KR20080108327A - 신규한 약학적 화합물 - Google Patents
신규한 약학적 화합물 Download PDFInfo
- Publication number
- KR20080108327A KR20080108327A KR1020087026652A KR20087026652A KR20080108327A KR 20080108327 A KR20080108327 A KR 20080108327A KR 1020087026652 A KR1020087026652 A KR 1020087026652A KR 20087026652 A KR20087026652 A KR 20087026652A KR 20080108327 A KR20080108327 A KR 20080108327A
- Authority
- KR
- South Korea
- Prior art keywords
- diol
- nitrobenzene
- compound
- trifluoromethyl
- oxadiazol
- 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.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 142
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 8
- 208000027232 peripheral nervous system disease Diseases 0.000 claims abstract description 8
- -1 1,3,4-oxadiazole-2,5-diyl Chemical group 0.000 claims description 285
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 69
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 67
- 229960004502 levodopa Drugs 0.000 claims description 63
- 238000006243 chemical reaction Methods 0.000 claims description 54
- 238000000034 method Methods 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 52
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 30
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 30
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- QTAOMKOIBXZKND-PPHPATTJSA-N carbidopa Chemical compound O.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 QTAOMKOIBXZKND-PPHPATTJSA-N 0.000 claims description 4
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 4
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
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- NRDPBGVIGJRUCE-UHFFFAOYSA-N 5-[3-(2-fluoropyridin-3-yl)-1,2,4-oxadiazol-5-yl]-3-nitrobenzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=2ON=C(N=2)C=2C(=NC=CC=2)F)=C1 NRDPBGVIGJRUCE-UHFFFAOYSA-N 0.000 claims description 2
- KPXNOSZGJLGLCP-UHFFFAOYSA-N 5-[5-(2-bromo-4,5,6-trimethylpyridin-3-yl)-1,2,4-oxadiazol-3-yl]-3-nitrobenzene-1,2-diol Chemical compound CC1=C(C)C(C)=NC(Br)=C1C1=NC(C=2C=C(C(O)=C(O)C=2)[N+]([O-])=O)=NO1 KPXNOSZGJLGLCP-UHFFFAOYSA-N 0.000 claims description 2
- ROAAJELRWCOSSE-UHFFFAOYSA-N 5-[5-(2-fluoropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-3-nitrobenzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=2N=C(ON=2)C=2C(=NC=CC=2)F)=C1 ROAAJELRWCOSSE-UHFFFAOYSA-N 0.000 claims description 2
- 239000005725 8-Hydroxyquinoline Substances 0.000 claims description 2
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 claims description 2
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 230000000144 pharmacologic effect Effects 0.000 claims description 2
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 208000016285 Movement disease Diseases 0.000 claims 5
- QJOAGGIONCIMFQ-UHFFFAOYSA-N 5-[3-(2,5-dichloro-4,6-dimethylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]-3-nitrobenzene-1,2-diol Chemical compound CC1=C(Cl)C(C)=NC(Cl)=C1C1=NOC(C=2C=C(C(O)=C(O)C=2)[N+]([O-])=O)=N1 QJOAGGIONCIMFQ-UHFFFAOYSA-N 0.000 claims 3
