DE60305063T2 - Ccr1-rezeptor-antagonisten zur behandlung von u.a. demyelinisierenden entzündlichen erkrankungen - Google Patents
Ccr1-rezeptor-antagonisten zur behandlung von u.a. demyelinisierenden entzündlichen erkrankungen Download PDFInfo
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- DE60305063T2 DE60305063T2 DE2003605063 DE60305063T DE60305063T2 DE 60305063 T2 DE60305063 T2 DE 60305063T2 DE 2003605063 DE2003605063 DE 2003605063 DE 60305063 T DE60305063 T DE 60305063T DE 60305063 T2 DE60305063 T2 DE 60305063T2
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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
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Landscapes
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (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)
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| 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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| DE60332663T Expired - Lifetime DE60332663D1 (de) | 2002-11-13 | 2003-11-12 | CCR1-Rezeptor-Antagonisten zur Behandlung u.a. Demyelinisierender entzündlicher Erkrankungen |
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| 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 |
| ATE553761T1 (de) | 2004-12-17 | 2012-05-15 | Millennium Pharm Inc | Solide formen eines chemokin-rezeptorantagonisten und anwendungsverfahren dafür |
| MX2007007599A (es) | 2004-12-21 | 2007-12-07 | Serono Lab | Dervivados ciclicos de sulfonilamino y uso de los mismos. |
| PL1844032T3 (pl) | 2005-01-31 | 2011-09-30 | Merck Serono Sa | Pochodne N-hydroksyamidu i ich zastosowanie |
| KR20080044836A (ko) | 2005-07-15 | 2008-05-21 | 라보라뚜와르 세로노 에스. 에이. | 자궁내막증 치료용 ｊｎｋ 억제제 |
| BRPI0613042A2 (pt) | 2005-07-15 | 2010-12-14 | Serono Lab | inibidores de jnk para o tratamento de endometriose |
| JP2009507003A (ja) | 2005-09-01 | 2009-02-19 | アレス トレーディング ソシエテ アノニム | 視神経炎の治療 |
| US7601844B2 (en) | 2006-01-27 | 2009-10-13 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
| BRPI0714811A2 (pt) * | 2006-07-14 | 2014-02-18 | Lilly Co Eli | Modulador de receptor de corticóide, seus sais, composições farmacêuticas compreendendo os mesmos e uso dos referidos compostos e sais na fabricação de medicamento |
| 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 |
| JP2011505364A (ja) * | 2007-11-30 | 2011-02-24 | 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 | ＴＭＥＤＡを用いた５−シクロプロピル−５，１１−ジヒドロ［１］ベンゾオキセピノ［３，４−ｂ］−ピリジン−５−オールの製造方法 |
| US20090286823A1 (en) * | 2007-12-17 | 2009-11-19 | Millennium Pharmaceuticals Inc. | CCR1 Inhibitors useful for the treatment of multiple myeloma and other disorders |
| ATE522537T1 (de) | 2008-01-11 | 2011-09-15 | Lilly Co Eli | (e)-n-ä3-ä1-(8-fluor-11h-10-oxa-1-aza-dibenzo-ä , dü-cyclohepten-5-yliden)-propylü-phenylü- methylsulfon-amid als glucocorticoid- rezeptormodulator zur behandlung rheumatoider 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 |
| CA2852160A1 (en) | 2011-10-28 | 2013-05-02 | Galderma Research & Development | New leukocyte infiltrate markers for rosacea and uses thereof |
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| JPS4830064B1 (https=) | 1968-12-23 | 1973-09-17 | ||
| GB1330966A (en) | 1970-12-22 | 1973-09-19 | Yoshitomi Pharmaceutical | N-substituted piperidine compounds methods for their production and pharmaceutical compositions containing them |
| US3770729A (en) * | 1970-12-22 | 1973-11-06 | Yoshitomi Pharmaceutical | N substituted piperidine compounds |
| 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 |
| WO1988000049A1 (fr) | 1986-06-26 | 1988-01-14 | Kyowa Hakko Kogyo Co., Ltd. | Agent antiarythmique |
| 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 |
| EP0411048A1 (en) | 1988-04-28 | 1991-02-06 | Schering Corporation | Novel benzopyrido piperidine, piperidylidene and piperazine compounds, compositions, methods of manufacture and methods of use |
| US5242931A (en) * | 1988-06-09 | 1993-09-07 | Kyowa Hakko Kogyo Co., Ltd. | Tricyclic compounds as TXA2 antagonists |
| CA1338625C (en) * | 1988-06-09 | 1996-10-01 | Kyowa Hakko Kogyo Co., Ltd. | Tricyclic compounds |
| 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 |
| EP0511477B1 (en) * | 1991-03-11 | 1996-07-10 | Kyowa Hakko Kogyo Co., Ltd. | Indole derivatives |
| 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 |
| WO1993002081A1 (en) | 1991-07-23 | 1993-02-04 | Schering Corporation | Novel 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 |
| DE69333885T2 (de) | 1992-11-10 | 2006-09-14 | Genentech, Inc., South San Francisco | 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 |
| AU5270796A (en) | 1995-04-07 | 1996-10-23 | Novo Nordisk A/S | N-substituted azaheterocyclic carboxylic acids and esters th ereof |
| 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 |
| WO1996031470A1 (en) | 1995-04-07 | 1996-10-10 | Novo Nordisk A/S | 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 |
| JPH0940662A (ja) | 1995-05-24 | 1997-02-10 | Kyowa Hakko Kogyo Co Ltd | 三環式化合物 |
| US6150355A (en) * | 1995-09-13 | 2000-11-21 | Kyowa Hakko Kogyo Co., Ltd. | Phenylpiperidine derivative |
| AU1208397A (en) | 1995-12-28 | 1997-07-28 | Takeda Chemical Industries Ltd. | Diphenylmethane derivatives as mip-1alpha/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 |
| DE69709647T2 (de) | 1996-05-20 | 2002-11-07 | Dupont Pharmaceuticals Research Laboratories, Inc. | Cyclischer diarylalkyl diaminederivate als antogoniste von chemokinerezeptoren |
| JP2000516210A (ja) | 1996-07-12 | 2000-12-05 | ロイコサイト，インコーポレーテッド | ケモカインレセプターアンタゴニストとその使用方法 |
| US6323206B1 (en) | 1996-07-12 | 2001-11-27 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| CA2261633A1 (en) | 1996-07-29 | 1998-02-05 | Banyu Pharmaceutical Co., Ltd. | Chemokine receptor antagonists |
| IL128949A0 (en) | 1996-09-13 | 2000-02-17 | Schering Corp | Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases |
| AU4801197A (en) | 1996-09-13 | 1998-04-02 | Schering Corporation | Tricyclic antitumor compounds being farnesyl protein transferase inhibit ors |
| CN1104427C (zh) | 1996-09-13 | 2003-04-02 | 先灵公司 | 法呢基蛋白转移酶的三环抑制剂 |
| CZ84199A3 (cs) | 1996-09-13 | 1999-11-17 | Schering Corporation | Nové, tricyklické piperidinylové sloučeniny použitelné jako inhibitory farnesylprotein transferasy |
| CN1237176A (zh) | 1996-09-13 | 1999-12-01 | 先灵公司 | 用作fpt抑制剂的三环化合物 |
| CA2264666A1 (en) | 1996-09-13 | 1998-03-19 | Schering Corporation | Substituted benzocycloheptapyridine useful as inhibitors of farnesyl-protein transferase |
| NZ334437A (en) | 1996-09-13 | 2000-09-29 | Schering Corp | Substituted benzocycloheptapyridine derivatives useful for inhibition of farnesyl protein transferase |
| CA2267500A1 (en) | 1996-10-04 | 1998-04-16 | Novo Nordisk A/S | N-substituted azaheterocyclic compounds |
| ZA978792B (en) | 1996-10-04 | 1998-04-06 | Novo Nordisk As | N-substituted azaheterocyclic compounds. |
| WO1998015548A1 (en) | 1996-10-04 | 1998-04-16 | Novo Nordisk A/S | 1,4-disubstituted piperazines |
| AU5604998A (en) | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Spiro-substituted azacycles as modulators of chemokine receptor activity |
| WO1998025605A1 (en) | 1996-12-13 | 1998-06-18 | Merck & Co., Inc. | Spiro-substituted azacycles as modulators of chemokine receptor activity |
| AU5522498A (en) | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Substituted aryl piperazines 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 |
| AU6517398A (en) | 1997-03-27 | 1998-10-22 | Kyowa Hakko Kogyo Co. Ltd. | Therapeutic agent for autoimmune diseases |
| ES2273413T3 (es) | 1997-04-15 | 2007-05-01 | Kyowa Hakko Kogyo Co., Ltd. | Compuestos triciclicos. |
| 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 |
| US6040318A (en) | 1997-06-25 | 2000-03-21 | Novo Nordisk A/S | Tricycle substituted with azaheterocyclic carboxylic acids |
| 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 |
| US6048856A (en) * | 1997-12-17 | 2000-04-11 | Novo Nordisk A/S | Heterocyclic compounds |
| US6433165B1 (en) * | 1998-01-21 | 2002-08-13 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| BR9910144A (pt) * | 1998-01-21 | 2002-04-02 | Millennium Pharm Inc | Antagonistas de receptores de quimiocinas e seu uso |
| US6613905B1 (en) * | 1998-01-21 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6509346B2 (en) * | 1998-01-21 | 2003-01-21 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| CA2343536A1 (en) | 1998-09-04 | 2000-03-16 | Yoshisuke Nakasato | Chemokine receptor antagonists and methods of use therefor |
| MXPA04004826A (es) | 1998-09-04 | 2004-08-11 | Millenium Pharmaceuticals Inc | Antagonista del receptor de quimioquinas y metodos para su uso. |
| 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 |
| US6288083B1 (en) * | 1998-09-04 | 2001-09-11 | 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 |
| EP1204664A1 (en) * | 1999-07-28 | 2002-05-15 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| EP1204640A2 (en) | 1999-07-28 | 2002-05-15 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| NZ596484A (en) * | 2001-11-21 | 2013-05-31 | 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 |
| DE112005000053T5 (de) | 2005-04-20 | 2007-05-31 | Mitsubishi Denki K.K. | Überstromrelais |
| 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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