KR20100072230A - 아자시티딘 유사체 및 이의 용도 - Google Patents
아자시티딘 유사체 및 이의 용도 Download PDFInfo
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- KR20100072230A KR20100072230A KR1020107007252A KR20107007252A KR20100072230A KR 20100072230 A KR20100072230 A KR 20100072230A KR 1020107007252 A KR1020107007252 A KR 1020107007252A KR 20107007252 A KR20107007252 A KR 20107007252A KR 20100072230 A KR20100072230 A KR 20100072230A
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- azacytidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/12—Triazine radicals
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- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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| US60/975,437 | 2007-09-26 |
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| KR20100072230A true KR20100072230A (ko) | 2010-06-30 |
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| KR1020107008902A Withdrawn KR20100102092A (ko) | 2007-09-26 | 2008-09-25 | 아자시티딘 유사체 및 이들의 용도 |
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| EP (2) | EP2197274A4 (enExample) |
| JP (2) | JP2010540556A (enExample) |
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| CN (2) | CN101877964A (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US8497292B2 (en) * | 2005-12-28 | 2013-07-30 | Translational Therapeutics, Inc. | Translational dysfunction based therapeutics |
| US8399420B2 (en) | 2007-09-26 | 2013-03-19 | Mount Sanai School of Medicine | Azacytidine analogues and uses thereof |
| SI2695609T1 (sl) | 2008-05-15 | 2020-03-31 | Celgene Corporation | Oral formulacije anologov citidina in postopki za njihovo uporabo |
| EP2321302B1 (en) * | 2008-08-01 | 2014-10-29 | Dr. Reddy's Laboratories Ltd. | Azacitidine process and polymorphs |
| EP2424845A4 (en) * | 2009-04-27 | 2014-03-05 | Reddys Lab Ltd Dr | PREPARATION OF DECITABIN |
| EP2670396A1 (en) | 2011-01-31 | 2013-12-11 | Celgene Corporation | Pharmaceutical compositions of cytidine analogs and methods of use thereof |
| WO2012142411A1 (en) * | 2011-04-15 | 2012-10-18 | Clavis Pharma Asa | Systems and methods for detecting hent1 expression in hematological disorders |
| EP2773322A1 (en) | 2011-11-01 | 2014-09-10 | Celgene Corporation | Methods for treating cancers using oral formulations of cytidine analogs |
| KR102064626B1 (ko) | 2012-02-24 | 2020-01-09 | 시그날 파마소티칼 엘엘씨 | Tor 키나제 억제자 복합 치료법을 사용한 비소세포 폐암의 치료 방법 |
| US9493500B2 (en) | 2012-07-19 | 2016-11-15 | Richard Daifuku | Fluorinated pyrimidine analogs and methods of use thereof |
| NZ631082A (en) * | 2013-04-17 | 2017-06-30 | Signal Pharm Llc | Methods for treating cancer using tor kinase inhibitor combination therapy |
| WO2015195786A2 (en) | 2014-06-17 | 2015-12-23 | Celgene Corporation | Methods for treating cancers using oral formulations of cytidine analogs |
| CN118286245A (zh) * | 2014-12-26 | 2024-07-05 | 埃莫里大学 | N4-羟基胞苷和衍生物及与其相关的抗病毒用途 |
| WO2017090264A1 (ja) | 2015-11-27 | 2017-06-01 | 大原薬品工業株式会社 | ５－アザシチジン又は其の２'－デオキシ体の５'位ジベンジル燐酸エステル |
| BR112018011324A2 (pt) | 2015-12-03 | 2018-12-04 | Epidestiny Inc | ?composições contendo decitabina, 5azacitidina e tetra-hidrouridina e usos das mesmas? |
| EP3600419B1 (en) | 2017-03-20 | 2023-08-09 | Vaccinex, Inc. | Treatment of cancer with a semaphorin-4d antibody in combination with an epigenetic modulating agent |
| IL271491B2 (en) | 2017-06-22 | 2023-09-01 | Celgene Corp | Treatment of carcinoma of the liver characterized by hepatitis b virus infection |
