CA2483594C - Use of edg receptor binding agents in cancer - Google Patents
Use of edg receptor binding agents in cancer Download PDFInfo
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- CA2483594C CA2483594C CA2483594A CA2483594A CA2483594C CA 2483594 C CA2483594 C CA 2483594C CA 2483594 A CA2483594 A CA 2483594A CA 2483594 A CA2483594 A CA 2483594A CA 2483594 C CA2483594 C CA 2483594C
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- alkyl
- inhibitor
- halogen
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- compound
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- A61P35/00—Antineoplastic agents
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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| US44973903P | 2003-02-24 | 2003-02-24 | |
| US60/449,739 | 2003-02-24 | ||
| PCT/EP2003/005125 WO2003097028A1 (en) | 2002-05-16 | 2003-05-15 | Use of edg receptor binding agents in cancer |
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| ITRM20010688A1 (it) | 2001-11-21 | 2003-05-21 | Univ Roma | Composti immunoregolatori. |
| MXPA04006709A (es) | 2002-01-11 | 2004-10-04 | Sankyo Co | Derivados de aminoalcohol o derivados de acido fosfonico y composiciones farmaceuticas que los contienen. |
| CA2488425A1 (en) | 2002-06-07 | 2003-12-18 | Es Cell International Pte Ltd | Methods of regulating differentiation in stem cells |
| DK1602660T3 (da) * | 2003-02-18 | 2011-05-23 | Kyorin Seiyaku Kk | Aminophosphonsyrederivater, additionssalte deraf og S1P-receptormodulatorer |
| GB0500020D0 (en) * | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
| KR20110136901A (ko) | 2004-02-24 | 2011-12-21 | 상꾜 가부시키가이샤 | 아미노 알코올 화합물 |
| US7794713B2 (en) | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
| JP4993407B2 (ja) | 2004-08-04 | 2012-08-08 | 大正製薬株式会社 | トリアゾール誘導体 |
| BRPI0514316A (pt) | 2004-08-13 | 2008-06-10 | Praecis Pharm Inc | métodos e composições para modulação de atividade de receptor de esfingosina-1-fosfato (s1p) |
| EP1812797B1 (en) * | 2004-10-28 | 2013-03-20 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
| GB0513431D0 (en) | 2005-06-30 | 2005-08-10 | Kherion Technology Ltd | Prophylactic compositions and uses |
| GT200600350A (es) * | 2005-08-09 | 2007-03-28 | Formulaciones líquidas | |
| PL1988083T3 (pl) | 2006-02-03 | 2014-08-29 | Taisho Pharmaceutical Co Ltd | Pochodna triazolowa |
| RU2395499C2 (ru) | 2006-02-06 | 2010-07-27 | Тайсо Фармасьютикал Ко., Лтд. | Ингибитор связывания сфингозин-1-фосфата |
| EP2004234A2 (en) * | 2006-04-06 | 2008-12-24 | Novartis AG | Combination of organic compounds |
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| US8614103B2 (en) * | 2006-10-27 | 2013-12-24 | Lpath, Inc. | Compositions and methods for treating sphingosine-1-phosphate (S1P) related ocular diseases and conditions |
| ATE554070T1 (de) | 2007-08-01 | 2012-05-15 | Taisho Pharmaceutical Co Ltd | Hemmer der s1p1-bindung |
| EP2177521A1 (en) | 2008-10-14 | 2010-04-21 | Almirall, S.A. | New 2-Amidothiadiazole Derivatives |
| JP2012508215A (ja) | 2008-11-11 | 2012-04-05 | ノバルティス アーゲー | 有機化合物 |
| CN104788325A (zh) * | 2008-11-11 | 2015-07-22 | 诺华股份有限公司 | 芬戈莫德的结晶形式 |
| US20100160259A1 (en) | 2008-12-22 | 2010-06-24 | Robert Schmouder | Dosage regimen for a s1p receptor agonist |
| MX367667B (es) | 2008-12-22 | 2019-08-30 | Novartis Ag | Régimen de dosificación de un agonista de los receptores de s1p. |
| EP2202232A1 (en) | 2008-12-26 | 2010-06-30 | Laboratorios Almirall, S.A. | 1,2,4-oxadiazole derivatives and their therapeutic use |
| EP2210890A1 (en) | 2009-01-19 | 2010-07-28 | Almirall, S.A. | Oxadiazole derivatives as S1P1 receptor agonists |
| KR20120032538A (ko) | 2009-07-24 | 2012-04-05 | 라티오팜 게엠베하 | 핀골리모드 염의 제조 방법 |
| EP2305660A1 (en) | 2009-09-25 | 2011-04-06 | Almirall, S.A. | New thiadiazole derivatives |
| EP3831371A1 (en) | 2009-09-29 | 2021-06-09 | Novartis AG | Dosage regimen of an s1p receptor modulator |
