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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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- 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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- 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)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Electroluminescent Light Sources (AREA)
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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 |
| US10760086B2 (en) | 2011-09-13 | 2020-09-01 | Monsanto Technology Llc | Methods and compositions for weed control |
| MX342856B (es) | 2011-09-13 | 2016-10-13 | Monsanto Technology Llc | Metodos y composiciones para el control de malezas. |
| CN103974967A (zh) | 2011-09-13 | 2014-08-06 | 孟山都技术公司 | 用于杂草控制的方法和组合物 |
| UA116089C2 (uk) | 2011-09-13 | 2018-02-12 | Монсанто Текнолоджи Ллс | Спосіб та композиція для боротьби з бур'янами (варіанти) |
| 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 |
| EP3434779A1 (en) | 2011-09-13 | 2019-01-30 | Monsanto Technology LLC | Methods and compositions for weed control |
| BR112014005958A2 (pt) | 2011-09-13 | 2020-10-13 | Monsanto Technology Llc | métodos e composições químicas agrícolas para controle de planta, método de redução de expressão de um gene accase em uma planta, cassete de expressão microbiana, método para fazer um polinucleotídeo, método de identificação de polinucleotídeos úteis na modulação de expressão do gene accase e composição herbicida |
| US10240161B2 (en) | 2012-05-24 | 2019-03-26 | A.B. Seeds Ltd. | Compositions and methods for silencing gene expression |
| WO2014106837A2 (en) | 2013-01-01 | 2014-07-10 | A. B. Seeds Ltd. | ISOLATED dsRNA MOLECULES AND METHODS OF USING SAME FOR SILENCING TARGET MOLECULES OF INTEREST |
| US10683505B2 (en) | 2013-01-01 | 2020-06-16 | Monsanto Technology Llc | Methods of introducing dsRNA to plant seeds for modulating gene expression |
| EP2971185A4 (en) | 2013-03-13 | 2017-03-08 | Monsanto Technology LLC | Methods and compositions for weed control |
| BR112015022797A2 (pt) | 2013-03-13 | 2017-11-07 | Monsanto Technology Llc | método para controle de ervas daninhas, composição herbicida, cassete de expressão microbiano e método de produção de polinucleotídeo |
| 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 |
| US9850496B2 (en) | 2013-07-19 | 2017-12-26 | Monsanto Technology Llc | Compositions and methods for controlling Leptinotarsa |
| RU2703498C2 (ru) | 2013-07-19 | 2019-10-17 | Монсанто Текнолоджи Ллс | Композиции и способы борьбы с leptinotarsa |
| HUE070313T2 (hu) | 2013-11-04 | 2025-05-28 | Greenlight Biosciences Inc | Ízeltlábú paraziták és kártevõfertõzöttség szabályozására szolgáló készítmények és eljárások |
| UA119253C2 (uk) | 2013-12-10 | 2019-05-27 | Біолоджикс, Інк. | Спосіб боротьби із вірусом у кліща varroa та у бджіл |
| AU2015206585A1 (en) | 2014-01-15 | 2016-07-21 | Monsanto Technology Llc | Methods and compositions for weed control using EPSPS polynucleotides |
| BR112016022711A2 (pt) | 2014-04-01 | 2017-10-31 | Monsanto Technology Llc | composições e métodos para controle de pragas de inseto |
| US10988764B2 (en) | 2014-06-23 | 2021-04-27 | Monsanto Technology Llc | Compositions and methods for regulating gene expression via RNA interference |
| EP3161138A4 (en) | 2014-06-25 | 2017-12-06 | Monsanto Technology LLC | Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression |
| RU2021123470A (ru) | 2014-07-29 | 2021-09-06 | Монсанто Текнолоджи Ллс | Композиции и способы борьбы с насекомыми-вредителями |
| JP6942632B2 (ja) | 2015-01-22 | 2021-09-29 | モンサント テクノロジー エルエルシー | Ｌｅｐｔｉｎｏｔａｒｓａ防除用組成物及びその方法 |
| US10883103B2 (en) | 2015-06-02 | 2021-01-05 | Monsanto Technology Llc | Compositions and methods for delivery of a polynucleotide into a plant |
| EP3302030A4 (en) | 2015-06-03 | 2019-04-24 | Monsanto Technology LLC | METHOD AND COMPOSITIONS FOR INTRODUCING NUCLEIC ACIDS IN PLANTS |
| US10173978B2 (en) * | 2015-08-05 | 2019-01-08 | 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 |
| AU610083B2 (en) | 1986-08-18 | 1991-05-16 | Clinical Technologies Associates, Inc. | Delivery systems for pharmacological agents |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| JP3507486B2 (ja) | 1991-03-15 | 2004-03-15 | アムジエン・インコーポレーテツド | 顆粒球コロニー刺激因子の肺内投与 |
| GB9215361D0 (en) | 1992-07-20 | 1992-09-02 | Wellcome Found | Heterocyclic compounds |
| ATE225334T1 (de) | 1993-07-26 | 2002-10-15 | Eisai Co Ltd | Sulfonamide und sulfonsäure-ester mit je einem trizyclischen heteroring |
| 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 |
| WO1999032463A1 (en) | 1997-12-22 | 1999-07-01 | Bayer Corporation | INHIBITION OF p38 KINASE USING SYMMETRICAL AND UNSYMMETRICAL DIPHENYL UREAS |
| EP1184373A4 (en) | 1999-04-20 | 2004-10-20 | Meiji Seika Kaisha | TRICYCLIC CONNECTIONS |
| AU1888501A (en) | 1999-12-16 | 2001-06-25 | Asahi Kasei Kabushiki Kaisha | Novel substituted tricyclic compounds |
| WO2001083452A1 (en) | 2000-04-28 | 2001-11-08 | 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 |
| JP4224566B2 (ja) | 2000-12-18 | 2009-02-18 | 株式会社医薬分子設計研究所 | 炎症性サイトカイン産生遊離抑制剤 |
| AU2002228316A1 (en) | 2001-01-29 | 2002-08-12 | 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 |
| WO2006002908A1 (en) | 2004-06-29 | 2006-01-12 | Jadolabs Gmbh | Carbazole-derived pharmaceutical compositions |
| CA2575046A1 (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 |
| ZA200803226B (en) * | 2005-10-13 | 2009-11-25 | Orchid Res Lab Ltd | Heterocyclic Compounds as Pstat3/IL-6 Inhibitors |
| IL186935A0 (en) * | 2006-10-31 | 2008-02-09 | Veridex Llc | Prostate cancer field effect analysis methods and kits |
| EP2238265A4 (en) * | 2007-12-28 | 2012-01-18 | Wayne John Cancer Inst | USE OF THE METHYLATION STATE OF MINT-LOCI AND TUMOR ASSOCIATED GENES AS A MARKER FOR MELANOMA AND MAMMARIAN CARCINOMA |
| AU2009228765B2 (en) | 2008-03-24 | 2012-05-31 | Novartis Ag | Arylsulfonamide-based matrix metalloprotease inhibitors |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008051523A2 (en) * | 2006-10-23 | 2008-05-02 | Georgetown University | Carbazole derivatives useful as medicaments in cancer therapy |
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| US20110152339A1 (en) | 2011-06-23 |
| WO2010019271A1 (en) | 2010-02-18 |
| EP2484666A1 (en) | 2012-08-08 |
| CN102186820A (zh) | 2011-09-14 |
| EP2323982A1 (en) | 2011-05-25 |
| BRPI0917411A2 (pt) | 2015-12-01 |
| US10457639B2 (en) | 2019-10-29 |
| AU2009282451A1 (en) | 2010-02-18 |
| CN102186820B (zh) | 2013-08-28 |
| ATE547403T1 (de) | 2012-03-15 |
| JP2012500197A (ja) | 2012-01-05 |
| EP2323982B1 (en) | 2012-02-29 |
| JP2014148545A (ja) | 2014-08-21 |
| CA2734225A1 (en) | 2010-02-18 |
| WO2010019271A8 (en) | 2011-03-31 |
| HK1158206A1 (en) | 2012-07-13 |
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