JP4644491B2 - Ｉ．ａ．脱髄炎症疾患の処置のためのｃｃｒ１アンタゴニスト - Google Patents
Ｉ．ａ．脱髄炎症疾患の処置のためのｃｃｒ１アンタゴニスト Download PDFInfo
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- JP4644491B2 JP4644491B2 JP2004552003A JP2004552003A JP4644491B2 JP 4644491 B2 JP4644491 B2 JP 4644491B2 JP 2004552003 A JP2004552003 A JP 2004552003A JP 2004552003 A JP2004552003 A JP 2004552003A JP 4644491 B2 JP4644491 B2 JP 4644491B2
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- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
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Classifications
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
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- Life Sciences & Earth Sciences (AREA)
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- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
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| US42594702P | 2002-11-13 | 2002-11-13 | |
| PCT/US2003/035817 WO2004043965A1 (en) | 2002-11-13 | 2003-11-12 | Ccr1 antagonists for the treatment of i.a. demyelinating inflammatory disease |
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| US7271176B2 (en) * | 1998-09-04 | 2007-09-18 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use thereof |
| US7541365B2 (en) * | 2001-11-21 | 2009-06-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| TWI291467B (en) | 2002-11-13 | 2007-12-21 | Millennium Pharm Inc | CCR1 antagonists and methods of use therefor |
| US7838522B2 (en) | 2004-11-17 | 2010-11-23 | Ares Trading S.A. | Benzothiazole formulations and use thereof |
| AU2005316340B2 (en) * | 2004-12-17 | 2012-01-19 | Millennium Pharmaceuticals, Inc. | Solid forms of a chemokine receptor antagonist and methods of use thereof |
| CN101124213B (zh) | 2004-12-21 | 2012-02-01 | 默克雪兰诺有限公司 | 磺酰氨基环状衍生物及其应用 |
| KR20070105326A (ko) | 2005-01-31 | 2007-10-30 | 라보라뚜와르 세로노 에스. 에이. | Ｎ-하이드록시아미드 유도체 및 그것의 용도 |
| BRPI0613042A2 (pt) | 2005-07-15 | 2010-12-14 | Serono Lab | inibidores de jnk para o tratamento de endometriose |
| KR20080044836A (ko) | 2005-07-15 | 2008-05-21 | 라보라뚜와르 세로노 에스. 에이. | 자궁내막증 치료용 ｊｎｋ 억제제 |
| AU2006286489B2 (en) | 2005-09-01 | 2012-08-09 | Ares Trading S.A. | Treatment of optic neuritis |
| US7601844B2 (en) | 2006-01-27 | 2009-10-13 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
| EP2043646B1 (en) * | 2006-07-14 | 2012-05-16 | Eli Lilly And Company | (E)-N-{3-(8-Chloro-11H-10-oxa-1-aza- dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-phenyl} -methanesulfonamide as a GLUCOCORTICOID RECEPTOR MODULATOR AND METHODS OF USE |
| EP2173713B1 (en) | 2007-07-24 | 2016-02-17 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
| WO2009082526A2 (en) * | 2007-10-05 | 2009-07-02 | Pharmacopeia, Inc. | Ortho pyrrolidine, benzyl-substituted heterocycle ccr1 antagonists for autoimmune diseases & inflammation |
| EP2231675A1 (en) * | 2007-11-30 | 2010-09-29 | Millennium Pharmaceuticals, Inc. | Process for the preparation of 5-cyclopropyl-5, 11-dihydro (1) benzoxepino (3, 4-b) -pyridin-5-ol using tmeda |
| US20090286823A1 (en) * | 2007-12-17 | 2009-11-19 | Millennium Pharmaceuticals Inc. | CCR1 Inhibitors useful for the treatment of multiple myeloma and other disorders |