| EP2343287A1 (en) | 2009-12-10 | 2011-07-13 | Almirall, S.A. | New 2-aminothiadiazole derivatives |
| EP2366702A1 (en) | 2010-03-18 | 2011-09-21 | Almirall, S.A. | New oxadiazole derivatives |
| EP2390252A1 (en) | 2010-05-19 | 2011-11-30 | Almirall, S.A. | New pyrazole derivatives |
| WO2012071524A1 (en) | 2010-11-24 | 2012-05-31 | Ratiopharm Gmbh | Arylsulfonate salts of fingolimod and processes for preparation thereof |
| FR2968556B1 (fr) | 2010-12-13 | 2013-12-27 | Centre Nat Rech Scient | Inhibiteurs des infections a vih et leurs utilisations |
| SG191286A1 (en) | 2011-01-07 | 2013-07-31 | Novartis Ag | Immunosuppressant formulations |
| CN106278999B (zh) | 2011-02-07 | 2019-10-25 | 比奥根Ma公司 | S1p调节剂 |
| CA2852142A1 (en) | 2011-10-21 | 2013-04-25 | Novartis Ag | Dosage regimen for an s1p receptor modulator or agonist |
| AU2012354695B2 (en) * | 2011-12-23 | 2016-11-03 | Meiji Seika Pharma Co., Ltd. | Novel S1P receptor modulator |
| EP2879673B1 (en) | 2012-08-06 | 2018-07-25 | Biogen MA Inc. | 1,5,6-substituted naphthalene derivatives as sphingosine 1 phosphate (S1P) receptor and/or autotaxin (ATX) modulators for treating inflammatory and autoimmune disorders |
| ES2660287T3 (es) | 2012-08-06 | 2018-03-21 | Biogen Ma Inc. | Compuestos que son agentes moduladores de s1p y/o agentes moduladores de atx |
| ES2636596T3 (es) | 2012-11-20 | 2017-10-06 | Biogen Ma Inc. | Agentes moduladores de S1P y/o ATX |
| US9771326B2 (en) | 2012-11-20 | 2017-09-26 | Biogen Ma Inc. | S1P and/or ATX modulating agents |
| CA2899322A1 (en) | 2013-01-29 | 2014-08-07 | Biogen Ma Inc. | S1p modulating agents |
| TW201446768A (zh) | 2013-03-15 | 2014-12-16 | Biogen Idec Inc | S1p及/或atx調節劑 |
| CN103417970A (zh) * | 2013-08-15 | 2013-12-04 | 泰山医学院 | 雌激素上调内皮系统保护分子鞘氨醇1-磷酸的应用 |
| WO2016135644A1 (en) | 2015-02-26 | 2016-09-01 | Novartis Ag | Treatment of autoimmune disease in a patient receiving additionally a beta-blocker |
| US11434200B2 (en) | 2017-03-09 | 2022-09-06 | Novartis Ag | Solid forms comprising an oxime ether compound and a coformer, compositions and methods of use thereof |
| EP3443986A1 (en) | 2017-08-17 | 2019-02-20 | AC BioScience | Enhancement of chemotherapy efficiency by sphingosine-1-phosphate |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL36730A0 (en) * | 1970-05-28 | 1971-06-23 | Chemagro Corp | Phosphonamidothioates,their preparation and their use as herbicides and/or plant growth regulators |
| GB1524747A (en) | 1976-05-11 | 1978-09-13 | Ici Ltd | Polypeptide |
| DE3372965D1 (en) | 1982-07-23 | 1987-09-17 | Ici Plc | Amide derivatives |
| GB8327256D0 (en) | 1983-10-12 | 1983-11-16 | Ici Plc | Steroid derivatives |
| GB8517360D0 (en) | 1985-07-09 | 1985-08-14 | Erba Farmitalia | Substituted androsta-1,4-diene-3,17-diones |
| IL86632A0 (en) | 1987-06-15 | 1988-11-30 | Ciba Geigy Ag | Derivatives substituted at methyl-amino nitrogen |
| US5010099A (en) | 1989-08-11 | 1991-04-23 | Harbor Branch Oceanographic Institution, Inc. | Discodermolide compounds, compositions containing same and method of preparation and use |
| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| TW225528B (enExample) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| KR0155015B1 (ko) | 1992-10-21 | 1998-12-01 | 고우야 마사시 | 2-아미노-1,3-프로판디올 화합물 및 면역 억제제 |
| KR100335584B1 (ko) | 1992-10-28 | 2002-11-29 | 제넨테크, 인코포레이티드 | 혈관내피세포성장인자에대한길항제 |
| GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| BR9408323A (pt) | 1993-12-17 | 1997-08-19 | Sandoz Ag | Derivados de rapamicina |
| US5362718A (en) | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| DE69524962T4 (de) * | 1994-08-22 | 2003-08-28 | Mitsubishi Pharma Corp., Osaka | Benzolderivate und deren medizinische verwendung |
