CA2652958C - Deoxynojirimycin and d-arabinitol analogs and methods of using - Google Patents
Deoxynojirimycin and d-arabinitol analogs and methods of using Download PDFInfo
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- CA2652958C CA2652958C CA2652958A CA2652958A CA2652958C CA 2652958 C CA2652958 C CA 2652958C CA 2652958 A CA2652958 A CA 2652958A CA 2652958 A CA2652958 A CA 2652958A CA 2652958 C CA2652958 C CA 2652958C
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
-
- 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
-
- 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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80277606P | 2006-05-24 | 2006-05-24 | |
| US60/802,776 | 2006-05-24 | ||
| PCT/US2007/069448 WO2007140184A2 (en) | 2006-05-24 | 2007-05-22 | Deoxynojirimycin and d-arabinitol analogs and methods of using |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2652958A1 CA2652958A1 (en) | 2007-12-06 |
| CA2652958C true CA2652958C (en) | 2015-11-17 |
Family
ID=38779322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2652958A Expired - Fee Related CA2652958C (en) | 2006-05-24 | 2007-05-22 | Deoxynojirimycin and d-arabinitol analogs and methods of using |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8975280B2 (https=) |
| EP (1) | EP2023927B1 (https=) |
| JP (2) | JP5241709B2 (https=) |
| CN (2) | CN104876855A (https=) |
| CA (1) | CA2652958C (https=) |
| ES (1) | ES2537572T3 (https=) |
| HK (1) | HK1214261A1 (https=) |
| WO (1) | WO2007140184A2 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009545621A (ja) * | 2006-08-02 | 2009-12-24 | ユナイテッド セラピューティクス コーポレーション | ウィルス感染症のリポソーム処置 |
| US20090252785A1 (en) * | 2008-03-26 | 2009-10-08 | University Of Oxford | Endoplasmic reticulum targeting liposomes |
| CA2753195C (en) * | 2009-02-23 | 2015-06-02 | United Therapeutics Corporation | Iminosugars and methods of treating viral diseases |
| ES2562635T3 (es) * | 2009-02-24 | 2016-03-07 | United Therapeutics Corporation | Iminoazúcares y métodos de tratamiento de infecciones producidas por arenavirus |
| KR20120059447A (ko) * | 2009-03-27 | 2012-06-08 | 더 챈슬러 마스터즈 앤드 스칼라스 오브 더 유니버시티 오브 옥스포드 | 콜레스테롤 수준 저하 리포좀 |
| CA2793276A1 (en) * | 2009-03-27 | 2010-09-30 | Zacharon Pharmaceuticals, Inc. | Ganglioside biosynthesis modulators |
| CN102639133B (zh) * | 2009-06-12 | 2015-03-11 | 联合治疗公司 | 亚氨基糖和治疗布尼亚病毒性疾病以及披膜病毒性疾病的方法 |
| WO2011028779A1 (en) | 2009-09-04 | 2011-03-10 | United Therapeutics Corporation | Iminosugars and methods of treating filoviral diseases |
| KR101497194B1 (ko) * | 2009-09-04 | 2015-02-27 | 유나이티드 세러퓨틱스 코오포레이션 | 오르토믹소바이러스 감염의 치료 방법 |
| CN102625801B (zh) * | 2009-09-04 | 2015-09-09 | 联合治疗公司 | 治疗痘病毒感染的方法 |
| IN2014MN02539A (https=) | 2012-06-06 | 2015-07-24 | Unither Virology Llc | |
| KR20150128899A (ko) | 2013-03-15 | 2015-11-18 | 유니터 바이롤로지, 엘엘씨 | 항박테리아 화합물 |
| CN106102464A (zh) * | 2013-05-02 | 2016-11-09 | 牛津大学之校长及学者 | 采用亚氨基糖的糖脂抑制 |
| KR20160055916A (ko) | 2013-09-16 | 2016-05-18 | 이머전트 바이롤로지 엘엘씨 | 데옥시노지리마이신 유도체 및 그의 이용 방법 |
| CA2966893C (en) * | 2014-11-05 | 2023-10-24 | Emergent Virology Llc | Iminosugars |
| EP3318277A1 (en) | 2016-11-04 | 2018-05-09 | Institut du Cerveau et de la Moelle Epiniere-ICM | Inhibitors of glucosylceramide synthase for the treatment of motor neuron diseases |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO154918C (no) | 1977-08-27 | 1987-01-14 | Bayer Ag | Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin. |
| JPS54106477A (en) * | 1978-02-03 | 1979-08-21 | Nippon Shinyaku Co Ltd | Moranoline derivative |
| JPS5943949B2 (ja) | 1978-09-29 | 1984-10-25 | 日本新薬株式会社 | モラノリンのｎ−置換誘導体 |
| JPS5943948B2 (ja) * | 1978-07-06 | 1984-10-25 | 日本新薬株式会社 | 置換モラノリン誘導体 |
| JPS5943947B2 (ja) * | 1978-05-03 | 1984-10-25 | 日本新薬株式会社 | Ｎ−置換モラノリン誘導体 |
| GB2020278B (en) * | 1978-05-03 | 1983-02-23 | Nippon Shinyaku Co Ltd | Moranoline dervitives |
| DE3007078A1 (de) * | 1980-02-26 | 1981-09-10 | Bayer Ag, 5090 Leverkusen | Neue derivate von 3,4,5-trihydroxypiperidin, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel sowie in der tierernaehrung |
| DE3024901A1 (de) | 1980-07-01 | 1982-01-28 | Bayer Ag, 5090 Leverkusen | Herbizide mittel auf basis von piperidin-derivaten |
| DE3620645A1 (de) * | 1985-12-20 | 1987-07-02 | Bayer Ag | 3-amino-4,5-dihydroxypiperidine, verfahren zu ihrer herstellung und ihre verwendung |
| JPS62155291A (ja) | 1985-12-20 | 1987-07-10 | バイエル・アクチエンゲゼルシヤフト | ３−アミノ−４，５−ジヒドロキシピペリジン類、それらの製造方法及びそれらの使用 |
| DE3737523A1 (de) * | 1987-11-05 | 1989-05-18 | Bayer Ag | Verwendung von substituierten hydroxypiperidinen als antivirale mittel |
| JPH0643306B2 (ja) * | 1988-02-12 | 1994-06-08 | 明治製菓株式会社 | 癌細胞転移抑制剤 |
| US4985445A (en) * | 1988-02-12 | 1991-01-15 | Meiji Seika Kaisha, Ltd. | Cancer cell metastasis inhibitors and novel compounds |
| EP0350012A3 (en) * | 1988-07-08 | 1990-09-05 | Meiji Seika Kaisha Ltd. | Antiviral composition |
| ES2086323T3 (es) * | 1988-11-03 | 1996-07-01 | Searle & Co | Derivados del didesoxi-arabinitol como compuestos antiviricos. |
| JPH0675510B2 (ja) | 1989-02-13 | 1994-09-28 | 日本新薬株式会社 | モラノリン誘導体の製法 |
| US5256788A (en) * | 1989-02-13 | 1993-10-26 | Nippon Shinyaku Co. Ltd. | Moranoline derivatives and their production and the use of moranoline and its derivatives as a stabilizing agent for enzymes |
| US5051401A (en) * | 1989-04-07 | 1991-09-24 | University Of South Alabama | Inhibition of mineral deposition by phosphorylated and related polyanionic peptides |
| DE4009561A1 (de) | 1990-03-24 | 1991-09-26 | Bayer Ag | Neue desoxynojirimycinderivate, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln |
| CA2086413A1 (en) | 1990-06-29 | 1991-12-30 | Yohji Ezure | Piperidine derivatives |
| US5290948A (en) | 1990-09-17 | 1994-03-01 | Mcneilab, Inc. | Process for producing polyhydroxylated piperidines and pyrrolidines and compounds thereof |
