CA2346085A1 - Propanolamine derivatives linked with bile acid used for treating disorders of the lipid metabolism - Google Patents
Propanolamine derivatives linked with bile acid used for treating disorders of the lipid metabolism Download PDFInfo
- Publication number
- CA2346085A1 CA2346085A1 CA002346085A CA2346085A CA2346085A1 CA 2346085 A1 CA2346085 A1 CA 2346085A1 CA 002346085 A CA002346085 A CA 002346085A CA 2346085 A CA2346085 A CA 2346085A CA 2346085 A1 CA2346085 A1 CA 2346085A1
- Authority
- CA
- Canada
- Prior art keywords
- bond
- compound
- alkyl
- pharmaceutical
- amino acid
- 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
- 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 title claims description 14
- 230000037356 lipid metabolism Effects 0.000 title claims description 8
- 150000003152 propanolamines Chemical class 0.000 title abstract description 4
- 239000003613 bile acid Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 229910006069 SO3H Inorganic materials 0.000 claims 5
- 239000003524 antilipemic agent Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- -1 amino acid radical Chemical class 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 16
- 235000001014 amino acid Nutrition 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000012528 membrane Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 210000000110 microvilli Anatomy 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- 229930195725 Mannitol Natural products 0.000 description 5
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 210000003405 ileum Anatomy 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- 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 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 238000005897 peptide coupling reaction Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 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 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 description 2
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- 150000001450 anions Chemical class 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
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- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
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- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
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- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- ZPGDWQNBZYOZTI-SFHVURJKSA-N (2s)-1-(9h-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZPGDWQNBZYOZTI-SFHVURJKSA-N 0.000 description 1
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- VEVRNHHLCPGNDU-MUGJNUQGSA-N (2s)-2-amino-5-[1-[(5s)-5-amino-5-carboxypentyl]-3,5-bis[(3s)-3-amino-3-carboxypropyl]pyridin-1-ium-4-yl]pentanoate Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(CC[C@H](N)C(O)=O)=C(CCC[C@H](N)C([O-])=O)C(CC[C@H](N)C(O)=O)=C1 VEVRNHHLCPGNDU-MUGJNUQGSA-N 0.000 description 1
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
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- C—CHEMISTRY; METALLURGY
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- A61P3/00—Drugs for disorders of the metabolism
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19845403.1 | 1998-10-02 | ||
| DE19845403A DE19845403B4 (de) | 1998-10-02 | 1998-10-02 | Mit Gallensäuren verknüpfte Propanolaminderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| PCT/EP1999/006930 WO2000020437A1 (de) | 1998-10-02 | 1999-09-18 | Mit gallensäuren verknüpfte propanolaminderivate zur behandlung von lipidstoffwechselstörungen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2346085A1 true CA2346085A1 (en) | 2000-04-13 |
Family
ID=7883185
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002346085A Abandoned CA2346085A1 (en) | 1998-10-02 | 1999-09-18 | Propanolamine derivatives linked with bile acid used for treating disorders of the lipid metabolism |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6180618B1 (https=) |
| EP (1) | EP1117676B1 (https=) |
| JP (1) | JP4598953B2 (https=) |
| KR (1) | KR20010075511A (https=) |
| CN (1) | CN1227259C (https=) |
| AR (1) | AR035003A1 (https=) |
| AT (1) | ATE273991T1 (https=) |
| AU (1) | AU757366B2 (https=) |
| BR (1) | BR9915019A (https=) |
| CA (1) | CA2346085A1 (https=) |
| DE (2) | DE19845403B4 (https=) |
| DK (1) | DK1117676T3 (https=) |
| ES (1) | ES2226440T3 (https=) |
| HK (1) | HK1040717A1 (https=) |
| HU (1) | HUP0103570A3 (https=) |
| ID (1) | ID29353A (https=) |
| PL (1) | PL347106A1 (https=) |
| PT (1) | PT1117676E (https=) |
| RU (1) | RU2234512C2 (https=) |
| TR (1) | TR200100897T2 (https=) |
| WO (1) | WO2000020437A1 (https=) |
| ZA (1) | ZA200102586B (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7053076B2 (en) | 2001-08-29 | 2006-05-30 | Xenoport, Inc. | Bile-acid derived compounds for enhancing oral absorption and systemic bioavailability of drugs |
