CA2697837C - Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity - Google Patents
Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity Download PDFInfo
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- CA2697837C CA2697837C CA2697837A CA2697837A CA2697837C CA 2697837 C CA2697837 C CA 2697837C CA 2697837 A CA2697837 A CA 2697837A CA 2697837 A CA2697837 A CA 2697837A CA 2697837 C CA2697837 C CA 2697837C
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- 230000000694 effects Effects 0.000 title claims abstract description 35
- 230000015572 biosynthetic process Effects 0.000 title abstract description 33
- 238000003786 synthesis reaction Methods 0.000 title abstract description 30
- 229960003752 oseltamivir Drugs 0.000 title abstract description 23
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 title abstract description 3
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 title description 43
- 206010022000 influenza Diseases 0.000 title description 33
- 239000000039 congener Substances 0.000 title description 15
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- 241000712461 unidentified influenza virus Species 0.000 claims description 35
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 26
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 9
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- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 claims description 9
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims description 9
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- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 9
- PWOSZCQLSAMRQW-UHFFFAOYSA-N beryllium(2+) Chemical compound [Be+2] PWOSZCQLSAMRQW-UHFFFAOYSA-N 0.000 claims description 9
- NCMHKCKGHRPLCM-UHFFFAOYSA-N caesium(1+) Chemical compound [Cs+] NCMHKCKGHRPLCM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002091 cationic group Chemical group 0.000 claims description 9
- 229940006165 cesium cation Drugs 0.000 claims description 9
- XBPCUCUWBYBCDP-UHFFFAOYSA-O dicyclohexylazanium Chemical compound C1CCCCC1[NH2+]C1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-O 0.000 claims description 9
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims description 9
- 229940006487 lithium cation Drugs 0.000 claims description 9
- 229940096405 magnesium cation Drugs 0.000 claims description 9
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 claims description 9
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 9
- 229940006486 zinc cation Drugs 0.000 claims description 9
- ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 claims description 6
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- PGZUMBJQJWIWGJ-ONAKXNSWSA-N oseltamivir phosphate Chemical compound OP(O)(O)=O.CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 PGZUMBJQJWIWGJ-ONAKXNSWSA-N 0.000 abstract description 41
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- MSIIIHISTLWEPM-YNEHKIRRSA-N [(3r,4r,5s)-4-acetamido-5-amino-3-pentan-3-yloxycyclohexen-1-yl]phosphonic acid Chemical compound CCC(CC)O[C@@H]1C=C(P(O)(O)=O)C[C@H](N)[C@H]1NC(C)=O MSIIIHISTLWEPM-YNEHKIRRSA-N 0.000 abstract description 37
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 35
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
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- NENPYTRHICXVCS-YNEHKIRRSA-N oseltamivir acid Chemical compound CCC(CC)O[C@@H]1C=C(C(O)=O)C[C@H](N)[C@H]1NC(C)=O NENPYTRHICXVCS-YNEHKIRRSA-N 0.000 description 20
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 18
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96949107P | 2007-08-31 | 2007-08-31 | |
| US60/969,491 | 2007-08-31 | ||
| US4850708P | 2008-04-28 | 2008-04-28 | |
| US61/048,507 | 2008-04-28 | ||
| PCT/US2008/074914 WO2009029888A2 (en) | 2007-08-31 | 2008-08-29 | Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity |
Publications (2)
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| CA2697837A1 CA2697837A1 (en) | 2009-03-05 |
| CA2697837C true CA2697837C (en) | 2016-08-16 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2697837A Expired - Fee Related CA2697837C (en) | 2007-08-31 | 2008-08-29 | Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity |
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| EP (1) | EP2190439B1 (enExample) |
| JP (1) | JP5509080B2 (enExample) |
| KR (1) | KR101535691B1 (enExample) |
| CN (1) | CN101883569B (enExample) |
| AU (1) | AU2008292859C1 (enExample) |
| CA (1) | CA2697837C (enExample) |
| WO (1) | WO2009029888A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
| DK2318832T3 (da) | 2008-07-15 | 2014-01-20 | Academia Sinica | Glycan-arrays på PTFE-lignende aluminiumcoatede objektglas og relaterede fremgangsmåder |
| BRPI1010981A2 (pt) | 2009-05-15 | 2018-12-04 | Redx Pharma Ltd | "derivados de fármaco redox" |
| 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 |
| WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
| DK2568976T3 (en) * | 2010-05-10 | 2016-01-11 | Academia Sinica | Zanamivir-phosphonate congener with the anti-influenza activity, and determining the sensitivity oseltamivir in influenza viruses |
| US8515882B2 (en) | 2010-11-18 | 2013-08-20 | International Business Machines Corporation | Efficient storage of individuals for optimization simulation |
| US8489526B2 (en) | 2010-11-24 | 2013-07-16 | International Business Machines Corporation | Controlling quarantining and biasing in cataclysms for optimization simulations |
| US9563844B2 (en) | 2011-06-30 | 2017-02-07 | International Business Machines Corporation | Speculative asynchronous sub-population evolutionary computing utilizing a termination speculation threshold |
| KR101331167B1 (ko) * | 2011-08-26 | 2013-11-19 | 주식회사 씨트리 | 신규한 오셀타미비르 유도체 및 그 제조방법 |
| DE102011117128A1 (de) * | 2011-10-28 | 2013-05-02 | Christian-Albrechts-Universität Zu Kiel | Verbindungen zur Therapie der Influenza |
| US9165247B2 (en) | 2012-01-04 | 2015-10-20 | International Business Machines Corporation | Using global and local catastrophes across sub-populations in parallel evolutionary computing |
| 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 |
| CN103848762B (zh) * | 2012-11-30 | 2016-08-31 | 北京普禄德医药科技有限公司 | 神经氨酸苷酶抑制剂的前药及其组合物和用途 |
| RU2521593C1 (ru) * | 2013-02-27 | 2014-06-27 | Общество с ограниченной ответственностью "Интеллектуальный Диалог" | Моно и дифторзамещенные этил (3r,4r,5s)-5-азидо-4-ацетиламино-3-(1-этилпропокси)-циклогексен-1-карбоксилаты, способ получения и применения |
| US9305257B2 (en) | 2013-05-20 | 2016-04-05 | International Business Machines Corporation | Adaptive cataclysms in genetic algorithms |
| WO2014210397A1 (en) | 2013-06-26 | 2014-12-31 | Academia Sinica | Rm2 antigens and use thereof |
| EP3013347B1 (en) | 2013-06-27 | 2019-12-11 | Academia Sinica | Glycan conjugates and use thereof |
| EP3041484B1 (en) | 2013-09-06 | 2021-03-03 | Academia Sinica | Human inkt cell activation using glycolipids with altered glycosyl groups |
| US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
| KR20160104727A (ko) | 2014-01-16 | 2016-09-05 | 아카데미아 시니카 | 암의 치료 및 검출을 위한 조성물 및 방법 |
| TWI797430B (zh) | 2014-03-27 | 2023-04-01 | 中央研究院 | 反應性標記化合物及其用途 |
| JP2017518989A (ja) | 2014-05-27 | 2017-07-13 | アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ | 抗ｃｄ２０糖操作抗体群およびその使用 |
| EP4116329A1 (en) | 2014-05-27 | 2023-01-11 | Academia Sinica | Anti-her2 glycoantibodies and uses thereof |
| KR20170010003A (ko) | 2014-05-27 | 2017-01-25 | 아카데미아 시니카 | 박테로이드 기원의 푸코시다제 및 이의 사용 방법 |
| US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
| JP7063538B2 (ja) | 2014-05-28 | 2022-05-09 | アカデミア シニカ | 抗ＴＮＦα糖操作抗体群およびその使用 |
| EP3191500A4 (en) | 2014-09-08 | 2018-04-11 | 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 |
| CA3034057A1 (en) | 2016-08-22 | 2018-03-01 | CHO Pharma Inc. | Antibodies, binding fragments, and methods of use |
| CN114315626A (zh) * | 2021-12-21 | 2022-04-12 | 艾希尔（深圳）药物研发有限公司 | 一种奥司他韦脱烷基杂质的制备方法 |
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| SK282950B6 (sk) * | 1990-04-24 | 2003-01-09 | Biota Scientific Management Pty Ltd | Deriváty alfa-D-neuramínovej kyseliny, spôsob ich prípravy, ich použitie a farmaceutické prípravky na ich báze |
| 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 |
| CN100409844C (zh) * | 1995-02-27 | 2008-08-13 | 吉里德科学公司 | 神经氨酸苷酶抑制剂 |
| US5763483A (en) | 1995-12-29 | 1998-06-09 | Gilead Sciences, Inc. | Carbocyclic compounds |
| US20080009639A1 (en) | 2006-07-10 | 2008-01-10 | Apotex Pharmachem Inc. | Preparation of oseltamivir phosphate (Tamiflu) and intermediates starting from D-glucose or D-xylose |
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2008
- 2008-08-29 CN CN2008801134612A patent/CN101883569B/zh not_active Expired - Fee Related
- 2008-08-29 CA CA2697837A patent/CA2697837C/en not_active Expired - Fee Related
- 2008-08-29 KR KR1020107006286A patent/KR101535691B1/ko not_active Expired - Fee Related
- 2008-08-29 AU AU2008292859A patent/AU2008292859C1/en not_active Ceased
- 2008-08-29 US US12/201,955 patent/US7888337B2/en not_active Expired - Fee Related
- 2008-08-29 JP JP2010523180A patent/JP5509080B2/ja not_active Expired - Fee Related
- 2008-08-29 EP EP08828468.2A patent/EP2190439B1/en not_active Not-in-force
- 2008-08-29 WO PCT/US2008/074914 patent/WO2009029888A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US20100113397A1 (en) | 2010-05-06 |
| US7888337B2 (en) | 2011-02-15 |
| CN101883569A (zh) | 2010-11-10 |
| AU2008292859C1 (en) | 2014-03-06 |
| EP2190439B1 (en) | 2016-03-09 |
| WO2009029888A2 (en) | 2009-03-05 |
| WO2009029888A3 (en) | 2009-05-07 |
| AU2008292859B2 (en) | 2013-09-19 |
| EP2190439A4 (en) | 2013-02-20 |
| CA2697837A1 (en) | 2009-03-05 |
| JP2010538019A (ja) | 2010-12-09 |
| KR101535691B1 (ko) | 2015-07-09 |
| JP5509080B2 (ja) | 2014-06-04 |
| AU2008292859A1 (en) | 2009-03-05 |
| KR20100074156A (ko) | 2010-07-01 |
| EP2190439A2 (en) | 2010-06-02 |
| CN101883569B (zh) | 2013-08-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20130711 |
|
| MKLA | Lapsed |
Effective date: 20220829 |