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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- KOWWOODYPWDWOJ-LVBPXUMQSA-N elatine Chemical compound C([C@]12CN(C3[C@@]45OCO[C@]44[C@H]6[C@@H](OC)[C@@H]([C@H](C4)OC)C[C@H]6[C@@]3([C@@H]1[C@@H]5OC)[C@@H](OC)CC2)CC)OC(=O)C1=CC=CC=C1N1C(=O)CC(C)C1=O KOWWOODYPWDWOJ-LVBPXUMQSA-N 0.000 description 1
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- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
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- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
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- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical group S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 description 1
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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)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic 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 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US5663165A (enExample) |
| EP (1) | EP0626952B1 (enExample) |
| JP (1) | JP2904926B2 (enExample) |
| KR (1) | KR100265529B1 (enExample) |
| AT (1) | ATE178897T1 (enExample) |
| AU (1) | AU675419B2 (enExample) |
| CA (1) | CA2117485A1 (enExample) |
| DE (1) | DE69324479T2 (enExample) |
| DK (1) | DK0626952T3 (enExample) |
| ES (1) | ES2131106T3 (enExample) |
| FI (1) | FI943775L (enExample) |
| GB (1) | GB9203347D0 (enExample) |
| GR (1) | GR3030491T3 (enExample) |
| HU (1) | HUT71487A (enExample) |
| IL (1) | IL104740A (enExample) |
| MX (1) | MX9300821A (enExample) |
| MY (1) | MY129970A (enExample) |
| NZ (1) | NZ249189A (enExample) |
| TW (1) | TW274547B (enExample) |
| WO (1) | WO1993016055A1 (enExample) |
| ZA (1) | ZA931073B (enExample) |
Families Citing this family (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2115650C1 (ru) * | 1992-11-09 | 1998-07-20 | Дзе Бутс Компани ПЛС | 2,3,4,5-тетрагидро-1,4-бензотиазепины, их стереоизомеры или их фармацевтически приемлемые соли, способ их получения, фармацевтическая композиция, обладающая противосудорожным действием |
| ZA941003B (en) * | 1993-02-15 | 1995-08-14 | Wellcome Found | Hypolipidaemic compounds |
| IL108634A0 (en) * | 1993-02-15 | 1994-05-30 | Wellcome Found | Hypolipidaemic heterocyclic compounds, their prepatation and pharmaceutical compositions 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. |
| CN1084741C (zh) * | 1994-09-13 | 2002-05-15 | 孟山都公司 | 具有回肠胆汁酸转运和牛磺胆酸盐摄入抑制剂作用的新的苯并硫杂䓬 |
| 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 |
| 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 |
| 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 |
| PL336415A1 (en) * | 1997-03-11 | 2000-06-19 | Searle & Co | Combined therapy employing ileic bile acid transport inhibiting benzothiepins as well as a hmg co-enzyme reductase inhibitors |
| PT864582E (pt) * | 1997-03-14 | 2003-10-31 | Aventis Pharma Gmbh | 1,4-benzotiazepina-1,1-dioxidos hipolipidemicos |
| DK0869121T3 (da) * | 1997-04-04 | 2004-09-20 | Aventis Pharma Gmbh | Hypolipidæmiske propanolaminderivater |
| US6221897B1 (en) | 1998-06-10 | 2001-04-24 | Aventis Pharma Deutschland Gmbh | Benzothiepine 1,1-dioxide derivatives, a process for their preparation, pharmaceuticals comprising these compounds, and their use |
