JP5095066B2 - 多価ノイラミニダーゼ阻害物質複合体 - Google Patents
多価ノイラミニダーゼ阻害物質複合体 Download PDFInfo
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- JP5095066B2 JP5095066B2 JP2002525135A JP2002525135A JP5095066B2 JP 5095066 B2 JP5095066 B2 JP 5095066B2 JP 2002525135 A JP2002525135 A JP 2002525135A JP 2002525135 A JP2002525135 A JP 2002525135A JP 5095066 B2 JP5095066 B2 JP 5095066B2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPR0010A AUPR001000A0 (en) | 2000-09-08 | 2000-09-08 | Novel chemical compounds and their use |
| AUPR0010 | 2000-09-08 | ||
| PCT/AU2001/001128 WO2002020514A1 (en) | 2000-09-08 | 2001-09-07 | Multivalent neuraminidase inhibitor conjugates |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004507564A JP2004507564A (ja) | 2004-03-11 |
| JP2004507564A5 JP2004507564A5 (OSRAM) | 2008-11-06 |
| JP5095066B2 true JP5095066B2 (ja) | 2012-12-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002525135A Expired - Fee Related JP5095066B2 (ja) | 2000-09-08 | 2001-09-07 | 多価ノイラミニダーゼ阻害物質複合体 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7205333B2 (OSRAM) |
| EP (1) | EP1315719A4 (OSRAM) |
| JP (1) | JP5095066B2 (OSRAM) |
| KR (1) | KR20030046406A (OSRAM) |
| AU (3) | AUPR001000A0 (OSRAM) |
| BR (1) | BR0113755A (OSRAM) |
| CA (1) | CA2416336A1 (OSRAM) |
| MX (1) | MXPA03002022A (OSRAM) |
| WO (1) | WO2002020514A1 (OSRAM) |
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| WO2002092555A1 (en) * | 2001-05-11 | 2002-11-21 | Sankyo Company, Limited | Sialic acid derivatives |
| ATE399779T1 (de) * | 2001-09-07 | 2008-07-15 | Biota Scient Management | Zwischenprodukte für die herstellung von neuraminidase-inhibitor-konjugaten |
| AU2002336823B2 (en) * | 2001-11-09 | 2008-03-20 | Biota Scientific Management Pty Ltd | Dimeric compounds and their use as anti-viral agents |
| AUPR879701A0 (en) * | 2001-11-09 | 2001-12-06 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
| AU2002340632B2 (en) * | 2001-11-09 | 2008-03-20 | Biota Scientific Management Pty Ltd | Dimeric compounds and their use as anti-viral agents |
| JP5183853B2 (ja) | 2001-11-09 | 2013-04-17 | バイオタ、サイアンティフィック、マネージメント、プロプライエタリ、リミテッド | 二量体化合物および抗ウイルス薬としてのそれらの使用 |
| AU2002340635B2 (en) * | 2001-11-09 | 2008-03-13 | Biota Scientific Management Pty Ltd | Dimeric compounds and their use as anti-viral agents |
| AUPR879401A0 (en) * | 2001-11-09 | 2001-12-06 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
| AUPR879601A0 (en) * | 2001-11-09 | 2001-12-06 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
| AUPR879501A0 (en) | 2001-11-09 | 2001-12-06 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
| EP1697543B1 (en) * | 2003-11-21 | 2014-08-20 | ANP Technologies, Inc. | Asymmetrically branched polymer conjugates and microarray assays |
| EP1808428B1 (en) | 2006-01-16 | 2010-12-22 | Research Institute of Petroleum Industry (RIPI) | Descaling solutions comprising EDDH |
| US7875747B2 (en) * | 2006-10-10 | 2011-01-25 | Afton Chemical Corporation | Branched succinimide dispersant compounds and methods of making the compounds |
| US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
| EP2192923A2 (en) * | 2007-08-27 | 2010-06-09 | Massachusetts Institute of Technology | Bi-functional polymer-attached inhibitors of influenza virus |
| WO2009148955A2 (en) * | 2008-05-29 | 2009-12-10 | Mdrna, Inc | Multi-arm amines and uses thereof |
| DK2318832T3 (da) | 2008-07-15 | 2014-01-20 | Academia Sinica | Glycan-arrays på PTFE-lignende aluminiumcoatede objektglas og relaterede fremgangsmåder |
| CA2768081A1 (en) * | 2009-07-16 | 2011-01-20 | Griffith University | Anti-influenza agents |
| US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
| US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
| WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
| US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
| US9914956B2 (en) | 2012-08-18 | 2018-03-13 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
| EP3013365B1 (en) | 2013-06-26 | 2019-06-05 | Academia Sinica | Rm2 antigens and use thereof |
| WO2014210564A1 (en) | 2013-06-27 | 2014-12-31 | Academia Sinica | Glycan conjugates and use thereof |
| KR102298172B1 (ko) | 2013-09-06 | 2021-09-06 | 아카데미아 시니카 | 변화된 글리코실 그룹을 갖는 당지질을 사용한 인간 iNKT 세포 활성화 |
| KR20160104727A (ko) | 2014-01-16 | 2016-09-05 | 아카데미아 시니카 | 암의 치료 및 검출을 위한 조성물 및 방법 |
| US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
| CN103819665B (zh) * | 2014-02-27 | 2015-10-28 | 中国科学院微生物研究所 | 四价扎那米韦及其制备方法与应用 |
| JP6562942B2 (ja) | 2014-03-27 | 2019-08-28 | アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ | 反応性標識化合物およびその使用 |
| US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
| CN107074945B (zh) | 2014-05-27 | 2021-08-24 | 中央研究院 | 增进抗体功效的通用糖型的组合物及方法 |
| CA2950440A1 (en) | 2014-05-27 | 2015-12-03 | Academia Sinica | Anti-her2 glycoantibodies and uses thereof |
| CA2950415A1 (en) | 2014-05-27 | 2015-12-03 | Academia Sinica | Anti-cd20 glycoantibodies and uses thereof |
| KR102494193B1 (ko) | 2014-05-28 | 2023-01-31 | 아카데미아 시니카 | 항-ｔｎｆ-알파 글리코항체 및 이의 용도 |
| KR102422375B1 (ko) | 2014-09-08 | 2022-07-18 | 아카데미아 시니카 | 당지질을 사용한 인간 iNKT 세포 활성화 |
| US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
| US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
| EP3248005B1 (en) | 2015-01-24 | 2020-12-09 | Academia Sinica | Novel glycan conjugates and methods of use thereof |
| ES2911027T3 (es) * | 2015-11-20 | 2022-05-17 | AusVir Therapeutics Pty Ltd | Compuestos para aplicaciones medicinales |
| WO2017156192A1 (en) | 2016-03-08 | 2017-09-14 | Academia Sinica | Methods for modular synthesis of n-glycans and arrays thereof |
| AU2017316663B2 (en) | 2016-08-22 | 2024-02-22 | CHO Pharma Inc. | Antibodies, binding fragments, and methods of use |
| TWI861205B (zh) * | 2019-09-06 | 2024-11-11 | 美商席達拉醫療有限公司 | 用於治療病毒感染之組合物及方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP249A (en) | 1990-04-24 | 1993-03-17 | Biota Scient Management Pty Ltd | Anti-viral compounds. |
| GB9400206D0 (en) | 1994-01-07 | 1994-03-02 | Glaxo Group Ltd | Chemical compound |
| AUPM354694A0 (en) | 1994-01-27 | 1994-02-17 | Biota Scientific Management Pty Ltd | Chemical compounds |
| AUPM623994A0 (en) * | 1994-06-15 | 1994-07-07 | Biomolecular Research Institute Limited | Antiviral dendrimers |
| SI9620042A (sl) | 1995-02-27 | 1998-12-31 | Gilead Sciences, Inc. | Novi selektivni inhibitorji virusnih ali bakterijskih neuraminidaz |
| GB9516276D0 (en) | 1995-08-08 | 1995-10-11 | Biota Scient Management | Chemical compounds |
| WO1997032214A1 (en) | 1996-03-01 | 1997-09-04 | Biota Scientific Management Pty. Ltd. | Method of detection of influenza virus and compounds for use therein |
| ES2180936T3 (es) * | 1996-03-06 | 2003-02-16 | Tsumura & Co | Nuevos derivados de iridoide e inhibidores de la neovascularizacion que tienen como ingrediente activo dichos derivados. |
| ATE322163T1 (de) | 1996-06-14 | 2006-04-15 | Biocryst Pharm Inc | Substituierte cyclopentanderivate die als neuramidase-inhibitoren nuetzlich sind |
| AUPO104396A0 (en) * | 1996-07-17 | 1996-08-08 | Biomolecular Research Institute Limited | Antiviral linear polymers |
| DE69709795T2 (de) | 1996-07-22 | 2002-09-26 | Sankyo Co., Ltd. | Neuraminsäuredervate, ihre Herstellung und medizinische Verwendung |
| DE69721553T2 (de) | 1996-08-13 | 2004-07-22 | Sankyo Co., Ltd. | Verbindungen der neuraminsaeure |
| TR199901081T2 (xx) * | 1996-11-14 | 1999-08-23 | Biota Scientific Management Pty.Ltd. | Y�ntem ve bu y�ntemde kullan�lan yeni bile�imler. |
| AU2200199A (en) | 1997-12-17 | 1999-07-19 | Biocryst Pharmaceuticals, Inc. | Substituted cyclopentane and cyclopentene compounds useful as neuraminidase inhibitors |
| AUPP913999A0 (en) * | 1999-03-12 | 1999-04-01 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
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| EP1315719A4 (en) | 2005-07-20 |
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| AUPR001000A0 (en) | 2000-10-05 |
| US20040058853A1 (en) | 2004-03-25 |
| WO2002020514A1 (en) | 2002-03-14 |
| US7205333B2 (en) | 2007-04-17 |
| JP2004507564A (ja) | 2004-03-11 |
| AU8560101A (en) | 2002-03-22 |
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