- 230000007160 gastrointestinal dysfunction Effects 0.000 claims 3
- 101710151768 Aromatic-L-amino-acid decarboxylase Proteins 0.000 claims 2
- IDRRCKUGGXLORG-FJXQXJEOSA-N (2s)-2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid;hydrate Chemical compound O.COC1=CC(C[C@H](N)C(O)=O)=CC=C1O IDRRCKUGGXLORG-FJXQXJEOSA-N 0.000 claims 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims 1
- XDPIBZPLNPBUNZ-UHFFFAOYSA-N 3-nitro-5-[3-[4-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl]benzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=2ON=C(N=2)C=2C(=CC=NC=2)C(F)(F)F)=C1 XDPIBZPLNPBUNZ-UHFFFAOYSA-N 0.000 claims 1
- AALAWVYPYCIVLB-UHFFFAOYSA-N 3-nitro-5-[5-[2-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-3-yl]benzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=2N=C(ON=2)C=2C(=NC=CC=2)C(F)(F)F)=C1 AALAWVYPYCIVLB-UHFFFAOYSA-N 0.000 claims 1
- LUMQLEJDPZJMOV-UHFFFAOYSA-N 3-nitro-5-[5-[5-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-3-yl]benzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=2N=C(ON=2)C=2C=C(C=NC=2)C(F)(F)F)=C1 LUMQLEJDPZJMOV-UHFFFAOYSA-N 0.000 claims 1
- WSGQDTOZGCZVEI-UHFFFAOYSA-N 5-[3-(2-bromo-4,5,6-trimethylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]-3-nitrobenzene-1,2-diol Chemical compound CC1=C(C)C(C)=NC(Br)=C1C1=NOC(C=2C=C(C(O)=C(O)C=2)[N+]([O-])=O)=N1 WSGQDTOZGCZVEI-UHFFFAOYSA-N 0.000 claims 1
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Images
Classifications
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D213/57—Nitriles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06007534.8 | 2006-04-10 | ||
| EP06007534A EP1845097A1 (en) | 2006-04-10 | 2006-04-10 | Oxadiazole derivatives as COMT inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080108327A true KR20080108327A (ko) | 2008-12-12 |
Family
ID=37188829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087026652A Withdrawn KR20080108327A (ko) | 2006-04-10 | 2007-04-10 | 신규한 약학적 화합물 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US8536203B2 (enExample) |
| EP (3) | EP1845097A1 (enExample) |
| JP (1) | JP5442434B2 (enExample) |
| KR (1) | KR20080108327A (enExample) |
| CN (1) | CN101454285B (enExample) |
| AR (1) | AR060421A1 (enExample) |
| AU (1) | AU2007235755A1 (enExample) |
| BR (1) | BRPI0711538A2 (enExample) |
| CA (1) | CA2648914C (enExample) |
| ES (1) | ES2565019T3 (enExample) |
| MX (1) | MX2008013020A (enExample) |
| NO (1) | NO20084712L (enExample) |
| RU (1) | RU2008143670A (enExample) |
| WO (1) | WO2007117165A1 (enExample) |
| ZA (1) | ZA200809479B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL169855A (en) * | 2005-07-25 | 2014-05-28 | Elta Systems Ltd | A system and method for locating a receiver location |
| SI1907382T1 (sl) * | 2005-07-26 | 2015-10-30 | Bial-Portela & Ca S.A., | Nitrokateholni derivati kot inhibitorji COMT |