| EP2231676B1 (en) | 2008-01-11 | 2011-08-31 | Eli Lilly & Company | (e)-n-{3-[1-(8-fluoro-11h-10-oxa-1-aza-dibenzo-[a,d]-cyclohepten-5-ylidene)-propyl]-phenyl }-methynsulfon amide as glucocorticoid receptor modulator for the treatment of rheumatoid arthritis |
| TWI433838B (zh) | 2008-06-25 | 2014-04-11 | 必治妥美雅史谷比公司 | 作為趨化因子受體活性調節劑之六氫吡啶衍生物 |
| EP2771484A1 (en) | 2011-10-28 | 2014-09-03 | Galderma Research & Development | New leukocyte infiltrate markers for rosacea and uses thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999037651A1 (en) * | 1998-01-21 | 1999-07-29 | Millenium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| WO2001009137A1 (en) * | 1999-07-28 | 2001-02-08 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| JP2002501072A (ja) * | 1998-01-21 | 2002-01-15 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | ケモカイン受容体アンタゴニストおよびその使用方法 |
| US20020119973A1 (en) * | 1998-01-21 | 2002-08-29 | Jay R. Luly | Chemokine receptor antagonists and methods of use therefor |
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| CH416624A (de) | 1962-10-23 | 1966-07-15 | Sandoz Ag | Verfahren zur Herstellung von neuen heterocyclischen Verbindungen |
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| CH421138A (de) | 1965-11-04 | 1966-09-30 | Wander Ag Dr A | Verfahren zur Herstellung von Thioxanthenderivaten |
| US3409621A (en) * | 1966-04-01 | 1968-11-05 | Schering Corp | Piperazino-aza-dibenzo-[a, d]-cycloheptenes |
| US3625974A (en) | 1967-04-28 | 1971-12-07 | Fujisawa Pharmaceutical Co | Dibenzothiazepine derivatives |
| GB1206216A (en) | 1967-07-18 | 1970-09-23 | Pfizer & Co C | Aminopropylidene dibenzoxepine tranquilizers |
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| GB1330966A (en) | 1970-12-22 | 1973-09-19 | Yoshitomi Pharmaceutical | N-substituted piperidine compounds methods for their production and pharmaceutical compositions containing them |
| DE2163657A1 (de) | 1970-12-22 | 1972-07-13 | Yoshitomi Pharmaceutical Industries Ltd., Osaka (Japan) | N-substituierte Piperidinverbindungen |
| JPS5146625Y2 (US07732459-20100608-C00017.png) | 1971-03-24 | 1976-11-10 | ||
| GB1347935A (en) | 1971-04-10 | 1974-02-27 | Yoshitomi Pharmaceutical | Piperazine derivatives methods for their production and phar maceutical compositions containing them |
| CA1010870A (en) * | 1972-12-08 | 1977-05-24 | Niels Lassen | Thiaxanthene derivative and method |
| US4250176A (en) * | 1976-12-21 | 1981-02-10 | Janssen Pharmaceutica N.V. | Piperazine derivatives |
| US4335122A (en) * | 1981-03-18 | 1982-06-15 | Hoechst-Roussel Pharmaceuticals Inc. | Dihydro-dibenzoxepines-thiepines and -morphanthridones, compositions and use |
| DE3326641A1 (de) | 1982-07-27 | 1984-02-02 | Basf Ag, 6700 Ludwigshafen | 5,6-dihydro-11-h-morphantridin-6-one, ihre herstellung und diese enthaltende arzneimittel |
| CA1237428A (en) * | 1983-06-24 | 1988-05-31 | Hiroshi Tanaka | ¬1| benzepino¬3,4-b|pyridine derivative |
| ES8502099A1 (es) | 1983-08-02 | 1984-12-16 | Espanola Farma Therapeut | Procedimiento de obtencion de nuevos compuestos derivados de la difenil-metilen-etilamina. |
