CA2117485A1 - Hypolipidaemic benzothiazepine compounds - Google Patents
Hypolipidaemic benzothiazepine compoundsInfo
- Publication number
- CA2117485A1 CA2117485A1 CA002117485A CA2117485A CA2117485A1 CA 2117485 A1 CA2117485 A1 CA 2117485A1 CA 002117485 A CA002117485 A CA 002117485A CA 2117485 A CA2117485 A CA 2117485A CA 2117485 A1 CA2117485 A1 CA 2117485A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- solvate
- ethyl
- butyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000000055 hyoplipidemic effect Effects 0.000 title description 7
- 150000007657 benzothiazepines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 151
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 239000012453 solvate Substances 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 28
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 238000011321 prophylaxis Methods 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 125000002071 phenylalkoxy group Chemical group 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 3
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 239000002775 capsule Substances 0.000 claims description 18
- 239000003613 bile acid Substances 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 16
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 14
- 238000010521 absorption reaction Methods 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- LRICCVYAIHJCLD-OAQYLSRUSA-N (3r)-3-butyl-3-ethyl-5-phenyl-2h-1,2-benzothiazepine Chemical compound N([C@](C=1)(CC)CCCC)SC2=CC=CC=C2C=1C1=CC=CC=C1 LRICCVYAIHJCLD-OAQYLSRUSA-N 0.000 claims 1
- LRICCVYAIHJCLD-UHFFFAOYSA-N 3-butyl-3-ethyl-5-phenyl-2h-1,2-benzothiazepine Chemical compound C=1C(CCCC)(CC)NSC2=CC=CC=C2C=1C1=CC=CC=C1 LRICCVYAIHJCLD-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000003516 hyperlipidaemic effect Effects 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 description 83
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- 239000000047 product Substances 0.000 description 48
- 239000000243 solution Substances 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- -1 hydrochloric Chemical class 0.000 description 29
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- 239000004480 active ingredient Substances 0.000 description 21
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 20
- 239000007787 solid Substances 0.000 description 18
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
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- 229920000642 polymer Polymers 0.000 description 10
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 8
- 239000008101 lactose Substances 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 210000002381 plasma Anatomy 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000013270 controlled release Methods 0.000 description 7
- 239000004014 plasticizer Substances 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 6
- 229920003136 Eudragit® L polymer Polymers 0.000 description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 229940069328 povidone Drugs 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 4
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
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- 230000005764 inhibitory process Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
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- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
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- NAALCXIRPYHTJX-UHFFFAOYSA-N 3,3-diethyl-5-phenyl-4,5-dihydro-2h-1,4-benzothiazepine Chemical compound N1C(CC)(CC)CSC2=CC=CC=C2C1C1=CC=CC=C1 NAALCXIRPYHTJX-UHFFFAOYSA-N 0.000 description 2
- WYTMZJBGDDXIRO-UHFFFAOYSA-N 3-ethyl-3-methyl-5-phenyl-4,5-dihydro-2h-1,4-benzothiazepine Chemical compound N1C(CC)(C)CSC2=CC=CC=C2C1C1=CC=CC=C1 WYTMZJBGDDXIRO-UHFFFAOYSA-N 0.000 description 2
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- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929203347A GB9203347D0 (en) | 1992-02-17 | 1992-02-17 | Hypolipidaemic compounds |
| GB9203347.1 | 1992-02-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2117485A1 true CA2117485A1 (en) | 1993-08-19 |
Family
ID=10710542
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002117485A Abandoned CA2117485A1 (en) | 1992-02-17 | 1993-02-16 | Hypolipidaemic benzothiazepine compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CZ288595B6 (cs) * | 1992-11-09 | 2001-07-11 | The Boots Company Plc | Farmaceutické prostředky obsahující deriváty 2,3,4,5-tetrahydro-1,4-benzothiazepinů, tyto deriváty a způsob jejich výroby |
| IL108634A0 (en) * | 1993-02-15 | 1994-05-30 | Wellcome Found | Hypolipidaemic heterocyclic compounds, their prepatation and pharmaceutical compositions containing them |
| IL108633A (en) * | 1993-02-15 | 1998-07-15 | Wellcome Found | History of Benzothiazepine Hypolipidemic Preparation and Pharmaceutical Preparations Containing Them |
| AU678503B2 (en) * | 1993-09-24 | 1997-05-29 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds and their use as squalene synthetase inhibitors |
| ZA956647B (en) * | 1994-08-10 | 1997-02-10 | Wellcome Found | Hypolipidaemic compounds. |
| PT781278E (pt) * | 1994-09-13 | 2001-08-30 | Monsanto Co | Novas benzotiepinas com actividade inibidora do transporte de acido biliar ileal e da remocao do taurocolato |
| US6107494A (en) * | 1994-09-13 | 2000-08-22 | G.D. Searle And Company | Substituted 5-aryl-benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
| US6262277B1 (en) | 1994-09-13 | 2001-07-17 | G.D. Searle And Company | Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
| US5994391A (en) * | 1994-09-13 | 1999-11-30 | G.D. Searle And Company | Benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
| US6642268B2 (en) | 1994-09-13 | 2003-11-04 | G.D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors |
| US6268392B1 (en) | 1994-09-13 | 2001-07-31 | G. D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors |
| GB9423172D0 (en) * | 1994-11-17 | 1995-01-04 | Wellcom Foundation The Limited | Hypolipidemic benzothiazepines |
| GB9616279D0 (en) * | 1996-08-02 | 1996-09-11 | Knoll Ag | Chemical process |
| GB9704208D0 (en) * | 1997-02-28 | 1997-04-16 | Glaxo Group Ltd | Chemical compounds |
| NZ337830A (en) * | 1997-03-11 | 2001-07-27 | G | Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors |
| DE69815180T2 (de) * | 1997-03-14 | 2004-04-29 | Aventis Pharma Deutschland Gmbh | Hypolipidemische 1,4-Benzothiazepin-1,1-dioxide |
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| US3362962A (en) * | 1964-01-24 | 1968-01-09 | Hoffmann La Roche | Certain benzothiazepine derivatives |
| US5276025A (en) * | 1992-09-09 | 1994-01-04 | Merck & Co., Inc. | Heterobicyclic sulfonamides |
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- 1993-02-16 AT AT93904212T patent/ATE178897T1/de not_active IP Right Cessation
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- 1993-02-16 JP JP5513928A patent/JP2904926B2/ja not_active Expired - Fee Related
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| NZ249189A (en) | 1996-02-27 |
| KR100265529B1 (ko) | 2000-11-01 |
| HU9402365D0 (en) | 1994-10-28 |
| FI943775L (fi) | 1994-08-16 |
| KR950700265A (ko) | 1995-01-16 |
| GR3030491T3 (en) | 1999-10-29 |
| FI943775A0 (fi) | 1994-08-16 |
| WO1993016055A1 (en) | 1993-08-19 |
| EP0626952B1 (en) | 1999-04-14 |
| ATE178897T1 (de) | 1999-04-15 |
| DE69324479D1 (de) | 1999-05-20 |
| US5663165A (en) | 1997-09-02 |
| EP0626952A1 (en) | 1994-12-07 |
| ZA931073B (en) | 1994-08-16 |
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| AU675419B2 (en) | 1997-02-06 |
| GB9203347D0 (en) | 1992-04-01 |
| IL104740A (en) | 1996-09-12 |
| HK1004217A1 (en) | 1998-11-20 |
| JPH07503724A (ja) | 1995-04-20 |
| TW274547B (cg-RX-API-DMAC7.html) | 1996-04-21 |
| DK0626952T3 (da) | 1999-10-25 |
| IL104740A0 (en) | 1993-06-10 |
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| DE69324479T2 (de) | 1999-09-16 |
| FI943775A7 (fi) | 1994-08-16 |
| AU3508293A (en) | 1993-09-03 |
| MX9300821A (es) | 1993-09-01 |
| US5859240A (en) | 1999-01-12 |
| MY129970A (en) | 2007-05-31 |
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| FZDE | Discontinued |