KR20170003667A - 카르복스아미드 유도체 - Google Patents
카르복스아미드 유도체 Download PDFInfo
- Publication number
- KR20170003667A KR20170003667A KR1020167034560A KR20167034560A KR20170003667A KR 20170003667 A KR20170003667 A KR 20170003667A KR 1020167034560 A KR1020167034560 A KR 1020167034560A KR 20167034560 A KR20167034560 A KR 20167034560A KR 20170003667 A KR20170003667 A KR 20170003667A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- triazole
- carboxamide
- dihydro
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461993046P | 2014-05-14 | 2014-05-14 | |
| US61/993,046 | 2014-05-14 | ||
| EP14168319 | 2014-05-14 | ||
| EP14168319.3 | 2014-05-14 | ||
| PCT/IB2015/001539 WO2015177646A1 (en) | 2014-05-14 | 2015-05-14 | Carboxamide derivatives |
Publications (1)
| Publication Number | Publication Date |
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| KR20170003667A true KR20170003667A (ko) | 2017-01-09 |
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| KR1020167034560A Withdrawn KR20170003667A (ko) | 2014-05-14 | 2015-05-14 | 카르복스아미드 유도체 |
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| Country | Link |
|---|---|
| US (2) | US9403833B2 (OSRAM) |
| EP (1) | EP3143014B1 (OSRAM) |
| JP (1) | JP6587637B2 (OSRAM) |
| KR (1) | KR20170003667A (OSRAM) |
| CN (1) | CN106536512B (OSRAM) |
| AP (1) | AP2016009554A0 (OSRAM) |
| AR (1) | AR100439A1 (OSRAM) |
| AU (1) | AU2015263049B2 (OSRAM) |
| CA (1) | CA2948582A1 (OSRAM) |
| EA (1) | EA201692298A1 (OSRAM) |
| MX (1) | MX2016014946A (OSRAM) |
| SG (1) | SG11201609311RA (OSRAM) |
| TN (1) | TN2016000491A1 (OSRAM) |
| TW (1) | TW201623288A (OSRAM) |
| UY (1) | UY36123A (OSRAM) |
| WO (1) | WO2015177646A1 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US9403833B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
| US9403810B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
| CN108007916B (zh) * | 2017-03-16 | 2020-08-04 | 黑龙江八一农垦大学 | 希尔伯特黄法建立稻株氮含量的共聚焦显微拉曼测量模型 |
| CN110749687B (zh) * | 2019-04-04 | 2021-05-28 | 中山大学 | 一种日本血吸虫病早期诊断尿液生物标志物及筛选方法和应用 |
| CN110038012B (zh) * | 2019-05-30 | 2021-06-11 | 济南大学 | 具有1,2,3-三氮唑结构片段的生物碱化合物在制备促血管生成药物中的应用 |
| DE102020116104A1 (de) | 2020-06-18 | 2021-12-23 | Charité - Universitätsmedizin Berlin, Körperschaft des öffentlichen Rechts | Metamizolderivate zur Prävention und Therapie der pulmonalen Hypertonie |
| CN113636977B (zh) * | 2021-09-01 | 2022-12-20 | 温州大学 | 2-芳基苯并氮杂卓及其衍生物的合成方法 |
Family Cites Families (14)
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| US7354722B1 (en) | 1999-06-11 | 2008-04-08 | Signal Pharmaceuticals | Modulators of Smurf and BMP/TGFβ signaling pathways |
| AU782355B2 (en) * | 1999-06-11 | 2005-07-21 | Hsc Research And Development Limited Partnership | Antagonists of BMP and TGFbeta signalling pathways |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| GB0312368D0 (en) | 2003-05-30 | 2003-07-02 | Univ Aston | Novel ureido- and amido-pyrazolone derivatives |
| JP2007506741A (ja) | 2003-09-23 | 2007-03-22 | メルク エンド カムパニー インコーポレーテッド | 向代謝性グルタミン酸受容体のピラゾール系調節剤 |
| US7291743B2 (en) | 2005-03-29 | 2007-11-06 | Geneblue Corporation | Isoxazole derivatives and methods of treating nitric oxide mediated diseases |
| EP1943234A1 (en) * | 2005-10-31 | 2008-07-16 | Biolipox AB | Triazole compounds as lipoxygenase inhibitors |
| WO2008121861A2 (en) | 2007-03-28 | 2008-10-09 | Xenon Pharmaceuticals Inc. | Pyrazole and pyrrole compounds useful in treating iron disorders |
| WO2009011850A2 (en) | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| WO2009016241A1 (en) | 2007-08-02 | 2009-02-05 | N.V. Organon | 5-phenyl-isoxazole-3-carboxamide derivatives as trpv1 modulators |
| JP2011507910A (ja) | 2007-12-21 | 2011-03-10 | ユニバーシティー オブ ロチェスター | 真核生物の寿命を変更するための方法 |
| WO2011151361A1 (en) | 2010-06-03 | 2011-12-08 | Glaxo Group Limited | Novel compounds |
| US9403833B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
| US9403810B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
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| AP2016009554A0 (en) | 2016-11-30 |
| WO2015177646A1 (en) | 2015-11-26 |
| AU2015263049B2 (en) | 2017-09-28 |
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