FI115629B - Menetelmä entsyymi-inhibiittorien valmistamiseksi - Google Patents
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- FI115629B FI115629B FI962315A FI962315A FI115629B FI 115629 B FI115629 B FI 115629B FI 962315 A FI962315 A FI 962315A FI 962315 A FI962315 A FI 962315A FI 115629 B FI115629 B FI 115629B
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
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Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939324803A GB9324803D0 (en) | 1993-12-03 | 1993-12-03 | Enzyme inhibitors |
| GB9324803 | 1993-12-03 | ||
| GB9324981 | 1993-12-06 | ||
| GB939324981A GB9324981D0 (en) | 1993-12-06 | 1993-12-06 | Enzyme inhibitors |
| GB9402615 | 1994-11-30 | ||
| PCT/GB1994/002615 WO1995015309A1 (en) | 1993-12-03 | 1994-11-30 | Dp-iv-serine protease inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI962315A0 FI962315A0 (fi) | 1996-06-03 |
| FI962315L FI962315L (fi) | 1996-08-05 |
| FI115629B true FI115629B (fi) | 2005-06-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI962315A FI115629B (fi) | 1993-12-03 | 1996-06-03 | Menetelmä entsyymi-inhibiittorien valmistamiseksi |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US5939560A (cs) |
| EP (1) | EP0731789A1 (cs) |
| JP (1) | JP3970317B2 (cs) |
| KR (1) | KR100347828B1 (cs) |
| CN (1) | CN1079792C (cs) |
| AU (1) | AU1113395A (cs) |
| CA (1) | CA2178066A1 (cs) |
| CZ (1) | CZ289931B6 (cs) |
| FI (1) | FI115629B (cs) |
| HU (1) | HUT76274A (cs) |
| IL (1) | IL111785A0 (cs) |
| NO (1) | NO306458B1 (cs) |
| PL (1) | PL182723B1 (cs) |
| WO (1) | WO1995015309A1 (cs) |
Families Citing this family (258)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6825169B1 (en) | 1991-10-22 | 2004-11-30 | Trustees Of Tufts College | Inhibitors of dipeptidyl-aminopeptidase type IV |
| AU2790895A (en) * | 1994-06-10 | 1996-01-05 | Universitaire Instelling Antwerpen | Purification of serine protease and synthetic inhibitors thereof |
| DE19616486C5 (de) * | 1996-04-25 | 2016-06-30 | Royalty Pharma Collection Trust | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| US20020006899A1 (en) * | 1998-10-06 | 2002-01-17 | Pospisilik Andrew J. | Use of dipeptidyl peptidase IV effectors for lowering blood pressure in mammals |
| US5965532A (en) * | 1996-06-28 | 1999-10-12 | Trustees Of Tufts College | Multivalent compounds for crosslinking receptors and uses thereof |
| US6011155A (en) * | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| US6100234A (en) * | 1997-05-07 | 2000-08-08 | Tufts University | Treatment of HIV |
| US6040145A (en) | 1997-05-07 | 2000-03-21 | Tufts University | Potentiation of the immune response |
| WO1999016864A1 (en) | 1997-09-29 | 1999-04-08 | Point Therapeutics, Inc. | Stimulation of hematopoietic cells in vitro |
| ES2288807T1 (es) * | 1998-02-02 | 2008-02-01 | Trustees Of Tufts College | Uso de inhibidores de dipeptidasa para regular el metabolismo de la glucosa. |
| JP2002513762A (ja) | 1998-05-04 | 2002-05-14 | ポイント セラピューティクス, インコーポレイテッド | 造血刺激 |
| DE19823831A1 (de) * | 1998-05-28 | 1999-12-02 | Probiodrug Ges Fuer Arzneim | Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen |
| KR100704814B1 (ko) | 1998-06-05 | 2007-04-10 | 포인트 써러퓨틱스, 인크. | 시클릭 보로프롤린 화합물 |
| DE19826972A1 (de) * | 1998-06-18 | 1999-12-23 | Univ Magdeburg Tech | Verwendung von Enzyminhibitoren und pharmazeutische Zubereitung zur Therapie von dermatologischen Erkrankungen mit follikulären und epidermalen Hyperkeratosen und einer verstärkten Keratinozytenproliferation |
| DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
| DE19828114A1 (de) | 1998-06-24 | 2000-01-27 | Probiodrug Ges Fuer Arzneim | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
| DE19834591A1 (de) | 1998-07-31 | 2000-02-03 | Probiodrug Ges Fuer Arzneim | Verfahren zur Steigerung des Blutglukosespiegels in Säugern |
| US6979697B1 (en) * | 1998-08-21 | 2005-12-27 | Point Therapeutics, Inc. | Regulation of substrate activity |
| IL141471A0 (en) * | 1998-08-21 | 2002-03-10 | Point Therapeutics Inc | Regulation of substrate activity |
| US20030176357A1 (en) * | 1998-10-06 | 2003-09-18 | Pospisilik Andrew J. | Dipeptidyl peptidase IV inhibitors and their uses for lowering blood pressure levels |
| CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| NZ514234A (en) | 1999-03-15 | 2004-02-27 | Axys Pharm Inc | N-cyanomethylamides as protease inhibitors |
| GB9906715D0 (en) * | 1999-03-23 | 1999-05-19 | Ferring Bv | Compositions for promoting growth |
| GB9906714D0 (en) | 1999-03-23 | 1999-05-19 | Ferring Bv | Compositions for improving fertility |
| EP1806138A1 (en) * | 1999-05-25 | 2007-07-11 | Point Therapeutics, Inc. | Anti-tumor agents comprising boroproline compounds |
| JP2003500360A (ja) * | 1999-05-25 | 2003-01-07 | ポイント セラピューティクス, インコーポレイテッド | ボロプロリン化合物類を含む抗癌剤 |
| US6890904B1 (en) | 1999-05-25 | 2005-05-10 | Point Therapeutics, Inc. | Anti-tumor agents |
| DE19926233C1 (de) | 1999-06-10 | 2000-10-19 | Probiodrug Ges Fuer Arzneim | Verfahren zur Herstellung von Thiazolidin |
| US6172081B1 (en) | 1999-06-24 | 2001-01-09 | Novartis Ag | Tetrahydroisoquinoline 3-carboxamide derivatives |
| 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 |
| US6617340B1 (en) | 1999-07-29 | 2003-09-09 | Novartis Ag | N-(substituted glycyl)-pyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| DE19940130A1 (de) * | 1999-08-24 | 2001-03-01 | Probiodrug Ges Fuer Arzneim | Neue Effektoren der Dipeptidyl Peptidase IV zur topischen Anwendung |
| 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 |
| US20040152745A1 (en) * | 1999-11-12 | 2004-08-05 | 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 |
| DK1741447T3 (da) | 2000-01-21 | 2013-12-09 | Novartis Ag | Kombinationer omfattende dipeptidylpeptidase-IV-inhibitorer og antidiabetiske midler |
| AU2001233622A1 (en) * | 2000-02-25 | 2001-09-03 | Novo-Nordisk A/S | Inhibition of beta cell degeneration |
| US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
| ES2320630T5 (es) * | 2000-03-31 | 2013-03-12 | Royalty Pharma Collection Trust | Método para la mejora de la señalización de los islotes en diabetes mellitus y para su prevención |
| GB0010183D0 (en) * | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| US6432969B1 (en) | 2000-06-13 | 2002-08-13 | Novartis Ag | N-(substituted glycyl)-2 cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| GB0014969D0 (en) | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
| EP1950199B1 (en) | 2000-08-10 | 2009-12-02 | Mitsubishi Tanabe Pharma Corporation | Proline derivatives and use thereof as drugs |
| PE20020617A1 (es) | 2000-08-22 | 2002-08-05 | Novartis Ag | Composicion que comprende un antagonista del receptor at1 y un potenciador de la secrecion de insulina o un sensibilizante a la insulina |
| NZ525443A (en) | 2000-10-12 | 2006-04-28 | Ferring Bv | Dipeptidyl peptidase IV related genes |
| US7132104B1 (en) | 2000-10-27 | 2006-11-07 | Probiodrug Ag | Modulation of central nervous system (CNS) dipeptidyl peptidase IV (DPIV) -like activity for the treatment of neurological and neuropsychological disorders |
| KR20030096227A (ko) * | 2000-10-27 | 2003-12-24 | 프로비오드룩 아게 | 신경 및 신경정신 질환의 치료방법 |
| US6492521B2 (en) * | 2000-11-03 | 2002-12-10 | Cytec Technology Corp. | Hindered amine light stabilizers based on multi-functional carbonyl compounds and methods of making same |
| TWI243162B (en) * | 2000-11-10 | 2005-11-11 | Taisho Pharmaceutical Co Ltd | Cyanopyrrolidine derivatives |
| US7030116B2 (en) | 2000-12-22 | 2006-04-18 | Aventis Pharmaceuticals Inc. | Compounds and compositions as cathepsin inhibitors |
| EP1383748A2 (en) | 2000-12-22 | 2004-01-28 | Axys Pharmaceuticals, Inc. | Novel compounds and compositions as cathepsin inhibitors |
| WO2002076450A1 (en) * | 2001-03-27 | 2002-10-03 | 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 |
| US6890905B2 (en) | 2001-04-02 | 2005-05-10 | Prosidion Limited | Methods for improving islet signaling in diabetes mellitus and for its prevention |
| 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 |
| ES2257555T3 (es) * | 2001-06-20 | 2006-08-01 | MERCK & CO., INC. | Inhibidores de dipeptidilpeptidasa para el tratamiento de la diabetes. |
| WO2003000180A2 (en) * | 2001-06-20 | 2003-01-03 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
| GB0115517D0 (en) * | 2001-06-25 | 2001-08-15 | Ferring Bv | Novel antidiabetic agents |
| EP1399420B1 (en) * | 2001-06-27 | 2007-12-05 | SmithKline Beecham Corporation | Pyrrolidines as dipeptidyl peptidase inhibitors |
| CZ20033521A3 (en) | 2001-06-27 | 2004-05-12 | Smithklineábeechamácorporation | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
| US20030135023A1 (en) * | 2001-06-27 | 2003-07-17 | Hans-Ulrich Demuth | Peptide structures useful for competitive modulation of dipeptidyl peptidase IV catalysis |
| JP2004530729A (ja) * | 2001-06-27 | 2004-10-07 | プロバイオドラッグ アーゲー | ジペプチジルペプチダーゼiv触媒作用の拮抗調節に有用なペプチド構造 |