| ATE446955T1 (de) | 1995-03-30 | 2009-11-15 | Pfizer Prod Inc | Chinazolinone derivate |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US5843901A (en) | 1995-06-07 | 1998-12-01 | Advanced Research & Technology Institute | LHRH antagonist peptides |
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| DE69624921T2 (de) | 1995-06-09 | 2003-09-11 | Novartis Ag, Basel | Rapamycinderivate |
| PL188959B1 (pl) | 1995-07-06 | 2005-05-31 | Novartis Ag | Pirolopirymidyny i sposoby ich wytwarzania |
| US5760041A (en) | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| CN100503580C (zh) | 1996-04-12 | 2009-06-24 | 沃尼尔·朗伯公司 | 酪氨酸激酶的不可逆抑制剂 |
| BR9709959A (pt) | 1996-06-24 | 2000-05-09 | Pfizer | Derivados tricìclicos de fenilamino substituìdo para o tratamento de doenças hiperproliferativas |
| WO1998002441A2 (en) | 1996-07-12 | 1998-01-22 | Ariad Pharmaceuticals, Inc. | Non immunosuppressive antifungal rapalogs |
| DE19638745C2 (de) | 1996-09-11 | 2001-05-10 | Schering Ag | Monoklonale Antikörper gegen die extrazelluläre Domäne des menschlichen VEGF - Rezeptorproteins (KDR) |
| WO1998010767A2 (en) | 1996-09-13 | 1998-03-19 | Sugen, Inc. | Use of quinazoline derivatives for the manufacture of a medicament in the treatment of hyperproliferative skin disorders |
| EP0837063A1 (en) | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
| CO4950519A1 (es) | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| ES2240868T3 (es) * | 1997-04-04 | 2005-10-16 | Mitsubishi Pharma Corporation | Compuesto de 2-aminopropano -1,3-diol, su uso farmaceutico e intermedios en su sintesis. |
| CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| JPH1180026A (ja) | 1997-09-02 | 1999-03-23 | Yoshitomi Pharmaceut Ind Ltd | 新規免疫抑制剤、その使用方法およびその同定方法 |
| TW557297B (en) | 1997-09-26 | 2003-10-11 | Abbott Lab | Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same |
| GB9721069D0 (en) | 1997-10-03 | 1997-12-03 | Pharmacia & Upjohn Spa | Polymeric derivatives of camptothecin |
| US6423508B1 (en) * | 1998-03-09 | 2002-07-23 | Smithkline Beecham Corporation | Polynucleotide sequences of human EDG-1c |
| ES2342240T3 (es) | 1998-08-11 | 2010-07-02 | Novartis Ag | Derivados de isoquinolina con actividad que inhibe la angiogenia. |
| GB9824579D0 (en) | 1998-11-10 | 1999-01-06 | Novartis Ag | Organic compounds |
| UA71587C2 (uk) | 1998-11-10 | 2004-12-15 | Шерінг Акцієнгезелльшафт | Аміди антранілової кислоти та їхнє застосування як лікарських засобів |
| EP1579871A1 (en) | 1998-12-22 | 2005-09-28 | Genentech, Inc. | Vascular endothelial cell growth factor antagonists and uses thereof |
| ATE329596T1 (de) | 1999-03-30 | 2006-07-15 | Novartis Pharma Gmbh | Phthalazinderivate zur behandlung von entzündlicher erkrankungen |
| EP1195165A4 (en) * | 1999-07-12 | 2005-08-10 | Ono Pharmaceutical Co | FIBROSIS INHIBITORS CONTAINING THE ACTIVE INGREDIENT OF SPHINGOSINE A PHOSPHATE OR ITS RECEPTOR AGONISTS |
| IL147803A0 (en) | 1999-08-24 | 2002-08-14 | Ariad Gene Therapeutics Inc | 28-epirapalogs |
| WO2001058899A1 (en) * | 2000-02-09 | 2001-08-16 | Novartis Ag | Pyridine derivatives inhibiting angiogenesis and/or vegf receptor tyrosine kinase |
| CZ200350A3 (cs) | 2000-07-13 | 2003-05-14 | Sankyo Company Limited | Aminoalkoholové deriváty |
| WO2002018395A1 (en) | 2000-08-31 | 2002-03-07 | Merck & Co., Inc. | Phosphate derivatives as immunoregulatory agents |
| US20020156023A1 (en) * | 2000-12-06 | 2002-10-24 | Tularik Inc. | Lometrexol combination therapy |
| MXPA03008755A (es) | 2001-03-26 | 2004-02-18 | Novartis Ag | Derivados de 2-amino-propanol. |
| JP2002316985A (ja) | 2001-04-20 | 2002-10-31 | Sankyo Co Ltd | ベンゾチオフェン誘導体 |
| GB0119249D0 (en) | 2001-08-07 | 2001-10-03 | Novartis Ag | Organic compounds |
| KR100913269B1 (ko) * | 2001-09-27 | 2009-08-21 | 교린 세이야꾸 가부시키 가이샤 | 디아릴 황화물 유도체, 그의 염 및 이를 이용한 면역억제제 |
| JP4152884B2 (ja) * | 2001-09-27 | 2008-09-17 | 杏林製薬株式会社 | ジアリールエーテル誘導体とその付加塩及び免疫抑制剤 |
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