AU2009282451B2 - Fluorescent regulators of RASSF1A expression and human cancer cell proliferation - Google Patents
Fluorescent regulators of RASSF1A expression and human cancer cell proliferation Download PDFInfo
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- AU2009282451B2 AU2009282451B2 AU2009282451A AU2009282451A AU2009282451B2 AU 2009282451 B2 AU2009282451 B2 AU 2009282451B2 AU 2009282451 A AU2009282451 A AU 2009282451A AU 2009282451 A AU2009282451 A AU 2009282451A AU 2009282451 B2 AU2009282451 B2 AU 2009282451B2
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- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Electroluminescent Light Sources (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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| AU2014202507A AU2014202507B2 (en) | 2008-08-15 | 2014-05-08 | Fluorescent regulators of RASSF1A expression and human cancer cell proliferation |
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| US61/189,059 | 2008-08-15 | ||
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| US8962584B2 (en) | 2009-10-14 | 2015-02-24 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Compositions for controlling Varroa mites in bees |
| ES2641642T3 (es) | 2010-03-08 | 2017-11-10 | Monsanto Technology Llc | Moléculas de polinucleótido para regulación génica en plantas |
| US8637679B2 (en) | 2011-03-11 | 2014-01-28 | Council Of Scientific And Industrial Research | Process for the isolation of organic compounds useful for the treatment of cancer |
| EP3382027A3 (en) | 2011-09-13 | 2018-10-31 | Monsanto Technology LLC | Methods and compositions for weed control |
| WO2013040057A1 (en) | 2011-09-13 | 2013-03-21 | Monsanto Technology Llc | Methods and compositions for weed control |
| CA2848695A1 (en) | 2011-09-13 | 2013-03-21 | Monsanto Technology Llc | Methods and composition for weed control comprising inhibiting ppg oxidase |
| MX348495B (es) | 2011-09-13 | 2017-06-14 | Monsanto Technology Llc | Metodos y composiciones para el control de malezas. |
| US10760086B2 (en) | 2011-09-13 | 2020-09-01 | Monsanto Technology Llc | Methods and compositions for weed control |
| US10806146B2 (en) | 2011-09-13 | 2020-10-20 | Monsanto Technology Llc | Methods and compositions for weed control |
| US10829828B2 (en) | 2011-09-13 | 2020-11-10 | Monsanto Technology Llc | Methods and compositions for weed control |
| MX361938B (es) | 2011-09-13 | 2018-12-19 | Monsanto Technology Llc | Métodos y composiciones para el control de malezas. |
| MX360866B (es) | 2012-05-24 | 2018-11-09 | A B Seeds Ltd | Composiciones y métodos para silenciar la expresión genética. |
| US10683505B2 (en) | 2013-01-01 | 2020-06-16 | Monsanto Technology Llc | Methods of introducing dsRNA to plant seeds for modulating gene expression |
| UY35252A (es) | 2013-01-01 | 2014-07-31 | Seeds Ltd Ab | MÉTODOS PARA INTRODUCIR dsRNA EN SEMILLAS DE PLANTAS PARA MODULAR LA EXPRESIÓN GENÉTICA |
| BR112015023051A2 (pt) | 2013-03-13 | 2017-11-14 | Monsanto Technology Llc | método para controle de ervas daninhas, composição herbicida, cassete de expressão microbiano e método de produção de polinucleotídeo |
| US10612019B2 (en) | 2013-03-13 | 2020-04-07 | Monsanto Technology Llc | Methods and compositions for weed control |
| WO2014151317A1 (en) * | 2013-03-15 | 2014-09-25 | Rush University Medical Center | Methods for treating cancer |
| US10568328B2 (en) | 2013-03-15 | 2020-02-25 | Monsanto Technology Llc | Methods and compositions for weed control |
| EP3030663B1 (en) | 2013-07-19 | 2019-09-04 | Monsanto Technology LLC | Compositions and methods for controlling leptinotarsa |
| US9850496B2 (en) | 2013-07-19 | 2017-12-26 | Monsanto Technology Llc | Compositions and methods for controlling Leptinotarsa |
| AU2014341879B2 (en) | 2013-11-04 | 2020-07-23 | Greenlight Biosciences, Inc. | Compositions and methods for controlling arthropod parasite and pest infestations |
| UA119253C2 (uk) | 2013-12-10 | 2019-05-27 | Біолоджикс, Інк. | Спосіб боротьби із вірусом у кліща varroa та у бджіл |
| WO2015108982A2 (en) | 2014-01-15 | 2015-07-23 | Monsanto Technology Llc | Methods and compositions for weed control using epsps polynucleotides |
| WO2015153339A2 (en) | 2014-04-01 | 2015-10-08 | Monsanto Technology Llc | Compositions and methods for controlling insect pests |
| CN106795515B (zh) | 2014-06-23 | 2021-06-08 | 孟山都技术公司 | 用于经由rna干扰调控基因表达的组合物和方法 |
| US11807857B2 (en) | 2014-06-25 | 2023-11-07 | Monsanto Technology Llc | Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression |
| CN106604993A (zh) | 2014-07-29 | 2017-04-26 | 孟山都技术公司 | 用于控制昆虫害虫的组合物和方法 |
| CN108064288B (zh) | 2015-01-22 | 2021-11-26 | 孟山都技术公司 | 用于控制叶甲属的组合物和方法 |
| EP3302053B1 (en) | 2015-06-02 | 2021-03-17 | Monsanto Technology LLC | Compositions and methods for delivery of a polynucleotide into a plant |
| WO2016196782A1 (en) | 2015-06-03 | 2016-12-08 | Monsanto Technology Llc | Methods and compositions for introducing nucleic acids into plants |
| WO2017023916A1 (en) | 2015-08-05 | 2017-02-09 | Georgetown University | Small molecule androgen receptor inhibitors and methods of use thereof |
| JP7236382B2 (ja) * | 2017-06-12 | 2023-03-09 | 昇平 宮田 | 抗癌剤及びその使用 |
| CN107266356B (zh) * | 2017-07-25 | 2020-06-26 | 山西省生物研究院有限公司 | 一种作为自分泌运动因子抑制剂的咔唑类化合物及其制备方法和应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051523A2 (en) * | 2006-10-23 | 2008-05-02 | Georgetown University | Carbazole derivatives useful as medicaments in cancer therapy |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2235815A1 (de) * | 1972-07-21 | 1974-01-31 | Bayer Ag | Polyazofarbstoffe |
| EP0545913B1 (en) | 1986-08-18 | 1999-02-24 | Emisphere Technologies, Inc. | Delivery systems for pharmacological agents |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| AU643141B2 (en) | 1991-03-15 | 1993-11-04 | Amgen, Inc. | Pulmonary administration of granulocyte colony stimulating factor |
| GB9215361D0 (en) | 1992-07-20 | 1992-09-02 | Wellcome Found | Heterocyclic compounds |
| US5834462A (en) * | 1993-07-26 | 1998-11-10 | Eisai Co., Ltd. | Tricyclic heterocyclic sulfonamide and sulfonic ester derivatives |
| JP3690825B2 (ja) * | 1993-07-26 | 2005-08-31 | エーザイ株式会社 | 三環式ヘテロ環含有スルホンアミドおよびスルホン酸エステル誘導体 |
| CA2186412A1 (en) * | 1995-10-31 | 1997-05-01 | Katherine S. Takaki | Ethylamino carbazole melatonergic agents |
| JP3887769B2 (ja) | 1997-12-22 | 2007-02-28 | バイエル コーポレイション | 対称および非対称ジフェニル尿素を用いるｐ３８キナーゼの阻害 |
| WO2000063171A1 (en) * | 1999-04-20 | 2000-10-26 | Meiji Seika Kaisha, Ltd. | Tricyclic compounds |
| KR20020069215A (ko) | 1999-12-16 | 2002-08-29 | 아사히 가세이 가부시키가이샤 | 신규한 치환기를 갖는 3환성 화합물 |
| AU2001252575A1 (en) | 2000-04-28 | 2001-11-12 | Asahi Kasei Kabushiki Kaisha | Novel tricyclic compounds |
| US6506901B2 (en) | 2000-07-17 | 2003-01-14 | Wyeth | Substituted 2-(S)-hydroxy-3-(piperidin-4-yl-methylamino)-propyl ethers and substituted 2-aryl-2-(R)-hydroxy-1-(piperidin-4-yl-methyl)-ethylamine β-3 adrenergic receptor agonists |
| KR20090090406A (ko) * | 2000-12-18 | 2009-08-25 | 가부시키가이샤 이야쿠 분지 셋케이 겐쿠쇼 | 염증성 사이토카인 생산 유리 억제제 |
| WO2002060867A2 (en) * | 2001-01-29 | 2002-08-08 | Insight Strategy And Marketing Ltd | Carbazole derivatives and their uses as heparanase inhibitors |
| JPWO2002074306A1 (ja) | 2001-03-19 | 2004-07-08 | 旭化成ファーマ株式会社 | 脂肪肝治療薬 |
| GB0319151D0 (en) | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Novel compounds |
| US20100063126A1 (en) | 2004-06-29 | 2010-03-11 | Jadolabs Gmbh | Carbazole-Derived Pharmaceutical Compositions |
| WO2006018405A1 (en) | 2004-08-18 | 2006-02-23 | Ciba Specialty Chemicals Holding Inc. | Oxime ester photoinitiators |
| ITMI20051523A1 (it) | 2005-08-03 | 2007-02-04 | Acraf | Composto del 3-ammino-carbazolo composizione farmaceutica che lo contiene e metodo per prepararlo |
| DE112006002340T5 (de) | 2005-09-01 | 2008-07-17 | Council Of Scientific And Industrial Research | Arzneimittel, verwendbar zur Behandlung von Prostatakrebs |
| CN1807413B (zh) * | 2005-09-28 | 2010-05-05 | 中国医学科学院医药生物技术研究所 | 咔唑磺酰胺衍生物及其制备方法 |
| NZ567266A (en) | 2005-10-13 | 2010-09-30 | Orchid Res Lab Ltd | Carbazole derivatives as pSTAT3/IL-6 inhibitors (carvedilol) |
| IL186935A0 (en) * | 2006-10-31 | 2008-02-09 | Veridex Llc | Prostate cancer field effect analysis methods and kits |
| AU2008345036A1 (en) * | 2007-12-28 | 2009-07-09 | John Wayne Cancer Institute | Use of methylation status of MINT loci and tumor-related genes as a marker for melanoma and breast cancer |
| WO2009118292A1 (en) | 2008-03-24 | 2009-10-01 | Novartis Ag | Arylsulfonamide-based matrix metalloprotease inhibitors |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051523A2 (en) * | 2006-10-23 | 2008-05-02 | Georgetown University | Carbazole derivatives useful as medicaments in cancer therapy |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010019271A1 (en) | 2010-02-18 |
| BRPI0917411A2 (pt) | 2015-12-01 |
| EP2323982B1 (en) | 2012-02-29 |
| JP2012500197A (ja) | 2012-01-05 |
| ATE547403T1 (de) | 2012-03-15 |
| CN102186820A (zh) | 2011-09-14 |
| JP2014148545A (ja) | 2014-08-21 |
| EP2484666A1 (en) | 2012-08-08 |
| HK1158206A1 (en) | 2012-07-13 |
| AU2009282451A1 (en) | 2010-02-18 |
| CA2734225A1 (en) | 2010-02-18 |
| US20110152339A1 (en) | 2011-06-23 |
| EP2323982A1 (en) | 2011-05-25 |
| US10457639B2 (en) | 2019-10-29 |
| WO2010019271A8 (en) | 2011-03-31 |
| CN102186820B (zh) | 2013-08-28 |
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