RU2235727C2 - Растворимые в воде фосфонооксиметиловые эфиры затрудненных спиртов или фенолов, фармацевтические композиции на их основе, способ анестезии и способ лечения опухолевых заболеваний - Google Patents
Растворимые в воде фосфонооксиметиловые эфиры затрудненных спиртов или фенолов, фармацевтические композиции на их основе, способ анестезии и способ лечения опухолевых заболеваний Download PDFInfo
- Publication number
- RU2235727C2 RU2235727C2 RU2001106614/04A RU2001106614A RU2235727C2 RU 2235727 C2 RU2235727 C2 RU 2235727C2 RU 2001106614/04 A RU2001106614/04 A RU 2001106614/04A RU 2001106614 A RU2001106614 A RU 2001106614A RU 2235727 C2 RU2235727 C2 RU 2235727C2
- Authority
- RU
- Russia
- Prior art keywords
- compound
- group
- camptothecin
- formula
- taxol
- Prior art date
Links
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- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 78
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 73
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 72
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07K—PEPTIDES
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| US6448401B1 (en) * | 2000-11-20 | 2002-09-10 | Bristol-Myers Squibb Company | Process for water soluble azole compounds |
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| KR20040080444A (ko) * | 2001-12-28 | 2004-09-18 | 길포드 파마슈티컬스 인코포레이티드 | 수용성인 프로포폴 전구약물의 약학적 수성 제제 |
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| US20090221532A1 (en) * | 2005-07-12 | 2009-09-03 | Mgi Gp, Inc. | Methods Of Dosing Propofol Prodrugs For Inducing Mild To Moderate Levels Of Sedation |
| US20080234229A1 (en) * | 2005-08-18 | 2008-09-25 | Auspex Pharmaceuticals, Inc. | Novel Therapeutic Agents for the Treatment of Cancer, Metabolic Diseases and Skin Disorders |
| EP2792373B1 (en) | 2005-08-18 | 2017-03-01 | Zimmer GmbH | Ultra high molecular weight polyethylene articles and methods of forming ultra high molecular weight polyethylene articles |
| WO2007028104A2 (en) * | 2005-09-02 | 2007-03-08 | Auspex Pharmaceuticals, Inc. | Novel therapeutic agents for the treatment of cancer, metabolic diseases and skin disorders |
| JP4981673B2 (ja) * | 2005-09-13 | 2012-07-25 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 安定性が改善されたクロロメチルフォスフェイト誘導体を含む組成物およびその製造方法 |
| PT2623113T (pt) | 2005-11-09 | 2017-07-14 | Onyx Therapeutics Inc | Compostos para inibição de enzimas |
| SI2041158T1 (sl) * | 2006-06-19 | 2013-09-30 | Onyx Therapeutics, Inc. | Peptidni epoksiketoni za inhibicijo proteasomov |
| WO2008045189A2 (en) * | 2006-10-05 | 2008-04-17 | Eisai Corporation Of North America | Aqueous based pharmaceutical formulations of water-soluble prodrugs of propofol |
| WO2008052044A2 (en) * | 2006-10-26 | 2008-05-02 | Xenoport, Inc. | Use of derivatives of propofol for treating diseases associated with oxidative stress |
| ATE544476T1 (de) | 2007-04-10 | 2012-02-15 | Zimmer Inc | Antioxidans-stabilisiertes vernetztes ultrahochmolekulares polyethylen für anwendungen in medizinprodukten |
