NO315470B1 - Kondenserte 1,2,4-tiadiazinderivater, farmasöytiske preparater som omfatterdisse forbindelsene, anvendelse av forbindelsene til fremstillingav medikamenter og fremgangsmåte for fremstilling av medikamenter - Google Patents
Kondenserte 1,2,4-tiadiazinderivater, farmasöytiske preparater som omfatterdisse forbindelsene, anvendelse av forbindelsene til fremstillingav medikamenter og fremgangsmåte for fremstilling av medikamenter Download PDFInfo
- Publication number
- NO315470B1 NO315470B1 NO20000185A NO20000185A NO315470B1 NO 315470 B1 NO315470 B1 NO 315470B1 NO 20000185 A NO20000185 A NO 20000185A NO 20000185 A NO20000185 A NO 20000185A NO 315470 B1 NO315470 B1 NO 315470B1
- Authority
- NO
- Norway
- Prior art keywords
- thiadiazine
- dioxide
- thieno
- chloro
- amino
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 115
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- 238000011282 treatment Methods 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 14
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
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- 201000008980 hyperinsulinism Diseases 0.000 claims description 10
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- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000008334 thiadiazines Chemical group 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000011684 zucker rat (obese) Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK87297 | 1997-07-16 | ||
DK36898 | 1998-03-17 | ||
PCT/DK1998/000288 WO1999003861A1 (en) | 1997-07-16 | 1998-06-30 | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20000185D0 NO20000185D0 (no) | 2000-01-14 |
NO20000185L NO20000185L (no) | 2000-01-14 |
NO315470B1 true NO315470B1 (no) | 2003-09-08 |
Family
ID=26063863
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20000185A NO315470B1 (no) | 1997-07-16 | 2000-01-14 | Kondenserte 1,2,4-tiadiazinderivater, farmasöytiske preparater som omfatterdisse forbindelsene, anvendelse av forbindelsene til fremstillingav medikamenter og fremgangsmåte for fremstilling av medikamenter |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP1000066A1 (ru) |
JP (1) | JP2001510195A (ru) |
KR (1) | KR20010021936A (ru) |
CN (1) | CN1264384A (ru) |
AU (1) | AU757693B2 (ru) |
BR (1) | BR9810592A (ru) |
CA (1) | CA2294830A1 (ru) |
HU (1) | HUP0003999A3 (ru) |
IL (1) | IL133604A0 (ru) |
NO (1) | NO315470B1 (ru) |
PL (1) | PL338013A1 (ru) |
RU (1) | RU2215004C2 (ru) |
WO (1) | WO1999003861A1 (ru) |
Families Citing this family (169)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999032494A1 (en) * | 1997-12-19 | 1999-07-01 | Novo Nordisk A/S | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
US6329367B1 (en) | 1998-12-18 | 2001-12-11 | Novo Nordisk A/S | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
IL143402A0 (en) * | 1998-12-18 | 2002-04-21 | Novo Nordisk As | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
AU5521800A (en) * | 1999-06-30 | 2001-01-22 | Novo Nordisk A/S | Novel process |
AU2001265840A1 (en) * | 2000-06-26 | 2002-01-08 | Novo-Nordisk A/S | Use of potassium channel agonists for reducing fat food comsumption |
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AU2002221577A1 (en) * | 2000-12-21 | 2002-07-01 | Novo-Nordisk A/S | A new process for preparing fused 1,2,4-thiadiazine derivatives |
AU2002216097B2 (en) | 2000-12-21 | 2006-09-07 | Sanofi-Aventis Deutschland Gmbh | Novel 1,2-diphenzylazetidinones, method for producing the same, medicaments containing said compounds, and the use thereof for treating disorders of the lipid metabolism |
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DE10142660A1 (de) | 2001-08-31 | 2003-03-20 | Aventis Pharma Gmbh | Verwendung von Derivaten von C2-substituierten Indan-1-ol-Systemen zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Obesitas |
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DE50212937D1 (de) | 2001-08-22 | 2008-12-04 | Sanofi Aventis Deutschland | Kombinationspräparate von 1,4- benzothiepin-1,1-dioxidderivaten mit weiteren wirkstoffen und deren verwendung |
DE10142668A1 (de) | 2001-08-31 | 2003-03-20 | Aventis Pharma Gmbh | Verwendung von C2-substituierten Indan-1-on-Systemen zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Obesitas |
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DE10142661B4 (de) | 2001-08-31 | 2004-06-09 | Aventis Pharma Deutschland Gmbh | Mehrfach substituierte Indan-1-ol-Systeme und ihre Verwendung als Arzneimittel |
DE10142722A1 (de) | 2001-08-31 | 2003-03-27 | Aventis Pharma Deutschland GmbH, 65929 Frankfurt | C2-substituierte Indan-1-one und ihre Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
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BR0212158A (pt) | 2001-08-31 | 2004-07-13 | Aventis Pharma Gmbh | Derivados de diarilcicloalquila, processos para a sua preparação e sua aplicação como ativadores de ppar |