| US7161008B2 (en) * | 2002-05-03 | 2007-01-09 | Sanofi - Aventis Deutschland GmbH | Optically active β-aminoketones, optically active 1,3-amino alcohols and processes for preparing them |
| GB0213669D0 (en) * | 2002-06-14 | 2002-07-24 | Astrazeneca Ab | Chemical compounds |
| GB0307918D0 (en) | 2003-04-05 | 2003-05-14 | Astrazeneca Ab | Therapeutic use |
| GB0817969D0 (en) * | 2008-10-01 | 2008-11-05 | Axcess Ltd | Pharmaceutical composition |
| EP2575821B1 (en) | 2010-05-26 | 2015-08-12 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| CA2852957C (en) | 2011-10-28 | 2020-08-04 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease |
| CN104023727B (zh) | 2011-10-28 | 2017-04-05 | 鲁美纳医药公司 | 用于治疗小儿胆汁淤积性肝病的胆汁酸再循环抑制剂 |
| US20140275090A1 (en) | 2013-03-15 | 2014-09-18 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease |
| CN105228615A (zh) | 2013-03-15 | 2016-01-06 | 鲁美纳医药公司 | 用于治疗巴雷特食管和胃食管返流疾病的胆汁酸再循环抑制剂 |
| PL3923943T3 (pl) | 2019-02-12 | 2024-12-09 | Mirum Pharmaceuticals, Inc. | Zależna od genotypu i dawki odpowiedź na asbti u pacjentów z niedoborem pompy eksportu soli żółciowych |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI892341A7 (fi) | 1988-06-10 | 1989-12-11 | Hoffmann La Roche | Propanoliamiinijohdannaisia |
| GB2250634A (en) * | 1990-12-04 | 1992-06-10 | Marconi Gec Ltd | Point contact diodes |
| NZ240846A (en) | 1990-12-06 | 1994-04-27 | Hoechst Ag | Dimeric bile acid derivatives; preparatory processes and pharmaceutical compositions |
| JP2616845B2 (ja) * | 1991-02-21 | 1997-06-04 | 清水化学株式会社 | システノール酸又はその胆汁酸抱合体を含有する血中コレステロール低下剤 |
| GB9203347D0 (en) * | 1992-02-17 | 1992-04-01 | Wellcome Found | Hypolipidaemic compounds |
| DK0557879T3 (da) * | 1992-02-22 | 1997-06-16 | Hoechst Ag | 4-amino-2-ureido-pyrimidin-5-carboxylsyreamider, fremgangsmåde til deres fremstilling, lægemidler med indhold af disse forbindelser og deres anvendelse |
| TW289021B (https=) * | 1993-05-08 | 1996-10-21 | Hoechst Ag | |
| EP0624593A3 (de) | 1993-05-08 | 1995-06-07 | Hoechst Ag | Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel. |
| DK0869121T3 (da) * | 1997-04-04 | 2004-09-20 | Aventis Pharma Gmbh | Hypolipidæmiske propanolaminderivater |
-
1998
- 1998-10-02 DE DE19845403A patent/DE19845403B4/de not_active Expired - Fee Related
-
1999
- 1999-09-18 DK DK99947385T patent/DK1117676T3/da active
- 1999-09-18 RU RU2001111816/04A patent/RU2234512C2/ru not_active IP Right Cessation
- 1999-09-18 CA CA002346085A patent/CA2346085A1/en not_active Abandoned
- 1999-09-18 ES ES99947385T patent/ES2226440T3/es not_active Expired - Lifetime
- 1999-09-18 PL PL99347106A patent/PL347106A1/xx unknown
- 1999-09-18 AT AT99947385T patent/ATE273991T1/de not_active IP Right Cessation
- 1999-09-18 KR KR1020017004131A patent/KR20010075511A/ko not_active Ceased
- 1999-09-18 JP JP2000574548A patent/JP4598953B2/ja not_active Expired - Fee Related
- 1999-09-18 AU AU60855/99A patent/AU757366B2/en not_active Ceased
- 1999-09-18 EP EP99947385A patent/EP1117676B1/de not_active Expired - Lifetime
- 1999-09-18 DE DE59910300T patent/DE59910300D1/de not_active Expired - Lifetime
- 1999-09-18 WO PCT/EP1999/006930 patent/WO2000020437A1/de not_active Ceased
- 1999-09-18 ID IDW20010737A patent/ID29353A/id unknown
- 1999-09-18 HK HK02102338.5A patent/HK1040717A1/zh unknown
- 1999-09-18 CN CNB998116343A patent/CN1227259C/zh not_active Expired - Fee Related
- 1999-09-18 HU HU0103570A patent/HUP0103570A3/hu unknown
- 1999-09-18 PT PT99947385T patent/PT1117676E/pt unknown
- 1999-09-18 TR TR2001/00897T patent/TR200100897T2/xx unknown
- 1999-09-18 BR BR9915019-0A patent/BR9915019A/pt not_active IP Right Cessation
- 1999-09-29 US US09/408,169 patent/US6180618B1/en not_active Expired - Lifetime
- 1999-09-30 AR ARP990104961A patent/AR035003A1/es unknown
-
2001
- 2001-03-29 ZA ZA200102586A patent/ZA200102586B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0103570A3 (en) | 2003-01-28 |
| DE19845403B4 (de) | 2005-02-10 |
| ID29353A (id) | 2001-08-23 |
| BR9915019A (pt) | 2001-08-14 |
| EP1117676B1 (de) | 2004-08-18 |
| DE59910300D1 (de) | 2004-09-23 |
| TR200100897T2 (tr) | 2001-10-22 |
| PT1117676E (pt) | 2004-11-30 |
| PL347106A1 (en) | 2002-03-25 |
| DK1117676T3 (da) | 2004-12-20 |
| CN1321166A (zh) | 2001-11-07 |
| EP1117676A1 (de) | 2001-07-25 |
| AR035003A1 (es) | 2004-04-14 |
| WO2000020437A1 (de) | 2000-04-13 |
| ZA200102586B (en) | 2001-10-03 |
| HUP0103570A2 (hu) | 2002-02-28 |
| JP4598953B2 (ja) | 2010-12-15 |
| RU2234512C2 (ru) | 2004-08-20 |
| ATE273991T1 (de) | 2004-09-15 |
| JP2002526550A (ja) | 2002-08-20 |
| HK1040717A1 (zh) | 2002-06-21 |
| AU6085599A (en) | 2000-04-26 |
| KR20010075511A (ko) | 2001-08-09 |
| AU757366B2 (en) | 2003-02-20 |
| US6180618B1 (en) | 2001-01-30 |
| ES2226440T3 (es) | 2005-03-16 |
| CN1227259C (zh) | 2005-11-16 |
| DE19845403A1 (de) | 2000-04-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |