JP2007511487A - ジペプチジルペプチダーゼｉｖ阻害剤の使用 - Google Patents
ジペプチジルペプチダーゼｉｖ阻害剤の使用 Download PDFInfo
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Landscapes
- Health & Medical Sciences (AREA)
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- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
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Applications Claiming Priority (5)
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| US52056203P | 2003-11-17 | 2003-11-17 | |
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| US54719204P | 2004-02-24 | 2004-02-24 | |
| US54719104P | 2004-02-24 | 2004-02-24 | |
| PCT/EP2004/012990 WO2005049022A2 (en) | 2003-11-17 | 2004-11-16 | Use of dipeptidyl peptidase iv inhibitors |
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| JP2012123284A Withdrawn JP2012211146A (ja) | 2003-11-17 | 2012-05-30 | ジペプチジルペプチダーゼｉｖ阻害剤の使用 |
| JP2014075331A Expired - Fee Related JP6312502B2 (ja) | 2003-11-17 | 2014-04-01 | ジペプチジルペプチダーゼｉｖ阻害剤の使用 |
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| JP2014075331A Expired - Fee Related JP6312502B2 (ja) | 2003-11-17 | 2014-04-01 | ジペプチジルペプチダーゼｉｖ阻害剤の使用 |
| JP2016123464A Withdrawn JP2016222677A (ja) | 2003-11-17 | 2016-06-22 | ジペプチジルペプチダーゼｉｖ阻害剤の使用 |
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| JP (6) | JP2007511487A (enExample) |
| KR (10) | KR20170005163A (enExample) |
| CN (1) | CN1905876B (enExample) |
| AU (2) | AU2004290897B2 (enExample) |
| BR (1) | BRPI0416628A (enExample) |
| CA (1) | CA2545641A1 (enExample) |
| MX (1) | MXPA06005518A (enExample) |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516410A (ja) * | 2008-02-27 | 2011-05-26 | ユリウス・マクシミリアンス−ウニヴェルジテート・ヴュルツブルク | 診断および治療のためのミクロＲＮＡ（ｍｉＲＮＡ）および下流標的 |
| JP2012522015A (ja) * | 2009-03-27 | 2012-09-20 | ブリストル−マイヤーズ スクイブ カンパニー | Ｄｐｐ−ｉｖ阻害剤を用いて主要有害心血管事象を予防する方法 |
| JP2016526555A (ja) * | 2013-06-26 | 2016-09-05 | ドン−ア エスティ カンパニー リミテッド | Ｄｐｐ−ｉｖ阻害剤を含有する腎疾患予防または治療用組成物 |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US7420079B2 (en) * | 2002-12-09 | 2008-09-02 | Bristol-Myers Squibb Company | Methods and compounds for producing dipeptidyl peptidase IV inhibitors and intermediates thereof |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| AU2005289728B2 (en) * | 2004-09-22 | 2011-11-24 | Tripath Imaging, Inc. | Methods and compositions for evaluating breast cancer prognosis |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| MX2007011453A (es) | 2005-04-22 | 2008-02-12 | Alantos Pharmaceuticals Holding Inc | Inhibidores de la dipeptidil peptidasa-iv. |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| LT2007416T (lt) * | 2006-04-19 | 2018-02-12 | Ludwig-Maximilians-Universität München | Paratiroidinis hormonas (pth), skirtas naudoti išemijos gydymui |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| SG174054A1 (en) | 2006-05-04 | 2011-09-29 | Boehringer Ingelheim Int | Polymorphs |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| WO2008094689A2 (en) * | 2007-02-01 | 2008-08-07 | Nephrogen, Llc | Potentiation of stem cell homing and treatment of organ dysfunction or organ failure |
| CL2008002427A1 (es) * | 2007-08-16 | 2009-09-11 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende 1-cloro-4-(b-d-glucopiranos-1-il)-2-[4-((s)-tetrahidrofurano-3-iloxi)bencil]-benceno combinado con 1-[(4-metilquinazolin-2-il)metil]-3-metil-7-(2-butin-1-il)-8-(3-(r)-aminopiperidin-1-il)xantina; y su uso para tratar diabetes mellitus tipo 2. |