| EP1845097A1 (en) | 2006-04-10 | 2007-10-17 | Portela & Ca., S.A. | Oxadiazole derivatives as COMT inhibitors |
| AU2007334436A1 (en) | 2006-12-15 | 2008-06-26 | Abbott Laboratories | Novel oxadiazole compounds |
| ES2597705T3 (es) * | 2007-01-31 | 2017-01-20 | Bial - Portela & Ca., S.A. | Derivados de nitrocatecol como inhibidores de COMT administrados con un régimen de dosificación específico |
| EP2217571A2 (en) * | 2007-10-24 | 2010-08-18 | BIAL - Portela & Ca., S.A. | Novel precursors |
| TWI415607B (zh) | 2007-12-25 | 2013-11-21 | Kissei Pharmaceutical | 新穎兒茶酚衍生物、含有其之醫藥組成物及該等之用途 |
| EP2259777A2 (en) * | 2008-02-28 | 2010-12-15 | BIAL - Portela & Ca., S.A. | Pharmaceutical composition for poorly soluble drugs |
| EP2276758B1 (en) | 2008-03-17 | 2016-01-06 | Bial-Portela & CA, S.A. | Crystal forms of 5- [3- (2, 5-dichloro-4, 6-dimethyl-1-oxy-pyridine-3-yl) [1,2,4] oxadiazol-5-yl]-3-nit robenzene-1, 2-diol |
| PT2307020T (pt) * | 2008-07-29 | 2019-05-28 | Bial Portela & Ca Sa | Regime de administração de nitrocatecólicos |
| KR102329271B1 (ko) | 2009-04-01 | 2021-11-22 | 바이알 - 포르텔라 앤드 씨에이 에스에이 | 니트로카테콜 유도체를 포함하는 제약 제제 및 그의 제조 방법 |
| AU2010231962B2 (en) * | 2009-04-01 | 2015-05-21 | Bial - Portela & Ca., S.A. | Pharmaceutical formulations comprising nitrocatechol derivatives and methods of making the same |
| JP5529639B2 (ja) * | 2009-06-18 | 2014-06-25 | キッセイ薬品工業株式会社 | 新規なカテコール−o−メチルトランスフェラーゼ阻害剤 |
| WO2011069075A2 (en) * | 2009-12-04 | 2011-06-09 | Grant Jon E | Treating impulse control disorders with catechol-o- methyl-transferase inhibitors |
| US20140045900A1 (en) | 2011-02-11 | 2014-02-13 | Bial-Portela & Ca, S.A. | Administration regime for nitrocatechols |
| PL2791134T3 (pl) * | 2011-12-13 | 2020-03-31 | BIAL - PORTELA & Cª S.A. | Związek chemiczny użyteczny jako związek pośredni do wytwarzania inhibitora katechol-o-metylotransferazy |
| TWI638802B (zh) | 2012-05-24 | 2018-10-21 | 芬蘭商奧利安公司 | 兒茶酚o-甲基轉移酶活性抑制化合物 |
| RU2017120184A (ru) | 2014-11-28 | 2018-12-28 | БИАЛ - ПОРТЕЛА ЭНД Ка, С.А. | Лекарства для замедления течения болезни паркинсона |
| US10532976B2 (en) * | 2015-06-23 | 2020-01-14 | National Institute Of Biological Sciences, Beijing | FTO inhibitors |
| WO2016206573A1 (en) * | 2015-06-23 | 2016-12-29 | National Institute Of Biological Sciences, Beijing | Fto inhibitors |
| DE102016009081A1 (de) * | 2016-07-26 | 2018-02-01 | Man Truck & Bus Ag | Verfahren und Vorrichtung zur Steuerung oder Regelung einer Fahrerhaus-Lagerung |
| CN108314631A (zh) * | 2018-04-19 | 2018-07-24 | 中国科学院昆明植物研究所 | 二芳基乙烯类化合物及其药物组合物和其应用 |
| US12097193B2 (en) | 2018-10-05 | 2024-09-24 | Bial—Portela & Ca, S.A. | Methods for the administration of COMT inhibitors |
| CN112375014A (zh) * | 2020-12-17 | 2021-02-19 | 重庆柳江医药科技有限公司 | 一种奥匹卡朋工艺杂质及制备方法和用途 |
| CN116283664B (zh) * | 2023-01-12 | 2025-05-16 | 中国药科大学 | 一种硝基儿茶酚衍生物、包含其的药物组合物及其应用 |