| DE3402060A1 (de) * | 1984-01-21 | 1985-08-01 | Dr. Karl Thomae Gmbh, 7950 Biberach | Substituierte 5,11-dihydro-6h-dibenz(b,e)azepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| CS236550B1 (cs) | 1984-02-02 | 1985-05-15 | Miroslav Protiva | Způsob přípravy esterů piperazinoalkanolů dibenzo(b,e)thiepinové řady a jejich solí s kyselinou maleinovou |
| CS236549B1 (cs) | 1984-02-02 | 1985-05-15 | Miroslav Protiva | Piperazinoalkanoly dibenzo(b,e)thiepinové řady a jejich soli s kyselinou maleinovou |
| CS240698B1 (cs) | 1984-10-12 | 1986-02-13 | Miroslav Protiva | Substituované ll-(piperidinoalkyl)-6,ll-dihydrodibenzo (b,e)thiepin-ll-karbonitrily |
| JPH0665664B2 (ja) | 1985-01-18 | 1994-08-24 | 大塚製薬株式会社 | モルフアントリジン誘導体 |
| SE8500273D0 (sv) * | 1985-01-22 | 1985-01-22 | Leo Ab | Nya tricykliska foreningar, kompositioner innehallande sadana foreningar, framstellningsforfaranden och behandlingsmetoder |
| JPS6310784A (ja) | 1986-03-03 | 1988-01-18 | Kyowa Hakko Kogyo Co Ltd | 抗アレルギー剤 |
| EP0270692A4 (en) | 1986-06-26 | 1990-12-12 | Kyowa Hakko Kogyo Co., Ltd. | Antiarrhythmic agent |
| US5089496A (en) * | 1986-10-31 | 1992-02-18 | Schering Corporation | Benzo[5,6]cycloheptapyridine compounds, compositions and method of treating allergies |
| IT8721978A0 (it) | 1987-09-21 | 1987-09-21 | Angeli Inst Spa | Nuovi derivati ammidinici triciclici. |
| US4882351A (en) * | 1987-10-14 | 1989-11-21 | Roussel Uclaf | Tricyclic compounds |
| AU612437B2 (en) | 1987-12-14 | 1991-07-11 | Kyowa Hakko Kogyo Co. Ltd. | Tricyclic compounds |
| ES2056214T3 (es) | 1988-04-28 | 1994-10-01 | Schering Corp | Compuestos de benzopirido-piperidina, -piperidilideno y -piperazina, composiciones, metodos de preparacion y metodos de uso. |
| CA1338625C (en) * | 1988-06-09 | 1996-10-01 | Kyowa Hakko Kogyo Co., Ltd. | Tricyclic compounds |
| US5242931A (en) * | 1988-06-09 | 1993-09-07 | Kyowa Hakko Kogyo Co., Ltd. | Tricyclic compounds as TXA2 antagonists |
| DE3827093A1 (de) | 1988-08-10 | 1990-02-15 | Nattermann A & Cie | Verfahren zur herstellung von hochreinem ebselen |
| DE3838912A1 (de) * | 1988-11-17 | 1990-05-23 | Thomae Gmbh Dr K | Mittel zur behandlung von akuten und chronischen obstruktiven atemwegserkrankungen |
| JPH0694464B2 (ja) * | 1991-01-23 | 1994-11-24 | 協和醗酵工業株式会社 | 三環式化合物およびその中間体 |
| US5239083A (en) * | 1991-03-11 | 1993-08-24 | Kyowa Hakko Kogyo Co., Ltd. | Indole derivatives which inhibit steroid 5α reductase |
| WO1992016226A1 (en) | 1991-03-19 | 1992-10-01 | Smithkline Beecham Corporation | Il-1 inhibitors |
| WO1992020681A1 (en) | 1991-05-23 | 1992-11-26 | Schering Corporation | Novel benzopyrido piperidylidene compounds, compositions, methods of manufacture and methods of use |
| EP0595989A1 (en) | 1991-07-23 | 1994-05-11 | Schering Corporation | Benzopyrido piperylidene compounds, compositions, methods of manufacture and methods of use |
| US5378701A (en) * | 1991-12-27 | 1995-01-03 | Kyowa Hakko Kogyo | Tricyclic compounds |
| US5679703A (en) * | 1992-09-16 | 1997-10-21 | Kyowa Hakko Kogyo, Co., Ltd. | Tricyclic compounds having ACAT inhibiting activity |
| ATE306549T1 (de) | 1992-11-10 | 2005-10-15 | Genentech Inc | C-c ckr-1, ein c-c chemokin rezeptor |
| US5538986A (en) * | 1993-12-06 | 1996-07-23 | Schering Corporation | Tricyclic derivatives, compositions and methods of use |
| MY113463A (en) * | 1994-01-04 | 2002-03-30 | Novo Nordisk As | Novel heterocyclic compounds |
