TWI835179B - 胰腺炎治療 - Google Patents
胰腺炎治療 Download PDFInfo
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- TWI835179B TWI835179B TW111123836A TW111123836A TWI835179B TW I835179 B TWI835179 B TW I835179B TW 111123836 A TW111123836 A TW 111123836A TW 111123836 A TW111123836 A TW 111123836A TW I835179 B TWI835179 B TW I835179B
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Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10703722B2 (en) | 2010-04-27 | 2020-07-07 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| JP6195684B2 (ja) * | 2014-06-03 | 2017-09-13 | アクテリオン ファーマシューティカルズ リミテッドActelion Pharmaceuticals Ltd | ピラゾール化合物及びt型カルシウムチャンネルブロッカーとしてのそれらの使用 |
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| CA2995094A1 (en) | 2015-08-07 | 2017-02-16 | Calcimedica, Inc. | Use of crac channel inhibitors for the treatment of stroke and traumatic brain injury |
| CA3051420A1 (en) * | 2017-01-26 | 2018-08-02 | Calcimedica, Inc. | Crac channel inhibitor compositions |
| KR101798840B1 (ko) | 2017-05-17 | 2017-11-17 | 주식회사 레고켐 바이오사이언스 | 신규 오토탁신 저해 화합물 및 이를 함유하는 약제학적 조성물 |
| US10961242B2 (en) | 2017-05-17 | 2021-03-30 | Legochem Biosciences, Inc. | Compounds as autotaxin inhibitors and pharmaceutical compositions comprising the same |
| CN110063945B (zh) * | 2019-04-15 | 2021-07-09 | 温州医科大学 | 一种用于急性胰腺炎治疗的胆红素纳米颗粒及其制备方法 |
| JP2022532875A (ja) * | 2019-05-06 | 2022-07-20 | カルシメディカ,インク. | Cracチャネル阻害剤の合成 |
| EP4043450A4 (en) * | 2019-09-25 | 2023-10-25 | Medshine Discovery Inc. | 2h-benzopyran derivatives as crac inhibitors |
| CA3172249A1 (en) | 2020-03-20 | 2021-09-23 | Calcimedica, Inc. | Methods and compositions for treating acute lung injury and acute respiratory distress syndrome |
| JP2023526505A (ja) * | 2020-05-20 | 2023-06-21 | カルシメディカ,インク. | 急性腎障害を治療するための方法および組成物 |
| US11413270B2 (en) * | 2020-06-22 | 2022-08-16 | Novmetapharma Co., Ltd. | Method for the treatment of pancreatitis |
| US12496309B2 (en) | 2020-06-22 | 2025-12-16 | Novmetapharma Co., Ltd. | Method for treatment of pancreatitis |
| EP4192480A4 (en) * | 2020-08-07 | 2024-09-04 | Board of Regents, The University of Texas System | METHODS AND COMPOSITIONS FOR THE EVALUATION AND TREATMENT OF PANCREATIC CANCER |
| CA3198798A1 (en) | 2020-11-13 | 2022-05-19 | Kenneth Stauderman | Improved synthesis of crac channel inhibitors |
| CN117098756A (zh) * | 2021-02-25 | 2023-11-21 | 辰欣药业股份有限公司 | 一种环丙基取代的苯并呋喃类化合物的晶型及其制备方法 |
| CN113424795B (zh) * | 2021-05-24 | 2022-09-09 | 四川大学华西医院 | 一种急性胰腺炎动物模型的构建方法和用途 |
| CN113903460A (zh) * | 2021-12-10 | 2022-01-07 | 中国医学科学院北京协和医院 | 一种预测重症急性胰腺炎的系统及其应用 |
| JP2025504467A (ja) * | 2022-01-20 | 2025-02-12 | カルシメディカ,インク. | 肺の炎症性損傷を処置するための方法および組成物 |
| CN114522157B (zh) * | 2022-02-23 | 2023-08-15 | 重庆大学 | 钙离子螯合剂在制备用于提高血管内皮细胞吞噬能力的制剂中的应用 |
| CN120272478B (zh) * | 2025-03-28 | 2025-12-09 | 山西医科大学 | 一种抗寨卡病毒的靶点抑制剂、重组基因、表达载体及应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120316182A1 (en) * | 2011-06-10 | 2012-12-13 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5424289A (en) | 1977-07-26 | 1979-02-23 | Mitsubishi Chem Ind Ltd | Production of spherical diatomaceous earth carrier |
| ATE240955T1 (de) | 1996-08-09 | 2003-06-15 | Boehringer Ingelheim Pharma | 4-substituierte beta-carboline als immunomodulatoren |
| AU751139B2 (en) | 1997-10-13 | 2002-08-08 | Astellas Pharma Inc. | Amide derivative |
| US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
| WO1999051580A1 (en) | 1998-04-08 | 1999-10-14 | Abbott Laboratories | Pyrazole inhibitors of cytokine production |
| CA2332957A1 (en) | 1998-06-05 | 1999-12-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted 1-(4-aminophenyl)pyrazoles and their use as anti-inflammatory agents |
| US20010044445A1 (en) | 1999-04-08 | 2001-11-22 | Bamaung Nwe Y. | Azole inhibitors of cytokine production |
| CN1237051C (zh) | 1999-08-20 | 2006-01-18 | 道农业科学公司 | 杀真菌的杂环芳族酰胺和它们的组合物、使用方法和制备 |
| JP3910319B2 (ja) | 1999-09-13 | 2007-04-25 | 株式会社小糸製作所 | 自動車用灯具 |
| EP1143013A1 (en) | 2000-04-03 | 2001-10-10 | Warner-Lambert Company | Methods and compositions for screening Icrac modulators |
| EP1390030A1 (en) | 2001-05-31 | 2004-02-25 | Cellegy Pharmaceuticals, Inc | Store operated calcium influx inhibitors and methods of use |
| GB0225554D0 (en) | 2002-11-01 | 2002-12-11 | Syngenta Participations Ag | Chemical compounds |
| SI1569907T1 (sl) | 2002-12-13 | 2016-06-30 | Ym Biosciences Australia Pty Ltd | Na nikotinamidu osnovani kinazni inhibitorji |
| WO2004056774A2 (en) | 2002-12-19 | 2004-07-08 | Neurogen Corporation | Substituted biphenyl-4-carboxylic acid arylamide analogues as capsaicin receptor modulators |
| US7645588B2 (en) | 2003-03-04 | 2010-01-12 | Calcimedica, Inc. | Composition comprising a cell comprising a STIM1 protein and an agent that modulates intracellular calcium and methods of use |
| CN1826121B (zh) | 2003-07-23 | 2013-05-29 | 幸讬制药公司 | 苯基与吡啶基衍生物用于制备调控钙离子释放活化钙离子通道的药物的用途 |
| DE102004005785A1 (de) | 2004-02-06 | 2005-08-25 | Bayer Cropscience Ag | 2-Halogenfuryl/thienyl-3-carboxamide |
| WO2006006569A1 (ja) | 2004-07-12 | 2006-01-19 | Nihon Nohyaku Co., Ltd. | フェニルピリジン類又はその塩類、これらを有効成分とする除草剤及びその使用方法 |
| CN101083985A (zh) | 2004-09-21 | 2007-12-05 | 幸讬制药公司 | 用于炎症及免疫相关用途的化合物 |
| US8557861B2 (en) | 2004-09-28 | 2013-10-15 | Mast Therapeutics, Inc. | Low oil emulsion compositions for delivering taxoids and other insoluble drugs |
| KR20070107022A (ko) | 2005-01-07 | 2007-11-06 | 신타 파마슈티칼스 코프. | 염증 및 면역 관련 용도를 위한 화합물 |
| PL1848435T3 (pl) | 2005-01-25 | 2016-08-31 | Synta Pharmaceuticals Corp | Związki przeciwko zapaleniom i zastosowania związane z odpornością |
| TWI444187B (zh) | 2005-01-25 | 2014-07-11 | Synta Pharmaceuticals Corp | 用於炎症及免疫相關用途之噻吩化合物 |
| NZ560712A (en) | 2005-02-17 | 2010-12-24 | Synta Pharmaceuticals Corp | (3,4,5-trisubstituted-phenyl)isoxazole combretastin derivatives for the treatment of disorders |
| EP2527337A1 (en) | 2005-04-14 | 2012-11-28 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
| WO2007035874A1 (en) | 2005-09-21 | 2007-03-29 | Bristol-Myers Squibb Company | Oral administration of n-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-1,3-thiazole-5-carboxamide and salts thereof |
| NL2000284C2 (nl) | 2005-11-04 | 2007-09-28 | Pfizer Ltd | Pyrazine-derivaten. |
| CN102775396B (zh) | 2005-11-08 | 2014-10-08 | 沃泰克斯药物股份有限公司 | Atp-结合弹夹转运蛋白的杂环调控剂 |
| BRPI0618661A2 (pt) | 2005-11-15 | 2011-09-06 | Baxter Int | composições de inibidores de lipoxigenase |
| WO2007081804A2 (en) | 2006-01-05 | 2007-07-19 | Immune Disease Institute, Inc. | Regulators of nfat |
| WO2007087441A2 (en) | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Substituted aromatic compounds for inflammation and immune-related uses |
| WO2007087442A2 (en) | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Substituted biaryl compounds for inflammation and immune-related uses |
| WO2007087443A2 (en) | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Vinyl-phenyl derivatives for inflammation and immune-related uses |
| US20070275960A1 (en) | 2006-01-25 | 2007-11-29 | Synta Pharmaceuticals Corp. | Phenyl and pyridyl compounds for inflammation and immune-related uses |
| CA2639910A1 (en) | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Thiazole and thiadiazole compounds for inflammation and immune-related uses |
| US20070254926A1 (en) | 2006-01-31 | 2007-11-01 | Jun Jiang | Pyridylphenyl compounds for inflammation and immune-related uses |
| US7951824B2 (en) | 2006-02-17 | 2011-05-31 | Hoffman-La Roche Inc. | 4-aryl-pyridine-2-carboxyamide derivatives |
| US8119643B2 (en) | 2006-03-20 | 2012-02-21 | Synta Pharmaceuticals Corp. | Benzoimidazolyl-pyrazine compounds for inflammation and immune-related uses |
| US8163777B2 (en) | 2006-03-23 | 2012-04-24 | Synta Pharmaceuticals Corp. | Benzimidazolyl-pyridine compounds for inflammation and immune-related uses |
| WO2007120600A2 (en) | 2006-04-10 | 2007-10-25 | Arena Pharmaceuticals, Inc. | 3-pyridinyl-pyrazole derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| BRPI0713350B1 (pt) | 2006-06-26 | 2022-04-12 | Akebia Therapeutics Inc | Composto, e, composição |
| CA2669695C (en) | 2006-11-13 | 2012-10-30 | Synta Pharmaceuticals Corp. | Tetrahydropyridinyl compounds for inflammation and immune-related uses |
| EP2129219A4 (en) | 2007-02-16 | 2012-08-29 | Synta Pharmaceuticals Corp | SUBSTITUTED FUSED CYCLE COMPOUNDS USED IN CASES OF INFLAMMATION OR IMMUNE DISORDERS |
| CA2688417C (en) | 2007-05-24 | 2017-04-25 | Calcimedica, Inc. | Calcium channel proteins and uses thereof |
| US8349841B2 (en) | 2007-08-01 | 2013-01-08 | Synta Pharmaceuticals Corp. | Vinyl-aryl derivatives for inflammation and immune-related uses |
| EP2184994B1 (en) | 2007-08-01 | 2013-09-25 | Synta Pharmaceuticals Corp. | Heterocycle-aryl compounds for inflammation and immune-related uses |
| US8003797B2 (en) | 2007-08-09 | 2011-08-23 | Merck Sharp & Dohme Corp. | Pyridine carboxamide orexin receptor antagonists |
| JP5411141B2 (ja) | 2007-09-10 | 2014-02-12 | カルシメディカ,インク. | 細胞内カルシウムを調節する化合物 |
| EP2240029A4 (en) | 2008-01-07 | 2012-08-22 | Synta Pharmaceuticals Corp | COMPOUNDS FOR USE AGAINST INFLAMMATORY AND IMMUNOMIC DISEASES |
| FR2927330B1 (fr) | 2008-02-07 | 2010-02-19 | Sanofi Aventis | Derives de 5,6-bisaryl-2-pyridine-carboxamide, leur preparation et leur application en therapeutique comme antagonistes des recepteurs a l'urotensine ii |
| JP2011513332A (ja) | 2008-02-29 | 2011-04-28 | アレイ バイオファーマ、インコーポレイテッド | 癌の治療のためのraf阻害剤としてのn−(6−アミノピリジン−3−イル)−3−(スルホンアミド)ベンズアミド誘導体 |
| WO2009115609A1 (en) | 2008-03-20 | 2009-09-24 | Csl Behring Gmbh | The calcium sensor STIM1 and the platelet SOC channel Orai1 (CRACM1) are essential for pathological thrombus formation |
| US20100016598A1 (en) | 2008-07-16 | 2010-01-21 | Wyeth | Alpha7 nicotinic acetylcholine receptor inhibitors |
| US7906553B2 (en) | 2008-08-27 | 2011-03-15 | Calcimedica, Inc. | Substituted thiophene modulators of intracellular calcium |
| US8524763B2 (en) | 2008-09-22 | 2013-09-03 | Calcimedica, Inc. | Inhibitors of store operated calcium release |
| US20110269743A1 (en) | 2008-09-22 | 2011-11-03 | CalciMedica, Inc | Phenylthiophenyldihydrobenzothiazepine inhibitors of store operated calcium release |
| EP2350064A1 (en) | 2008-10-01 | 2011-08-03 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
| EP2350006A1 (en) | 2008-10-01 | 2011-08-03 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
| WO2010048559A2 (en) | 2008-10-24 | 2010-04-29 | Calcimedica Inc. | Phenylpyrazole inhibitors of store operated calcium release |
| UY32571A (es) | 2009-04-24 | 2010-11-30 | Glaxo Group Ltd | Compuestos derivados de pirazol amida |
| WO2010122088A1 (en) | 2009-04-24 | 2010-10-28 | Glaxo Group Limited | Pyrazole and triazole carboxamides as crac channel inhibitors |
| HUE032426T2 (en) | 2009-05-27 | 2017-09-28 | Alkermes Pharma Ireland Ltd | Inhibition of flake aggregation in nanoparticulate meloxicam formulations |
| WO2011034962A2 (en) | 2009-09-16 | 2011-03-24 | Calcimedica Inc. | Compounds that modulate intracellular calcium |
| US8377970B2 (en) | 2009-10-08 | 2013-02-19 | Rhizen Pharmaceuticals Sa | Modulators of calcium release-activated calcium channel |
| US8993612B2 (en) * | 2009-10-08 | 2015-03-31 | Rhizen Pharmaceuticals Sa | Modulators of calcium release-activated calcium channel and methods for treatment of non-small cell lung cancer |
| AU2010321832B2 (en) | 2009-11-20 | 2014-08-14 | Amgen Inc. | Anti-Orai1 antigen binding proteins and uses thereof |
| US8476006B2 (en) * | 2009-11-30 | 2013-07-02 | National Center For Biological Sciences | Store-operated calcium cellular assay |
| EP2531490B1 (en) | 2010-02-02 | 2014-10-15 | Novartis AG | Cyclohexyl amide derivatives as crf receptor antagonists |
| US10703722B2 (en) | 2010-04-27 | 2020-07-07 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| AU2011248579A1 (en) | 2010-04-27 | 2012-11-29 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| DK2563776T3 (en) * | 2010-04-27 | 2016-09-19 | Calcimedica Inc | Relations that modulate intracellular calcium |
| EP2609095A4 (en) | 2010-08-27 | 2014-06-18 | Calcimedica Inc | COMPOUNDS MODULATING INTRACELLULAR CALCIUM |
| EP2704701B1 (en) | 2011-05-03 | 2018-01-03 | PRCL Research Inc. | Compounds for inflammation and immune-related uses |
| WO2012170951A2 (en) | 2011-06-10 | 2012-12-13 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| US9856240B2 (en) | 2011-10-19 | 2018-01-02 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| AU2012325901A1 (en) | 2011-10-19 | 2014-05-15 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| JP5936350B2 (ja) | 2011-12-27 | 2016-06-22 | キヤノン株式会社 | 新規有機化合物 |
| WO2013164769A1 (en) * | 2012-05-02 | 2013-11-07 | Lupin Limited | Substituted pyridine compounds as crac modulators |
| WO2014043715A1 (en) * | 2012-09-17 | 2014-03-20 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| WO2014059333A1 (en) | 2012-10-12 | 2014-04-17 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| EP3010586A1 (en) | 2013-06-21 | 2016-04-27 | Lupin Limited | Substituted heterocyclic compounds as crac modulators |
| ES3033759T3 (en) | 2015-02-27 | 2025-08-07 | Calcimedica Inc | Pancreatitis treatment |
| CA2995094A1 (en) | 2015-08-07 | 2017-02-16 | Calcimedica, Inc. | Use of crac channel inhibitors for the treatment of stroke and traumatic brain injury |
| CA3051420A1 (en) | 2017-01-26 | 2018-08-02 | Calcimedica, Inc. | Crac channel inhibitor compositions |
| WO2020072942A1 (en) | 2018-10-04 | 2020-04-09 | The Trustees Of Indiana University | Methods to treat renal disorders using calcium channel inhibitors |
| CA3172249A1 (en) | 2020-03-20 | 2021-09-23 | Calcimedica, Inc. | Methods and compositions for treating acute lung injury and acute respiratory distress syndrome |
| JP2023526505A (ja) | 2020-05-20 | 2023-06-21 | カルシメディカ,インク. | 急性腎障害を治療するための方法および組成物 |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120316182A1 (en) * | 2011-06-10 | 2012-12-13 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
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