| US7368421B2 (en) | 2001-06-27 | 2008-05-06 | Probiodrug Ag | Use of dipeptidyl peptidase IV inhibitors in the treatment of multiple sclerosis |
| DE10150203A1 (de) * | 2001-10-12 | 2003-04-17 | Probiodrug Ag | Peptidylketone als Inhibitoren der DPIV |
| DE60224879D1 (de) * | 2001-06-27 | 2008-03-20 | Probiodrug Ag | Verwendung von dpiv-inhibitoren als therapeutika für krankhafte neurologische zustände |
| US20030130199A1 (en) * | 2001-06-27 | 2003-07-10 | Von Hoersten Stephan | Dipeptidyl peptidase IV inhibitors and their uses as anti-cancer agents |
| 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 |
| JP2005504766A (ja) * | 2001-08-16 | 2005-02-17 | プロバイオドラッグ アーゲー | プロリンエンドペプチダーゼ阻害剤の、細胞内シグナルカスケード依存性イノシトール(1,4,5)トリホスフェート濃度調節への使用。 |
| US6844316B2 (en) * | 2001-09-06 | 2005-01-18 | Probiodrug Ag | Inhibitors of dipeptidyl peptidase I |
| RS19504A (en) | 2001-09-14 | 2007-02-05 | Aventis Pharmaceuticals Inc., | Novel compounds and compositions as cathepsin inhibitors |
| JPWO2003024942A1 (ja) * | 2001-09-14 | 2004-12-24 | 三菱ウェルファーマ株式会社 | チアゾリジン誘導体およびその医薬用途 |
| GB0125446D0 (en) | 2001-10-23 | 2001-12-12 | Ferring Bv | Novel anti-diabetic agents |
| CN1604968A (zh) * | 2001-10-31 | 2005-04-06 | 诺瓦提斯公司 | 基于tcf1基因多态性治疗糖尿病和相关病症的方法 |
| EP1446392A1 (en) | 2001-11-14 | 2004-08-18 | Aventis Pharmaceuticals, Inc. | Oligopeptides and compositions containing them as cathepsin s inhibitors |
| CA2466870A1 (en) * | 2001-11-26 | 2003-06-05 | Trustees Of Tufts College | Methods for treating autoimmune disorders, and reagents related thereto |
| US7727964B2 (en) | 2001-11-26 | 2010-06-01 | Trustees Of Tufts College | Peptidomimetic inhibitors of post-proline cleaving enzymes |
| AU2002360732A1 (en) * | 2001-12-26 | 2003-07-24 | Guilford Pharmaceuticals | Change inhibitors of dipeptidyl peptidase iv |
| EP1695970A1 (en) * | 2002-02-28 | 2006-08-30 | Prosidion Limited | Peptides useful for competitive modulation of dipeptidyl peptidase IV catalysis |
| MXPA04008278A (es) * | 2002-02-28 | 2005-09-20 | Prosidion Ltd | Inhibidores de dipeptidil peptidasa iv a base de glutaminil. |
| DE60316416T2 (de) * | 2002-03-25 | 2008-06-26 | Merck & Co., Inc. | Heterocyclische beta-aminoverbindungen als inhibitoren der dipeptidylpeptidase zur behandlung bzw. prävention von diabetes |
| US20030232761A1 (en) * | 2002-03-28 | 2003-12-18 | Hinke Simon A. | Novel analogues of glucose-dependent insulinotropic polypeptide |
| KR20040105853A (ko) * | 2002-04-08 | 2004-12-16 | 토렌트 파마슈티칼스 리미티드 | 티아졸리딘-4-카르보니트릴 및 유사체와디펩티딜-펩티다아제 억제제로서의 용도 |
| US6710040B1 (en) | 2002-06-04 | 2004-03-23 | Pfizer Inc. | Fluorinated cyclic amides as dipeptidyl peptidase IV inhibitors |
| RU2317101C2 (ru) * | 2002-06-27 | 2008-02-20 | Пробиодруг Аг | Новое применение ингибиторов дипептидилпептидазы iv |
| WO2004004658A2 (en) * | 2002-07-09 | 2004-01-15 | Point Therapeutics, Inc. | Methods and compositions relating to isoleucine boroproline compounds |
| AU2003251869A1 (en) * | 2002-07-15 | 2004-02-02 | Merck & Co., Inc. | Piperidino pyrimidine dipeptidyl peptidase inhibitors for the treatment of diabetes |
| US20040033051A1 (en) * | 2002-08-16 | 2004-02-19 | Ip Kiril Kun Wan | Method and system for producing and displaying visual presentations which inhibit off-screen duplication |
| TW200404796A (en) * | 2002-08-19 | 2004-04-01 | Ono Pharmaceutical Co | Nitrogen-containing compound |
| US20040058876A1 (en) * | 2002-09-18 | 2004-03-25 | Torsten Hoffmann | Secondary binding site of dipeptidyl peptidase IV (DP IV) |
| ATE461212T1 (de) * | 2002-09-18 | 2010-04-15 | Prosidion Ltd | Sekundäre bindungsstelle von dipeptidylpeptidase iv (dp iv) |
| US7390809B2 (en) * | 2002-10-07 | 2008-06-24 | Merck & Co., Inc. | Beta-amino heterocyclic dipeptidyl peptidase inhibitors for diabetes |
| HRP20050343A2 (en) * | 2002-10-18 | 2007-03-31 | Merck & Co. Inc. | Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| MXPA05004890A (es) * | 2002-11-07 | 2005-07-22 | Merck & Co Inc | Derivados de fenilalanina como inhibidores de dipeptidilpeptidasa para el tratamiento o prevencion de diabetes. |
| JP2005170792A (ja) * | 2002-11-22 | 2005-06-30 | Mitsubishi Pharma Corp | L−プロリン誘導体およびその医薬としての用途。 |
| CA2508487A1 (en) * | 2002-12-04 | 2004-06-17 | Merck & Co., Inc. | Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| CA2508947A1 (en) * | 2002-12-20 | 2004-07-15 | Merck & Co., Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| WO2004064778A2 (en) * | 2003-01-17 | 2004-08-05 | Merck & Co. Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| JP2006516573A (ja) * | 2003-01-31 | 2006-07-06 | メルク エンド カムパニー インコーポレーテッド | 糖尿病の治療および予防のためのジペプチジルペプチダーゼ阻害薬としての3−アミノ−4−フェニルブタン酸誘導体 |
| WO2004067509A1 (ja) | 2003-01-31 | 2004-08-12 | Sanwa Kagaku Kenkyusho Co., Ltd. | ジペプチジルペプチダーゼivを阻害する化合物 |
| WO2004087053A2 (en) | 2003-03-25 | 2004-10-14 | Syrrx, Inc. | Dipeptidyl peptidase inhibitors |
| AU2004237408C9 (en) | 2003-05-05 | 2010-04-15 | Probiodrug Ag | Medical use of inhibitors of glutaminyl and glutamate cyclases |
| EP1622870A2 (en) * | 2003-05-05 | 2006-02-08 | Prosidion Ltd. | Glutaminyl based dp iv-inhibitors |
| WO2004098591A2 (en) | 2003-05-05 | 2004-11-18 | Probiodrug Ag | Inhibitors of glutaminyl cyclase and their use in the treatment of neurological diseases |
| NZ572274A (en) | 2003-05-05 | 2009-06-26 | Probiodrug Ag | Use of effectors of glutaminyl and glutamate cyclases |
| US7638638B2 (en) | 2003-05-14 | 2009-12-29 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| EP1624874B1 (en) * | 2003-05-14 | 2009-11-04 | Merck & Co., Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| DE602004026440D1 (de) * | 2003-06-06 | 2010-05-20 | Merck Sharp & Dohme | Kondensierte indole als dipeptidyl-peptidase-hemmer zur behandlung oder prävention von diabetes |
| JP4579239B2 (ja) * | 2003-06-17 | 2010-11-10 | メルク・シャープ・エンド・ドーム・コーポレイション | 糖尿病の治療または予防するためのジペプチジルペプチダーゼ阻害剤としてのシクロヘキシルグリシン誘導体 |
| DE10330842A1 (de) * | 2003-07-08 | 2005-02-10 | Institut für Medizintechnologie Magdeburg GmbH, IMTM | Verwendung der Inhibitoren von Enzymen mit Aktivitäten der Aminopeptidase N und/oder der Dipeptidylpeptidase IV und pharmazeutischen Zubereitungen daraus zur Therapie und Prävention dermatologischer Erkrankungen mit Hyperproliferation und veränderten Differenzierungszuständen von Fibroblasten |
| CN1882551A (zh) * | 2003-07-31 | 2006-12-20 | 麦克公司 | 用作用于治疗或预防糖尿病的二肽基肽酶-iv酶抑制剂的六氢二氮杂吖庚因酮 |
| US6995183B2 (en) * | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7678909B1 (en) | 2003-08-13 | 2010-03-16 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7723344B2 (en) | 2003-08-13 | 2010-05-25 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| US7169926B1 (en) | 2003-08-13 | 2007-01-30 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7205409B2 (en) | 2003-09-04 | 2007-04-17 | Abbott Laboratories | Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV) |
| WO2005030751A2 (en) * | 2003-09-08 | 2005-04-07 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| JP2007505121A (ja) | 2003-09-08 | 2007-03-08 | 武田薬品工業株式会社 | ジペプチジルぺプチダーゼ阻害剤 |
| AU2003269307A1 (en) * | 2003-10-06 | 2005-04-21 | Torrent Pharmaceuticals Ltd. | Azolidinecarbonitriles and their use as dpp-iv inhibitors |
| KR101121882B1 (ko) | 2003-10-15 | 2012-04-12 | 프로비오드룩 아게 | 글루타미닐 및 글루타메이트 사이클라제 이펙터의 용도 |
| US20070123470A1 (en) * | 2003-10-24 | 2007-05-31 | Wladimir Hogenhuis | Enhancement of growth hormone levels with a dipeptidyl peptidase IV inhibitor and a growth hormone secretagogue |
| US20100099721A1 (en) * | 2003-11-03 | 2010-04-22 | Probiodrug Ag | Novel compounds for the treatment of neurological disorders |
| JP2007509898A (ja) | 2003-11-03 | 2007-04-19 | プロビオドルグ エージー | 神経障害治療に有用な組合せ |
| US20050171112A1 (en) * | 2003-11-03 | 2005-08-04 | Probiodrug Ag | Combinations useful for the treatment of neuronal disorders |
| JP2007510651A (ja) * | 2003-11-04 | 2007-04-26 | メルク エンド カムパニー インコーポレーテッド | 糖尿病の治療又は予防のためのジペプチジルペプチダーゼ−iv阻害剤としての縮合フェニルアラニン誘導体 |
| CN101362773B (zh) * | 2003-11-12 | 2013-07-24 | 芬诺密克斯公司 | 杂环硼酸化合物 |
| US7767828B2 (en) | 2003-11-12 | 2010-08-03 | Phenomix Corporation | Methyl and ethyl substituted pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7317109B2 (en) | 2003-11-12 | 2008-01-08 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7576121B2 (en) | 2003-11-12 | 2009-08-18 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| EA013684B1 (ru) | 2003-11-12 | 2010-06-30 | Феномикс Корпорейшн | Гетероциклические соединения бороновой кислоты |
| CA2545641A1 (en) | 2003-11-17 | 2005-06-02 | Novartis Ag | Use of organic compounds |
| EP2165703A3 (en) | 2004-01-20 | 2012-03-28 | Novartis Pharma AG | Direct compression formulation and process |
| US7230002B2 (en) * | 2004-02-03 | 2007-06-12 | Glenmark Pharmaceuticals Ltd. | Dipeptidyl peptidase IV inhibitors; processes for their preparation and compositions thereof |
| HRP20120006T1 (hr) * | 2004-02-05 | 2012-01-31 | Kyorin Pharmaceutical Co. | Derivat bicikloestera |
| AU2005210004B2 (en) | 2004-02-05 | 2010-10-28 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
| EP1717225A4 (en) * | 2004-02-18 | 2009-10-21 | Kyorin Seiyaku Kk | BICYCLIC AMIDE DERIVATIVES |
| CA2557275C (en) * | 2004-02-27 | 2012-06-05 | Kyorin Pharmaceutical Co., Ltd. | Bicyclo derivative |
| US7348346B2 (en) | 2004-03-08 | 2008-03-25 | Abbott Laboratories | Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV) |
| US7732446B1 (en) | 2004-03-11 | 2010-06-08 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| CN102127057A (zh) | 2004-03-15 | 2011-07-20 | 武田药品工业株式会社 | 二肽基肽酶抑制剂 |
| CN1950349A (zh) * | 2004-05-04 | 2007-04-18 | 默克公司 | 作为用于治疗或预防糖尿病的二肽基肽酶-ⅳ抑制剂的1,2,4-噁二唑衍生物 |
| WO2005116029A1 (en) * | 2004-05-18 | 2005-12-08 | Merck & Co., Inc. | Cyclohexylalanine derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
| JP2008501714A (ja) | 2004-06-04 | 2008-01-24 | 武田薬品工業株式会社 | ジペプチジルペプチダーゼインヒビター |
| US20110104186A1 (en) | 2004-06-24 | 2011-05-05 | Nicholas Valiante | Small molecule immunopotentiators and assays for their detection |
| WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| EP1794120B1 (en) | 2004-07-23 | 2012-04-11 | Nuada, LLC | Peptidase inhibitors |
| PE20060652A1 (es) | 2004-08-27 | 2006-08-11 | Novartis Ag | Composiciones farmaceuticas de liberacion inmediata que comprenden granulos de fusion |
| US20060063719A1 (en) * | 2004-09-21 | 2006-03-23 | Point Therapeutics, Inc. | Methods for treating diabetes |
| MX2007004305A (es) * | 2004-10-12 | 2007-06-18 | Glenmark Pharmaceuticals Sa | Inhibidores novedosos de dipeptidil peptidasa iv, composiciones farmaceuticas que los contienen y procedimientos para su preparacion. |
| EP1828192B1 (en) * | 2004-12-21 | 2014-12-03 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| 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 |
| CN102372704B (zh) | 2005-02-18 | 2014-10-08 | 田边三菱制药株式会社 | 脯氨酸衍生物的盐,其溶剂合物,及其生产方法 |
| CA2599419A1 (en) | 2005-04-22 | 2006-11-02 | Alantos Pharmaceuticals Holding, Inc. | Dipeptidyl peptidase-iv inhibitors |
| US7825139B2 (en) | 2005-05-25 | 2010-11-02 | Forest Laboratories Holdings Limited (BM) | Compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| MY152185A (en) | 2005-06-10 | 2014-08-29 | Novartis Ag | Modified release 1-[(3-hydroxy-adamant-1-ylamino)-acetyl]-pyrrolidine-2(s)-carbonitrile formulation |
| MX2008001799A (es) * | 2005-08-11 | 2008-04-16 | Hoffmann La Roche | Composicion farmaceutica que comprende un inhibidor de dipeptidil peptidasa iv. |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| BRPI0616077B8 (pt) * | 2005-09-14 | 2021-05-25 | Takeda Pharmaceuticals Co | composição farmacêutica formulada em uma dose única, kit, artigo de manufatura, uso da composição farmacêutica e uso de um ou mais compostos antidiabéticos |
| CN101374523B (zh) * | 2005-09-14 | 2012-04-11 | 武田药品工业株式会社 | 用于治疗糖尿病的二肽基肽酶抑制剂 |
| WO2007033265A1 (en) * | 2005-09-14 | 2007-03-22 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors for treating diabetis |
| CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
| TW200745080A (en) * | 2005-09-16 | 2007-12-16 | Takeda Pharmaceuticals Co | Polymorphs of tartrate salt of 2-[2-(3-(R)-amino-piperidin-1-yl)-5-fluoro-6-oxo-6H-pyrimidin-1-ylmethyl]-benzonitrile and methods of use therefor |
| TW200745079A (en) * | 2005-09-16 | 2007-12-16 | Takeda Pharmaceuticals Co | Polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile and methods of use therefor |
| EP2545935A1 (en) | 2005-10-07 | 2013-01-16 | Molecular Discovery Systems | HLS-5, a control sumoylation agent |
| DE102005054700B4 (de) * | 2005-11-16 | 2009-01-08 | Imtm Gmbh | Neue duale Peptidase-Inhibitoren als Prodrugs zur Therapie von entzündlichen und anderen Erkrankungen |
| KR20080077024A (ko) | 2005-12-19 | 2008-08-20 | 트러스티즈 오브 터프츠 칼리지 | 소프트 단백질분해효소 억제자 및 이의 프로-소프트 폼 |
| GB0526291D0 (en) | 2005-12-23 | 2006-02-01 | Prosidion Ltd | Therapeutic method |
| CA2645154C (en) * | 2006-03-08 | 2011-11-29 | Kyorin Pharmaceutical Co., Ltd. | Method for producing aminoacetylpyrrolidinecarbonitrile derivative and production intermediate thereof |
| US20100029941A1 (en) * | 2006-03-28 | 2010-02-04 | Takeda Pharmaceutical Company Limited | Preparation of (r)-3-aminopiperidine dihydrochloride |
| WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP2004216A4 (en) * | 2006-03-28 | 2012-02-01 | Molecular Discovery Systems | AGENT FOR THE TREATMENT OF HORMONO-DEPENDENT DISORDERS AND USES THEREOF |
| AU2007236546B2 (en) | 2006-04-07 | 2013-02-21 | Molecular Discovery Systems | Transcription factor modulator |
| 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 |
| JP2009533393A (ja) | 2006-04-12 | 2009-09-17 | プロビオドルグ エージー | 酵素阻害薬 |
| ES2370873T3 (es) * | 2006-09-13 | 2011-12-23 | Takeda Pharmaceutical Company Limited | Utilización del 2-6-(3-amino-piperidin-1-il)-3-metil-2,4-dioxo-3,4-dihidro-2h-pirimidin-1-ilmetil-4-fluoro-benzonitrilo para el tratamiento de la diabetes, el cáncer, los trastornos autoinmunitarios y la infección por el vih. |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| EP2089383B1 (en) | 2006-11-09 | 2015-09-16 | Probiodrug AG | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| TW200838536A (en) * | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| WO2008065141A1 (en) | 2006-11-30 | 2008-06-05 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
| KR100848491B1 (ko) * | 2007-01-16 | 2008-07-28 | 영진약품공업주식회사 | 베타아미노기를 갖는 2-싸이아졸리딘 유도체, 이의약학적으로 허용 가능한 염 및 이의 제조 방법 |
| KR100913495B1 (ko) * | 2007-01-16 | 2009-08-25 | 영진약품공업주식회사 | 베타아미노기를 갖는 1,4-디아제펜 유도체, 이의약학적으로 허용 가능한 염 및 이의 제조 방법 |
| JP2010120851A (ja) * | 2007-02-09 | 2010-06-03 | Kyorin Pharmaceut Co Ltd | 二量化シクロ誘導体 |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| US8143427B2 (en) * | 2007-03-22 | 2012-03-27 | Kyorin Pharmaceutical Co., Ltd. | Method for producing aminoacetylpyrrolidinecarbonitrile derivative |
| CN103330939A (zh) | 2007-04-03 | 2013-10-02 | 田边三菱制药株式会社 | 二肽基肽酶iv抑制化合物和甜味剂的并用 |
| ES2533484T3 (es) | 2007-04-18 | 2015-04-10 | Probiodrug Ag | Derivados de tiourea como inhibidores de la glutaminil ciclasa |
| GB2465132B (en) * | 2007-09-21 | 2012-06-06 | Lupin Ltd | Compounds as dipeptidyl peptidase IV (DPP IV) inhibitors |
| CN101468988A (zh) | 2007-12-26 | 2009-07-01 | 上海恒瑞医药有限公司 | 哌嗪类衍生物,其制备方法及其在医药上的应用 |
| CL2008003653A1 (es) | 2008-01-17 | 2010-03-05 | Mitsubishi Tanabe Pharma Corp | Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica. |
| 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 |
| WO2010016584A1 (ja) * | 2008-08-07 | 2010-02-11 | 杏林製薬株式会社 | ビシクロ[2.2.2]オクチルアミン誘導体の製造方法 |
| CA2733778A1 (en) * | 2008-08-14 | 2010-02-18 | Hiroshi Uchida | Stabilized pharmaceutical composition |
| RU2011113690A (ru) | 2008-09-12 | 2012-10-20 | Кадила Фармасьютикалз Лтд. (In) | Новые ингибиторы дипептидилпептидазы iv (dp-iv) |
| JO2870B1 (en) | 2008-11-13 | 2015-03-15 | ميرك شارب اند دوهم كورب | Amino Tetra Hydro Pirans as Inhibitors of Peptide Dipeptide IV for the Treatment or Prevention of Diabetes |
| US20100144140A1 (en) * | 2008-12-10 | 2010-06-10 | Novellus Systems, Inc. | Methods for depositing tungsten films having low resistivity for gapfill applications |
| US8404727B2 (en) * | 2009-01-07 | 2013-03-26 | Glenmark Pharmaceuticals S.A. | Pharmaceutical composition that includes a dipeptidyl peptidase-IV inhibitor |
| SG175925A1 (en) | 2009-05-15 | 2011-12-29 | Novartis Ag | Aryl pyridine as aldosterone synthase inhibitors |
| US8455522B2 (en) | 2009-05-15 | 2013-06-04 | Novartis Ag | Benzoxazolone derivatives as aldosterone synthase inhibitors |
| CN101899048B (zh) | 2009-05-27 | 2013-04-17 | 上海恒瑞医药有限公司 | (R)-7-[3-氨基-4-(2,4,5-三氟-苯基)-丁酰]-3-三氟甲基-5,6,7,8-四氢-咪唑并[1,5-a]吡嗪-1-羧酸甲酯的盐 |
| MX2011012627A (es) | 2009-05-28 | 2011-12-14 | Novartis Ag | Derivados aminobutiricos sustituidos como inhibidores de nepralisina. |
| EP2594557B1 (en) | 2009-05-28 | 2016-08-10 | Novartis AG | Substituted aminopropionic derivatives as neprilysin inhibitors |
| US8748457B2 (en) | 2009-06-18 | 2014-06-10 | Lupin Limited | 2-amino-2- [8-(dimethyl carbamoyl)- 8-aza- bicyclo [3.2.1] oct-3-yl]-exo- ethanoyl derivatives as potent DPP-IV inhibitors |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| WO2011028455A1 (en) | 2009-09-02 | 2011-03-10 | Merck Sharp & Dohme Corp. | Aminotetrahydropyrans as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
| SG178953A1 (en) | 2009-09-11 | 2012-04-27 | Probiodrug Ag | Heterocylcic derivatives as inhibitors of glutaminyl cyclase |
| CA2774015A1 (en) | 2009-09-15 | 2011-03-24 | Cerulean Pharma Inc. | A cdp-camptothecin conjugate, particle or composition and uses thereof |
| US8519134B2 (en) | 2009-11-17 | 2013-08-27 | Novartis Ag | Aryl-pyridine derivatives as aldosterone synthase inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| EP2503888A4 (en) | 2009-11-23 | 2015-07-29 | Cerulean Pharma Inc | POLYMERS ON CYCLODEXTRINBASIS FOR THERAPEUTIC ADMINISTRATION |
| EP2507234B1 (en) | 2009-11-30 | 2014-03-12 | Novartis AG | Imidazole derivatives as aldosterone synthase inhibitors |
| US20110178287A1 (en) | 2010-01-19 | 2011-07-21 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
| US8853212B2 (en) | 2010-02-22 | 2014-10-07 | Merck Sharp & Dohme Corp | Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes |
| ES2586231T3 (es) | 2010-03-03 | 2016-10-13 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
| EA022420B1 (ru) | 2010-03-10 | 2015-12-30 | Пробиодруг Аг | Гетероциклические ингибиторы глутаминилциклазы (qc, ec 2.3.2.5) |
| JP2013523819A (ja) | 2010-04-06 | 2013-06-17 | アリーナ ファーマシューティカルズ, インコーポレイテッド | Gpr119レセプターのモジュレーターおよびそれに関連する障害の処置 |
| US8581001B2 (en) | 2010-04-16 | 2013-11-12 | Codman & Shurtleff | Metformin-cysteine prodrug |
| EP2560953B1 (en) | 2010-04-21 | 2016-01-06 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
| US8980929B2 (en) | 2010-05-21 | 2015-03-17 | Merck Sharp & Dohme Corp. | Substituted seven-membered heterocyclic compounds as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
| JP5941916B2 (ja) | 2010-09-22 | 2016-06-29 | アリーナ ファーマシューティカルズ, インコーポレイテッド | Gpr119レセプターのモジュレーターおよびそれに関連する障害の処置 |
| WO2012049566A1 (en) | 2010-10-14 | 2012-04-19 | Japan Tobacco Inc. | Combination therapy for use in treating diabetes |
| US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| US8530670B2 (en) | 2011-03-16 | 2013-09-10 | Probiodrug Ag | Inhibitors |
| WO2012135570A1 (en) | 2011-04-01 | 2012-10-04 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012145361A1 (en) | 2011-04-19 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140038889A1 (en) | 2011-04-22 | 2014-02-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| US20140051714A1 (en) | 2011-04-22 | 2014-02-20 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2013006526A2 (en) | 2011-07-05 | 2013-01-10 | Merck Sharp & Dohme Corp. | Tricyclic heterocycles useful as dipeptidyl peptidase-iv inhibitors |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US9115082B2 (en) | 2012-01-18 | 2015-08-25 | Catherine Yang | Dipeptidyl-peptidase-IV inhibitors for treatment of type 2 diabetes complex with hypertension |
| EP2814485A4 (en) | 2012-02-17 | 2015-08-26 | Merck Sharp & Dohme | DIPEPTIDYLPEPTIDASE IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES |
| EP2874622A4 (en) | 2012-07-23 | 2015-12-30 | Merck Sharp & Dohme | TREATMENT OF DIABETES WITH DIPEPTIDYLPEPTIDASE IV INHIBITORS |
| TWI500613B (zh) | 2012-10-17 | 2015-09-21 | Cadila Healthcare Ltd | 新穎之雜環化合物 |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
| ES2675216T3 (es) | 2013-02-14 | 2018-07-09 | Novartis Ag | Derivados de ácido bisfenil-butanoico fosfónico sustituido como inhibidores de NEP (endopeptidasa neutra) |
| EA201690278A1 (ru) | 2013-07-25 | 2016-06-30 | Новартис Аг | Циклические полипептиды для лечения сердечной недостаточности |
| BR112016001376A2 (pt) | 2013-07-25 | 2017-10-24 | Novartis Ag | bioconjugados de polipeptídeos de apelin sintéticos |
| EA201791668A1 (ru) | 2015-01-23 | 2017-11-30 | Новартис Аг | Синтетические конъюгаты апелина с жирной кислотой с улучшенным периодом полураспада |
| HK1249847A1 (zh) | 2015-03-09 | 2018-11-16 | Intekrin Therapeutics, Inc. | 用於治疗非酒精性脂肪肝疾病和/或脂肪营养不良的方法 |
| WO2018049027A1 (en) * | 2016-09-07 | 2018-03-15 | Trustees Of Tufts College | Combination therapies using immuno-dash inhibitors and pge2 antagonists |
| JOP20190086A1 (ar) | 2016-10-21 | 2019-04-18 | Novartis Ag | مشتقات نافثيريدينون جديدة واستخدامها في معالجة عدم انتظام ضربات القلب |
| WO2018162722A1 (en) | 2017-03-09 | 2018-09-13 | Deutsches Institut Für Ernährungsforschung Potsdam-Rehbrücke | Dpp-4 inhibitors for use in treating bone fractures |
| EP3606527A1 (en) | 2017-04-03 | 2020-02-12 | Coherus Biosciences, Inc. | Ppar-gamma agonist for treatment of progressive supranuclear palsy |
| ES2733477T3 (es) | 2017-07-04 | 2019-11-29 | Fis Fabbrica Italiana Sintetici Spa | Procedimiento eficaz para la preparación de sitagliptina a través de una preparación muy eficaz del intermedio ácido 2,4,5-trifluorofenilacético |
| EP3461819B1 (en) | 2017-09-29 | 2020-05-27 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
| CN108003080A (zh) * | 2017-12-12 | 2018-05-08 | 湖北科技学院 | 一种n-氨基酸氰基吡咯烷类衍生物及其制备方法 |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| EP3524605B1 (en) | 2018-02-13 | 2019-11-27 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | New efficient process for the preparation of sitagliptin |
| CN113166101A (zh) | 2018-11-27 | 2021-07-23 | 诺华股份有限公司 | 作为治疗代谢障碍的蛋白质原转换酶枯草杆菌蛋白酶/kexin 9型(PCSK9)抑制剂的环状五聚体化合物 |
| UY38485A (es) | 2018-11-27 | 2020-06-30 | Novartis Ag | Compuestos tetrámeros cíclicos como inhibidores de proproteína convertasa subtilisina/kexina tipo 9 (pcsk9), método de tratamiento, uso y su preparación |
| EP3887388A1 (en) | 2018-11-27 | 2021-10-06 | Novartis AG | Cyclic peptides as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorders |
| WO2022029220A1 (en) | 2020-08-05 | 2022-02-10 | Ellipses Pharma Ltd | Treatment of cancer using a cyclodextrin-containing polymer-topoisomerase inhibitor conjugate and a parp inhibitor |
| WO2023084449A1 (en) | 2021-11-12 | 2023-05-19 | Novartis Ag | Diaminocyclopentylpyridine derivatives for the treatment of a disease or disorder |
| AR127698A1 (es) | 2021-11-23 | 2024-02-21 | Novartis Ag | Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno |
| WO2024241229A1 (en) | 2023-05-24 | 2024-11-28 | Novartis Ag | Naphthyridinone derivatives for the treatment of a disease or disorder |
| CN117778204A (zh) * | 2023-12-25 | 2024-03-29 | 浙江工业大学 | 曲霉L14-OE::laeA2及在生产环三肽类化合物中的应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3639382A (en) * | 1967-12-22 | 1972-02-01 | Merck & Co Inc | O-ethyl threonine derivatives |
| JPS5283749A (en) * | 1976-01-01 | 1977-07-12 | Shionogi & Co Ltd | Novel polypeptide |
| DD158109A1 (de) * | 1981-04-10 | 1982-12-29 | Gunter Fischer | Verfahren zur hemmung der katalytischen aktivitaet von peptidhydrolasen |
| DD296075A5 (de) * | 1989-08-07 | 1991-11-21 | Martin-Luther-Universitaet Halle-Wittenberg,De | Verfahren zur herstellung neuer inhibitoren der dipeptidyl peptidase iv |
| DE69124371T2 (de) * | 1990-04-14 | 1997-06-12 | New England Medical Center Inc | Typ-iv-dipeptidyl-aminopeptidase-inhibitoren |
| US5162336A (en) * | 1990-06-21 | 1992-11-10 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Tetrahydro-pyrido-indoles as cholecystokinin and gastrin antagonists |
| PT98674B (pt) * | 1990-08-15 | 1999-01-29 | British Bio Technology | Processo para a preparacao de compostos que sao antagonistas do factor de activacao de plaquetas por exemplo derivados de imidazole e de seus intermedriarios |
| DE69231674T2 (de) * | 1991-10-22 | 2001-08-09 | New England Medical Center Hospitals, Inc. | Inhibitoren der dipeptidyl-aminopeptidase vom typ-iv |
-
1994
- 1994-11-28 IL IL11178595A patent/IL111785A0/xx not_active IP Right Cessation
- 1994-11-30 US US08/647,887 patent/US5939560A/en not_active Expired - Fee Related
- 1994-11-30 KR KR1019960702901A patent/KR100347828B1/ko not_active Expired - Fee Related
- 1994-11-30 AU AU11133/95A patent/AU1113395A/en not_active Abandoned
- 1994-11-30 CA CA002178066A patent/CA2178066A1/en not_active Abandoned
- 1994-11-30 PL PL94314838A patent/PL182723B1/pl not_active IP Right Cessation
- 1994-11-30 CN CN94194782A patent/CN1079792C/zh not_active Expired - Fee Related
- 1994-11-30 JP JP51547795A patent/JP3970317B2/ja not_active Expired - Fee Related
- 1994-11-30 WO PCT/GB1994/002615 patent/WO1995015309A1/en active IP Right Grant
- 1994-11-30 EP EP95902193A patent/EP0731789A1/en not_active Withdrawn
- 1994-11-30 HU HU9601508A patent/HUT76274A/hu unknown
- 1994-11-30 CZ CZ19961595A patent/CZ289931B6/cs not_active IP Right Cessation
-
1996
- 1996-05-31 NO NO962269A patent/NO306458B1/no unknown
- 1996-06-03 FI FI962315A patent/FI115629B/fi not_active IP Right Cessation
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1999
- 1999-04-21 US US09/295,453 patent/US6201132B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH09509921A (ja) | 1997-10-07 |
| CZ159596A3 (en) | 1997-01-15 |
| US5939560A (en) | 1999-08-17 |
| NO962269D0 (no) | 1996-05-31 |
| HUT76274A (en) | 1997-07-28 |
| FI962315L (fi) | 1996-08-05 |
| CA2178066A1 (en) | 1995-06-08 |
| CN1141033A (zh) | 1997-01-22 |
| US6201132B1 (en) | 2001-03-13 |
| CZ289931B6 (cs) | 2002-04-17 |
| PL182723B1 (pl) | 2002-02-28 |
| HU9601508D0 (en) | 1996-07-29 |
| NO306458B1 (no) | 1999-11-08 |
| CN1079792C (zh) | 2002-02-27 |
| JP3970317B2 (ja) | 2007-09-05 |
| PL314838A1 (en) | 1996-09-30 |
| NO962269L (no) | 1996-07-30 |
| EP0731789A1 (en) | 1996-09-18 |
| WO1995015309A1 (en) | 1995-06-08 |
| IL111785A0 (en) | 1995-01-24 |
| KR100347828B1 (ko) | 2003-01-06 |
| AU1113395A (en) | 1995-06-19 |
| FI962315A0 (fi) | 1996-06-03 |
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