| EP3781584A4 (en) * | 2018-04-19 | 2022-05-11 | Southern Research Institute | 4'-THIO-NUCLEOTIDE AND NUCLEOSIDE PRODRUGS FOR THE TREATMENT OF CANCER |
| US20230416294A1 (en) * | 2020-08-10 | 2023-12-28 | The Johns Hopkins University | Decitabine analogs for immunological and oncological therapy |
Family Cites Families (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE612384A (fr) | 1961-01-10 | 1962-05-02 | Spofa Vereinigte Pharma Werke | Procédé de préparation des 1-glycosyle-6-aza-uraciles |
| GB1050899A (enExample) * | 1963-12-22 | |||
| DE2012888C3 (de) * | 1970-03-14 | 1981-04-02 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 5-Azapyrimidinnucleosiden |
| DE2122991C2 (de) * | 1971-05-04 | 1982-06-09 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von Cytosin- und 6-Azacytosinnucleosiden |
| US3984396A (en) * | 1971-06-01 | 1976-10-05 | Icn Pharmaceuticals, Inc. | 1-(β,-D-ribofuranosyl)-1,2,4-triazole acid esters |
| US3998807A (en) * | 1972-03-03 | 1976-12-21 | Syntex (U.S.A.) Inc. | Arabinofuranosyl cytosines and methods of making |
| US4172889A (en) * | 1976-03-29 | 1979-10-30 | The Upjohn Company | Method of treating rheumatoid arthritis |
| US4405611A (en) * | 1980-06-27 | 1983-09-20 | The United States Of America As Represented By The Department Of Health And Human Services | Bisulfite stabilization of 5-azacytidine |
| DE3100478A1 (de) | 1981-01-09 | 1982-08-12 | Dr. Thilo & Co GmbH, 8021 Sauerlach | 5'ester von pyrimidinnucleosiden mit antiviraler wirksamkeit, verfahren zur herstellung und daraus hergestellte arzneimittel |
| US5223263A (en) * | 1988-07-07 | 1993-06-29 | Vical, Inc. | Liponucleotide-containing liposomes |
| US4981613A (en) | 1986-11-04 | 1991-01-01 | Fuji Photo Film Co., Ltd. | Laser light source |
| CS264456B1 (cs) | 1987-08-28 | 1989-08-14 | Piskala Alois | Způsob výroby 5,6-dihydro-S-azacytidinu |
| CS264454B1 (cs) | 1987-08-28 | 1989-08-14 | Piskala Alois | 2'-Deoxy-5,6-dihydro-5-azacytidin a způsob jeho výroby |
| US5994392A (en) * | 1988-02-26 | 1999-11-30 | Neuromedica, Inc. | Antipsychotic prodrugs comprising an antipsychotic agent coupled to an unsaturated fatty acid |
| US4984396A (en) * | 1988-08-29 | 1991-01-15 | Uragami Fukashi | Cleaning device |
| DE3834435A1 (de) * | 1988-10-10 | 1990-06-13 | Basf Ag | Verbrueckte, wasserloesliche copolymerisate, verfahren zu ihrer herstellung und ihre verwendung |
| US5216142A (en) | 1989-04-17 | 1993-06-01 | Efamol Holdings Plc | Anti-virals |
| JP2559917B2 (ja) * | 1990-06-15 | 1996-12-04 | 三共株式会社 | ピリミジンヌクレオシド誘導体 |
| DE4026265A1 (de) | 1990-08-20 | 1992-02-27 | Boehringer Mannheim Gmbh | Neue phospholipid-derivate von nucleosiden, deren herstellung sowie deren verwendung als antivirale arzneimittel |
| WO1992015113A1 (en) * | 1991-02-19 | 1992-09-03 | Fujitsu Limited | Semiconductor device having an isolation region enriched in oxygen and a fabrication process thereof |
| US5385912A (en) * | 1991-03-08 | 1995-01-31 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Multicyclic tertiary amine polyaromatic squalene synthase inhibitors |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| ZA923641B (en) | 1991-05-21 | 1993-02-24 | Iaf Biochem Int | Processes for the diastereoselective synthesis of nucleosides |
| CA2115029C (en) * | 1991-08-14 | 2002-03-26 | Stanford Salvatore Pelosi, Jr. | Cyclic urethanes useful as antiarrhythmic and antifibrillatory agents |
| GB2260319B (en) * | 1991-10-07 | 1995-12-06 | Norsk Hydro As | Acyl derivatives of nucleosides and nucleoside analogues having anti-viral activity |
| GB9515279D0 (en) * | 1995-07-25 | 1995-09-20 | Norsk Hydro As | Improved therapeutic agents |
| GB9307043D0 (en) * | 1993-04-05 | 1993-05-26 | Norsk Hydro As | Chemical compounds |
| DE19505168A1 (de) | 1995-02-16 | 1996-08-22 | Boehringer Mannheim Gmbh | Spezifische Lipidkonjugate von Nucleosid-Diphosphonaten und deren Verwendung als Arzneimittel |
| WO1997005143A1 (en) | 1995-07-25 | 1997-02-13 | Asahi Kasei Kogyo Kabushiki Kaisha | Novel group 4 transition metal compounds |
| EP0871710A4 (en) * | 1995-08-08 | 2001-03-07 | Univ Jefferson | RECOMBINANT C-PROTEINASE AND RELATED METHODS, METHODS AND APPLICATIONS |
| EP0881878A4 (en) | 1995-09-15 | 2004-08-04 | Anadys Pharmaceuticals Inc | ARYLHYDRAZONE DERIVATIVES AS AN ANTIBACTERIAL AGENT |
| US5919815A (en) | 1996-05-22 | 1999-07-06 | Neuromedica, Inc. | Taxane compounds and compositions |
| US6576636B2 (en) * | 1996-05-22 | 2003-06-10 | Protarga, Inc. | Method of treating a liver disorder with fatty acid-antiviral agent conjugates |
| CA2255615C (en) * | 1996-05-22 | 2006-08-29 | Neuromedica, Inc. | Compositions comprising conjugates of cis-docosahexaenoic acid and docetaxel |
| US5795909A (en) | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
| JPH10158192A (ja) | 1996-10-03 | 1998-06-16 | Eisai Co Ltd | 移植片対宿主疾患（ｇｖｈｄ）の治療および臓器移植時の移植片拒絶反応抑制のための医薬組成物 |
| GB2321455A (en) * | 1997-01-24 | 1998-07-29 | Norsk Hydro As | Lipophilic derivatives of biologically active compounds |
| ATE236188T1 (de) * | 1997-01-24 | 2003-04-15 | Conpharma As | Gemcitabin-derivate |
| ES2194320T3 (es) * | 1997-06-03 | 2003-11-16 | Itochu Techno Chem Inc | Sustancias naturales antivirales o antitumorales y uso de las mismas. |
| WO1999026958A1 (en) | 1997-11-25 | 1999-06-03 | Protarga, Inc. | Nucleoside analog compositions and uses thereof |
| AU2300699A (en) * | 1998-02-17 | 1999-08-30 | Ono Pharmaceutical Co. Ltd. | Amidino derivatives and drugs containing the same as the active ingredient |
| WO2000076979A1 (de) | 1999-06-09 | 2000-12-21 | Bayer Aktiengesellschaft | Pyridincarboxamide und ihre verwendung als pflanzenschutzmittel |
| US6752981B1 (en) | 1999-09-08 | 2004-06-22 | Metabasis Therapeutics, Inc. | Prodrugs for liver specific drug delivery |
| HRP20020259A2 (en) * | 1999-10-15 | 2004-04-30 | Hoffmann La Roche | Benzodiazepine derivatives |
| US6670341B1 (en) | 1999-10-28 | 2003-12-30 | Wake Forest University Health Sciences | Compositions and methods for double-targeting virus infections and targeting cancer cells |
| US20050090659A1 (en) | 2001-11-21 | 2005-04-28 | Dieter Herrmann | Phospholepid derivatives of nucleosides as antitumaorl medicaments |
| US6998391B2 (en) * | 2002-02-07 | 2006-02-14 | Supergen.Inc. | Method for treating diseases associated with abnormal kinase activity |
| EP1545558A4 (en) * | 2002-09-24 | 2010-02-17 | Koronis Pharmaceuticals Inc | 1, 3, 5-TRIAZINES FOR THE TREATMENT OF VIRAL DISEASES |
| US7038038B2 (en) | 2003-03-17 | 2006-05-02 | Pharmion Corporation | Synthesis of 5-azacytidine |
| US6943249B2 (en) * | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| US6887855B2 (en) | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| JPWO2004101593A1 (ja) | 2003-05-16 | 2006-07-13 | キッセイ薬品工業株式会社 | ５’−修飾ヌクレオシド誘導体及びその医薬用途 |
| US7244732B2 (en) * | 2003-06-20 | 2007-07-17 | Koronis Pharmaceuticals, Incorporated | Prodrugs of heteroaryl compounds |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| AU2004311702A1 (en) | 2003-12-19 | 2005-07-21 | Koronis Pharmaceuticals, Inc. | Mutagenic heterocycles |
| US20080188527A1 (en) | 2003-12-23 | 2008-08-07 | Cashman John R | Synthetic Compounds and Derivatives as Modulators of Smoking or Nicotine Ingestion and Lung Cancer |
| US20080227772A1 (en) | 2004-02-04 | 2008-09-18 | Neurosearch A/S | Diazabicyclic Aryl Derivatives as Nicotinic Acetylcholine Receptor Ligands |
| US7192781B2 (en) | 2004-04-13 | 2007-03-20 | Pharmion Corporation | Methods for stabilizing 5-azacytidine in plasma |
| US8158770B2 (en) | 2004-05-06 | 2012-04-17 | University Of Rochester | Content dependent inhibitors of cytidine deaminases and uses thereof |
| GB0419416D0 (en) | 2004-09-01 | 2004-10-06 | Inst Of Ex Botany Ascr | 4-Arylazo-3,5-Diamino-Pyrazole compounds and use thereof |
| US20060063735A1 (en) | 2004-09-17 | 2006-03-23 | Supergen, Inc. | Salts of 5-azacytidine |
| WO2006048771A1 (en) | 2004-11-04 | 2006-05-11 | Addex Pharmaceuticals Sa | Novel tetrazole derivatives as positive allosteric modulators of metabotropic glutamate receptors |
| US20060128654A1 (en) | 2004-12-10 | 2006-06-15 | Chunlin Tang | Pharmaceutical formulation of cytidine analogs and derivatives |
| US7250416B2 (en) | 2005-03-11 | 2007-07-31 | Supergen, Inc. | Azacytosine analogs and derivatives |
| WO2007035783A2 (en) | 2005-09-19 | 2007-03-29 | Celator Pharmaceuticals, Inc. | Combination formulations of cytidine analogs and platinum agents |
| EP1939175B1 (en) | 2005-09-27 | 2017-03-01 | Shionogi&Co., Ltd. | Sulfonamide derivative having pgd2 receptor antagonistic activity |
| NO324263B1 (no) | 2005-12-08 | 2007-09-17 | Clavis Pharma Asa | Kjemiske forbindelser, anvendelse derav ved behandling av kreft, samt farmasoytiske preparater som omfatter slike forbindelser |
| US20070225248A1 (en) * | 2006-03-21 | 2007-09-27 | Clavis Pharma As | Oral dosage forms of gemcitabine derivatives |
| US8399420B2 (en) | 2007-09-26 | 2013-03-19 | Mount Sanai School of Medicine | Azacytidine analogues and uses thereof |
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| EP2197274A1 (en) | 2010-06-23 |
| UA99308C2 (ru) | 2012-08-10 |
| WO2009042766A9 (en) | 2009-05-28 |
| WO2009042766A1 (en) | 2009-04-02 |
| WO2009042767A1 (en) | 2009-04-02 |
| US20090209477A1 (en) | 2009-08-20 |
| RU2488591C2 (ru) | 2013-07-27 |
| RU2010116274A (ru) | 2011-11-10 |
| CN101877964A (zh) | 2010-11-03 |
| BRPI0817269A2 (pt) | 2014-10-07 |
| UA99836C2 (en) | 2012-10-10 |
| AU2008304380A1 (en) | 2009-04-02 |
| US8158605B2 (en) | 2012-04-17 |
| US8399420B2 (en) | 2013-03-19 |
| EP2205073A4 (en) | 2013-03-06 |
| CA2700267A1 (en) | 2009-04-02 |
| CN101815437A (zh) | 2010-08-25 |
| IL204690A0 (en) | 2010-11-30 |
| MX2010003261A (es) | 2010-08-18 |
| CA2700207A1 (en) | 2009-04-02 |
| EP2205073A1 (en) | 2010-07-14 |
| MX2010003002A (es) | 2010-07-05 |
| BRPI0817234A2 (pt) | 2014-09-30 |
| ZA201001660B (en) | 2011-05-25 |
| JP2010540556A (ja) | 2010-12-24 |
| KR20100102092A (ko) | 2010-09-20 |
| US20090209482A1 (en) | 2009-08-20 |
| EP2197274A4 (en) | 2013-03-06 |
| JP2010540555A (ja) | 2010-12-24 |
| RU2010116154A (ru) | 2011-11-10 |
| NZ583923A (en) | 2012-05-25 |
| AU2008304381A1 (en) | 2009-04-02 |
| NZ583824A (en) | 2012-06-29 |
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