JP2013544277A - Katii阻害剤 - Google Patents
Katii阻害剤 Download PDFInfo
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- JP2013544277A JP2013544277A JP2013541446A JP2013541446A JP2013544277A JP 2013544277 A JP2013544277 A JP 2013544277A JP 2013541446 A JP2013541446 A JP 2013541446A JP 2013541446 A JP2013541446 A JP 2013541446A JP 2013544277 A JP2013544277 A JP 2013544277A
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- Prior art keywords
- alkyl
- aryl
- cycloalkyl
- heteroaryl
- mmol
- Prior art date
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Landscapes
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| US41880210P | 2010-12-01 | 2010-12-01 | |
| US61/418,802 | 2010-12-01 | ||
| PCT/IB2011/055158 WO2012073143A1 (en) | 2010-12-01 | 2011-11-17 | Kat ii inhibitors |
Publications (2)
| Publication Number | Publication Date |
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| JP2013544277A true JP2013544277A (ja) | 2013-12-12 |
| JP2013544277A5 JP2013544277A5 (enExample) | 2014-09-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2013541446A Ceased JP2013544277A (ja) | 2010-12-01 | 2011-11-17 | Katii阻害剤 |
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| EP (1) | EP2646443B1 (enExample) |
| JP (1) | JP2013544277A (enExample) |
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| SG (1) | SG190207A1 (enExample) |
| WO (1) | WO2012073143A1 (enExample) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015163339A1 (ja) * | 2014-04-23 | 2015-10-29 | 田辺三菱製薬株式会社 | 新規二環性または三環性複素環化合物 |
| WO2017069275A1 (ja) * | 2015-10-22 | 2017-04-27 | 田辺三菱製薬株式会社 | 新規二環性複素環化合物 |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101522803B1 (ko) | 2010-12-01 | 2015-05-26 | 화이자 인코포레이티드 | Kat ii 억제제 |
| WO2014078568A1 (en) | 2012-11-14 | 2014-05-22 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| WO2016164703A1 (en) | 2015-04-09 | 2016-10-13 | Eisai R & D Management Co., Ltd. | Fgfr4 inhibitors |
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| CN114599650A (zh) * | 2019-06-20 | 2022-06-07 | 肯塔基大学研究基金会 | DCN1/2介导的cullin类泛素化修饰的药学活性吡唑并-吡啶酮调节剂 |
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| BR112022022530A2 (pt) | 2020-05-05 | 2023-02-23 | Nuvalent Inc | Composto, composição farmacêutica, método de tratamento de câncer, método de inibição seletiva, método de redução de um nível de ros1 ou alk |
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| US12435087B2 (en) | 2023-11-03 | 2025-10-07 | Cellarity, Inc. | Modulators of DCN-1 and methods of use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050009870A1 (en) * | 2003-07-11 | 2005-01-13 | Sher Philip M. | Tetrahydroquinoline derivatives as cannabinoid receptor modulators |
| WO2009095752A1 (en) * | 2008-01-29 | 2009-08-06 | Glenmark Pharmaceuticals, S.A. | Fused pyrazole derivatives as cannabinoid receptor modulators |
| WO2010146488A1 (en) * | 2009-06-18 | 2010-12-23 | Pfizer Inc. | Bicyclic and tricyclic compounds as kat ii inhibitors |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4282361A (en) | 1978-03-16 | 1981-08-04 | Massachusetts Institute Of Technology | Synthesis for 7-alkylamino-3-methylpyrazolo [4,3-d]pyrimidines |
| US5519055A (en) * | 1993-08-06 | 1996-05-21 | University Of Maryland At Baltimore | Substituted kynurenines and process for their preparation |
| GT200500186A (es) | 2004-07-07 | 2006-03-02 | Regimenes anticonceptivos con antagonistas del receptor de progesterona y kits | |
| WO2006046135A2 (en) | 2004-10-28 | 2006-05-04 | Pharmacia & Upjohn Company Llc | Pyrazolo[4,3-d] pyrimidine derivatives useful as pde-5 inhibitors |
| CA2626897A1 (en) | 2005-11-03 | 2007-05-18 | Joshua Close | Histone deacetylase inhibitors with aryl-pyrazolyl motifs |
| US20090012075A1 (en) | 2006-01-12 | 2009-01-08 | Miller Thomas A | Fluorinated Arylamide Derivatives |
| EP2049548A1 (en) | 2006-07-27 | 2009-04-22 | UCB Pharma, S.A. | Fused oxazoles & thiazoles as histamine h3- receptor ligands |
| WO2009064836A2 (en) * | 2007-11-15 | 2009-05-22 | University Of Maryland, Baltimore | Kynurenine-aminotransferase inhibitors |
| WO2010014688A2 (en) | 2008-07-30 | 2010-02-04 | Bal Seal Engineering | Canted coil multi-metallic wire |
-
2011
- 2011-11-17 EP EP11804801.6A patent/EP2646443B1/en not_active Not-in-force
- 2011-11-17 MX MX2013005773A patent/MX2013005773A/es active IP Right Grant
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- 2011-11-17 WO PCT/IB2011/055158 patent/WO2012073143A1/en not_active Ceased
- 2011-11-17 DK DK11804801.6T patent/DK2646443T3/en active
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- 2013-05-09 ZA ZA2013/03360A patent/ZA201303360B/en unknown
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050009870A1 (en) * | 2003-07-11 | 2005-01-13 | Sher Philip M. | Tetrahydroquinoline derivatives as cannabinoid receptor modulators |
| WO2009095752A1 (en) * | 2008-01-29 | 2009-08-06 | Glenmark Pharmaceuticals, S.A. | Fused pyrazole derivatives as cannabinoid receptor modulators |
| WO2010146488A1 (en) * | 2009-06-18 | 2010-12-23 | Pfizer Inc. | Bicyclic and tricyclic compounds as kat ii inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| JPN6015020202; Davis, A. L. et al: Journal of Medicinal Chemistry vol. 18, No. 7, 1975, p. 752-755 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015163339A1 (ja) * | 2014-04-23 | 2015-10-29 | 田辺三菱製薬株式会社 | 新規二環性または三環性複素環化合物 |
| JPWO2015163339A1 (ja) * | 2014-04-23 | 2017-04-20 | 田辺三菱製薬株式会社 | 新規二環性または三環性複素環化合物 |
| WO2017069275A1 (ja) * | 2015-10-22 | 2017-04-27 | 田辺三菱製薬株式会社 | 新規二環性複素環化合物 |
| JPWO2017069275A1 (ja) * | 2015-10-22 | 2018-08-09 | 田辺三菱製薬株式会社 | 新規二環性複素環化合物 |
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| US20140057938A1 (en) | 2014-02-27 |
| ZA201303360B (en) | 2014-07-30 |
| SG190207A1 (en) | 2013-06-28 |
| US8598200B2 (en) | 2013-12-03 |
| EP2646443A1 (en) | 2013-10-09 |
| DK2646443T3 (en) | 2014-11-17 |
| CN103228660A (zh) | 2013-07-31 |
| MX2013005773A (es) | 2013-06-18 |
| AU2011336214B2 (en) | 2015-08-20 |
| US20120302599A1 (en) | 2012-11-29 |
| AU2011336214A1 (en) | 2013-05-30 |
| KR101544290B1 (ko) | 2015-08-12 |
| WO2012073143A1 (en) | 2012-06-07 |
| US8933095B2 (en) | 2015-01-13 |
| EP2646443B1 (en) | 2014-09-24 |
| ES2524423T3 (es) | 2014-12-09 |
| CA2819102A1 (en) | 2012-06-07 |
| KR20130108618A (ko) | 2013-10-04 |
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