DE69813616T2 - Cyclohexencarboxylate als inhibitoren der neuraminidase - Google Patents
Cyclohexencarboxylate als inhibitoren der neuraminidase Download PDFInfo
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- DE69813616T2 DE69813616T2 DE69813616T DE69813616T DE69813616T2 DE 69813616 T2 DE69813616 T2 DE 69813616T2 DE 69813616 T DE69813616 T DE 69813616T DE 69813616 T DE69813616 T DE 69813616T DE 69813616 T2 DE69813616 T2 DE 69813616T2
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- Prior art keywords
- compound
- neuraminidase
- och
- salts
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- 108010006232 Neuraminidase Proteins 0.000 title claims description 33
- 102000005348 Neuraminidase Human genes 0.000 title claims description 32
- 239000003112 inhibitor Substances 0.000 title description 4
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- 150000001875 compounds Chemical class 0.000 claims description 61
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- 150000003839 salts Chemical class 0.000 claims description 27
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- 239000012453 solvate Substances 0.000 claims description 14
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic 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
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- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/52—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/14—Compounds containing azido groups with azido groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/26—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/38—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D303/40—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US6955397P | 1997-12-12 | 1997-12-12 | |
| US69553P | 1997-12-12 | ||
| PCT/US1998/026327 WO1999031047A1 (en) | 1997-12-12 | 1998-12-10 | Cyclohexene carboxylates as neuraminidase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69813616D1 DE69813616D1 (de) | 2003-05-22 |
| DE69813616T2 true DE69813616T2 (de) | 2004-02-05 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69813616T Expired - Lifetime DE69813616T2 (de) | 1997-12-12 | 1998-12-10 | Cyclohexencarboxylate als inhibitoren der neuraminidase |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6111132A (enExample) |
| EP (1) | EP1040095B1 (enExample) |
| JP (1) | JP4422895B2 (enExample) |
| AR (1) | AR015493A1 (enExample) |
| AT (1) | ATE237582T1 (enExample) |
| AU (1) | AU1722699A (enExample) |
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| DE (1) | DE69813616T2 (enExample) |
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| WO (1) | WO1999031047A1 (enExample) |
| ZA (1) | ZA9811314B (enExample) |
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| US6518438B2 (en) | 1996-08-23 | 2003-02-11 | Gilead Sciences, Inc. | Preparation of cyclohexene carboxylate derivatives |
| US5859284A (en) * | 1996-08-23 | 1999-01-12 | Gilead Sciences, Inc. | Preparation of carbocyclic compounds |
| US5994377A (en) | 1996-10-21 | 1999-11-30 | Gilead Sciences, Inc. | Piperidine compounds |
| US20040053999A1 (en) * | 1997-09-17 | 2004-03-18 | Bischofberger Norbert W. | Novel compounds and methods for synthesis and therapy |
| US6455571B1 (en) | 1998-04-23 | 2002-09-24 | Abbott Laboratories | Inhibitors of neuraminidases |
| US6518305B1 (en) | 1998-04-23 | 2003-02-11 | Abbott Laboratories | Five-membered carbocyclic and heterocyclic inhibitors of neuraminidases |
| US6593314B1 (en) | 1999-10-19 | 2003-07-15 | Abbott Laboratories | Neuraminidase inhibitors |
| WO2001028981A1 (en) * | 1999-10-19 | 2001-04-26 | Abbott Laboratories | 1-cyclohexene-1-carboxylic acid and 1-cyclohexene-1-carboxylates as neuraminidase inhibitors |
| US6383037B2 (en) * | 2000-01-17 | 2002-05-07 | Harting Automotive Gmbh & Co., Kg | Safety disconnector |
| WO2003033437A2 (en) * | 2001-10-15 | 2003-04-24 | Therascope Ag | A method of forming neuraminidase inhibitors by dynamic combinatorial chemistry and compounds obtained |
| US6964784B2 (en) * | 2002-03-07 | 2005-11-15 | Optigenex, Inc. | Method of preparation and composition of a water soluble extract of the bioactive component of the plant species uncaria for enhancing immune, anti-inflammatory, anti-tumor and dna repair processes of warm blooded animals |
| US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
| JP5986745B2 (ja) | 2008-07-15 | 2016-09-06 | アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ | Ｐｔｆｅ様のアルミニウム・コート・ガラススライド上のグリカンアレイおよび関連する方法 |
| AU2010247141A1 (en) | 2009-05-15 | 2011-12-15 | Redx Pharma Plc | Redox drug derivatives |
| US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
| US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
| US10338069B2 (en) | 2010-04-12 | 2019-07-02 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
| CN102964267B (zh) * | 2011-09-01 | 2015-06-10 | 中山大学 | 一种具有流感病毒神经氨酸酶抑制活性的环己烯化合物及其制备方法以及其应用 |
| US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
| AU2013306098A1 (en) | 2012-08-18 | 2015-02-12 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
| CN103224464B (zh) * | 2013-04-15 | 2016-05-04 | 广州市恒诺康医药科技有限公司 | 环己烯类衍生物或其药学上可接受的盐及其用途 |
| US10086054B2 (en) | 2013-06-26 | 2018-10-02 | Academia Sinica | RM2 antigens and use thereof |
| WO2014210564A1 (en) | 2013-06-27 | 2014-12-31 | Academia Sinica | Glycan conjugates and use thereof |
| AU2014317889B2 (en) | 2013-09-06 | 2020-03-05 | Academia Sinica | Human iNKT cell activation using glycolipids with altered glycosyl groups |
| TW201620939A (zh) | 2014-01-16 | 2016-06-16 | 中央研究院 | 治療及檢測癌症之組合物及方法 |
| US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
| TWI687428B (zh) | 2014-03-27 | 2020-03-11 | 中央研究院 | 反應性標記化合物及其用途 |
| AU2015267051B2 (en) | 2014-05-27 | 2022-03-17 | Academia Sinica | Fucosidase from bacteroides and methods using the same |
| JP7062361B2 (ja) | 2014-05-27 | 2022-05-06 | アカデミア シニカ | 抗ｈｅｒ２糖操作抗体群およびその使用 |
| AU2015267047A1 (en) | 2014-05-27 | 2017-01-05 | Academia Sinica | Anti-CD20 glycoantibodies and uses thereof |
| US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
| WO2015184001A1 (en) | 2014-05-28 | 2015-12-03 | Academia Sinica | Anti-tnf-alpha glycoantibodies and uses thereof |
| GB2532178A (en) * | 2014-06-09 | 2016-05-18 | Redx Pharma Plc | Antiviral compounds |
| US9879042B2 (en) | 2014-09-08 | 2018-01-30 | Academia Sinica | Human iNKT cell activation using glycolipids |
| 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 |
| AU2015378564A1 (en) | 2015-01-24 | 2017-07-13 | Academia Sinica | Novel glycan conjugates and methods of use thereof |
| CN109195996A (zh) | 2016-03-08 | 2019-01-11 | 中央研究院 | N-聚醣及其阵列的模组化合成方法 |
| CN107325040B (zh) * | 2016-04-28 | 2019-05-03 | 广州市恒诺康医药科技有限公司 | 环己烯类衍生物或其药学上可接受的盐及其用途 |
| KR102588027B1 (ko) | 2016-08-22 | 2023-10-12 | 초 파마 인크. | 항체, 결합 단편 및 사용 방법 |
| CN106496100B (zh) * | 2016-09-09 | 2021-01-22 | 广州市恒诺康医药科技有限公司 | 环己烯类化合物及其用途 |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4968788A (en) * | 1986-04-04 | 1990-11-06 | Board Of Regents, The University Of Texas System | Biologically reversible phosphate and phosphonate protective gruops |
| US5206400A (en) * | 1986-07-07 | 1993-04-27 | Ohio State University | Diastereomeric mono- and di-substituted diamino cyclohexane compounds and the method of preparation thereof |
| US5175273A (en) * | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5270340A (en) * | 1988-12-27 | 1993-12-14 | Bayer Aktiengesellschaft | Substituted 2-cyclohexen-1-yl-amine fungicidal and herbicidal agents |
| AP249A (en) * | 1990-04-24 | 1993-03-17 | Biota Scient Management Pty Ltd | Anti-viral compounds. |
| WO1992006691A1 (en) * | 1990-10-19 | 1992-04-30 | Biota Scientific Management Pty. Ltd. | Anti-viral compounds that bind the active site of influenza neuramidase and display in vivo activity against orthomyxovirus and paramyxovirus |
| DE4033415A1 (de) * | 1990-10-20 | 1992-04-23 | Bayer Ag | Antimikrobielle mittel sowie substituierte 2-cyclohexan-1-yl-amin-derivate und deren herstellung |
| DE4131311A1 (de) * | 1991-09-20 | 1993-04-01 | Basf Ag | Dihydropyranderivate und diese enthaltende pflanzenschutzmittel |
| CA2081068C (en) * | 1991-10-23 | 2005-11-29 | Laurence Mark Von Itzstein | Antiviral 4-substituted-2-deoxy-2,3-didehydro-derivatives of .alpha.-d-neuraminic acid |
| GB9126725D0 (en) * | 1991-12-17 | 1992-02-12 | Glaxo Group Ltd | Process |
| FR2687674B1 (fr) * | 1992-02-07 | 1995-05-19 | Roussel Uclaf | Nouveaux derives de la pyridone, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant. |
| US5292938A (en) * | 1992-04-13 | 1994-03-08 | Associated Universities, Inc. | Synthesis of 4-substituted-trans-1, 2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and spect and pet imaging |
| US5633360A (en) * | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| GB9220327D0 (en) * | 1992-09-25 | 1992-11-11 | Glaxo Group Ltd | Process |
| GB9220241D0 (en) * | 1992-09-25 | 1992-11-11 | Glaxo Group Ltd | Process |
| US5514798A (en) * | 1993-06-02 | 1996-05-07 | Gilead Sciences, Inc. | Method and cyclic carbonates for nucleotide analogues |
| GB9311873D0 (en) * | 1993-06-09 | 1993-07-28 | Glaxo Group Ltd | Process |
| US5819730A (en) * | 1993-06-09 | 1998-10-13 | Glaxo Wellcome Australia Ltd. | Device for administering pharmaceutical substances |
| GB9312531D0 (en) * | 1993-06-17 | 1993-08-04 | Glaxo Group Ltd | Process |
| GB9325841D0 (en) * | 1993-12-17 | 1994-02-23 | Glaxo Group Ltd | Chemical 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 |
| US5985859A (en) * | 1994-04-14 | 1999-11-16 | The University Of Alabama | Methods of inhibiting bacterial sialidase |
| GB9410817D0 (en) * | 1994-05-28 | 1994-07-20 | Glaxo Group Ltd | Medicaments |
| AUPM725794A0 (en) * | 1994-08-03 | 1994-08-25 | Biota Scientific Management Pty Ltd | Chemical compounds |
| US5556963A (en) * | 1994-08-05 | 1996-09-17 | Oklahoma Medical Research Foundation | Synthesis of 4-alkoxy-N-acetylneuraminic acid |
| US5512596A (en) * | 1994-09-02 | 1996-04-30 | Gilead Sciences, Inc. | Aromatic compounds |
| JP2002515849A (ja) * | 1994-11-04 | 2002-05-28 | ギリアード サイエンシーズ，インコーポレイテッド | Ｈｉｖプロテアーゼを阻害および検出するチエパン化合物 |
| US5866601A (en) * | 1995-02-27 | 1999-02-02 | Gilead Sciences, Inc. | Carbocyclic compounds |
| PL194173B1 (pl) * | 1995-02-27 | 2007-05-31 | Gilead Sciences | Preparat farmaceutyczny zawierający związki będące selektywnymi inhibitorami neuraminidaz wirusowych i bakteryjnych oraz zastosowania tych związków |
| US5602277A (en) * | 1995-03-30 | 1997-02-11 | Biocryst Pharmaceuticals, Inc. | Substituted benzene derivatives useful as neuraminidase inhibitors |
| US5714509A (en) * | 1995-05-03 | 1998-02-03 | The University Of Alabama | Inhibitors of bacterial sialidase and methods of making and using the same |
| GB9510141D0 (en) | 1995-05-19 | 1995-07-12 | Biota Scient Management | Chemical compounds |
| GB9525389D0 (en) | 1995-12-12 | 1996-02-14 | Biota Scient Management Ltd | Chemical compounds |
| DE69615555T2 (de) * | 1995-05-19 | 2002-05-29 | Biota Scientific Management Pty. Ltd., Melbourne | 6-carboxamido-dihydropyran-derivate |
| GB9516276D0 (en) * | 1995-08-08 | 1995-10-11 | Biota Scient Management | Chemical compounds |
| US5763483A (en) * | 1995-12-29 | 1998-06-09 | Gilead Sciences, Inc. | Carbocyclic compounds |
-
1998
- 1998-12-08 TW TW087120362A patent/TW477783B/zh not_active IP Right Cessation
- 1998-12-08 TW TW090111328A patent/TW480247B/zh not_active IP Right Cessation
- 1998-12-10 ZA ZA9811314A patent/ZA9811314B/xx unknown
- 1998-12-10 EP EP98962059A patent/EP1040095B1/en not_active Expired - Lifetime
- 1998-12-10 US US09/208,646 patent/US6111132A/en not_active Expired - Lifetime
- 1998-12-10 ES ES98962059T patent/ES2196636T3/es not_active Expired - Lifetime
- 1998-12-10 CA CA002313638A patent/CA2313638C/en not_active Expired - Lifetime
- 1998-12-10 AU AU17226/99A patent/AU1722699A/en not_active Abandoned
- 1998-12-10 AT AT98962059T patent/ATE237582T1/de not_active IP Right Cessation
- 1998-12-10 JP JP2000538977A patent/JP4422895B2/ja not_active Expired - Lifetime
- 1998-12-10 DE DE69813616T patent/DE69813616T2/de not_active Expired - Lifetime
- 1998-12-10 WO PCT/US1998/026327 patent/WO1999031047A1/en not_active Ceased
- 1998-12-11 AR ARP980106313A patent/AR015493A1/es active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| AR015493A1 (es) | 2001-05-02 |
| ZA9811314B (en) | 1999-06-14 |
| CA2313638C (en) | 2008-07-22 |
| CA2313638A1 (en) | 1999-06-24 |
| HK1033932A1 (en) | 2001-10-05 |
| ES2196636T3 (es) | 2003-12-16 |
| JP2002508347A (ja) | 2002-03-19 |
| WO1999031047A1 (en) | 1999-06-24 |
| EP1040095B1 (en) | 2003-04-16 |
| EP1040095A1 (en) | 2000-10-04 |
| US6111132A (en) | 2000-08-29 |
| JP4422895B2 (ja) | 2010-02-24 |
| TW477783B (en) | 2002-03-01 |
| AU1722699A (en) | 1999-07-05 |
| DE69813616D1 (de) | 2003-05-22 |
| ATE237582T1 (de) | 2003-05-15 |
| TW480247B (en) | 2002-03-21 |
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| 8364 | No opposition during term of opposition |