| WO2024260874A1 (en) | 2023-06-19 | 2024-12-26 | Medichem, S.A. | Process for preparing opicapone |
Family Cites Families (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1532178A (en) * | 1921-07-25 | 1925-04-07 | Louis A Godbold | Lubricator |
| FR1260080A (fr) | 1960-03-22 | 1961-05-05 | Materiel De Forage Soc De Fab | Trépan à molettes étanche |
| US3647809A (en) * | 1968-04-26 | 1972-03-07 | Chinoin Gyogyszer Es Vegyeszet | Certain pyridyl-1 2 4-oxadiazole derivatives |
| US4022901A (en) * | 1975-03-05 | 1977-05-10 | E. R. Squibb & Sons, Inc. | 3-Pyridinyl-5-isothiocyanophenyl oxadiazoles |
| US4264573A (en) | 1979-05-21 | 1981-04-28 | Rowell Laboratories, Inc. | Pharmaceutical formulation for slow release via controlled surface erosion |
| JPS599374B2 (ja) * | 1979-10-11 | 1984-03-02 | 株式会社小松製作所 | ブルド−ザ作業における自動減速装置 |
| US4386668A (en) | 1980-09-19 | 1983-06-07 | Hughes Tool Company | Sealed lubricated and air cooled rock bit bearing |
| DK175069B1 (da) * | 1986-03-11 | 2004-05-24 | Hoffmann La Roche | Pyrocatecholderivater |
| US5236952A (en) * | 1986-03-11 | 1993-08-17 | Hoffmann-La Roche Inc. | Catechol derivatives |
| YU213587A (en) * | 1986-11-28 | 1989-06-30 | Orion Yhtymae Oy | Process for obtaining new pharmacologic active cateholic derivatives |
| DE3840954A1 (de) | 1988-12-05 | 1990-06-07 | Shell Int Research | Herstellung von 2-chlornicotinsaeureestern |
| US5206372A (en) | 1990-06-05 | 1993-04-27 | Shell Research Limited | Preparation of 2-chloropyridine derivatives |
| DE69013689T2 (de) * | 1990-11-29 | 1995-03-02 | Wei Ming Pharmaceutical Mfg Co | Hilfsträger für direkte Verpressung. |
| AU3171493A (en) | 1991-12-31 | 1993-07-28 | Fujisawa Pharmaceutical Co., Ltd. | Oxadiazole derivatives having acetylcholinesterase-inhibitory and muscarinic agonist activity |
| FR2730322B1 (fr) | 1995-02-02 | 1997-04-30 | Imago | Monture de lunettes metallique |
| DE19628617A1 (de) | 1996-07-16 | 1998-01-22 | Basf Ag | Direkttablettierhilfsmittel |
| US6206110B1 (en) * | 1996-09-09 | 2001-03-27 | Smith International, Inc. | Protected lubricant reservoir with pressure control for sealed bearing earth boring drill bit |
| CA2337755C (en) * | 1998-09-18 | 2008-07-29 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| GB2344819A (en) * | 1998-12-18 | 2000-06-21 | Portela & Ca Sa | 2-Phenyl-1-(3,4-dihydroxy-5-nitrophenyl)-1-ethanones |
| FI109453B (fi) | 1999-06-30 | 2002-08-15 | Orion Yhtymae Oyj | Farmaseuttinen koostumus |
| ATE307129T1 (de) | 1999-08-19 | 2005-11-15 | Nps Pharma Inc | Heteropolycyclische verbindungen und ihre verwendung als antagonisten von metabotropen glutamatrezeptoren |
| US6660753B2 (en) * | 1999-08-19 | 2003-12-09 | Nps Pharmaceuticals, Inc. | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| FI20000635A0 (fi) | 2000-03-17 | 2000-03-17 | Orion Yhtymae Oyj | COMT-inhibiittoreiden käyttö analgeettina |