| US8664290B2 (en) | 2007-04-10 | 2014-03-04 | Zimmer, Inc. | Antioxidant stabilized crosslinked ultra-high molecular weight polyethylene for medical device applications |
| JP2010526827A (ja) | 2007-05-09 | 2010-08-05 | ファーマコフォア，インク． | 治療用化合物 |
| EP2301908B8 (en) | 2007-05-09 | 2014-09-03 | Sowood Healthcare LLC | (-)-stereoisomer of 2,6-di-sec-butylphenol and analogs thereof for promoting antiemetic effect, treatment of nausea and vomiting and treatment of migraine |
| US20090005444A1 (en) * | 2007-06-21 | 2009-01-01 | Xenoport, Inc. | Use of propofol prodrugs for treating alcohol withdrawal, central pain, anxiety or pruritus |
| FI20070574A0 (fi) * | 2007-07-30 | 2007-07-30 | Kuopion Yliopisto | Vesiliukoinen propofolin etylideenifosfaatti-aihiolääke |
| US8427384B2 (en) | 2007-09-13 | 2013-04-23 | Aerosat Corporation | Communication system with broadband antenna |
| WO2009036305A1 (en) * | 2007-09-13 | 2009-03-19 | Aerosat Corporation | Communication system with broadband antenna |
| US20090076141A1 (en) * | 2007-09-14 | 2009-03-19 | Xenoport, Inc. | Use of Propofol Prodrugs for Treating Neuropathic Pain |
| US20090075947A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched fospropofol |
| TWI501773B (zh) | 2007-10-04 | 2015-10-01 | Onyx Therapeutics Inc | 結晶肽環氧酮蛋白酶抑制劑以及胺基酸酮環氧化物之合成 |
| US20090098209A1 (en) * | 2007-10-15 | 2009-04-16 | University Of Kansas | Pharmaceutical compositions containing water-soluble derivatives of propofol and methods of administering same via pulmonary administration |
| EP2291084A4 (en) | 2008-05-20 | 2012-04-25 | Neurogesx Inc | CARBONATE PRODRUGS AND METHOD FOR THEIR USE |
| JP5757864B2 (ja) * | 2008-05-20 | 2015-08-05 | ニューロジェシックス， インコーポレイテッド | 水溶性アセトアミノフェン類似体 |
| WO2010047737A2 (en) | 2008-09-02 | 2010-04-29 | Micurx Pharmaceuticals, Inc. | Antimicrobial indoline compounds for treatment of bacterial infections |
| BRPI0919668A2 (pt) | 2008-10-21 | 2018-05-29 | Onyx Therapeutics, Inc. | terapia de combinação com epóxi-cetonas de peptídeo |
| CN101798302B (zh) | 2009-02-06 | 2014-11-05 | 上海盟科药业有限公司 | 抗生素类药物1-(邻-氟苯基)二氢吡啶酮的合成及生产的方法和工艺 |
| AR075899A1 (es) | 2009-03-20 | 2011-05-04 | Onyx Therapeutics Inc | Tripeptidos epoxicetonas cristalinos inhibidores de proteasa |
| CN101845057B (zh) * | 2009-03-27 | 2013-10-23 | 四川大学 | 取代苯酚的甲缩醛磷酸盐麻醉镇静药用化合物及制备方法 |
| GB0905834D0 (en) | 2009-04-03 | 2009-05-20 | Seps Pharma Nv | Phosphonyl-containing phenolic derivatives useful as medicaments |
| US9150600B2 (en) | 2009-05-07 | 2015-10-06 | Regents Of The University Of Minnesota | Triptolide prodrugs |
| WO2010129918A1 (en) * | 2009-05-07 | 2010-11-11 | Regents Of The University Of Minnesota | Triptolide prodrugs |
| CN101648973B (zh) * | 2009-09-03 | 2012-05-30 | 漆又毛 | 水溶性紫杉烷及制备方法 |
| US8853147B2 (en) | 2009-11-13 | 2014-10-07 | Onyx Therapeutics, Inc. | Use of peptide epoxyketones for metastasis suppression |
| EP2531047A4 (en) | 2010-02-05 | 2014-03-19 | Phosphagenics Ltd | CARRIER WITH AN UNINUTRALIZED TOCOPHERYL PHOSPHATE |
| CN102153607B (zh) * | 2010-02-11 | 2015-07-15 | 湖南方盛华美医药科技有限公司 | 水溶性喜树碱衍生物及包含其的药物组合物 |
| MX2012010017A (es) | 2010-03-01 | 2012-10-01 | Onyx Therapeutics Inc | Compuestos de para la inhibicion de inmunoproteasomas. |
| ES2829386T3 (es) | 2010-03-30 | 2021-05-31 | Phosphagenics Ltd | Parche de administración transdérmica |
| MX2012011604A (es) | 2010-04-07 | 2013-02-27 | Onyx Therapeutics Inc | Inhibidor de inmunoproteasoma de péptido epoxicetona cristalino. |
| US8399535B2 (en) * | 2010-06-10 | 2013-03-19 | Zimmer, Inc. | Polymer [[s]] compositions including an antioxidant |
| WO2012033952A1 (en) | 2010-09-10 | 2012-03-15 | Micurx Pharmaceuticals, Inc. | 3 - phenyl- 2 -oxo- 1, 3 -oxazolidines for treatment of bacterial infections |
| ES2573116T3 (es) * | 2010-12-02 | 2016-06-06 | The University Of Kansas | Profármacos de 6-ciclohexil-1-hidroxi-4-metilpiridin-2(1H)-ona y sus derivados |
| WO2012122586A1 (en) | 2011-03-15 | 2012-09-20 | Phosphagenics Limited | New composition |
| ITMI20110580A1 (it) * | 2011-04-08 | 2012-10-09 | Chemelectiva S R L | Iintermedi utili per la preparazione di fospropofol e processo per la loro preparazione |
| UY34072A (es) | 2011-05-17 | 2013-01-03 | Novartis Ag | Derivados sustituidos de indol |
| JP6029670B2 (ja) | 2011-09-22 | 2016-11-24 | アコーダ セラピューティクス、インク． | アセトアミノフェンコンジュゲートおよびその組成物ならびにその使用方法 |
| CN102516258B (zh) * | 2011-11-11 | 2014-06-25 | 正大天晴药业集团股份有限公司 | 水溶性维生素e衍生物修饰的脂溶性抗癌药物化合物和制剂、该化合物的制备方法及应用 |
| CN102382133B (zh) * | 2011-12-02 | 2016-03-23 | 陕西合成药业股份有限公司 | 一种磷丙泊酚钠的制备及纯化方法 |
| WO2014011695A2 (en) | 2012-07-09 | 2014-01-16 | Onyx Therapeutics, Inc. | Prodrugs of peptide epoxy ketone protease inhibitors |
| US9580459B2 (en) * | 2013-04-26 | 2017-02-28 | Metselex, Inc. | Water-soluble ursodeoxycholic acid prodrugs |
| WO2015050851A1 (en) | 2013-10-01 | 2015-04-09 | Zimmer, Inc. | Polymer compositions comprising one or more protected antioxidants |
| WO2015117024A1 (en) | 2014-01-31 | 2015-08-06 | Mayo Foundation For Medical Education And Research | Novel therapeutics for the treatment of glaucoma |
| CN105612166B (zh) | 2014-02-21 | 2019-02-19 | 上海盟科药业有限公司 | 治疗用水溶性(o-羰基)氨基磷酸酯前药 |
| AU2015229947A1 (en) | 2014-03-12 | 2016-10-27 | Zimmer, Inc. | Melt-stabilized ultra high molecular weight polyethylene and method of making the same |
| RU2743347C2 (ru) | 2014-10-21 | 2021-02-17 | Эббви Инк. | Пролекарства карбидопа и l-dopa и их применение для лечения болезни паркинсона |
| AU2015358476B2 (en) | 2014-12-03 | 2019-08-15 | Zimmer, Inc. | Antioxidant-infused ultra high molecular weight polyethylene |
| CN106674270A (zh) * | 2015-11-11 | 2017-05-17 | 陕西合成药业股份有限公司 | 一种磷丙泊酚钠无水合物及晶型及其制备方法和用途 |
| CN106674268A (zh) * | 2015-11-11 | 2017-05-17 | 陕西合成药业股份有限公司 | 一种磷丙泊酚钠三水合物及晶型及其制备方法和用途 |
| CN106674269A (zh) * | 2015-11-11 | 2017-05-17 | 陕西合成药业股份有限公司 | 一种磷丙泊酚钠四水合物及晶型及其制备方法和用途 |
| CN108601732A (zh) | 2015-12-09 | 2018-09-28 | 磷肌酸有限公司 | 药物制剂 |
| US10851123B2 (en) * | 2016-02-23 | 2020-12-01 | Concentric Analgesics, Inc. | Prodrugs of phenolic TRPV1 agonists |