| DE19845403B4 (de) * | 1998-10-02 | 2005-02-10 | Aventis Pharma Deutschland Gmbh | Mit Gallensäuren verknüpfte Propanolaminderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| DE19845406C2 (de) * | 1998-10-02 | 2001-10-18 | Aventis Pharma Gmbh | Substituierte 1,3-Diaryl-2-pyridin-2-yl-3-(pyridin-2-ylamino)- propanolderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| DE19845405C2 (de) | 1998-10-02 | 2000-07-13 | Aventis Pharma Gmbh | Arylsubstituierte Propanolaminderivate und deren Verwendung |
| EP1140190B1 (en) | 1998-12-23 | 2002-11-20 | G.D. Searle LLC. | Combinations of ileal bile acid transport inhibitors and bile acid sequestering agents for cardiovascular indications |
| DK1140185T3 (da) | 1998-12-23 | 2003-09-29 | Searle Llc | Kombinationer af cholesterylestertransferhæmmere og galdesyre kompleksdannende forbindelser til hjertekar indikationer |
| AU2157400A (en) | 1998-12-23 | 2000-07-31 | G.D. Searle & Co. | Combinations of cholesteryl ester transfer protein inhibitors and hmg coa reductase inhibitors for cardiovascular indications |
| PT1140187E (pt) * | 1998-12-23 | 2004-01-30 | Searle Llc | Combinacoes de um inibidor de ibat e de um inibidor de mtp para indicacoes cardiovasculares |
| IL143949A0 (en) | 1998-12-23 | 2002-04-21 | Searle Llc | Combinations of cholesteryl ester transfer protein inhibitors and fibric acid derivatives for cardiovascular indications |
| WO2000038721A1 (en) | 1998-12-23 | 2000-07-06 | G.D. Searle Llc | Combinations of cholesteryl ester transfer protein inhibitors and nicotinic acid derivatives for cardiovascular indications |
| WO2000038726A1 (en) * | 1998-12-23 | 2000-07-06 | G.D. Searle Llc | Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications |
| ATE240120T1 (de) * | 1998-12-23 | 2003-05-15 | Searle Llc | Kombinationen von ileumgallensäuretransports inhibitoren und fibronsäure derivaten für kardiovaskuläre indikationen |
| DE19916108C1 (de) * | 1999-04-09 | 2001-01-11 | Aventis Pharma Gmbh | Mit Zuckerresten substituierte 1,4-Benzothiazepin-1,1-dioxidderivate, Verfahren zu deren Herstellung und deren Verwendung |
| GB9914745D0 (en) * | 1999-06-24 | 1999-08-25 | Knoll Ag | Therapeutic agents |
| SE0000772D0 (sv) | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | Chemical compounds |
| HK1052183A1 (zh) | 2000-03-10 | 2003-09-05 | Pharmacia Corporation | 制造tetrahydrobenzothiepines的方法 |
| US20020061888A1 (en) * | 2000-03-10 | 2002-05-23 | Keller Bradley T. | Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders |
| DK1265859T3 (da) | 2000-03-24 | 2006-05-01 | Pharmacia Corp | Amidinoforbindelser der er nyttige som nitrogenoxidsyntaseinhibitorer |
| US6787668B2 (en) | 2000-04-13 | 2004-09-07 | Pharmacia Corporation | 2-amino-4,5 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| AR030416A1 (es) | 2000-04-13 | 2003-08-20 | Pharmacia Corp | COMPUESTO DERIVADO HALOGENADO DEL ACIDO 2-AMINO-3,4 HEPTENOICO, COMPOSICION FARMACEUTICA QUE LO COMPRENDE Y SU USO EN LA FABRICACION DE UN MEDICAMENTO uTIL COMO INHIBIDOR DE LA OXIDO NITRICO SINTETASA |
| AR032318A1 (es) | 2000-04-13 | 2003-11-05 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-5,6 heptenoico; composicion farmaceutica que lo comprende y su uso en la fabricacion de un medicamento util como inhibidor de la oxido nitrico sintetasa |