| CN1074921C (zh) | 1994-01-13 | 2001-11-21 | G·D·瑟尔公司 | 使用1,5－二脱氧－1,5－亚氨基－d－葡糖醇的n－烷基衍生物治疗乙型肝炎病毒感染 |
| WO1995022975A1 (en) | 1994-02-25 | 1995-08-31 | G.D. Searle & Co. | Use of 1-deoxynojirimycin and its derivatives for treating mammals infected with respiratory syncytial virus |
| DK1030839T3 (da) | 1997-11-10 | 2004-05-03 | Searle & Co | Anvendelse af alkylerede iminosukkere til behandling af multidrugresistens |
| US6809083B1 (en) * | 1998-02-12 | 2004-10-26 | Richard A. Mueller | Use of N-substituted-1, 5-dideoxy-1, 5-imino-D-glucitol compounds for treating hepatitis virus infections |
| GB0100889D0 (en) * | 2001-01-12 | 2001-02-21 | Oxford Glycosciences Uk Ltd | Compounds |
| WO2001060366A1 (en) | 2000-02-14 | 2001-08-23 | Pharmacia Corporation | Use of n-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds for treating hepatitis virus infections |
| DE60308378T2 (de) * | 2002-03-13 | 2007-09-20 | Unither Pharmaceuticals, Inc. | Nicht-Hormonal Verfahren zur männlichen Verhütung |
| AU2003248960B2 (en) * | 2002-07-17 | 2009-06-25 | Idorsia Pharmaceuticals Ltd | Piperidinetriol derivatives as inhibitors of glycosylceramidsynthase |
| EP2932982B1 (en) * | 2005-05-17 | 2018-10-03 | Amicus Therapeutics, Inc. | A method for the treatment of pompe disease using 1-deoxynojirimycin and derivatives |
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2007
- 2007-05-22 US US11/752,015 patent/US8975280B2/en not_active Expired - Fee Related
- 2007-05-22 EP EP07797651.2A patent/EP2023927B1/en not_active Not-in-force
- 2007-05-22 WO PCT/US2007/069448 patent/WO2007140184A2/en not_active Ceased
- 2007-05-22 JP JP2009512260A patent/JP5241709B2/ja not_active Expired - Fee Related
- 2007-05-22 CN CN201510202505.0A patent/CN104876855A/zh active Pending
- 2007-05-22 CN CNA2007800273721A patent/CN101489554A/zh active Pending
- 2007-05-22 CA CA2652958A patent/CA2652958C/en not_active Expired - Fee Related
- 2007-05-22 ES ES07797651.2T patent/ES2537572T3/es active Active
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2013
- 2013-02-28 JP JP2013039548A patent/JP2013129662A/ja active Pending
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2016
- 2016-03-02 HK HK16102398.6A patent/HK1214261A1/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2023927B1 (en) | 2015-02-25 |
| US20070275998A1 (en) | 2007-11-29 |
| CN104876855A (zh) | 2015-09-02 |
| EP2023927A2 (en) | 2009-02-18 |
| HK1214261A1 (zh) | 2016-07-22 |
| JP5241709B2 (ja) | 2013-07-17 |
| EP2023927A4 (en) | 2013-04-10 |
| CA2652958A1 (en) | 2007-12-06 |
| WO2007140184A2 (en) | 2007-12-06 |
| JP2009538336A (ja) | 2009-11-05 |
| CN101489554A (zh) | 2009-07-22 |
| WO2007140184A3 (en) | 2008-11-27 |
| JP2013129662A (ja) | 2013-07-04 |
| US8975280B2 (en) | 2015-03-10 |
| ES2537572T3 (es) | 2015-06-09 |
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