| EP4295909A2 (en) * | 2016-04-20 | 2023-12-27 | AbbVie Inc. | Carbidopa and l-dopa prodrugs and methods of use |
| WO2017205632A1 (en) * | 2016-05-27 | 2017-11-30 | The Johns Hopkins University | Buccal, sublingual and intranasal delivery of fospropofol |
| US11929552B2 (en) | 2016-07-21 | 2024-03-12 | Astronics Aerosat Corporation | Multi-channel communications antenna |
| MX2019006845A (es) | 2016-12-21 | 2019-10-15 | Avecho Biotechnology Ltd | Proceso. |
| US10992052B2 (en) | 2017-08-28 | 2021-04-27 | Astronics Aerosat Corporation | Dielectric lens for antenna system |
| US10174138B1 (en) * | 2018-01-25 | 2019-01-08 | University Of Massachusetts | Method for forming highly reactive olefin functional polymers |
| CN109456360B (zh) * | 2018-12-17 | 2021-05-14 | 河南中医药大学 | 一种磷丙泊酚钠的制备方法 |
| WO2020156189A1 (zh) * | 2019-01-30 | 2020-08-06 | 四川科伦博泰生物医药股份有限公司 | 喜树碱衍生物及其水溶性前药、包含其的药物组合物及其制备方法和用途 |
| US11628178B2 (en) | 2019-03-26 | 2023-04-18 | Epalex Corporation | Fospropofol methods and compositions |
| US11478490B1 (en) | 2021-03-30 | 2022-10-25 | Epalex Corporation | Fospropofol formulations |
| US11439653B1 (en) | 2021-03-30 | 2022-09-13 | Epalex Corporation | Fospropofol formulations |
| US11547714B2 (en) | 2020-02-05 | 2023-01-10 | Epalex Corporation | Fospropofol salts, methods and compositions |
| WO2021228150A1 (zh) * | 2020-05-13 | 2021-11-18 | 成都百裕制药股份有限公司 | 大麻素衍生物及其制备方法和在医药上的应用 |
| CN117279664A (zh) | 2021-04-10 | 2023-12-22 | 普方生物制药美国公司 | Folr1结合剂、其偶联物及其使用方法 |
| EP4326768A1 (en) | 2021-04-23 | 2024-02-28 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
| TW202320857A (zh) | 2021-07-06 | 2023-06-01 | 美商普方生物製藥美國公司 | 連接子、藥物連接子及其結合物及其使用方法 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2829151A (en) | 1952-11-03 | 1958-04-01 | Dow Chemical Co | Chlorotoloxy-ethyl phosphates |
| US3271314A (en) | 1958-12-04 | 1966-09-06 | Ethyl Corp | 2, 6-diisopropylphenol |
| GB1146173A (en) | 1966-06-18 | 1969-03-19 | Geigy Uk Ltd | Production of triaryl phosphates |
| US3723578A (en) | 1970-10-13 | 1973-03-27 | Gaf Corp | Phosphate esters of ethers of thiol substituted phenols |
| US4171272A (en) | 1977-12-02 | 1979-10-16 | Fmc Corporation | Turbine lubricant |
| FR2601259B1 (fr) | 1986-07-11 | 1990-06-22 | Rhone Poulenc Chimie | Nouvelles compositions tensio-actives a base d'esters phosphoriques leur procede de preparation et leur application a la formulation de matieres actives. |
| US4894456A (en) | 1987-03-31 | 1990-01-16 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| US5053512A (en) | 1987-04-14 | 1991-10-01 | Research Triangle Institute | Total synthesis of 20(S) and 20(R)-camptothecin and compthothecin derivatives |
| US5364858A (en) | 1987-03-31 | 1994-11-15 | Research Triangle Institute | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US4981968A (en) | 1987-03-31 | 1991-01-01 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| US5244903A (en) | 1987-03-31 | 1993-09-14 | Research Triangle Institute | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US5122526A (en) | 1987-03-31 | 1992-06-16 | Research Triangle Institute | Camptothecin and analogs thereof and pharmaceutical compositions and method using them |