| SE0001438D0 (sv) * | 2000-04-18 | 2000-04-18 | Axon Chemicals Bv | New chemical compounds and their use in therapy |
| DE10029201A1 (de) | 2000-06-19 | 2001-12-20 | Basf Ag | Verfahren zur Herstellung fester oraler Darreichungsformen mit retardierender Wirkstoffreisetzung |
| GB2363792A (en) * | 2000-06-21 | 2002-01-09 | Portela & Ca Sa | Nitrocatechols |
| JP3965361B2 (ja) | 2000-08-24 | 2007-08-29 | 佐川急便株式会社 | 物流又は運送に関わるサービス料金のカード決済方法及びそのシステム |
| CN1166626C (zh) * | 2000-08-30 | 2004-09-15 | 李凌松 | 三或四取代苯基化合物、其制备方法及应用 |
| DE60140213D1 (de) | 2000-11-28 | 2009-11-26 | Zymogenetics L L C | Zytokine rezeptor zcytor19 |
| CA2436739A1 (en) | 2000-12-26 | 2002-07-04 | Takeda Chemical Industries, Ltd. | Combination agent |
| US20040097555A1 (en) * | 2000-12-26 | 2004-05-20 | Shinegori Ohkawa | Concomitant drugs |
| DE10107528B4 (de) | 2001-02-17 | 2006-05-11 | Chiroblock Gmbh | Verfahren zur Herstellung der Enantiomere der 2-substituierten beta-Aminosäuren |
| PL369598A1 (en) | 2001-02-21 | 2005-05-02 | Nps Pharmaceuticals, Inc. | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| AU2002310187A1 (en) | 2001-05-30 | 2002-12-09 | Lg Biomedical Institute | Inhibitors of protein kinase for the treatment of disease |
| CN1638776A (zh) * | 2001-06-08 | 2005-07-13 | 西托维亚公司 | 取代的3-芳基-5-芳基-[1,2,4]-噁二唑和类似物 |
| MXPA04000775A (es) * | 2001-07-26 | 2004-04-20 | Merck Patent Ges Mit Baschrank | Uso novedoso del 2 -[5-(4-fluorofenil) -3-piridilmetilamino-metil] -cromano y sus sales fisiologicamente aceptables. |
| JP4379853B2 (ja) | 2001-10-05 | 2009-12-09 | 惠民製藥股▲分▼有限公司 | 直接錠剤化用調合物および補助剤の調合方法 |
| PE20081058A1 (es) * | 2002-08-03 | 2008-09-04 | Clariant Produkte Deutschland | Proceso para la flotacion de menas del tipo de sulfuros |
| EP1581213A4 (en) * | 2002-12-18 | 2008-11-19 | Cytovia Inc | 3,5-DISUBSTITUTED 1,2,4-OXADIAZOLE AND ANALOGUE TO ACTIVATE CASPASE AND INTRODUCTION OF APOPTOSIS AND THEIR USE |
| WO2005006945A2 (en) * | 2003-07-03 | 2005-01-27 | The Salk Institute For Biological Studies | Methods for treating neural disorders and compounds useful therefor |
| AR045731A1 (es) | 2003-08-06 | 2005-11-09 | Vertex Pharma | Compuestos de aminotriazol utiles como inhibidores de quinasas de proteinas |
| DE10338174A1 (de) | 2003-08-20 | 2005-03-24 | Lts Lohmann Therapie-Systeme Ag | Transdermale Arzneimittelzubereitungen mit Wirkstoffkombinationen zur Behandlung der Parkinson-Krankheit |
| US7300406B2 (en) | 2003-09-30 | 2007-11-27 | Carter Vandette B | Medical examination apparatus |
| GB0325956D0 (en) * | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| EP1751133B1 (en) * | 2004-04-28 | 2010-04-14 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of rock and other protein kinases |
| GB0510143D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds A1 |
| US20060173074A1 (en) | 2004-11-10 | 2006-08-03 | Juha Ellmen | Treatment of restless legs syndrome |
