DK2989095T3 - Tartratsalt af 5-chlorthiophen-2-carboxylsyre [(s)-2-[methyl-3-(2-oxopyrrolidin-1-yl)-benzensulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amid - Google Patents
Tartratsalt af 5-chlorthiophen-2-carboxylsyre [(s)-2-[methyl-3-(2-oxopyrrolidin-1-yl)-benzensulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amid Download PDFInfo
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- DK2989095T3 DK2989095T3 DK14719340.3T DK14719340T DK2989095T3 DK 2989095 T3 DK2989095 T3 DK 2989095T3 DK 14719340 T DK14719340 T DK 14719340T DK 2989095 T3 DK2989095 T3 DK 2989095T3
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- DK
- Denmark
- Prior art keywords
- methyl
- compound
- carboxylic acid
- oxopyrrolidin
- methylpiperazin
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- QZLSBOVWPHXCLT-UHFFFAOYSA-N 5-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)S1 QZLSBOVWPHXCLT-UHFFFAOYSA-N 0.000 title description 11
- 150000003892 tartrate salts Chemical class 0.000 title description 6
- -1 2-OXOPYRROLIDIN-1-YL Chemical class 0.000 title 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 5
- 208000001435 Thromboembolism Diseases 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- JHRMQXYTUPGQEA-UHFFFAOYSA-N 2-methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonyl chloride Chemical compound C1=CC=C(S(Cl)(=O)=O)C(C)=C1N1C(=O)CCC1 JHRMQXYTUPGQEA-UHFFFAOYSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- FJYKPWJRJKMJIC-UHFFFAOYSA-N n-[2-amino-3-(4-methylpiperazin-1-yl)-3-oxopropyl]-5-chlorothiophene-2-carboxamide Chemical compound C1CN(C)CCN1C(=O)C(N)CNC(=O)C1=CC=C(Cl)S1 FJYKPWJRJKMJIC-UHFFFAOYSA-N 0.000 claims description 2
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- OMCHOCCLLNHGGJ-IBGZPJMESA-N CN([C@@H](CNC(=O)C=1SC(=CC=1)Cl)C(=O)N1CCN(CC1)C)S(=O)(=O)C1=CC(=CC=C1)N1C(CCC1)=O Chemical compound CN([C@@H](CNC(=O)C=1SC(=CC=1)Cl)C(=O)N1CCN(CC1)C)S(=O)(=O)C1=CC(=CC=C1)N1C(CCC1)=O OMCHOCCLLNHGGJ-IBGZPJMESA-N 0.000 claims 9
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
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- 229940116871 l-lactate Drugs 0.000 description 8
- 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 7
- 150000003839 salts Chemical class 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
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- 159000000000 sodium salts Chemical class 0.000 description 2
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
- PHDQRWBGPIIVET-UHFFFAOYSA-N 1-(3-benzylsulfanyl-2-methylphenyl)pyrrolidin-2-one Chemical compound C1=CC=C(N2C(CCC2)=O)C(C)=C1SCC1=CC=CC=C1 PHDQRWBGPIIVET-UHFFFAOYSA-N 0.000 description 1
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- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
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- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
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- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 1
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
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- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
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- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
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- SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
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- GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 1
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- 235000015320 potassium carbonate Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- KIZOIUZIMWKFFP-UHFFFAOYSA-N tert-butyl n-[3-[(5-chlorothiophene-2-carbonyl)amino]-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]carbamate Chemical compound C1CN(C)CCN1C(=O)C(NC(=O)OC(C)(C)C)CNC(=O)C1=CC=C(Cl)S1 KIZOIUZIMWKFFP-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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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
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
- C07C59/255—Tartaric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
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Claims (6)
1. L-tartratsalt af 5-chlorthiophen-2-carboxylsyre [ (S)—2 — [methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid.
2. L-tartratsalt af 5-chlorthiophen-2-carboxylsyre [ (S)—2 — [methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid ifølge krav 1, der er kendetegnet ved, at det er krystallinsk.
3. L-tartratsalt af 5-chlorthiophen-2-carboxylsyre [(S)—2— [methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid ifølge et hvilket som helst af krav 1 eller 2, der er kendetegnet ved, at det har et røntgendiffraktogram ifølge figur 1.
4. Fremgangsmåde til fremstilling af L-tartratsaltet af 5-chlorthiophen-2-carboxylsyre [(S)-2-[methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl] amid, der er kendetegnet ved, at den frie baseform af 5-chlorthiophen-2-carboxylsyre [(S)-2-[methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid reageres med L-vinsyre i et opløsningsmiddel.
5. Fremgangsmåde ifølge krav 4, der er kendetegnet ved, at den frie form af 5-chlorthiophen-2-carboxylsyre [(S)—2— [methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid opnås ved tilsætning af 5-chlorthiophen-2-carboxylsyre [2-amino-3-(4-methylpiperazin-1-yl)-3-oxopropyl]-amid og 2-methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylchlorid.
6. Medikament, der er kendetegnet ved, at det omfatter L- tartratsaltet af 5-chlorthiophen-2-carboxylsyre [(S)—2— [methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid. Ί. Farmaceutisk sammensætning, der er kendetegnet ved, at den som aktiv bestanddel omfatter L-tartratsaltet af 5-chlorthiophen-2-carboxylsyre [(S)-2-[methyl-3-(2- oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amid og endvidere mindst ét farmaceutisk acceptabelt excipiens. 8. L-tartratsalt af 5-chlorthiophen-2-carboxylsyre [(S)—2— [methyl-3-(2-oxopyrrolidin-l-yl)-benzensulfonylamino]-3-(4-methylpiperazin-l-yl)-3-oxopropyl]amid ifølge et hvilket som helst af kravene 1 til 3 til anvendelse til behandling eller forebyggelse af kardiovaskulære forstyrrelser, tromboemboliske sygdomme eller restenoser.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13305556 | 2013-04-26 | ||
| PCT/EP2014/058513 WO2014174102A1 (en) | 2013-04-26 | 2014-04-25 | Tartrate salt of 5-chloro-thiophene-2-carboxylic acid [(s)-2-[methyl-3-(2-oxo-pyrrolidin-1-yl)-benzenesulfonylamino]-3-(4-methyl piperazin-1 -yl)-3-oxo-propryl]amide |
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| Publication Number | Publication Date |
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| DK2989095T3 true DK2989095T3 (da) | 2019-03-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14719340.3T DK2989095T3 (da) | 2013-04-26 | 2014-04-25 | Tartratsalt af 5-chlorthiophen-2-carboxylsyre [(s)-2-[methyl-3-(2-oxopyrrolidin-1-yl)-benzensulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amid |
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| Country | Link |
|---|---|
| US (1) | US9637479B2 (da) |
| EP (1) | EP2989095B1 (da) |
| JP (1) | JP6393310B2 (da) |
| KR (1) | KR102388926B1 (da) |
| CN (1) | CN105143213B (da) |
| AU (1) | AU2014259378B2 (da) |
| BR (1) | BR112015026841A8 (da) |
| CA (1) | CA2910085C (da) |
| CY (1) | CY1123536T1 (da) |
| DK (1) | DK2989095T3 (da) |
| ES (1) | ES2711144T3 (da) |
| HR (1) | HRP20190245T1 (da) |
| HU (1) | HUE042250T2 (da) |
| IL (1) | IL242081B (da) |
| LT (1) | LT2989095T (da) |
| MX (1) | MX360896B (da) |
| PL (1) | PL2989095T3 (da) |
| PT (1) | PT2989095T (da) |
| RU (1) | RU2664538C2 (da) |
| SG (1) | SG11201508515WA (da) |
| SI (1) | SI2989095T1 (da) |
| TR (1) | TR201901931T4 (da) |
| TW (1) | TWI615390B (da) |
| WO (1) | WO2014174102A1 (da) |
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| PE20240798A1 (es) | 2021-09-03 | 2024-04-18 | Bayer Ag | Derivados de s-alaninato sustituidos |
| WO2024175450A1 (en) | 2023-02-21 | 2024-08-29 | Bayer Aktiengesellschaft | Substituted s-alaninate derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0778835A4 (en) * | 1994-08-25 | 1999-02-03 | Univ Virginia | 7-AZABICYCLO (2.2.1) -HEPTANE AND -HEPTENE DERIVATIVES AS LIGANDS OF THE CHOLI ENERGY RECEPTORS |
| PT914315E (pt) * | 1996-05-31 | 2001-07-31 | Sigma Tau Ind Farmaceuti | Sais nao higroscopicos estaveis de l(-)carnitina e alcanoil l(-)carnitinas processo para a sua preparacao e composicoes solidas administraveis oralmente contendo tais sais |
| SE510305C2 (sv) * | 1997-05-30 | 1999-05-10 | Astra Ab | Nytt salt |
| GB0030304D0 (en) * | 2000-12-13 | 2001-01-24 | Lilly Co Eli | Compounds |
| GB0114005D0 (en) * | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
| GB0127568D0 (en) * | 2001-11-16 | 2002-01-09 | Glaxo Group Ltd | Chemical compounds |
| GB0228552D0 (en) * | 2002-12-06 | 2003-01-15 | Glaxo Group Ltd | Chemical compounds |
| CN102048723A (zh) * | 2003-08-28 | 2011-05-11 | 梅恩医药有限公司 | 含有酸的奥沙利铂制剂 |
| US7371743B2 (en) * | 2004-02-28 | 2008-05-13 | Boehringer Ingelheim International Gmbh | Carboxylic acid amides, the preparation thereof and their use as medicaments |
| PT2254881E (pt) * | 2008-02-21 | 2012-12-10 | Sanofi Sa | Clorotiofeno-amidas como inibidores de factores de coagulação xa e da trombina |
| KR100953535B1 (ko) | 2008-07-17 | 2010-04-21 | 재단법인 포항산업과학연구원 | 염소계 화합물을 이용한 배가스 내 수은 제거 방법 |
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