JP4344110B2 - ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 - Google Patents
ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 Download PDFInfo
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- JP4344110B2 JP4344110B2 JP2001529753A JP2001529753A JP4344110B2 JP 4344110 B2 JP4344110 B2 JP 4344110B2 JP 2001529753 A JP2001529753 A JP 2001529753A JP 2001529753 A JP2001529753 A JP 2001529753A JP 4344110 B2 JP4344110 B2 JP 4344110B2
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- biphenyl
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- 125000000524 functional group Chemical group 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 239000004305 biphenyl Substances 0.000 claims description 34
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
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- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polyethers (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1999/023536 WO2001026692A1 (en) | 1999-10-08 | 1999-10-08 | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008033703A Division JP5150297B2 (ja) | 2008-02-14 | 2008-02-14 | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2003511422A JP2003511422A (ja) | 2003-03-25 |
| JP2003511422A5 JP2003511422A5 (enExample) | 2005-05-26 |
| JP4344110B2 true JP4344110B2 (ja) | 2009-10-14 |
Family
ID=22273776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001529753A Expired - Lifetime JP4344110B2 (ja) | 1999-10-08 | 1999-10-08 | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 |
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|---|---|
| EP (1) | EP1455839B1 (enExample) |
| JP (1) | JP4344110B2 (enExample) |
| KR (1) | KR100499655B1 (enExample) |
| CN (1) | CN1284603C (enExample) |
| AU (1) | AU781336B2 (enExample) |
| BR (1) | BR9917517A (enExample) |
| CA (1) | CA2386762C (enExample) |
| CY (1) | CY1114128T1 (enExample) |
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| ES (1) | ES2404685T3 (enExample) |
| HU (1) | HU228491B1 (enExample) |
| IL (2) | IL148890A0 (enExample) |
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| NO (1) | NO331781B1 (enExample) |
| NZ (1) | NZ518143A (enExample) |
| PT (1) | PT1455839E (enExample) |
| WO (1) | WO2001026692A1 (enExample) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100361933B1 (ko) | 1993-09-08 | 2003-02-14 | 라 졸라 파마슈티칼 컴파니 | 화학적으로정의된비중합성결합가플랫폼분자및그것의콘주게이트 |
| CA2414076A1 (en) | 2000-06-08 | 2001-12-13 | La Jolla Pharmaceutical Company | Multivalent platform molecules comprising high molecular weight polyethylene oxide |
| US6761824B2 (en) | 2000-08-17 | 2004-07-13 | Reeve Lorraine E | Process for the fractionation of polymers |
| US7118737B2 (en) | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| US7829074B2 (en) | 2001-10-18 | 2010-11-09 | Nektar Therapeutics | Hydroxypatite-targeting poly(ethylene glycol) and related polymers |
| US7053150B2 (en) | 2000-12-18 | 2006-05-30 | Nektar Therapeutics Al, Corporation | Segmented polymers and their conjugates |
| TW593427B (en) * | 2000-12-18 | 2004-06-21 | Nektar Therapeutics Al Corp | Synthesis of high molecular weight non-peptidic polymer derivatives |
| US7550512B2 (en) | 2001-11-28 | 2009-06-23 | Keio University | Medical polymers and uses thereof |
| JP3493608B2 (ja) * | 2001-11-28 | 2004-02-03 | 学校法人慶應義塾 | 医用高分子及びその用途 |
| GB0209539D0 (en) * | 2002-04-26 | 2002-06-05 | Avecia Ltd | Monomer Polymer and process |
| BR0313212A (pt) | 2002-07-24 | 2005-06-28 | Hoffmann La Roche | Aditivos de ácido de polialquileno glicol |
| US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| US8129330B2 (en) | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| WO2004035657A1 (en) * | 2002-10-15 | 2004-04-29 | Baxter International Inc. | Process for the preparation of polyethylene glycol bis amine |