| WO2006061697A1 (en) | 2004-12-06 | 2006-06-15 | Themis Laboratories Private Limited | Sulfonylurea compositions and a process for its preparation |
| WO2006071184A1 (en) | 2004-12-28 | 2006-07-06 | Astrazeneca Ab | Aryl sulphonamide modulators |
| US20080051441A1 (en) * | 2004-12-28 | 2008-02-28 | Astrazeneca Ab | Aryl Sulphonamide Modulators |
| JP2008539195A (ja) | 2005-04-26 | 2008-11-13 | ノイロサーチ アクティーゼルスカブ | 新規のオキサジアゾール誘導体及びそれらの医学的使用 |
| US20060257473A1 (en) | 2005-05-11 | 2006-11-16 | Porranee Puranajoti | Extended release tablet |
| GB0510139D0 (en) * | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B1 |
| US7553964B2 (en) * | 2005-06-03 | 2009-06-30 | Abbott Laboratories | Cyclobutyl amine derivatives |
| JP2007024970A (ja) | 2005-07-12 | 2007-02-01 | Miyakawa:Kk | 液晶表示装置の開口効率を上昇させるための樹脂レンズ製造法及びその製造装置 |
| US20090000437A1 (en) | 2005-07-14 | 2009-01-01 | Provo Craft And Novelty, Inc. | Methods for Cutting |
| SI1907382T1 (sl) | 2005-07-26 | 2015-10-30 | Bial-Portela & Ca S.A., | Nitrokateholni derivati kot inhibitorji COMT |
| FR2889525A1 (fr) * | 2005-08-04 | 2007-02-09 | Palumed Sa | Nouveaux derives de polyquinoleines et leur utilisation therapeutique. |
| US20070048384A1 (en) * | 2005-08-26 | 2007-03-01 | Joerg Rosenberg | Pharmaceutical compositions |
| EP1954137A4 (en) * | 2005-11-18 | 2008-12-17 | Janssen Pharmaceutica Nv | 2-KETO-OXAZOLE AS MODULATORS OF FATTY ACID AMIDHYDROLASE |
| US8022075B2 (en) * | 2005-11-30 | 2011-09-20 | Fujifilm Ri Pharma Co., Ltd. | Diagnostic and remedy for disease caused by amyloid aggregation and/or deposition |
| GB0606774D0 (en) | 2006-04-03 | 2006-05-10 | Novartis Ag | Organic compounds |
| EP1845097A1 (en) | 2006-04-10 | 2007-10-17 | Portela & Ca., S.A. | Oxadiazole derivatives as COMT inhibitors |
| PE20080906A1 (es) | 2006-08-17 | 2008-07-05 | Kemia Inc | Derivados heteroarilo como inhibidores de citocina |
| US20080167286A1 (en) * | 2006-12-12 | 2008-07-10 | Abbott Laboratories | Pharmaceutical compositions and their methods of use |
| US8486979B2 (en) * | 2006-12-12 | 2013-07-16 | Abbvie Inc. | 1,2,4 oxadiazole compounds and methods of use thereof |
| ES2597705T3 (es) | 2007-01-31 | 2017-01-20 | Bial - Portela & Ca., S.A. | Derivados de nitrocatecol como inhibidores de COMT administrados con un régimen de dosificación específico |
| JP5718053B2 (ja) | 2007-08-27 | 2015-05-13 | ヘリコン・セラピューティクス・インコーポレーテッド | 治療用イソオキサゾール化合物 |
| EP2259777A2 (en) * | 2008-02-28 | 2010-12-15 | BIAL - Portela & Ca., S.A. | Pharmaceutical composition for poorly soluble drugs |
| EP2276758B1 (en) | 2008-03-17 | 2016-01-06 | Bial-Portela & CA, S.A. | Crystal forms of 5- [3- (2, 5-dichloro-4, 6-dimethyl-1-oxy-pyridine-3-yl) [1,2,4] oxadiazol-5-yl]-3-nit robenzene-1, 2-diol |
| PT2307020T (pt) | 2008-07-29 | 2019-05-28 | Bial Portela & Ca Sa | Regime de administração de nitrocatecólicos |
| AU2010231962B2 (en) | 2009-04-01 | 2015-05-21 | Bial - Portela & Ca., S.A. | Pharmaceutical formulations comprising nitrocatechol derivatives and methods of making the same |
| KR102329271B1 (ko) | 2009-04-01 | 2021-11-22 | 바이알 - 포르텔라 앤드 씨에이 에스에이 | 니트로카테콜 유도체를 포함하는 제약 제제 및 그의 제조 방법 |
| WO2011107653A2 (en) | 2010-03-04 | 2011-09-09 | Orion Corporation | Method for treating parkinson's disease |
| US20140045900A1 (en) | 2011-02-11 | 2014-02-13 | Bial-Portela & Ca, S.A. | Administration regime for nitrocatechols |
| PL2791134T3 (pl) | 2011-12-13 | 2020-03-31 | BIAL - PORTELA & Cª S.A. | Związek chemiczny użyteczny jako związek pośredni do wytwarzania inhibitora katechol-o-metylotransferazy |
-
2006
- 2006-04-10 EP EP06007534A patent/EP1845097A1/en not_active Withdrawn
-
2007
- 2007-04-10 US US12/226,260 patent/US8536203B2/en not_active Expired - Fee Related
- 2007-04-10 RU RU2008143670/04A patent/RU2008143670A/ru not_active Application Discontinuation
- 2007-04-10 ES ES07747756.0T patent/ES2565019T3/es active Active
- 2007-04-10 CN CN2007800191312A patent/CN101454285B/zh not_active Expired - Fee Related
- 2007-04-10 MX MX2008013020A patent/MX2008013020A/es not_active Application Discontinuation
- 2007-04-10 WO PCT/PT2007/000016 patent/WO2007117165A1/en not_active Ceased
- 2007-04-10 AU AU2007235755A patent/AU2007235755A1/en not_active Abandoned
- 2007-04-10 AR ARP070101517A patent/AR060421A1/es unknown
- 2007-04-10 CA CA2648914A patent/CA2648914C/en active Active
- 2007-04-10 EP EP12179360.8A patent/EP2617713A1/en not_active Withdrawn
- 2007-04-10 KR KR1020087026652A patent/KR20080108327A/ko not_active Withdrawn
- 2007-04-10 BR BRPI0711538-5A patent/BRPI0711538A2/pt not_active IP Right Cessation
- 2007-04-10 EP EP07747756.0A patent/EP2027091B1/en active Active
- 2007-04-10 JP JP2009505314A patent/JP5442434B2/ja active Active
-
2008
- 2008-11-06 ZA ZA200809479A patent/ZA200809479B/xx unknown
- 2008-11-07 NO NO20084712A patent/NO20084712L/no not_active Application Discontinuation
-
2013
- 2013-08-30 US US14/014,548 patent/US9446012B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| NO20084712L (no) | 2008-12-30 |
| CN101454285B (zh) | 2012-06-27 |
| EP2027091A1 (en) | 2009-02-25 |
| CN101454285A (zh) | 2009-06-10 |
| US20140024682A1 (en) | 2014-01-23 |
| EP2027091B1 (en) | 2016-01-06 |
| JP2009533423A (ja) | 2009-09-17 |
| WO2007117165A1 (en) | 2007-10-18 |
| EP2617713A1 (en) | 2013-07-24 |
| RU2008143670A (ru) | 2010-05-20 |
| AU2007235755A1 (en) | 2007-10-18 |
| AR060421A1 (es) | 2008-06-18 |
| MX2008013020A (es) | 2008-12-18 |
| JP5442434B2 (ja) | 2014-03-12 |
| ES2565019T3 (es) | 2016-03-30 |
| US8536203B2 (en) | 2013-09-17 |
| EP1845097A1 (en) | 2007-10-17 |
| US9446012B2 (en) | 2016-09-20 |
| CA2648914A1 (en) | 2007-10-18 |
| BRPI0711538A2 (pt) | 2011-11-01 |
| US20100168113A1 (en) | 2010-07-01 |
| CA2648914C (en) | 2016-08-02 |
| ZA200809479B (en) | 2009-10-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20081030 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |