CN101602756B - 化合物、含该化合物的药物组合物以及该化合物的应用方法 - Google Patents
化合物、含该化合物的药物组合物以及该化合物的应用方法 Download PDFInfo
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- CN101602756B CN101602756B CN200910203849.8A CN200910203849A CN101602756B CN 101602756 B CN101602756 B CN 101602756B CN 200910203849 A CN200910203849 A CN 200910203849A CN 101602756 B CN101602756 B CN 101602756B
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Engineering & Computer Science (AREA)
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- Obesity (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| JP (3) | JP2005533835A (enExample) |
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| AU2003265267B2 (en) * | 2002-07-09 | 2010-03-11 | Fasgen, Llc | Novel compounds, pharmaceutical compositions containing same, and methods of use for same |
| CN101721412A (zh) * | 2002-07-09 | 2010-06-09 | 法斯根有限责任公司 | 治疗人和动物中微生物感染的方法 |
| MXPA06013687A (es) * | 2004-05-26 | 2007-10-18 | Fasgen Llc | Compuestos novedosos, composiciones farmaceuticas que los contienen y metodos para utilizar los mismos. |
| AU2007283113A1 (en) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use |
| CA2668840A1 (en) * | 2006-11-08 | 2008-05-15 | Fasgen Llc | Novel compounds, pharmaceutical compositions containing same, and methods of use for same |
| WO2008059214A1 (en) * | 2006-11-13 | 2008-05-22 | Astrazeneca Ab | Bisamlde derivatives and use thereof as fatty acid synthase inhibitors |
| EP2285215A4 (en) * | 2008-06-02 | 2012-04-04 | Fasgen Inc | NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREFOR AND METHOD OF USE THEREOF |
| US8470841B2 (en) | 2008-07-09 | 2013-06-25 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| WO2010118324A2 (en) | 2009-04-09 | 2010-10-14 | Nuclea Biotechnologies, LLC | Antibodies against fatty acid synthase |
| US9149445B2 (en) | 2009-07-27 | 2015-10-06 | The Trustees Of Princeton University | Inhibition of glycerol-3-phosphate acyltransferase (GPAT) and associated enzymes for treatment of viral infections |
| JP2013503135A (ja) | 2009-08-26 | 2013-01-31 | サノフイ | 新規な結晶性複素芳香族フルオログリコシド水和物、その化合物を含んでなる医薬及びその使用 |
| WO2011140296A1 (en) | 2010-05-05 | 2011-11-10 | Infinity Pharmaceuticals | Triazoles as inhibitors of fatty acid synthase |
| CA2798330A1 (en) | 2010-05-05 | 2011-11-10 | Infinity Pharmaceuticals, Inc. | Tetrazolones as inhibitors of fatty acid synthase |
| EP2683703B1 (de) | 2011-03-08 | 2015-05-27 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120058A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit benzyl- oder heteromethylengruppen substituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8809324B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
| EP2683698B1 (de) | 2011-03-08 | 2017-10-04 | Sanofi | Mit adamantan- oder noradamantan substituierte benzyl-oxathiazinderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012135027A2 (en) * | 2011-03-25 | 2012-10-04 | The Research Foundation Of State University Of New York | Thiolactone antibiotics |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| JP6228198B2 (ja) * | 2012-06-25 | 2017-11-08 | トーマス・ジェファーソン・ユニバーシティＴｈｏｍａｓ Ｊｅｆｆｅｒｓｏｎ Ｕｎｉｖｅｒｓｉｔｙ | 異常な脂質生合成シグナル伝達を有するがんを処置するための組成物および方法 |
| CA2884355C (en) * | 2012-09-07 | 2022-05-17 | Janssen Pharmaceutica Nv | Imidazolin-5-one derivative useful as fasn inhobitors for the treatment of cancer |
| CN112521369A (zh) | 2013-03-13 | 2021-03-19 | 福马治疗股份有限公司 | 用于抑制fasn的化合物及组合物 |
| US11202795B2 (en) | 2014-11-20 | 2021-12-21 | Vib Vzw | Means and methods for treatment of early-onset Parkinson's disease |
| WO2020092395A1 (en) | 2018-10-29 | 2020-05-07 | Forma Therapeutics, Inc. | SOLID FORMS OF (4-(2-FLUORO-4-(1-METHYL-1 H-BENZO[d]IMIDAZOL-5-YL)BENZOYL) PIPERAZIN-1-YL)(1-HYDROXYCYCLOPROPYL)METHANONE |
| CN114480521B (zh) * | 2020-11-13 | 2024-07-26 | 中国科学院青岛生物能源与过程研究所 | 一种三氮菌素c的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1278256A (zh) * | 1997-09-05 | 2000-12-27 | 罗赫诊断器材股份有限公司 | 用作抗肿瘤剂的4－氨基－2(5h)－呋喃酮和4－氨基－2(5h)－噻吩酮的脲基和硫脲基衍生物 |
| WO2001047916A1 (en) * | 1999-12-23 | 2001-07-05 | Novuspharma S.P.A. | 2-(1h-indol-3-yl)-2-oxo-acetamides with antitumor activity |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3496187A (en) * | 1967-03-20 | 1970-02-17 | American Home Prod | N-(heterocyclyl)aconamides |
| US3472878A (en) * | 1969-01-27 | 1969-10-14 | American Home Prod | N-(hydroxyaryl)aconamides |
| JPS5859920A (ja) * | 1981-10-05 | 1983-04-09 | Chugai Pharmaceut Co Ltd | 生体防禦能賦活剤 |
| US4565699A (en) * | 1983-07-18 | 1986-01-21 | The Upjohn Company | Composition of matter and process |
| US4720503A (en) * | 1985-08-02 | 1988-01-19 | Merck & Co., Inc. | N-substituted fused-heterocyclic carboxamide derivatives as dual cyclooxygenase and lipoxygenase inhibitors |
| CH667655A5 (de) * | 1986-09-24 | 1988-10-31 | Lonza Ag | Verfahren zur herstellung von 4-alkoxy-2(5h)-thiophenonen. |
| US4753871A (en) * | 1986-12-12 | 1988-06-28 | Eastman Kodak Company | Cyan dye-forming couplers and photographic materials containing same |
| WO1988004652A1 (fr) * | 1986-12-17 | 1988-06-30 | Nippon Soda Co., Ltd. | Composes heterocycliques possedant un squelette triketo |
| US5759837A (en) | 1989-01-17 | 1998-06-02 | John Hopkins University | Chemotherapy for cancer by inhibiting the fatty acid biosynthetic pathway |
| US5759791A (en) * | 1989-01-17 | 1998-06-02 | The Johns Hopkins University | Cancer related antigen |
| US5665874A (en) * | 1989-01-17 | 1997-09-09 | John Hopkins University | Cancer related antigen |
| US5679801A (en) * | 1991-04-12 | 1997-10-21 | American Home Products Corporation | Tetronic and thiotetronic acid derivatives as phospholipase A2 inhibitors |
| US5614551A (en) | 1994-01-24 | 1997-03-25 | The Johns Hopkins University | Inhibitors of fatty acid synthesis as antimicrobial agents |
| CA2220440A1 (en) * | 1995-05-09 | 1996-11-14 | Bayer Aktiengesellschaft | Alkyl dihalogenated phenyl-substituted ketoenols useful as pesticides and herbicides |
| US5981575A (en) | 1996-11-15 | 1999-11-09 | Johns Hopkins University, The | Inhibition of fatty acid synthase as a means to reduce adipocyte mass |
| JPH10212284A (ja) * | 1996-11-27 | 1998-08-11 | Sagami Chem Res Center | テトロン酸−３−カルボン酸誘導体、その製造方法、製造中間体、抗がん剤、及び蛋白脱リン酸化酵素阻害剤 |
| US6391912B1 (en) * | 1996-12-12 | 2002-05-21 | Bayer Aktiengesellschaft | Substituted phenylketoenols |
| HN2000000051A (es) * | 1999-05-19 | 2001-02-02 | Pfizer Prod Inc | Derivados heterociclicos utiles como agentes anticancerosos |
| GB0000131D0 (en) * | 2000-01-06 | 2000-02-23 | Univ Cardiff | Thiolactomycin analogues,compositions containing the same and uses thereof |
| US6376682B1 (en) * | 2000-02-01 | 2002-04-23 | Takama System, Ltd. | Compound with α-glucosidase inhibiting action and method for producing the same |
| EP1383493A4 (en) * | 2001-05-02 | 2005-09-21 | Univ New York | INHIBITION OF PIGMENTATION BY INHIBITION OF FATTY ACID SYNTHASE |
| CA2474884A1 (en) * | 2002-02-08 | 2003-08-14 | John Hopkins University School Of Medicine | Stimulation of cpt-1 as a means to reduce weight |
| AU2003265267B2 (en) * | 2002-07-09 | 2010-03-11 | Fasgen, Llc | Novel compounds, pharmaceutical compositions containing same, and methods of use for same |
| CN101721412A (zh) * | 2002-07-09 | 2010-06-09 | 法斯根有限责任公司 | 治疗人和动物中微生物感染的方法 |
| US9690894B1 (en) | 2015-11-02 | 2017-06-27 | Altera Corporation | Safety features for high level design |
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2003
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- 2010-01-13 US US12/686,691 patent/US20100120901A1/en not_active Abandoned
- 2010-10-08 JP JP2010228956A patent/JP2011037881A/ja active Pending
-
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- 2013-06-04 JP JP2013117677A patent/JP2013189464A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1278256A (zh) * | 1997-09-05 | 2000-12-27 | 罗赫诊断器材股份有限公司 | 用作抗肿瘤剂的4－氨基－2(5h)－呋喃酮和4－氨基－2(5h)－噻吩酮的脲基和硫脲基衍生物 |
| WO2001047916A1 (en) * | 1999-12-23 | 2001-07-05 | Novuspharma S.P.A. | 2-(1h-indol-3-yl)-2-oxo-acetamides with antitumor activity |
Non-Patent Citations (1)
| Title |
|---|
| JP特许出愿公开昭58-59920A 1983.04.09 * |
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| EP1539730A4 (en) | 2007-03-28 |
| CN101602756A (zh) | 2009-12-16 |
| CA2767092C (en) | 2013-10-15 |
| HK1083835A1 (zh) | 2006-07-14 |
| KR101087559B1 (ko) | 2011-11-29 |
| EP2386550A1 (en) | 2011-11-16 |
| AU2003265267B2 (en) | 2010-03-11 |
| JP2013189464A (ja) | 2013-09-26 |
| JP2011037881A (ja) | 2011-02-24 |
| JP2005533835A (ja) | 2005-11-10 |
| EP2386551A1 (en) | 2011-11-16 |
| CN100513404C (zh) | 2009-07-15 |
| IL166108A0 (en) | 2006-01-15 |
| US7649012B2 (en) | 2010-01-19 |
| SG169236A1 (en) | 2011-03-30 |
| MXPA05000365A (es) | 2005-09-20 |
| WO2004005277A1 (en) | 2004-01-15 |
| EA200500178A1 (ru) | 2006-02-24 |
| CA2767092A1 (en) | 2004-01-15 |
| BRPI0312649A2 (pt) | 2017-05-16 |
| US20060247302A1 (en) | 2006-11-02 |
| EA013371B1 (ru) | 2010-04-30 |
| IL190218A0 (en) | 2008-11-03 |
| CA2491802A1 (en) | 2004-01-15 |
| KR20060002007A (ko) | 2006-01-06 |
| EP1539730A1 (en) | 2005-06-15 |
| CA2491802C (en) | 2012-04-10 |
| AU2003265267A1 (en) | 2004-01-23 |
| CN1675192A (zh) | 2005-09-28 |
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