ES2428543T3 - Compuestos de tiofenopirazolopirimidina - Google Patents
Compuestos de tiofenopirazolopirimidina Download PDFInfo
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- ES2428543T3 ES2428543T3 ES07814842T ES07814842T ES2428543T3 ES 2428543 T3 ES2428543 T3 ES 2428543T3 ES 07814842 T ES07814842 T ES 07814842T ES 07814842 T ES07814842 T ES 07814842T ES 2428543 T3 ES2428543 T3 ES 2428543T3
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Classifications
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- 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
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- 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
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
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- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Pregnancy & Childbirth (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82627306P | 2006-09-20 | 2006-09-20 | |
| US826273P | 2006-09-20 | ||
| PCT/US2007/078352 WO2008036541A1 (en) | 2006-09-20 | 2007-09-13 | Thiophene pyrazolopyrimidine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2428543T3 true ES2428543T3 (es) | 2013-11-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES07814842T Active ES2428543T3 (es) | 2006-09-20 | 2007-09-13 | Compuestos de tiofenopirazolopirimidina |
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| Country | Link |
|---|---|
| US (1) | US8110580B2 (enExample) |
| EP (1) | EP2076515B1 (enExample) |
| JP (1) | JP5184536B2 (enExample) |
| KR (1) | KR101088196B1 (enExample) |
| CN (1) | CN101516886B (enExample) |
| AU (1) | AU2007297481B2 (enExample) |
| BR (1) | BRPI0717070A2 (enExample) |
| CA (1) | CA2662000C (enExample) |
| EA (1) | EA016056B1 (enExample) |
| ES (1) | ES2428543T3 (enExample) |
| MX (1) | MX2009003098A (enExample) |
| WO (1) | WO2008036541A1 (enExample) |
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| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| WO2009094224A1 (en) | 2008-01-25 | 2009-07-30 | Millennium Pharmaceuticals, Inc. | Thiophenes and their use as phosphatidylinositol 3-kinase (pi3k) inhibitors |
| US8796314B2 (en) | 2009-01-30 | 2014-08-05 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US9090601B2 (en) | 2009-01-30 | 2015-07-28 | Millennium Pharmaceuticals, Inc. | Thiazole derivatives |
| CA2750935A1 (en) | 2009-01-30 | 2010-08-12 | Millennium Pharmaceuticals, Inc. | Heteroaryls and their use as pi3k inhibitors |
| EP2603216A4 (en) | 2010-08-11 | 2013-12-18 | Millennium Pharm Inc | HETEROARYLE AND USES THEREOF |
| EP2603214A4 (en) | 2010-08-11 | 2013-12-18 | Millennium Pharm Inc | HETEROARYLE AND USES THEREOF |
| US9062038B2 (en) | 2010-08-11 | 2015-06-23 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| MX2013004003A (es) | 2010-10-13 | 2013-10-01 | Millenium Pharmaceuticals Inc | Heteroarilos y usos de los mismos. |
| EP2729455B1 (en) | 2011-07-05 | 2016-09-14 | Lupin Limited | Biaryl derivatives as nachr modulators |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| HRP20241046T1 (hr) | 2014-01-21 | 2024-11-08 | Neurocrine Biosciences, Inc. | Antagonisti crf1 receptora za liječenje kongenitalne adrenalne hiperplazije |
| JP6364967B2 (ja) * | 2014-05-30 | 2018-08-01 | 東ソー株式会社 | ジチエノベンゾジチオフェンの製造方法 |
| EP3238676B1 (en) | 2016-04-29 | 2019-01-02 | The Procter and Gamble Company | Absorbent core with profiled distribution of absorbent material |
| CA3064445A1 (en) * | 2017-08-14 | 2019-02-21 | Spruce Biosciences, Inc. | Corticotropin releasing factor receptor antagonists |
| US20210361664A1 (en) | 2017-08-14 | 2021-11-25 | Spruce Biosciences, Inc. | Corticotropin releasing factor receptor antagonists |
| DK3984523T3 (da) | 2018-12-07 | 2025-09-29 | Neurocrine Biosciences Inc | Crf1-receptorantagonist, farmaceutiske formuleringer og faste former heraf til behandling af medfødt binyrebarkhyperplasi |
| CN114502162B (zh) | 2019-09-27 | 2025-03-28 | 纽罗克里生物科学有限公司 | Crf受体拮抗剂及使用方法 |
| ES3039926T3 (en) * | 2019-12-04 | 2025-10-27 | Neurocrine Biosciences Inc | Crf receptor antagonists and methods of use |
| WO2022036123A1 (en) | 2020-08-12 | 2022-02-17 | Spruce Biosciences, Inc. | Methods and compositions for treating polycystic ovary syndrome |
| US11708372B2 (en) | 2021-11-19 | 2023-07-25 | Spruce Biosciences, Inc. | Crystalline composition of tildacerfont and methods of use and preparation thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69323768T2 (de) | 1992-12-17 | 1999-07-01 | Pfizer Inc., New York, N.Y. | Pyrrolopyrimidine als crf antagonisten |
| ATE336495T1 (de) * | 1996-02-07 | 2006-09-15 | Neurocrine Biosciences Inc | Pyrazolopyrimidine als crf rezeptor-antagonisten |
| DE69738197T2 (de) | 1996-07-24 | 2008-07-17 | Bristol-Myers Squibb Pharma Co. | Azolotriazine und pyrimidine |
| EP0923582B1 (en) | 1996-08-28 | 2006-09-20 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
| OA12049A (en) * | 1999-09-30 | 2006-05-02 | Neurogen Corp | Amino substituted pyrazoloÄ1,5,-aÜ-1,5-pyrimidinesand pyrazoloÄ1,5,-aÜ-1,3,5-triazines. |
| CN1938309B (zh) * | 2003-12-22 | 2011-11-09 | 史密斯克莱.比奇曼（科克）有限公司 | Crf受体拮抗剂及其相关方法 |
| EP1869049B1 (en) * | 2005-03-21 | 2009-03-04 | Eli Lilly And Company | Imidazopyridazine compounds |
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2007
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- 2007-09-13 WO PCT/US2007/078352 patent/WO2008036541A1/en not_active Ceased
- 2007-09-13 MX MX2009003098A patent/MX2009003098A/es active IP Right Grant
- 2007-09-13 US US12/438,953 patent/US8110580B2/en active Active
- 2007-09-13 CA CA2662000A patent/CA2662000C/en not_active Expired - Fee Related
- 2007-09-13 CN CN2007800349472A patent/CN101516886B/zh not_active Expired - Fee Related
- 2007-09-13 EP EP07814842.6A patent/EP2076515B1/en not_active Not-in-force
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| CA2662000A1 (en) | 2008-03-27 |
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| KR101088196B1 (ko) | 2011-11-30 |
| EA200970302A1 (ru) | 2009-10-30 |
| CN101516886A (zh) | 2009-08-26 |
| US8110580B2 (en) | 2012-02-07 |
| KR20090053921A (ko) | 2009-05-28 |
| CA2662000C (en) | 2013-01-08 |
| MX2009003098A (es) | 2009-04-01 |
| CN101516886B (zh) | 2012-02-29 |
| EA016056B1 (ru) | 2012-01-30 |
| WO2008036541A1 (en) | 2008-03-27 |
| US20100022560A1 (en) | 2010-01-28 |
| EP2076515B1 (en) | 2013-07-17 |
| JP5184536B2 (ja) | 2013-04-17 |
| EP2076515A1 (en) | 2009-07-08 |
| JP2010504343A (ja) | 2010-02-12 |
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