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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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
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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)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (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 |
| KR20100127842A (ko) * | 2008-03-26 | 2010-12-06 | 유니버시티 오브 옥스퍼드 | 소포체 표적화 리포좀 |
| EP2398321B1 (en) | 2009-02-23 | 2015-11-25 | United Therapeutics Corporation | Iminosugars and methods of treating viral diseases |
| EP2400843B1 (en) * | 2009-02-24 | 2015-11-11 | United Therapeutics Corporation | Iminosugars and methods of treating arenaviral infections |
| US8703744B2 (en) * | 2009-03-27 | 2014-04-22 | The Chancellor, Masters And Scholars Of The University Of Oxford | Cholesterol level lowering liposomes |
| EP2411526A4 (en) * | 2009-03-27 | 2012-09-19 | Zacharon Pharmaceuticals Inc | MODULATORS OF GANGLIOSID BIOSYNTHESIS |
| ES2524361T3 (es) * | 2009-06-12 | 2014-12-05 | United Therapeutics Corporation | Iminoazúcares para su uso en el tratamiento de enfermedades por bunyavirus y togavirus |
| JP5653438B2 (ja) * | 2009-09-04 | 2015-01-14 | ユナイテッド セラピューティクス コーポレイション | オルトミクソウイルス感染の治療方法 |
| CA2772807A1 (en) * | 2009-09-04 | 2011-03-10 | The Chancellor, Masters And Scholars Of The University Of Oxford | Methods of treating poxviral infections |
| CA2772813A1 (en) * | 2009-09-04 | 2011-03-10 | The Chancellor, Masters And Scholars Of The University Of Oxford | Iminosugars and methods of treating filoviral diseases |
| KR20150035767A (ko) | 2012-06-06 | 2015-04-07 | 유니터 바이롤로지, 엘엘씨 | 신규 이미노당 및 그의 용도 |
| JP2016513729A (ja) * | 2013-03-15 | 2016-05-16 | ユニザー ヴィロロジー，エルエルシー | 抗菌化合物 |
| 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 |
| JP6456393B2 (ja) | 2013-09-16 | 2019-01-23 | エマージェント バイロロジー エルエルシー | デオキシノジリマイシン誘導体およびその使用方法 |
| BR112017008898B1 (pt) * | 2014-11-05 | 2022-11-29 | Emergent Virology Llc | Compostos de iminoaçúcares, suas composições farmacêuticas e usos dos mesmos para tratar doenças virais |
| 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 |
| US4985445A (en) * | 1988-02-12 | 1991-01-15 | Meiji Seika Kaisha, Ltd. | Cancer cell metastasis inhibitors and novel compounds |
| JPH0643306B2 (ja) * | 1988-02-12 | 1994-06-08 | 明治製菓株式会社 | 癌細胞転移抑制剤 |
| 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 |
| CA2181033C (en) | 1994-01-13 | 2007-09-04 | Timothy M. Block | Use of n-alkyl derivatives of 1,5-dideoxy-1,5-imino-d-glucitol for the treatment of hepatitis b virus infections |
| AU1876095A (en) * | 1994-02-25 | 1995-09-11 | G.D. Searle & Co. | Use of 1-deoxynojirimycin and its derivatives for treating mammals infected with respiratory syncytial virus |
| PT1030839E (pt) | 1997-11-10 | 2004-05-31 | Searle & Co | Utilizacao de iminoacucares para tratar a resistencia a multifarmacos |
| DE69932154T2 (de) * | 1998-02-12 | 2007-05-31 | G.D. Searle Llc, Chicago | Verwendung von n-substituirten-1,5-dideoxy-1,5-imino-d-glucitolen zur behandlung von hepatitis infektionen |
| GB0100889D0 (en) | 2001-01-12 | 2001-02-21 | Oxford Glycosciences Uk Ltd | Compounds |
| JP2003522791A (ja) | 2000-02-14 | 2003-07-29 | ファルマシア コーポレイション | 肝炎ウイルス感染症治療用ｎ‐置換‐１，５‐ジデオキシ‐１，５‐イミノ‐ｄ‐グルシトール化合物の使用 |
| KR20050025144A (ko) * | 2002-03-13 | 2005-03-11 | 데르 스포엘 아아르노우드 씨 반 | 수컷 피임에 대한 비호르몬적 접근법 |
| US7994198B2 (en) * | 2002-07-17 | 2011-08-09 | Actelion Pharmaceuticals Ltd. | Piperidinetriol derivatives as inhibitors of glycosylceramidsynthase |
| EP3782655A1 (en) * | 2005-05-17 | 2021-02-24 | Amicus Therapeutics, Inc. | A method for the treatment of pompe disease using 1-deoxynojirimycin and derivatives |
-
2007
- 2007-05-22 CN CN201510202505.0A patent/CN104876855A/zh active Pending
- 2007-05-22 JP JP2009512260A patent/JP5241709B2/ja not_active Expired - Fee Related
- 2007-05-22 WO PCT/US2007/069448 patent/WO2007140184A2/en not_active Ceased
- 2007-05-22 ES ES07797651.2T patent/ES2537572T3/es active Active
- 2007-05-22 CA CA2652958A patent/CA2652958C/en not_active Expired - Fee Related
- 2007-05-22 US US11/752,015 patent/US8975280B2/en not_active Expired - Fee Related
- 2007-05-22 CN CNA2007800273721A patent/CN101489554A/zh active Pending
- 2007-05-22 EP EP07797651.2A patent/EP2023927B1/en not_active Not-in-force
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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 |
|---|---|
| US20070275998A1 (en) | 2007-11-29 |
| WO2007140184A3 (en) | 2008-11-27 |
| JP5241709B2 (ja) | 2013-07-17 |
| EP2023927B1 (en) | 2015-02-25 |
| CN101489554A (zh) | 2009-07-22 |
| EP2023927A4 (en) | 2013-04-10 |
| ES2537572T3 (es) | 2015-06-09 |
| WO2007140184A2 (en) | 2007-12-06 |
| JP2013129662A (ja) | 2013-07-04 |
| CN104876855A (zh) | 2015-09-02 |
| HK1214261A1 (zh) | 2016-07-22 |
| CA2652958A1 (en) | 2007-12-06 |
| US8975280B2 (en) | 2015-03-10 |
| EP2023927A2 (en) | 2009-02-18 |
| JP2009538336A (ja) | 2009-11-05 |
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