| AU2003303595A1 (en) | 2002-12-30 | 2004-07-29 | Gryphon Therapeutics, Inc. | Water-soluble thioester and selenoester compounds and methods for making and using the same |
| DE60322111D1 (de) | 2002-12-31 | 2008-08-21 | Nektar Therapeutics Al Co | Verfahren zur herstellung von hydrogelen aus thiosulfonat-zusammensetzungen und ihre verwendungen |
| CN1777440A (zh) | 2003-04-11 | 2006-05-24 | Pr药品有限公司 | 位点特异性蛋白质偶联物的制备方法 |
| US8637650B2 (en) | 2003-11-05 | 2014-01-28 | Genovoxx Gmbh | Macromolecular nucleotide compounds and methods for using the same |
| US20050214250A1 (en) * | 2003-11-06 | 2005-09-29 | Harris J M | Method of preparing carboxylic acid functionalized polymers |
| WO2006105993A2 (en) | 2005-04-05 | 2006-10-12 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Method for shielding functional sites or epitopes on proteins |
| WO2007022780A1 (en) * | 2005-08-26 | 2007-03-01 | Novo Nordisk A/S | A method of modifying a macromolecular system |
| EP2049148B1 (en) | 2006-07-06 | 2016-09-28 | Daewoong Co., Ltd. | A stable liquid formulation of human growth hormone |
| US7985783B2 (en) | 2006-09-21 | 2011-07-26 | The Regents Of The University Of California | Aldehyde tags, uses thereof in site-specific protein modification |
| CN106139123A (zh) | 2009-08-05 | 2016-11-23 | 爱力根公司 | 脂质运载蛋白突变蛋白的控制释放制剂 |
| WO2011050938A1 (de) | 2009-10-26 | 2011-05-05 | Genovoxx Gmbh | Konjugate von nukleotiden und methoden zu deren anwendung |
| EP2717917B1 (en) | 2011-07-05 | 2016-04-20 | biOasis Technologies Inc | P97-antibody conjugates |
| CA3140358A1 (en) | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| JP2016500058A (ja) | 2012-11-12 | 2016-01-07 | レッドウッド バイオサイエンス， インコーポレイテッド | 化合物および抱合体を生成するための方法 |
| US9310374B2 (en) | 2012-11-16 | 2016-04-12 | Redwood Bioscience, Inc. | Hydrazinyl-indole compounds and methods for producing a conjugate |
| JP2016505528A (ja) | 2012-11-16 | 2016-02-25 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | タンパク質の化学修飾のためのピクテ−スペングラーライゲーション |
| CN103044677A (zh) * | 2012-12-28 | 2013-04-17 | 上海景宇生物科技有限公司 | 一种异端基遥爪聚乙二醇及其制备方法 |
| AU2014243816B2 (en) | 2013-03-13 | 2019-01-31 | Bioasis Technologies Inc. | Fragments of p97 and uses thereof |
| WO2015031673A2 (en) | 2013-08-28 | 2015-03-05 | Bioasis Technologies Inc. | Cns-targeted conjugates having modified fc regions and methods of use thereof |
| CA3178867A1 (en) | 2013-11-27 | 2015-06-04 | Redwood Bioscience, Inc. | Hydrazinyl-pyrrolo compounds and methods for producing a conjugate |
| CN104774161B (zh) * | 2014-01-13 | 2017-08-25 | 成都福瑞康生物科技有限公司 | 多肽、蛋白质peg修饰剂合成方法 |
| PL3359515T3 (pl) * | 2015-10-07 | 2020-07-27 | Elementis Specialties, Inc. | Środek zwilżający i przeciwpieniący |
| ES2908470T3 (es) | 2015-11-09 | 2022-04-29 | Scherer Technologies Llc R P | Conjugados de anticuerpo anti-CD22-maitansina y métodos de uso de los mismos |
| KR102247701B1 (ko) | 2016-02-26 | 2021-05-03 | 한미정밀화학주식회사 | 폴리에틸렌글리콜 디알데히드 유도체의 제조방법 |
| EP4183853B1 (en) | 2016-04-15 | 2024-10-02 | Beckman Coulter, Inc. | Photoactive macromolecules and uses thereof |
| US11492493B2 (en) | 2017-12-26 | 2022-11-08 | Becton, Dickinson And Company | Deep ultraviolet-excitable water-solvated polymeric dyes |
| CN119220109A (zh) | 2018-03-30 | 2024-12-31 | 贝克顿·迪金森公司 | 含侧基发色团的水溶性聚合染料 |
| CA3107332A1 (en) | 2018-07-22 | 2020-01-30 | Bioasis Technologies Inc. | Treatment of lymphatic metastases |
| EP3950655B1 (en) * | 2019-03-29 | 2023-11-15 | NOF Corporation | Method for producing hetero type monodisperse polyethylene glycol derivative |
| US20210355468A1 (en) | 2020-05-18 | 2021-11-18 | Bioasis Technologies, Inc. | Compositions and methods for treating lewy body dementia |
| US20210393787A1 (en) | 2020-06-17 | 2021-12-23 | Bioasis Technologies, Inc. | Compositions and methods for treating frontotemporal dementia |
| CN113583230A (zh) * | 2021-06-30 | 2021-11-02 | 苏州欣影生物医药技术有限公司 | 一种peg双胺选择性反应制备异双官能团的方法 |
| EP4155349A1 (en) | 2021-09-24 | 2023-03-29 | Becton, Dickinson and Company | Water-soluble yellow green absorbing dyes |
| US20250383357A1 (en) | 2022-07-01 | 2025-12-18 | Beckman Coulter, Inc. | Novel fluorescent dyes and polymers from dihydrophenanthrene derivatives |
| WO2024044327A1 (en) | 2022-08-26 | 2024-02-29 | Beckman Coulter, Inc. | Dhnt monomers and polymer dyes with modified photophysical properties |
| CN115959992A (zh) * | 2022-12-13 | 2023-04-14 | 武汉翱飞科技有限公司 | 一种单分子量聚乙二醇单乙酸的合成方法 |
| WO2024196805A1 (en) | 2023-03-17 | 2024-09-26 | Beckman Coulter, Inc. | Benzothienopyrrole cyanine dyes |
| WO2025064842A1 (en) | 2023-09-21 | 2025-03-27 | Beckman Coulter, Inc. | Dihydrophenanthrene (dhp) bridged dyes for use in flow cytometry |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3871713B2 (ja) * | 1995-05-10 | 2007-01-24 | 協和醗酵工業株式会社 | 新規毒素複合体 |
| US5672662A (en) * | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| US20020064546A1 (en) * | 1996-09-13 | 2002-05-30 | J. Milton Harris | Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor |
| AU755051B2 (en) * | 1998-01-07 | 2002-12-05 | Debio Recherche Pharmaceutique S.A. | Degradable heterobifunctional poly(ethylene glycol) acrylates and gels and conjugates derived therefrom |
| ES2222689T3 (es) * | 1998-03-12 | 2005-02-01 | Nektar Therapeutics Al, Corporation | Derivados del polietilenglicol con grupos reactivos proximales. |
-
1999
- 1999-10-08 CA CA002386762A patent/CA2386762C/en not_active Expired - Lifetime
- 1999-10-08 CN CNB998169714A patent/CN1284603C/zh not_active Expired - Lifetime
- 1999-10-08 MX MXPA02003540A patent/MXPA02003540A/es active IP Right Grant
- 1999-10-08 IL IL14889099A patent/IL148890A0/xx active IP Right Grant
- 1999-10-08 KR KR10-2002-7004507A patent/KR100499655B1/ko not_active Expired - Lifetime
- 1999-10-08 EP EP99951885A patent/EP1455839B1/en not_active Expired - Lifetime
- 1999-10-08 JP JP2001529753A patent/JP4344110B2/ja not_active Expired - Lifetime
- 1999-10-08 NZ NZ518143A patent/NZ518143A/en not_active IP Right Cessation
- 1999-10-08 WO PCT/US1999/023536 patent/WO2001026692A1/en not_active Ceased
- 1999-10-08 DK DK99951885.5T patent/DK1455839T3/da active
- 1999-10-08 BR BR9917517-7A patent/BR9917517A/pt not_active Application Discontinuation
- 1999-10-08 HU HU0203149A patent/HU228491B1/hu unknown
- 1999-10-08 AU AU64230/99A patent/AU781336B2/en not_active Expired
- 1999-10-08 ES ES99951885T patent/ES2404685T3/es not_active Expired - Lifetime
- 1999-10-08 PT PT99951885T patent/PT1455839E/pt unknown
-
2002
- 2002-03-26 IL IL148890A patent/IL148890A/en not_active IP Right Cessation
- 2002-04-02 NO NO20021555A patent/NO331781B1/no not_active IP Right Cessation
-
2013
- 2013-04-23 CY CY20131100332T patent/CY1114128T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0203149A2 (en) | 2002-12-28 |
| WO2001026692A1 (en) | 2001-04-19 |
| NZ518143A (en) | 2004-04-30 |
| JP2003511422A (ja) | 2003-03-25 |
| CN1284603C (zh) | 2006-11-15 |
| CA2386762C (en) | 2009-06-16 |
| IL148890A (en) | 2007-09-20 |
| NO331781B1 (no) | 2012-03-26 |
| NO20021555D0 (no) | 2002-04-02 |
| CN1374875A (zh) | 2002-10-16 |
| EP1455839A1 (en) | 2004-09-15 |
| BR9917517A (pt) | 2002-07-30 |
| CY1114128T1 (el) | 2016-07-27 |
| HU228491B1 (en) | 2013-03-28 |
| NO20021555L (no) | 2002-06-04 |
| PT1455839E (pt) | 2013-04-24 |
| KR20020040841A (ko) | 2002-05-30 |
| KR100499655B1 (ko) | 2005-07-07 |
| EP1455839B1 (en) | 2013-01-23 |
| AU6423099A (en) | 2001-04-23 |
| IL148890A0 (en) | 2002-09-12 |
| DK1455839T3 (da) | 2013-05-06 |
| CA2386762A1 (en) | 2001-04-19 |
| ES2404685T3 (es) | 2013-05-28 |
| MXPA02003540A (es) | 2003-09-12 |
| AU781336B2 (en) | 2005-05-19 |
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