| US5712280A (en) | 1995-04-07 | 1998-01-27 | Schering Corporation | Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| UA54385C2 (uk) | 1995-04-07 | 2003-03-17 | Ново Нордіск А/С | N-заміщені азагетероциклічні карбонові кислоти та їх ефіри, спосіб їх одержання, фармацевтична композиція та спосіб лікування |
| AU5270796A (en) | 1995-04-07 | 1996-10-23 | Novo Nordisk A/S | N-substituted azaheterocyclic carboxylic acids and esters th ereof |
| AU5271096A (en) | 1995-04-07 | 1996-10-23 | Novo Nordisk A/S | Novel heterocyclic compounds |
| US5801175A (en) * | 1995-04-07 | 1998-09-01 | Schering Corporation | Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| JPH0940662A (ja) | 1995-05-24 | 1997-02-10 | Kyowa Hakko Kogyo Co Ltd | 三環式化合物 |
| DE69621469T2 (de) * | 1995-09-13 | 2002-12-12 | Kyowa Hakko Kogyo Co., Ltd. | Phenylpiperidin-derivate |
| WO1997024325A1 (en) | 1995-12-28 | 1997-07-10 | Takeda Chemical Industries, Ltd. | DIPHENYLMETHANE DERIVATIVES AS MIP-1α/RANTES RECEPTOR ANTAGONISTS |
| DE29602088U1 (de) | 1996-02-07 | 1996-04-04 | Bümach Engineering International B.V., Emmen | Verschraubbarer druckmittelbetätigter Arbeitszylinder mit Verschlußteilen zur Kopplung des Zylinderrohres |
| EP0914319B1 (en) | 1996-05-20 | 2001-11-21 | Teijin Limited | Diarylalkyl cyclic diamine derivatives as chemokine receptor antagonists |
| US6323206B1 (en) * | 1996-07-12 | 2001-11-27 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| WO1998002151A2 (en) | 1996-07-12 | 1998-01-22 | Leukosite, Inc. | Chemokine receptor antagonists and methods of use therefor |
| CA2261633A1 (en) | 1996-07-29 | 1998-02-05 | Banyu Pharmaceutical Co., Ltd. | Chemokine receptor antagonists |
| HUP0001109A2 (hu) | 1996-09-13 | 2001-04-28 | Schering Corporation | Triciklusos farnezil-protein transzferáz inhibitorok mint tumorellenes vegyületek |
| KR20000036102A (ko) | 1996-09-13 | 2000-06-26 | 둘락 노먼 씨. | 파르네실-단백질 트랜스퍼라제 억제제로서 유용한 치환된 벤조사이클로헵타피리딘 |
| ES2276435T3 (es) | 1996-09-13 | 2007-06-16 | Schering Corporation | Nuevos compuestos triciclicos de piperidinilo utiles como inhibidores de la farnesil-proteina transferasa. |
| NZ334453A (en) | 1996-09-13 | 2000-08-25 | Schering Corp | Tricyclic inhibitors of farnesyl protein transferase |
| WO1998011106A1 (en) | 1996-09-13 | 1998-03-19 | Schering Corporation | Tricyclic compounds useful as fpt inhibitors |
| KR20000036103A (ko) | 1996-09-13 | 2000-06-26 | 둘락 노먼 씨. | 파르네실 단백질 트랜스퍼라제의 억제에 유용한 치환된벤조사이클로헵타피리딘 유도체 |
| DE69710741T2 (de) | 1996-09-13 | 2002-10-24 | Schering Corp., Kenilworth | Tricyclische verbindungen zur inhibierung der g-protein funktion und für die behandlung von proliferativen erkrankungen |
| ZA978792B (en) | 1996-10-04 | 1998-04-06 | Novo Nordisk As | N-substituted azaheterocyclic compounds. |
| CN1088459C (zh) | 1996-10-04 | 2002-07-31 | 诺沃挪第克公司 | 1,4－二取代的哌嗪 |
| CZ114199A3 (cs) | 1996-10-04 | 1999-09-15 | Novo Nordisk A/S | N-Substituované azaheterocyklické sloučeniny |
| WO1998025617A1 (en) | 1996-12-13 | 1998-06-18 | Merck & Co., Inc. | Substituted aryl piperazines as modulators of chemokine receptor activity |
| AU5604998A (en) | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Spiro-substituted azacycles as modulators of chemokine receptor activity |