| US6956131B2 (en) | 2000-04-13 | 2005-10-18 | Pharmacia Corporation | 2-amino-3, 4 heptenoic compounds useful as nitric oxide synthase inhibitors |
| US6545170B2 (en) | 2000-04-13 | 2003-04-08 | Pharmacia Corporation | 2-amino-5, 6 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| AR034120A1 (es) | 2000-04-13 | 2004-02-04 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-4,5 heptenoico, composicion farmaceutica que lo comprende y el uso de dicho compuesto y dicha composicion en la fabricacion de un medicamento para inhibir o modular la sintesis de acido nitrico |
| US6489125B1 (en) * | 2000-05-10 | 2002-12-03 | The Trustees Of Columbia University In The City Of New York | Methods for identifying chemical compounds that inhibit dissociation of FKBP12.6 binding protein from type 2 ryanodine receptor |
| US7879840B2 (en) * | 2005-08-25 | 2011-02-01 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7718644B2 (en) * | 2004-01-22 | 2010-05-18 | The Trustees Of Columbia University In The City Of New York | Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US20060293266A1 (en) * | 2000-05-10 | 2006-12-28 | The Trustees Of Columbia | Phosphodiesterase 4D in the ryanodine receptor complex protects against heart failure |
| US7393652B2 (en) * | 2000-05-10 | 2008-07-01 | The Trustees Of Columbia University In The City Of New York | Methods for identifying a chemical compound that directly enhances binding of FKBP12.6 to PKA-phosphorylated type 2 ryanodine receptor (RyR2) |
| US20040229781A1 (en) * | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| US20040048780A1 (en) * | 2000-05-10 | 2004-03-11 | The Trustees Of Columbia University In The City Of New York | Method for treating and preventing cardiac arrhythmia |
| US20020183307A1 (en) * | 2000-07-26 | 2002-12-05 | Tremont Samuel J. | Novel 1,4-benzothiazephine and 1,5-benzothiazepine compounds as inhibitors of apical sodium co-dependent bile acid transport and taurocholate uptake |
| AR031129A1 (es) | 2000-09-15 | 2003-09-10 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-4-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa |
| AR030741A1 (es) | 2000-09-15 | 2003-09-03 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-5-heptenoico y - heptinoico utiles como inhibidores de oxido nitrico sintetasa |
| EG26979A (en) | 2000-12-21 | 2015-03-01 | Astrazeneca Ab | Chemical compounds |
| WO2002083944A2 (en) * | 2001-04-17 | 2002-10-24 | Astrazeneca Ab | Chemical compounds for identification of slc10a2 gene polymorphisms |
| US20040072903A1 (en) * | 2001-05-08 | 2004-04-15 | Auerbach Bruce Jeffrey | Carboxyalkylether-acat inhibitors combinations |
| US20040077625A1 (en) * | 2001-07-25 | 2004-04-22 | Tremont Samuel J. | Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake |
| GB0121337D0 (en) | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| GB0121622D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| GB0121621D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| MXPA04002179A (es) | 2001-09-08 | 2004-06-29 | Astrazeneca Ab | Derivados de benzotiazepina y benzotiadiazepina con actividad inhibidora de transporte del acido ileal biliar (ibat) para tratar hiperlipidemia. |
| JP2005518347A (ja) * | 2001-11-02 | 2005-06-23 | ジー．ディー． サール エルエルシー | 頂端ナトリウム共依存性胆汁酸輸送（ａｓｂｔ）およびタウロコール酸塩取り込みの阻害剤としての新規一および二フッ化ベンゾチエピン化合物 |
| BR0306643A (pt) | 2002-01-17 | 2004-10-19 | Pharmacia Corp | Novos compostos de hidroxi alquil/aril ou ceto tiepina como inibidores do transporte co-dependente de ácido biliar-sódio apical |
| GB0209467D0 (en) | 2002-04-25 | 2002-06-05 | Astrazeneca Ab | Chemical compounds |
| GB0213669D0 (en) | 2002-06-14 | 2002-07-24 | Astrazeneca Ab | Chemical compounds |
| US7312208B2 (en) | 2002-08-28 | 2007-12-25 | Asahi Kasei Pharma Corporation | Quaternary ammonium compounds |
| US7544678B2 (en) * | 2002-11-05 | 2009-06-09 | The Trustees Of Columbia University In The City Of New York | Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| GB0304194D0 (en) | 2003-02-25 | 2003-03-26 | Astrazeneca Ab | Chemical compounds |
| JP2007525165A (ja) | 2003-03-07 | 2007-09-06 | トラスティーズ・オブ・コロンビア・ユニバーシティ・イン・ザ・シティ・オブ・ニューヨーク | タイプ１ライアノジン受容体に基づく方法 |
| GB0307918D0 (en) * | 2003-04-05 | 2003-05-14 | Astrazeneca Ab | Therapeutic use |
| US8710045B2 (en) * | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| CA2557576C (en) | 2004-02-27 | 2010-02-09 | Asahi Kasei Pharma Corporation | Novel benzothiazepine and benzothiepine compounds |
| US7704990B2 (en) * | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| EP2367554A4 (en) * | 2008-11-26 | 2020-03-25 | Satiogen Pharmaceuticals, Inc. | Bile acid reflux inhibitor for the treatment of obesity and diabetes |
| JO3131B1 (ar) * | 2010-04-27 | 2017-09-20 | Glaxosmithkline Llc | مركبات كيميائية |
| EP4137137A1 (en) | 2010-05-26 | 2023-02-22 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| PL3400944T3 (pl) | 2010-11-04 | 2020-11-16 | Albireo Ab | Inhibitory ibat w leczeniu chorób wątroby |
| PT2637646T (pt) | 2010-11-08 | 2016-08-17 | Albireo Ab | Uma combinação farmacêutica que compreende um inibidor do ibat e um sequestrador de ácido biliar |
| US20140323412A1 (en) | 2011-10-28 | 2014-10-30 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease |
| SG10201909122QA (en) | 2011-10-28 | 2019-11-28 | Lumena Pharmaceuticals Inc | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| CA2907214A1 (en) | 2013-03-15 | 2014-09-18 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of barrett's esophagus and gastroesophageal reflux disease |
| CA2907230A1 (en) | 2013-03-15 | 2014-09-18 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease |
| JO3301B1 (ar) | 2013-04-26 | 2018-09-16 | Albireo Ab | تعديلات بلورية على إيلوبيكسيبات |
| TWI499846B (zh) * | 2014-04-16 | 2015-09-11 | Au Optronics Corp | 顯示器模組 |
| KR102560954B1 (ko) | 2014-06-25 | 2023-07-31 | 이에이 파마 가부시키가이샤 | 고형 제제 및 그의 착색 방지 또는 착색 감소 방법 |
| EP3012252A1 (en) | 2014-10-24 | 2016-04-27 | Ferring BV | Crystal modifications of elobixibat |
| US10441605B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10786529B2 (en) | 2016-02-09 | 2020-09-29 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| CN108601745B (zh) | 2016-02-09 | 2021-12-07 | 阿尔比里奥公司 | 口服考来烯胺制剂及其用途 |
| ES2874669T3 (es) | 2016-02-09 | 2021-11-05 | Albireo Ab | Formulación oral de colestiramina y uso de la misma |
| US10441604B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Cholestyramine pellets and methods for preparation thereof |
| WO2018002827A1 (en) * | 2016-06-27 | 2018-01-04 | Glaxosmithkline Intellectual Property (No.2) Limited | Synthetic methods |
| CN111032019B (zh) | 2017-08-09 | 2022-07-05 | 阿尔比里奥公司 | 考来烯胺颗粒、口服考来烯胺制剂及其用途 |
| WO2019032027A1 (en) | 2017-08-09 | 2019-02-14 | Albireo Ab | CHOLESTYRAMINE TABLETS, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE |
| US10793534B2 (en) | 2018-06-05 | 2020-10-06 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| EP3802504B1 (en) | 2018-06-05 | 2023-01-18 | Albireo AB | Benzothia(di)azepine compounds and their use as bile acid modulators |
| EP3810084A1 (en) | 2018-06-20 | 2021-04-28 | Albireo AB | Pharmaceutical formulation of odevixibat |
| US11801226B2 (en) | 2018-06-20 | 2023-10-31 | Albireo Ab | Pharmaceutical formulation of odevixibat |
| US11007142B2 (en) | 2018-08-09 | 2021-05-18 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US11549878B2 (en) | 2018-08-09 | 2023-01-10 | Albireo Ab | In vitro method for determining the adsorbing capacity of an insoluble adsorbant |
| US10722457B2 (en) | 2018-08-09 | 2020-07-28 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10975045B2 (en) | 2019-02-06 | 2021-04-13 | Aibireo AB | Benzothiazepine compounds and their use as bile acid modulators |
| DK3921028T3 (da) | 2019-02-06 | 2023-01-23 | Albireo Ab | Benzothiadiazepinforbindelser og anvendelse deraf som galdesyremodulatorer |
| CN118834175A (zh) | 2019-02-06 | 2024-10-25 | 阿尔比里奥公司 | 苯并硫氮杂环庚三烯化合物及其用作胆汁酸调节剂的用途 |
| US10941127B2 (en) | 2019-02-06 | 2021-03-09 | Albireo Ab | Benzothiadiazepine compounds and their use as bile acid modulators |
| JP7562546B2 (ja) | 2019-02-12 | 2024-10-07 | ミルム ファーマシューティカルズ インコーポレイテッド | 胆汁うっ滞性肝疾患を有する小児対象の成長を増加させる方法 |
| PT4069360T (pt) | 2019-12-04 | 2024-03-06 | Albireo Ab | Compostos de benzotia(di)azepina e a sua utilização como moduladores de ácido biliar |
| US11014898B1 (en) | 2020-12-04 | 2021-05-25 | Albireo Ab | Benzothiazepine compounds and their use as bile acid modulators |
| CN114761018B (zh) | 2019-12-04 | 2025-12-02 | 阿尔比里奥公司 | 苯并硫杂二氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途 |
| AR120674A1 (es) | 2019-12-04 | 2022-03-09 | Albireo Ab | Compuestos de benzotiazepina y su uso como ácido biliar |
| DK4069360T3 (da) | 2019-12-04 | 2024-02-26 | Albireo Ab | Benzothia(di)azepinforbindelser og anvendelse deraf som galdesyremodulatorer |
| TWI877263B (zh) | 2019-12-04 | 2025-03-21 | 瑞典商艾爾比瑞歐公司 | 苯并噻二氮呯化合物及其作為膽酸調節劑之用途 |
| WO2021110884A1 (en) | 2019-12-04 | 2021-06-10 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| JP7696897B2 (ja) | 2019-12-04 | 2025-06-23 | アルビレオ・アクチボラグ | ベンゾチア（ジ）アゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用 |
| ES2972045T3 (es) | 2019-12-04 | 2024-06-10 | Albireo Ab | Compuestos de benzotia(di)azepina y su uso como moduladores del ácido biliar |
| WO2021110886A1 (en) | 2019-12-04 | 2021-06-10 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| WO2022029101A1 (en) | 2020-08-03 | 2022-02-10 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
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| WO2022117778A1 (en) | 2020-12-04 | 2022-06-09 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| TW202313579A (zh) | 2021-06-03 | 2023-04-01 | 瑞典商艾爾比瑞歐公司 | 苯并噻(二)氮呯(benzothia(di)azepine)化合物及其作為膽酸調節劑之用途 |
| JP2025516153A (ja) | 2022-04-22 | 2025-05-27 | アルビレオ・アクチボラグ | Ａｓｂｔ阻害剤の皮下投与 |
| AU2023285002A1 (en) | 2022-06-09 | 2024-12-05 | Albireo Ab | Treating hepatitis |
| US20240067617A1 (en) | 2022-07-05 | 2024-02-29 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| US20240207286A1 (en) | 2022-12-09 | 2024-06-27 | Albireo Ab | Asbt inhibitors in the treatment of renal diseases |
| WO2025146508A1 (en) | 2024-01-05 | 2025-07-10 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| WO2025146507A1 (en) | 2024-01-05 | 2025-07-10 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
Family Cites Families (2)
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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
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- 1993-02-16 FI FI943775A patent/FI943775L/fi unknown
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- 1993-02-16 WO PCT/GB1993/000328 patent/WO1993016055A1/en not_active Ceased
- 1993-02-16 US US08/290,805 patent/US5663165A/en not_active Expired - Fee Related
- 1993-02-16 IL IL10474093A patent/IL104740A/en not_active IP Right Cessation
- 1993-02-16 ES ES93904212T patent/ES2131106T3/es not_active Expired - Lifetime
- 1993-02-16 MX MX9300821A patent/MX9300821A/es not_active IP Right Cessation
- 1993-02-16 JP JP5513928A patent/JP2904926B2/ja not_active Expired - Fee Related
- 1993-02-16 DK DK93904212T patent/DK0626952T3/da active
- 1993-02-16 ZA ZA931073A patent/ZA931073B/xx unknown
- 1993-02-16 AT AT93904212T patent/ATE178897T1/de not_active IP Right Cessation
- 1993-02-16 NZ NZ249189A patent/NZ249189A/en unknown
- 1993-02-16 MY MYPI93000254A patent/MY129970A/en unknown
- 1993-02-16 KR KR1019940702834A patent/KR100265529B1/ko not_active Expired - Fee Related
- 1993-02-16 EP EP93904212A patent/EP0626952B1/en not_active Expired - Lifetime
- 1993-02-16 DE DE69324479T patent/DE69324479T2/de not_active Expired - Fee Related
- 1993-02-16 HU HU9402365A patent/HUT71487A/hu unknown
- 1993-02-16 TW TW082101074A patent/TW274547B/zh active
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1997
- 1997-08-28 US US08/919,980 patent/US5859240A/en not_active Expired - Fee Related
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|---|---|
| DE69324479D1 (de) | 1999-05-20 |
| JP2904926B2 (ja) | 1999-06-14 |
| ZA931073B (en) | 1994-08-16 |
| HU9402365D0 (en) | 1994-10-28 |
| US5663165A (en) | 1997-09-02 |
| AU3508293A (en) | 1993-09-03 |
| US5859240A (en) | 1999-01-12 |
| KR100265529B1 (ko) | 2000-11-01 |
| FI943775A0 (fi) | 1994-08-16 |
| EP0626952A1 (en) | 1994-12-07 |
| FI943775A7 (fi) | 1994-08-16 |
| HK1004217A1 (en) | 1998-11-20 |
| GB9203347D0 (en) | 1992-04-01 |
| KR950700265A (ko) | 1995-01-16 |
| AU675419B2 (en) | 1997-02-06 |
| IL104740A (en) | 1996-09-12 |
| ES2131106T3 (es) | 1999-07-16 |
| WO1993016055A1 (en) | 1993-08-19 |
| DE69324479T2 (de) | 1999-09-16 |
| MY129970A (en) | 2007-05-31 |
| EP0626952B1 (en) | 1999-04-14 |
| GR3030491T3 (en) | 1999-10-29 |
| ATE178897T1 (de) | 1999-04-15 |
| JPH07503724A (ja) | 1995-04-20 |
| HUT71487A (en) | 1995-11-28 |
| IL104740A0 (en) | 1993-06-10 |
| FI943775L (fi) | 1994-08-16 |
| TW274547B (enExample) | 1996-04-21 |
| DK0626952T3 (da) | 1999-10-25 |
| NZ249189A (en) | 1996-02-27 |
| MX9300821A (es) | 1993-09-01 |
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|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |