JP5961683B2 - Ｈｓｐ９０阻害物質 - Google Patents
Ｈｓｐ９０阻害物質 Download PDFInfo
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- JP5961683B2 JP5961683B2 JP2014503996A JP2014503996A JP5961683B2 JP 5961683 B2 JP5961683 B2 JP 5961683B2 JP 2014503996 A JP2014503996 A JP 2014503996A JP 2014503996 A JP2014503996 A JP 2014503996A JP 5961683 B2 JP5961683 B2 JP 5961683B2
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- Prior art keywords
- cancer
- pharmaceutically acceptable
- acceptable salt
- alkyl
- compound according
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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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
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
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- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US201161472061P | 2011-04-05 | 2011-04-05 | |
| US61/472,061 | 2011-04-05 | ||
| PCT/US2012/032373 WO2012138896A1 (en) | 2011-04-05 | 2012-04-05 | Hsp90 inhibitors |
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| JP2014510149A JP2014510149A (ja) | 2014-04-24 |
| JP2014510149A5 JP2014510149A5 (enExample) | 2015-05-21 |
| JP5961683B2 true JP5961683B2 (ja) | 2016-08-02 |
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| JP2014503996A Expired - Fee Related JP5961683B2 (ja) | 2011-04-05 | 2012-04-05 | Ｈｓｐ９０阻害物質 |
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|---|---|
| US (2) | US9546170B2 (enExample) |
| EP (1) | EP2694506B1 (enExample) |
| JP (1) | JP5961683B2 (enExample) |
| KR (1) | KR101984480B1 (enExample) |
| CN (1) | CN103596955B (enExample) |
| AU (1) | AU2012240079B2 (enExample) |
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| CA (1) | CA2832099C (enExample) |
| EA (1) | EA024647B1 (enExample) |
| ES (1) | ES2647889T3 (enExample) |
| MX (1) | MX354215B (enExample) |
| WO (1) | WO2012138896A1 (enExample) |
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| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| JP5599610B2 (ja) | 2006-06-30 | 2014-10-01 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｓｐ９０の阻害による神経変性疾患の処置 |
| AU2010303343B2 (en) | 2009-10-07 | 2015-11-19 | Sloan-Kettering Institute For Cancer Research | Purine derivatives useful as HSP90 inhibitors |
| EP2694505B1 (en) | 2011-04-05 | 2022-04-27 | Sloan-kettering Institute For Cancer Research | Hsp90 inhibitors |
| EA024647B1 (ru) | 2011-04-05 | 2016-10-31 | Слоун-Кеттеринг Инститьют Фо Кэнсэ Рисерч | ИНГИБИТОРЫ Hsp90 |
| CN109374889B (zh) | 2011-07-08 | 2022-04-19 | 索隆-基特林癌症研究协会 | 标记的hsp90抑制剂的用途 |
| RS59719B1 (sr) | 2012-02-09 | 2020-01-31 | Univ Kansas | C-terminalni inhibitori hsp90 |
| TW201533043A (zh) | 2013-04-18 | 2015-09-01 | Lundbeck & Co As H | 作爲ｌｒｒｋ２抑制劑的芳基吡咯并吡啶衍生化合物 |
| WO2015023976A2 (en) | 2013-08-16 | 2015-02-19 | Memorial Sloan-Kettering Cancer Center | Selective grp94 inhibitors and uses thereof |
| US9994573B2 (en) | 2013-12-23 | 2018-06-12 | Memorial Sloan-Kettering Cancer Center | Methods and reagents for radiolabeling |
| EA201790070A1 (ru) * | 2014-06-24 | 2017-10-31 | Дзе Юниверсити оф Канзас | Бифениламиды, содержащие модифицированные простые эфирные группы, в качестве ингибиторов hsp90 и стимуляторов hsp70 |
| JP6835709B2 (ja) | 2014-09-17 | 2021-02-24 | メモリアル スローン ケタリング キャンサー センター | Ｈｓｐ９０を標的とした炎症及び感染のイメージング及び療法 |
| EA201890623A1 (ru) | 2015-10-05 | 2018-09-28 | Мемориал Слоун Кеттеринг Кэнсер Сентр | Рациональная комбинированная терапия для лечения рака |
| EA202092727A1 (ru) | 2018-05-14 | 2021-04-20 | Рита Фармасьютикалз, Инк. | Биариламиды с модифицированными сахарными группами для лечения заболеваний, связанных с путем белка теплового шока |
| WO2023006993A1 (en) | 2021-07-30 | 2023-02-02 | Atmosr | Fused amino pyridine or pyrimidine derivatives for the treatment of congenital central hypoventilation syndrome |
| EP4680606A1 (en) * | 2023-03-17 | 2026-01-21 | AtmosR | Adenine derivatives as hsp90 inhibitors |
Family Cites Families (29)
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| WO2000061578A1 (en) | 1999-04-09 | 2000-10-19 | Sloan-Kettering Institute For Cancer Research | Methods and compositions for degradation and/or inhibition of her-family tyrosine kinases |
| JP2005519848A (ja) | 2000-11-02 | 2005-07-07 | スローン−ケッタリング・インスティテュート・フォー・キャンサー・リサーチ | Ｈｓｐ９０に結合するための小分子組成物 |
| BR0210391A (pt) * | 2001-06-12 | 2004-06-15 | Elan Pharm Inc | Composto, métodos de tratar um paciente que tenha ou de prevenir um paciente de contrair uma doença ou condição e de preparar um composto, e, uso de um composto |
| EP2336133A1 (en) | 2001-10-30 | 2011-06-22 | Conforma Therapeutics Corporation | Purine analogs having HSP90-inhibiting activity |
| EP1450784A4 (en) | 2001-11-09 | 2005-02-09 | Conforma Therapeutics Corp | HSP90-INHIBITABLE ZEARALANOL COMPOUNDS AND METHOD FOR THEIR PREPARATION AND USE |
| US7473699B2 (en) | 2002-02-28 | 2009-01-06 | Astrazeneca Ab | 3-cyclyl-5-(nitrogen-containing 5-membered ring)methyl-oxazolidinone derivatives and their use as antibacterial agents |
| EP1620564A4 (en) | 2003-04-18 | 2008-03-12 | Cytovia Inc | METHODS FOR TREATING DISEASES INDUCING APOPTOSIS INDUCTION AND SCREENING ASSAYS |
| EP2145888A1 (en) | 2003-09-18 | 2010-01-20 | Conforma Therapeutics Corporation | Deazapurine derivatives as HSP90-Inhibitors |
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| WO2007023186A1 (en) | 2005-08-26 | 2007-03-01 | Laboratoires Serono S.A. | Pyrazine derivatives and use as pi3k inhibitors |
| EP1962863A4 (en) | 2005-12-22 | 2010-11-24 | Conforma Therapeutics Corp | ORALLY ACTIVE PURINE INHIBITORS OF THERMAL SHOCK PROTEIN 90 |
| WO2007134298A2 (en) | 2006-05-12 | 2007-11-22 | Myriad Genetics, Inc. | Therapeutic compounds and their use in cancer |
| JP5599610B2 (ja) | 2006-06-30 | 2014-10-01 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｓｐ９０の阻害による神経変性疾患の処置 |
| CA2662937A1 (en) | 2006-09-11 | 2008-03-20 | Curis, Inc. | Multi-functional small molecules as anti-proliferative agents |
| FR2906824B1 (fr) | 2006-10-09 | 2008-12-26 | Roger Mondelin Sas Soc Par Act | Dispositif support de butees pour la pose de plaques de platre de largeur variable avec des appareils de levage et de manutention desdites plaques |
| CL2007002994A1 (es) | 2006-10-19 | 2008-02-08 | Wyeth Corp | Compuestos derivados heterociclicos que contienen sulfamoilo, inhibidores de hsp90; composicion farmaceutica; y uso para el tratamiento del cancer, tal como cancer de mama, de colon y prostata, entre otros. |
| GB0622084D0 (en) | 2006-11-06 | 2006-12-13 | Chroma Therapeutics Ltd | Inhibitors of HSP90 |
| US20080234297A1 (en) | 2007-03-20 | 2008-09-25 | Changgeng Qian | HSP90 Inhibitors Containing a Zinc Binding Moiety |
| NZ579635A (en) * | 2007-03-20 | 2011-07-29 | Curis Inc | Fused amino pyridine as hsp90 inhibitors |
| US20100240656A1 (en) | 2007-07-12 | 2010-09-23 | Oryzon Genomics, S.A. | Compounds as hsp90 inhibitors |
| WO2009042646A1 (en) | 2007-09-24 | 2009-04-02 | Curis, Inc. | Anti-proliferative agents |
| CA2705579A1 (en) | 2007-11-14 | 2009-05-22 | Myriad Pharmaceuticals, Inc. | Therapeutic compounds and their use in treating diseases and disorders |
| MX2011007612A (es) | 2009-01-16 | 2012-01-20 | Curis Inc | Aminopiridinas fusionadas para el tratamiento de tumores del cerebro. |
| AU2010303343B2 (en) | 2009-10-07 | 2015-11-19 | Sloan-Kettering Institute For Cancer Research | Purine derivatives useful as HSP90 inhibitors |
| EA024647B1 (ru) | 2011-04-05 | 2016-10-31 | Слоун-Кеттеринг Инститьют Фо Кэнсэ Рисерч | ИНГИБИТОРЫ Hsp90 |
| EP2694505B1 (en) | 2011-04-05 | 2022-04-27 | Sloan-kettering Institute For Cancer Research | Hsp90 inhibitors |
| WO2015023976A2 (en) | 2013-08-16 | 2015-02-19 | Memorial Sloan-Kettering Cancer Center | Selective grp94 inhibitors and uses thereof |
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| CN103596955B (zh) | 2016-11-16 |
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| AU2012240079A1 (en) | 2013-11-07 |
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| US10064867B2 (en) | 2018-09-04 |
| KR101984480B1 (ko) | 2019-05-31 |
| CN103596955A (zh) | 2014-02-19 |
| US20170151247A1 (en) | 2017-06-01 |
| US20140045867A1 (en) | 2014-02-13 |
| EA024647B1 (ru) | 2016-10-31 |
| MX354215B (es) | 2018-02-19 |
| NZ616890A (en) | 2016-01-29 |
| CA2832099A1 (en) | 2012-10-11 |
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