| AU5803398A (en) | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Spiro-substituted azacycles as modulators of chemokine receptor activity |
| US5919776A (en) * | 1996-12-20 | 1999-07-06 | Merck & Co., Inc. | Substituted aminoquinolines as modulators of chemokine receptor activity |
| AU5812498A (en) | 1996-12-20 | 1998-07-17 | Merck & Co., Inc. | Substituted aminoquinolines as modulators of chemokine receptor activity |
| WO1998043638A1 (fr) | 1997-03-27 | 1998-10-08 | Kyowa Hakko Kogyo Co., Ltd. | Agent therapeutique pour maladies auto-immunes |
| US5877177A (en) * | 1997-06-17 | 1999-03-02 | Schering Corporation | Carboxy piperidylacetamide tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
| JP2002515914A (ja) | 1997-06-25 | 2002-05-28 | ノボ ノルディスク アクティーゼルスカブ | 新規へテロ環式化合物 |
| US6040318A (en) | 1997-06-25 | 2000-03-21 | Novo Nordisk A/S | Tricycle substituted with azaheterocyclic carboxylic acids |
| US6048856A (en) * | 1997-12-17 | 2000-04-11 | Novo Nordisk A/S | Heterocyclic compounds |
| AU2335699A (en) * | 1998-01-21 | 1999-08-09 | Kyowa Hakko Kogyo Co. Ltd. | Chemokine receptor antagonists and methods of use therefor |
| US6288083B1 (en) | 1998-09-04 | 2001-09-11 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6503926B2 (en) * | 1998-09-04 | 2003-01-07 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US7271176B2 (en) * | 1998-09-04 | 2007-09-18 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use thereof |
| EA008060B1 (ru) | 1998-09-04 | 2007-02-27 | Милленниум Фармасьютикалз, Инк. | Антагонисты хемокинного рецептора и способы их применения |
| WO2000014089A1 (en) | 1998-09-04 | 2000-03-16 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US20020169155A1 (en) * | 1998-09-04 | 2002-11-14 | Millennium Pharmaceuticals, Inc. | Chemokine receptor anagonists and methods of use therefor |
| AU1549500A (en) | 1998-12-02 | 2000-06-19 | Novo Nordisk A/S | Use of n-substituted azaheterocyclic compounds for the manufacture of a pharmaceutical composition for the treatment of indications related to angiogenesis |
| WO2001009094A2 (en) | 1999-07-28 | 2001-02-08 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| NZ532827A (en) * | 2001-11-21 | 2007-09-28 | Millennium Pharm Inc | Chemokine receptor antagonists and methods of use thereof |
| TWI291467B (en) * | 2002-11-13 | 2007-12-21 | Millennium Pharm Inc | CCR1 antagonists and methods of use therefor |
| WO2006114870A1 (ja) | 2005-04-20 | 2006-11-02 | Mitsubishi Denki Kabushiki Kaisha | 過電流継電器 |
| JP4715952B2 (ja) | 2009-02-18 | 2011-07-06 | 村田機械株式会社 | フロッグレッグ型移載装置 |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999037651A1 (en) * | 1998-01-21 | 1999-07-29 | Millenium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6329385B1 (en) * | 1998-01-21 | 2001-12-11 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| JP2002501072A (ja) * | 1998-01-21 | 2002-01-15 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | ケモカイン受容体アンタゴニストおよびその使用方法 |
| US20020119973A1 (en) * | 1998-01-21 | 2002-08-29 | Jay R. Luly | Chemokine receptor antagonists and methods of use therefor |
| WO2001009137A1 (en) * | 1999-07-28 | 2001-02-08 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
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