| US5106742A (en) | 1987-03-31 | 1992-04-21 | Wall Monroe E | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US5180722A (en) | 1987-04-14 | 1993-01-19 | Research Triangle Institute | 10,11-methylenedioxy-20(RS)-camptothecin and 10,11-methylenedioxy-20(S)-camptothecin analogs |
| US5049668A (en) | 1989-09-15 | 1991-09-17 | Research Triangle Institute | 10,11-methylenedioxy-20(RS)-camptothecin analogs |
| US5122606A (en) | 1987-04-14 | 1992-06-16 | Research Triangle Institute | 10,11-methylenedioxy camptothecins |
| MY103951A (en) | 1988-01-12 | 1993-10-30 | Kao Corp | Detergent composition |
| CA2014539C (en) | 1989-04-17 | 2000-07-25 | Shinichiro Umeda | Water borne metallic coating composition |
| US5091211A (en) | 1989-08-17 | 1992-02-25 | Lord Corporation | Coating method utilizing phosphoric acid esters |
| JPH03209414A (ja) | 1990-01-12 | 1991-09-12 | Nikon Corp | 焦点調節装置 |
| DK0553074T3 (da) | 1990-10-17 | 1996-07-01 | Tomen Corp | Fremgangsmåde og sammensætning til at fremme optagelse og transport af bioaktive midler i planter |
| CA2111527C (en) | 1992-12-24 | 2000-07-18 | Jerzy Golik | Phosphonooxymethyl ethers of taxane derivatives |
| US5646176A (en) | 1992-12-24 | 1997-07-08 | Bristol-Myers Squibb Company | Phosphonooxymethyl ethers of taxane derivatives |
| CA2129288C (en) | 1993-08-17 | 2000-05-16 | Jerzy Golik | Phosphonooxymethyl esters of taxane derivatives |
| US5731356A (en) * | 1994-03-22 | 1998-03-24 | Zeneca Limited | Pharmaceutical compositions of propofol and edetate |
| US5786344A (en) * | 1994-07-05 | 1998-07-28 | Arch Development Corporation | Camptothecin drug combinations and methods with reduced side effects |
| US5646159A (en) | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| IT1270093B (it) | 1994-09-28 | 1997-04-28 | Zambon Spa | Processo per la purificazione di 2,6-diisopropilfenolo |
| TW354293B (en) | 1995-06-06 | 1999-03-11 | Bristol Myers Squibb Co | Prodrugs of paclitaxel derivatives |
| US5804682A (en) | 1995-11-29 | 1998-09-08 | Henkel Corporation | Aqueous dispersions of polyamides |
| US5637625A (en) | 1996-03-19 | 1997-06-10 | Research Triangle Pharmaceuticals Ltd. | Propofol microdroplet formulations |
| US5746973A (en) | 1996-07-10 | 1998-05-05 | Naraghi; Ali | Method for reducing odorant depletion |
| DE69912250T2 (de) * | 1998-01-29 | 2004-07-29 | Bristol-Myers Squibb Co., Wallingford | Phosphorylierte derivate des diaryl 1,3,4 oxadiazolon |
| US6204257B1 (en) * | 1998-08-07 | 2001-03-20 | Universtiy Of Kansas | Water soluble prodrugs of hindered alcohols |
-
1998
- 1998-08-07 US US09/131,385 patent/US6204257B1/en not_active Expired - Lifetime
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1999
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009120162A1 (ru) * | 2008-03-25 | 2009-10-01 | Zhukovskij Oleg Igorevich | Субстанция "ua' orion" |
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