| RU2569749C2 (ru) * | 2007-08-17 | 2015-11-27 | Бёрингер Ингельхайм Интернациональ Гмбх | Производные пурина, предназначенные для применения для лечения заболеваний, связанных с баф (белок-активатор фибробластов) |
| PE20140960A1 (es) | 2008-04-03 | 2014-08-15 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| EP2146210A1 (en) | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| BRPI0916997A2 (pt) | 2008-08-06 | 2020-12-15 | Boehringer Ingelheim International Gmbh | Inibidor de dpp-4 e seu uso |
| RU2011113823A (ru) | 2008-09-10 | 2012-10-20 | БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) | Комбинированная терапия, предназначенная для лечения диабета и связанных с ним состояний |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| EP2382216A1 (en) | 2008-12-23 | 2011-11-02 | Boehringer Ingelheim International GmbH | Salt forms of organic compound |
| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| SG173619A1 (en) | 2009-02-13 | 2011-09-29 | Boehringer Ingelheim Int | Pharmaceutical composition comprising a sglt2 inhibitor, a dpp-iv inhibitor and optionally a further antidiabetic agent and uses thereof |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| US10610489B2 (en) | 2009-10-02 | 2020-04-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, pharmaceutical dosage form, process for their preparation, methods for treating and uses thereof |
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| AU2011305525B2 (en) | 2010-09-22 | 2016-08-18 | Arena Pharmaceuticals, Inc. | Modulators of the GPR119 receptor and the treatment of disorders related thereto |
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| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| AU2012285904C1 (en) | 2011-07-15 | 2017-08-31 | Boehringer Ingelheim International Gmbh | Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| EP4151218A1 (en) | 2012-05-14 | 2023-03-22 | Boehringer Ingelheim International GmbH | Linagliptin, a xanthine derivative as dpp-4 inhibitor, for use in the treatment of sirs and/or sepsis |
| US20130303462A1 (en) | 2012-05-14 | 2013-11-14 | Boehringer Ingelheim International Gmbh | Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| CA2812519A1 (en) | 2013-04-05 | 2014-10-05 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| HK1213818A1 (zh) | 2013-04-05 | 2016-07-15 | 勃林格殷格翰国际有限公司 | 依帕列净的治疗用途 |
| PT2981271T (pt) | 2013-04-05 | 2019-02-19 | Boehringer Ingelheim Int | Utilizações terapêuticas de empagliflozina |
| US11813275B2 (en) | 2013-04-05 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| SI2986304T1 (sl) | 2013-04-18 | 2022-04-29 | Boehringer Ingelheim International Gmbh | Farmacevtski sestavek, postopki za zdravljenje in njegove uporabe |
| EP3110449B1 (en) | 2014-02-28 | 2023-06-28 | Boehringer Ingelheim International GmbH | Medical use of a dpp-4 inhibitor |
| AU2016229982B2 (en) | 2015-03-09 | 2020-06-18 | Intekrin Therapeutics, Inc. | Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy |
| EP3468562A1 (en) | 2016-06-10 | 2019-04-17 | Boehringer Ingelheim International GmbH | Combinations of linagliptin and metformin |
| CN109922813A (zh) | 2016-11-10 | 2019-06-21 | 勃林格殷格翰国际有限公司 | 药物组合物、治疗方法及其用途 |
| SG11201909046XA (en) | 2017-04-03 | 2019-10-30 | Coherus Biosciences Inc | PPARγ AGONIST FOR TREATMENT OF PROGRESSIVE SUPRANUCLEAR PALSY |
| KR20190019542A (ko) | 2017-08-18 | 2019-02-27 | 현대자동차주식회사 | 차량용 쿨러 |
| KR102142559B1 (ko) | 2018-07-31 | 2020-08-07 | 가톨릭대학교 산학협력단 | Dpp4 억제제를 유효성분으로 포함하는 심근섬유증의 예방 또는 치료용 조성물 |
| KR20220063157A (ko) | 2019-09-17 | 2022-05-17 | 노파르티스 아게 | 빌다글립틴 및 메트포르민을 이용한 조합 요법 |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000051559A (ja) * | 1998-08-06 | 2000-02-22 | Duerkopp Adler Ag | ボタン穴用スリットを形成する切断装置 |
| WO2001097808A1 (en) * | 2000-06-19 | 2001-12-27 | Smithkline Beecham Plc | Combinations of depeptidyl peptidase iv inhibitors and other antidiabetic agents for the treatment of diabete mellitus |
| WO2002053169A2 (de) * | 2001-01-02 | 2002-07-11 | Keyneurotek Ag I.G. | Verwendung von dipeptidylpeptidase iv und aminopeptidase-n inhibotoren zur behandlung von ischämie-induzierter neurodegeneration |
| JP2002523365A (ja) * | 1998-08-21 | 2002-07-30 | ポイント セラピューティクス， インコーポレイテッド | 基質の活性の調節 |
| JP2002531547A (ja) * | 1998-12-10 | 2002-09-24 | ノバルティス アクチエンゲゼルシャフト | Ｎ置換されている２−シアノピロリジン |
| WO2002083128A1 (en) * | 2001-04-12 | 2002-10-24 | Bristol-Myers Squibb Company | 2,1-oxazoline and 1,2-pyrazoline-based inhibitors of dipeptidyl peptidase iv and method |
| WO2003002530A2 (en) * | 2001-06-27 | 2003-01-09 | Smithkline Beecham Corporation | Pyrrolidines as dipeptidyl peptidase inhibitors |
| WO2003002553A2 (en) * | 2001-06-27 | 2003-01-09 | Smithkline Beecham Corporation | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
| WO2003038123A2 (en) * | 2001-10-31 | 2003-05-08 | Novartis Ag | Methods to treat diabetes and related conditions based on polymorphisms in the tcf1 gene |
| JP2003518496A (ja) * | 1999-12-23 | 2003-06-10 | ノバルティス アクチエンゲゼルシャフト | グルコース代謝障害を処置するための血糖降下薬の使用 |
| WO2003074500A2 (en) * | 2002-03-06 | 2003-09-12 | Sanofi-Aventis | N-aminoacetyl-pyrrolidine-2-carbonitriles and their use as ddp-iv inhibitors |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX9206628A (es) | 1991-11-22 | 1993-05-01 | Boehringer Ingelheim Pharma | Ester de prolinaboronato y metodo para su preparacion. |
| IL111785A0 (en) | 1993-12-03 | 1995-01-24 | Ferring Bv | Dp-iv inhibitors and pharmaceutical compositions containing them |
| US5935924A (en) | 1994-04-15 | 1999-08-10 | Genentech, Inc. | Treatment of congestive heart failure |
| US5543396A (en) | 1994-04-28 | 1996-08-06 | Georgia Tech Research Corp. | Proline phosphonate derivatives |
| DE69733557T2 (de) | 1996-04-04 | 2005-11-03 | Banyu Pharmaceutical Co., Ltd. | Endothelin-antagonisten zur behandlung von herzversagen |
| DE19616486C5 (de) | 1996-04-25 | 2016-06-30 | Royalty Pharma Collection Trust | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| TW492957B (en) * | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| US5998458A (en) | 1997-06-25 | 1999-12-07 | University Technology Corporation | Method of treating heart failure |
| CA2310400C (en) | 1997-11-18 | 2008-02-19 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | Novel physiologically active substance sulphostin, process for producing the same, and use thereof |
| CA2319195A1 (en) | 1998-02-02 | 1999-08-05 | Trustees Of Tufts College | Method of regulating glucose metabolism, and reagents related thereto |
| EP1062222A1 (en) | 1998-03-09 | 2000-12-27 | Fondatech Benelux N.V. | Serine peptidase modulators |
| DE19823831A1 (de) | 1998-05-28 | 1999-12-02 | Probiodrug Ges Fuer Arzneim | Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen |
| DE19828114A1 (de) | 1998-06-24 | 2000-01-27 | Probiodrug Ges Fuer Arzneim | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
| DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
| US6110949A (en) | 1999-06-24 | 2000-08-29 | Novartis Ag | N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| US6414002B1 (en) | 1999-09-22 | 2002-07-02 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
| WO2001034594A1 (en) | 1999-11-12 | 2001-05-17 | Guilford Pharmaceuticals, Inc. | Dipeptidyl peptidase iv inhibitors and methods of making and using dipeptidyl peptidase iv inhibitors |
| GB9928330D0 (en) | 1999-11-30 | 2000-01-26 | Ferring Bv | Novel antidiabetic agents |
| JP2003520226A (ja) | 2000-01-21 | 2003-07-02 | ノバルティス アクチエンゲゼルシャフト | ジペプチジルペプチダーゼ−ｉｖ阻害剤および抗糖尿病薬剤を含む組合せ物 |
| JP2003520849A (ja) | 2000-01-24 | 2003-07-08 | ノボ ノルディスク アクティーゼルスカブ | 酵素ｄｐｐ−ｉｖの阻害剤であるｎ−置換２−シアノピロールおよび−ピロリン |
| US7087608B2 (en) | 2000-03-03 | 2006-08-08 | Robert Charles Atkins | Use of PDGF receptor tyrosine kinase inhibitors for the treatment of diabetic nephropathy |
| US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
| DE60137216D1 (de) | 2000-03-31 | 2009-02-12 | Prosidion Ltd | Verbesserung der aktivität der inselzellen bei diabetes mellitus und dessen prävention |
| US6482844B1 (en) | 2000-04-07 | 2002-11-19 | Neurogen Corporation | 1-benzylimidazole derivatives |
| GB0010188D0 (en) | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| GB0010183D0 (en) | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| WO2002002560A2 (en) | 2000-07-04 | 2002-01-10 | Novo Nordisk A/S | Purine-2,6-diones which are inhibitors of the enzyme dipeptidyl peptidase iv (dpp-iv) |
| EP1930319B1 (en) | 2000-08-10 | 2012-05-02 | Mitsubishi Tanabe Pharma Corporation | Proline derivatives and use thereof as drugs |
| DK1325910T3 (da) | 2000-10-06 | 2008-11-10 | Mitsubishi Tanabe Pharma Corp | Aliphatiske nitrogenholdige femleddede ringforbindelser |
| TWI243162B (en) | 2000-11-10 | 2005-11-11 | Taisho Pharmaceutical Co Ltd | Cyanopyrrolidine derivatives |
| CA2433090A1 (en) | 2000-12-27 | 2002-07-04 | Kyowa Hakko Kogyo Co., Ltd. | Dipeptidyl peptidase iv inhibitor |
| WO2002053548A1 (fr) | 2000-12-27 | 2002-07-11 | Banyu Pharmaceutical Co.,Ltd. | Derives de la benzothiazepine |
| BR0206831A (pt) | 2001-02-02 | 2004-07-06 | Takeda Chemical Industries Ltd | Composto, cristal, agente farmacêutico, agentes para profilaxia ou tratamento de diabetes, de complicações diabéticas, de tolerância prejudicada à glucose e de obesidade, inibidor de peptidase, uso de um composto, e, método de produção de um composto |
| WO2002066627A1 (en) | 2001-02-16 | 2002-08-29 | Bayer Aktiengesellschaft | Regulation of human dipeptidyl peptidase 8 |
| MXPA03007349A (es) | 2001-02-24 | 2003-12-04 | Boehringer Ingelheim Pharma | Derivados de xantina, su preparacion y su empleo como medicamentos. |
| WO2002067918A1 (en) | 2001-02-27 | 2002-09-06 | Banyu Pharmaceutical Co., Ltd. | Novel diallylmethylamine derivative |
| EP1385508B1 (en) | 2001-03-27 | 2008-05-21 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| FR2822826B1 (fr) | 2001-03-28 | 2003-05-09 | Servier Lab | Nouveaux derives sulfonyles d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| GB0109146D0 (en) | 2001-04-11 | 2001-05-30 | Ferring Bv | Treatment of type 2 diabetes |
| FR2824825B1 (fr) | 2001-05-15 | 2005-05-06 | Servier Lab | Nouveaux derives d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US20030060494A1 (en) | 2001-05-18 | 2003-03-27 | Nobuyuki Yasuda | Pharmaceutical use of N-carbamoylazole derivatives |
| SE523510C2 (sv) | 2001-05-18 | 2004-04-27 | Jan G Faeger | Förfarande för att fastställa en varelses position och/eller orientering i förhållande till en omgivning |
| US7098239B2 (en) | 2001-06-20 | 2006-08-29 | Merck & Co., Inc | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
| AU2002310465B2 (en) | 2001-06-20 | 2006-06-15 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
| GB0115517D0 (en) | 2001-06-25 | 2001-08-15 | Ferring Bv | Novel antidiabetic agents |
| CN1471538A (zh) | 2001-06-27 | 2004-01-28 | 前体生物药物股份有限公司 | 用于竞争性调节二肽基肽酶iv催化的肽结构 |
| PL367527A1 (en) | 2001-06-27 | 2005-02-21 | Smithkline Beecham Corporation | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
| US20030005443A1 (en) | 2001-06-27 | 2003-01-02 | Karin Axelsson | EPG having PIP window history and sample view functionality |
| WO2003003250A1 (en) | 2001-06-28 | 2003-01-09 | Hywire Ltd. | Range content-addressable memory |
| JP2003012575A (ja) | 2001-06-29 | 2003-01-15 | Idemitsu Petrochem Co Ltd | アダマンタノール及びアダマンタノンの製造法 |
| ATE388951T1 (de) | 2001-07-03 | 2008-03-15 | Novo Nordisk As | Dpp-iv-inhibierende purin-derivative zur behandlung von diabetes |
| UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
| US20040259883A1 (en) | 2001-09-14 | 2004-12-23 | Hiroshi Sakashita | Thiazolidine derivative and medicinal use thereof |
| EP1463727A2 (en) | 2001-09-19 | 2004-10-06 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme dpp-iv |
| GB0125445D0 (en) | 2001-10-23 | 2001-12-12 | Ferring Bv | Protease Inhibitors |
| GB0125446D0 (en) | 2001-10-23 | 2001-12-12 | Ferring Bv | Novel anti-diabetic agents |
| US6861440B2 (en) | 2001-10-26 | 2005-03-01 | Hoffmann-La Roche Inc. | DPP IV inhibitors |
| JP2005513165A (ja) | 2002-01-11 | 2005-05-12 | ノボ ノルディスク アクティーゼルスカブ | 糖尿病、高血圧、慢性心不全および体液貯留状態の治療のための方法および組成物 |
| CN1324015C (zh) | 2002-02-13 | 2007-07-04 | 霍夫曼-拉罗奇有限公司 | 吡啶－和嘧啶－衍生物 |
| AR039090A1 (es) * | 2002-03-22 | 2005-02-09 | Novartis Ag | Combinacion de compuestos organicos |
| EP1492777A1 (en) | 2002-04-08 | 2005-01-05 | Torrent Pharmaceuticals Ltd | Thiazolidine-4-carbonitriles and analogues and their use as dipeptidyl-peptidase inhibitors |
| AU2003262059A1 (en) | 2002-09-11 | 2004-04-30 | Takeda Pharmaceutical Company Limited | Sustained release preparation |
| JP4352001B2 (ja) | 2002-10-18 | 2009-10-28 | メルク エンド カムパニー インコーポレーテッド | 糖尿病の治療または予防のためのベータ−アミノ複素環式ジペプチジルペプチダーゼ阻害剤 |
| WO2004037181A2 (en) | 2002-10-23 | 2004-05-06 | Bristol-Myers Squibb Company | Glycinenitrile-based inhibitors of dipeptidyl peptidase iv and methods |
| DE10256264A1 (de) | 2002-12-03 | 2004-06-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue substituierte Imidazo-pyridinone und Imidazo-pyridazinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| US7420079B2 (en) | 2002-12-09 | 2008-09-02 | Bristol-Myers Squibb Company | Methods and compounds for producing dipeptidyl peptidase IV inhibitors and intermediates thereof |
| WO2004071454A2 (en) | 2003-02-13 | 2004-08-26 | Guilford Pharmaceuticals Inc. | Substituted azetidine compounds as inhibitors of dipeptidyl peptidase iv |
| AU2003207881A1 (en) | 2003-02-28 | 2004-09-17 | Aic | Dipeptidyl peptidase inhibitors |
-
2004
- 2004-11-16 CN CN2004800405089A patent/CN1905876B/zh not_active Expired - Fee Related
- 2004-11-16 CA CA002545641A patent/CA2545641A1/en not_active Abandoned
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- 2004-11-16 KR KR1020177024680A patent/KR20170104639A/ko not_active Withdrawn
- 2004-11-16 MX MXPA06005518A patent/MXPA06005518A/es active IP Right Grant
- 2004-11-16 EP EP14190100.9A patent/EP2839832A3/en not_active Withdrawn
- 2004-11-16 KR KR1020067009502A patent/KR20060109911A/ko not_active Withdrawn
- 2004-11-16 AU AU2004290897A patent/AU2004290897B2/en not_active Ceased
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- 2004-11-16 KR KR1020127028863A patent/KR20120126133A/ko not_active Withdrawn
- 2004-11-16 JP JP2006538825A patent/JP2007511487A/ja not_active Withdrawn
- 2004-11-16 KR KR1020137021480A patent/KR20130105741A/ko not_active Withdrawn
- 2004-11-16 KR KR1020157032295A patent/KR20150132601A/ko not_active Ceased
- 2004-11-16 KR KR1020147014776A patent/KR20140089408A/ko not_active Withdrawn
- 2004-11-16 KR KR1020127000489A patent/KR20120008093A/ko not_active Withdrawn
- 2004-11-16 KR KR20157002440A patent/KR20150028829A/ko not_active Withdrawn
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-
2009
- 2009-05-26 AU AU2009202080A patent/AU2009202080A1/en not_active Abandoned
-
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- 2012-05-30 JP JP2012123284A patent/JP2012211146A/ja not_active Withdrawn
-
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- 2014-04-01 JP JP2014075331A patent/JP6312502B2/ja not_active Expired - Fee Related
-
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- 2016-06-22 JP JP2016123464A patent/JP2016222677A/ja not_active Withdrawn
-
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- 2017-09-28 JP JP2017188912A patent/JP2018039816A/ja not_active Withdrawn
-
2020
- 2020-07-13 JP JP2020119890A patent/JP2020183412A/ja active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000051559A (ja) * | 1998-08-06 | 2000-02-22 | Duerkopp Adler Ag | ボタン穴用スリットを形成する切断装置 |
| JP2002523365A (ja) * | 1998-08-21 | 2002-07-30 | ポイント セラピューティクス， インコーポレイテッド | 基質の活性の調節 |
| JP2002531547A (ja) * | 1998-12-10 | 2002-09-24 | ノバルティス アクチエンゲゼルシャフト | Ｎ置換されている２−シアノピロリジン |
| JP2003518496A (ja) * | 1999-12-23 | 2003-06-10 | ノバルティス アクチエンゲゼルシャフト | グルコース代謝障害を処置するための血糖降下薬の使用 |
| WO2001097808A1 (en) * | 2000-06-19 | 2001-12-27 | Smithkline Beecham Plc | Combinations of depeptidyl peptidase iv inhibitors and other antidiabetic agents for the treatment of diabete mellitus |
| WO2002053169A2 (de) * | 2001-01-02 | 2002-07-11 | Keyneurotek Ag I.G. | Verwendung von dipeptidylpeptidase iv und aminopeptidase-n inhibotoren zur behandlung von ischämie-induzierter neurodegeneration |
| WO2002083128A1 (en) * | 2001-04-12 | 2002-10-24 | Bristol-Myers Squibb Company | 2,1-oxazoline and 1,2-pyrazoline-based inhibitors of dipeptidyl peptidase iv and method |
| WO2003002530A2 (en) * | 2001-06-27 | 2003-01-09 | Smithkline Beecham Corporation | Pyrrolidines as dipeptidyl peptidase inhibitors |
| WO2003002553A2 (en) * | 2001-06-27 | 2003-01-09 | Smithkline Beecham Corporation | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
| WO2003038123A2 (en) * | 2001-10-31 | 2003-05-08 | Novartis Ag | Methods to treat diabetes and related conditions based on polymorphisms in the tcf1 gene |
| WO2003074500A2 (en) * | 2002-03-06 | 2003-09-12 | Sanofi-Aventis | N-aminoacetyl-pyrrolidine-2-carbonitriles and their use as ddp-iv inhibitors |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516410A (ja) * | 2008-02-27 | 2011-05-26 | ユリウス・マクシミリアンス−ウニヴェルジテート・ヴュルツブルク | 診断および治療のためのミクロＲＮＡ（ｍｉＲＮＡ）および下流標的 |
| JP2015107971A (ja) * | 2008-02-27 | 2015-06-11 | ユリウス・マクシミリアンス−ウニヴェルジテート・ヴュルツブルクＪｕｌｉｕｓ Ｍａｘｉｍｉｌｉａｎｓ−Ｕｎｉｖｅｒｓｉｔａｅｔ Ｗｕｅｒｚｂｕｒｇ | 診断および治療のためのミクロＲＮＡ（ｍｉＲＮＡ）および下流標的 |
| JP2012522015A (ja) * | 2009-03-27 | 2012-09-20 | ブリストル−マイヤーズ スクイブ カンパニー | Ｄｐｐ−ｉｖ阻害剤を用いて主要有害心血管事象を予防する方法 |
| JP2016526555A (ja) * | 2013-06-26 | 2016-09-05 | ドン−ア エスティ カンパニー リミテッド | Ｄｐｐ−ｉｖ阻害剤を含有する腎疾患予防または治療用組成物 |
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| KR20140089408A (ko) | 2014-07-14 |
| AU2009202080A1 (en) | 2009-06-18 |
| JP2012211146A (ja) | 2012-11-01 |
| CN1905876A (zh) | 2007-01-31 |
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