AU2011281015B2 - Tricyclic proteasome activity enhancing compounds - Google Patents
Tricyclic proteasome activity enhancing compounds Download PDFInfo
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- AU2011281015B2 AU2011281015B2 AU2011281015A AU2011281015A AU2011281015B2 AU 2011281015 B2 AU2011281015 B2 AU 2011281015B2 AU 2011281015 A AU2011281015 A AU 2011281015A AU 2011281015 A AU2011281015 A AU 2011281015A AU 2011281015 B2 AU2011281015 B2 AU 2011281015B2
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- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
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- Neurology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36717310P | 2010-07-23 | 2010-07-23 | |
| US61/367,173 | 2010-07-23 | ||
| PCT/US2011/044999 WO2012012712A2 (en) | 2010-07-23 | 2011-07-22 | Tricyclic proteasome activity enhancing compounds |
Publications (2)
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| AU2011281015A1 AU2011281015A1 (en) | 2013-03-07 |
| AU2011281015B2 true AU2011281015B2 (en) | 2015-09-24 |
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| EP (1) | EP2595993B1 (https=) |
| JP (1) | JP6042331B2 (https=) |
| CN (1) | CN103119047B (https=) |
| AU (1) | AU2011281015B2 (https=) |
| CA (1) | CA2808432C (https=) |
| WO (1) | WO2012012712A2 (https=) |
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| KR20120117905A (ko) * | 2010-01-28 | 2012-10-24 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 프로테아좀 활성을 향상시키는 조성물 및 방법 |
| EP2595993B1 (en) | 2010-07-23 | 2018-04-18 | President and Fellows of Harvard College | Tricyclic proteasome activity enhancing compounds |
| WO2012097013A1 (en) | 2011-01-10 | 2012-07-19 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| HUE044867T2 (hu) | 2011-05-12 | 2019-11-28 | Proteostasis Therapeutics Inc | Proteosztázis szabályzók |
| JP6126131B2 (ja) | 2012-01-10 | 2017-05-10 | ニンバス アイリス， インコーポレイテッド | Ｉｒａｋ阻害剤およびその使用 |
| EP2806875B1 (en) * | 2012-01-25 | 2017-07-19 | Proteostasis Therapeutics, Inc. | Proteasome activity modulating compounds |
| WO2014011906A2 (en) | 2012-07-11 | 2014-01-16 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| WO2014011902A1 (en) | 2012-07-11 | 2014-01-16 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| EP2938610A2 (en) | 2012-12-28 | 2015-11-04 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Inhibitors of the usp1/uaf1 deubiquitinase complex and uses thereof |
| CA2890911A1 (en) | 2013-01-10 | 2014-07-17 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| US9849135B2 (en) | 2013-01-25 | 2017-12-26 | President And Fellows Of Harvard College | USP14 inhibitors for treating or preventing viral infections |
| WO2014145576A2 (en) | 2013-03-15 | 2014-09-18 | Northwestern University | Substituted pyrrolo(2,3-d)pyrimidines for the treatment of cancer |
| CN106232122A (zh) | 2013-09-27 | 2016-12-14 | 林伯士艾瑞斯公司 | Irak抑制剂和其用途 |
| WO2015073528A1 (en) | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002088138A1 (en) * | 2001-04-30 | 2002-11-07 | Bayer Corporation | Novel 4-amino-5,6-substituted thiopheno[2,3-d]pyrimidines |
| WO2007061764A2 (en) * | 2005-11-22 | 2007-05-31 | Merck & Co., Inc. | Tricyclic compounds useful as inhibitors of kinases |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3577420A (en) * | 1968-01-05 | 1971-05-04 | Pfizer | Certain 4-aminofuro(2,3-d)pyrimidines |
| GB1570494A (en) * | 1975-11-28 | 1980-07-02 | Ici Ltd | Thienopyrimidine derivatives and their use as pesticides |
| DD245666A1 (de) | 1985-09-20 | 1987-05-13 | Univ Halle Wittenberg | Verfahren zur herstellung von 4-aminosubstituierten thieno 2,3-d-pyrimidin-2-ylessigsaeureestern |
| JPH01313480A (ja) | 1988-06-14 | 1989-12-18 | Nippon Soda Co Ltd | ピリミジン誘導体、その製造方法及び農園芸用殺菌剤 |
| WO1998029397A1 (en) | 1996-12-27 | 1998-07-09 | Yoshitomi Pharmaceutical Industries, Ltd. | Fused pyrimidine compounds and medicinal use thereof |
| CN1346358A (zh) | 1999-03-30 | 2002-04-24 | 日本曹达株式会社 | 噻吩并嘧啶化合物及其盐和制备方法 |
| WO2000066585A1 (en) | 1999-04-30 | 2000-11-09 | Neurogen Corporation | 9H-PYRIMIDO[4,5-b]INDOLE DERIVATIVES: CRF1 SPECIFIC LIGANDS |
| JP2002105082A (ja) | 2000-09-29 | 2002-04-10 | Nippon Soda Co Ltd | 縮合チエノピリミジン化合物、その塩及び製造法 |
| DE10064994A1 (de) | 2000-12-23 | 2002-07-04 | Merck Patent Gmbh | Sulfamidothienopyrimidine |
| HUP0302987A2 (hu) | 2001-01-31 | 2003-12-29 | Merck Patent Gmbh | Pirazolo [4,3-d] pirimidinszármazékokat vagy tienopirimidinszármazékokat és nitrátvegyületeket tartalmazó gyógyászati készítmények |
| DE10148883A1 (de) | 2001-10-04 | 2003-04-10 | Merck Patent Gmbh | Pyrimidinderivate |
| JP2003137886A (ja) * | 2001-10-31 | 2003-05-14 | Bayer Ag | ピリミド［４，５−ｂ］インドール |
| JP2005515173A (ja) * | 2001-10-31 | 2005-05-26 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | ピリミド［４，５−ｂ］インドール誘導体 |
| WO2004041285A1 (en) | 2002-10-31 | 2004-05-21 | Amgen Inc. | Antiinflammation agents |
| ES2217956B1 (es) | 2003-01-23 | 2006-04-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de 4-aminotieno(2,3-d)pirimidin-6-carbonitrilo. |
| NZ542236A (en) * | 2003-03-31 | 2008-05-30 | Predix Pharmaceuticals Holding | New piperidinylamino-thieno[2,3-d]pyrimidine compounds |
| US7612078B2 (en) | 2003-03-31 | 2009-11-03 | Epix Delaware, Inc. | Piperidinylamino-thieno[2,3-D] pyrimidine compounds |
| US7960400B2 (en) | 2007-08-27 | 2011-06-14 | Duquesne University Of The Holy Ghost | Tricyclic compounds having cytostatic and/or cytotoxic activity and methods of use thereof |
| US7982035B2 (en) | 2007-08-27 | 2011-07-19 | Duquesne University Of The Holy Spirit | Tricyclic compounds having antimitotic and/or antitumor activity and methods of use thereof |
| CA2699349C (en) | 2007-09-14 | 2016-04-19 | Bayer Schering Pharma Aktiengesellschaft | Substituted tricyclic heterocyclic compounds for use as egfr inhibitors |
| US20100227853A1 (en) | 2008-04-18 | 2010-09-09 | Trustees Of Boston College | Inhibitors of cyclic amp phosphodiesterases |
| US8507502B2 (en) | 2008-11-10 | 2013-08-13 | National Health Research Institutes | Fused bicyclic and tricyclic pyrimidine compounds as tyrosine kinase inhibitors |
| CN104856991A (zh) | 2009-02-27 | 2015-08-26 | 西佳技术公司 | 用于治疗和预防登革热病毒感染的噻吩并吡啶衍生物 |
| KR20120117905A (ko) | 2010-01-28 | 2012-10-24 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 프로테아좀 활성을 향상시키는 조성물 및 방법 |
| EP2595993B1 (en) | 2010-07-23 | 2018-04-18 | President and Fellows of Harvard College | Tricyclic proteasome activity enhancing compounds |
| TW201219401A (en) | 2010-09-14 | 2012-05-16 | Lexicon Pharmaceuticals Inc | Bicyclic inhibitors of Notum Pectinacetylesterase and methods of their use |
| CN102532159B (zh) | 2010-11-12 | 2015-02-11 | 姚雪彪 | 动点马达蛋白CENP-E小分子抑制剂Syntelin |
| WO2012097013A1 (en) | 2011-01-10 | 2012-07-19 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| JP6126131B2 (ja) | 2012-01-10 | 2017-05-10 | ニンバス アイリス， インコーポレイテッド | Ｉｒａｋ阻害剤およびその使用 |
-
2011
- 2011-07-22 EP EP11810459.5A patent/EP2595993B1/en not_active Not-in-force
- 2011-07-22 WO PCT/US2011/044999 patent/WO2012012712A2/en not_active Ceased
- 2011-07-22 US US13/811,129 patent/US8933087B2/en active Active
- 2011-07-22 JP JP2013520880A patent/JP6042331B2/ja not_active Expired - Fee Related
- 2011-07-22 AU AU2011281015A patent/AU2011281015B2/en not_active Ceased
- 2011-07-22 CN CN201180045618.4A patent/CN103119047B/zh not_active Expired - Fee Related
- 2011-07-22 CA CA2808432A patent/CA2808432C/en not_active Expired - Fee Related
-
2014
- 2014-12-17 US US14/572,927 patent/US9981981B2/en active Active
-
2018
- 2018-05-21 US US15/984,937 patent/US20180265519A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002088138A1 (en) * | 2001-04-30 | 2002-11-07 | Bayer Corporation | Novel 4-amino-5,6-substituted thiopheno[2,3-d]pyrimidines |
| WO2007061764A2 (en) * | 2005-11-22 | 2007-05-31 | Merck & Co., Inc. | Tricyclic compounds useful as inhibitors of kinases |
Non-Patent Citations (2)
| Title |
|---|
| Briel, D. et al., "Thieno[2,3-d]pyrimidine als Glutamatantagonisten", Die Pharmazie, 208, 63(11), 823-826. * |
| Pedeboscq, S. et al., "Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells", Europe Journal of Medicinal Chemistry, 2010, 45, 2473-2479. * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012012712A3 (en) | 2012-05-31 |
| JP6042331B2 (ja) | 2016-12-14 |
| US20160039839A1 (en) | 2016-02-11 |
| US8933087B2 (en) | 2015-01-13 |
| WO2012012712A2 (en) | 2012-01-26 |
| CN103119047B (zh) | 2016-06-15 |
| AU2011281015A1 (en) | 2013-03-07 |
| EP2595993A4 (en) | 2014-01-08 |
| US20180265519A1 (en) | 2018-09-20 |
| US9981981B2 (en) | 2018-05-29 |
| CA2808432A1 (en) | 2012-01-26 |
| CN103119047A (zh) | 2013-05-22 |
| US20130210845A1 (en) | 2013-08-15 |
| JP2013532662A (ja) | 2013-08-19 |
| EP2595993B1 (en) | 2018-04-18 |
| EP2595993A2 (en) | 2013-05-29 |
| CA2808432C (en) | 2019-06-04 |
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