Industrial process for the production ivabradin salts |
| EP2522647B1 (en) * | 2011-05-10 | 2014-04-30 | DSM IP Assets B.V. | Process of separating chiral isomers of chroman compounds and their derivatives and precursors |
| 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 |
| FR2984319B1 (fr) * | 2011-12-20 | 2013-12-27 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2986804A1 (fr) * | 2012-02-09 | 2013-08-16 | Servier Lab | Procede de synthese enzymatique de l'acide (7s) 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene 7-carboxylique ou de ses esters, et application a la synthese de l'ivabradine et de ses sels |
| FR2993561B1 (fr) * | 2012-07-17 | 2014-10-31 | Servier Lab | Procede de synthese enzymatique de la (7s)-1-(3,4-dimethoxy bicyclo[4.2.0]octa-1,3,5-triene 7-yl) n-methyl methanamine, et application a la synthese de l'ivabradine et de ses sels |
| FR3002542B1 (fr) | 2013-02-28 | 2016-01-22 | Servier Lab | Procede de synthese enzymatique de l'acide (7s) 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene 7-carboxylique et application a la synthese de l'ivabradine et de ses sels |
| EP3101010A1 (en) | 2015-06-03 | 2016-12-07 | Urquima S.A. | New method for the preparation of highly pure ivabradine base and salts thereof |
| CN106390519A (zh) * | 2016-09-12 | 2017-02-15 | 华东理工大学 | 多柱模拟移动床色谱技术连续分离氨鲁米特外消旋体的方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5246948B2 (ar) * | 1972-04-26 | 1977-11-29 | ||
| IE52768B1 (en) * | 1981-04-06 | 1988-02-17 | Boots Co Ltd | 1-arylcyclobutylalkylamine compounds useful as therapeutic agents |
| DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| FR2539415B1 (fr) * | 1983-01-14 | 1985-09-13 | Adir | Derives de la d-2 imidazoline, leur preparation et leur application en therapeutique |
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| US5269482A (en) * | 1991-09-30 | 1993-12-14 | Shearing Ernest J | Protective enclosure apparatus for magnetic propulsion space vehicle |
| JP3752640B2 (ja) * | 1997-04-15 | 2006-03-08 | 秀幸 西澤 | 固液間向流抽出連続分離装置 |
| GB0325055D0 (en) * | 2003-10-27 | 2003-12-03 | Smithkline Beecham Corp | New process |
| 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 |
| FR2870537A1 (fr) * | 2004-05-19 | 2005-11-25 | Servier Lab | Nouveau procede de synthese du (1s)-4,5-dimethoxy-1-(methyl aminomethyl-)-benzocyclobutane et de ses sels d'addition, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| AU2007301436B2 (en) * | 2006-09-29 | 2013-03-14 | Council Of Scientific & Industrial Research | Organic-inorganic hybrid chiral sorbent and process for the preparation thereof |
| 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 |
-
2008
- 2008-08-29 FR FR0804755A patent/FR2935381B1/fr not_active Expired - Fee Related
-
2009
- 2009-08-03 SG SG200905168-1A patent/SG159454A1/en unknown
- 2009-08-03 PE PE2009001000A patent/PE20100234A1/es active IP Right Grant
- 2009-08-04 UY UY0001032034A patent/UY32034A/es not_active Application Discontinuation
- 2009-08-06 MY MYPI20093265A patent/MY145992A/en unknown
- 2009-08-07 MX MX2009008443A patent/MX2009008443A/es active IP Right Grant
- 2009-08-07 AU AU2009208068A patent/AU2009208068B2/en not_active Ceased
- 2009-08-11 ZA ZA200905566A patent/ZA200905566B/xx unknown
- 2009-08-12 MA MA32165A patent/MA31228B1/ar unknown
- 2009-08-13 JO JO2009309A patent/JO2786B1/ar active
- 2009-08-19 TW TW098127907A patent/TWI404705B/zh not_active IP Right Cessation
- 2009-08-21 CL CL2009001758A patent/CL2009001758A1/es unknown
- 2009-08-24 US US12/583,632 patent/US8536365B2/en not_active Expired - Fee Related
- 2009-08-25 GE GEAP200911437A patent/GEP20125409B/en unknown
- 2009-08-25 SA SA109300533A patent/SA109300533B1/ar unknown
- 2009-08-25 CN CN2009101673775A patent/CN101659631B/zh not_active Expired - Fee Related
- 2009-08-26 NZ NZ579270A patent/NZ579270A/en not_active IP Right Cessation
- 2009-08-27 EP EP09290646A patent/EP2166004B1/fr active Active
- 2009-08-27 CA CA2676712A patent/CA2676712C/fr not_active Expired - Fee Related
- 2009-08-27 PT PT09290646T patent/PT2166004E/pt unknown
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