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US6884812B2 (en) | 2001-08-31 | 2005-04-26 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmaceuticals |
DE10142667B4 (de) | 2001-08-31 | 2004-06-09 | Aventis Pharma Deutschland Gmbh | C2-substituierte Indan-1-ole und ihre Derivate und ihre Verwendung als Arzneimittel |
DE10142663B4 (de) | 2001-08-31 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | C2-Disubstituierte Indan-1-ol-Systeme |
WO2003031432A1 (en) | 2001-10-12 | 2003-04-17 | Novo Nordisk A/S | Substituted piperidines and their use for the treatment of diseases related to the histamine h3 receptor |
AU2002342600A1 (en) * | 2001-11-30 | 2003-06-10 | Novo Nordisk A/S | Use of selective potassium channel openers |
WO2003045955A1 (en) * | 2001-11-30 | 2003-06-05 | Novo Nordisk A/S | Use of selective potassium channel openers |
JP2005518391A (ja) | 2001-12-21 | 2005-06-23 | ノボ ノルディスク アクティーゼルスカブ | Gk活性化剤としてのアミド誘導体 |
US7223796B2 (en) | 2002-04-11 | 2007-05-29 | Sanofi-Aventis Deutschland Gmbh | Acyl-4-carboxyphenylurea derivatives, processes for preparing them and their use |
US7078404B2 (en) | 2002-04-11 | 2006-07-18 | Sanofi-Aventis Deutschland Gmbh | Acyl-3-carboxyphenylurea derivatives, processes for preparing them and their use |
US7049341B2 (en) | 2002-06-07 | 2006-05-23 | Aventis Pharma Deutschland Gmbh | N-benzoylureidocinnamic acid derivatives, processes for preparing them and their use |
WO2003105896A1 (en) * | 2002-06-14 | 2003-12-24 | Novo Nordisk A/S | Combined use of a modulator of cd3 and a beta cell resting compound |
US7671047B2 (en) | 2002-06-19 | 2010-03-02 | Sanofi-Aventis Deutschland Gmbh | Cationically substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use |
US7176193B2 (en) | 2002-06-19 | 2007-02-13 | Sanofi-Aventis Deutschland Gmbh | Acid-group-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use |
US7176194B2 (en) | 2002-06-19 | 2007-02-13 | Sanofi-Aventis Deutschland Gmbh | Ring-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use |
CA2744893A1 (en) | 2002-06-27 | 2004-01-08 | Novo Nordisk A/S | Aryl carbonyl derivatives as glucokinase activators |
US7262220B2 (en) | 2002-07-11 | 2007-08-28 | Sanofi-Aventis Deutschland Gmbh | Urea- and urethane-substituted acylureas, process for their preparation and their use |
DE10231370B4 (de) | 2002-07-11 | 2006-04-06 | Sanofi-Aventis Deutschland Gmbh | Thiophenglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
RS20050019A (en) | 2002-07-12 | 2007-09-21 | Sanofi - Aventis Pharma Deutschland Gmbh., | Heterocyclically substituted benzoylureas,method for their production and their use as medicaments |
US7141561B2 (en) | 2002-07-25 | 2006-11-28 | Sanofi-Aventis Deutschland Gmbh | Substituted diaryl heterocycles, process for their preparation and their use as medicaments |
US20040157922A1 (en) | 2002-10-04 | 2004-08-12 | Aventis Pharma Deutschland Gmbh | Carboxyalkoxy-substituted acyl-carboxyphenylurea derivatives and their use as medicaments |
US7208504B2 (en) | 2002-10-12 | 2007-04-24 | Sanofi-Aventis Deutschland Gmbh | Bicyclic inhibitors of hormone sensitive lipase |
DE10258007B4 (de) | 2002-12-12 | 2006-02-09 | Sanofi-Aventis Deutschland Gmbh | Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
US20040242583A1 (en) | 2003-01-20 | 2004-12-02 | Aventis Pharma Deutschland Gmbh | Pyrimido[5,4-e][1,2,4]triazine-5,7-diones, processes for preparing them and their use |
US7179941B2 (en) | 2003-01-23 | 2007-02-20 | Sanofi-Aventis Deutschland Gmbh | Carbonylamino-substituted acyl phenyl urea derivatives, process for their preparation and their use |
US7390814B2 (en) | 2003-02-13 | 2008-06-24 | Sanofi-Aventis Deutschland Gmbh | Substituted hexahydropyrazino [1,2-a] pyrimidine-4,7-dione derivatives, process for their preparation and their use as medicaments |
US7652007B2 (en) | 2003-02-13 | 2010-01-26 | Sanofi-Aventis Deutschland Gmbh | Nitrogen-substituted hexahydropyrazino[1,2-A]pyrimidine-4,7-dione derivatives, processes for their preparation and their use as medicaments |
DE10306250A1 (de) | 2003-02-14 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE10308352A1 (de) | 2003-02-27 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Arylcycloalkylderivate mit verzweigten Seitenketten, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
DE10308355A1 (de) | 2003-02-27 | 2004-12-23 | Aventis Pharma Deutschland Gmbh | Aryl-cycloalkyl substituierte Alkansäurederivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
DE10308353A1 (de) | 2003-02-27 | 2004-12-02 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkylderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE10308351A1 (de) | 2003-02-27 | 2004-11-25 | Aventis Pharma Deutschland Gmbh | 1,3-substituierte Cycloalkylderivate mit sauren, meist heterocyclischen Gruppen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
US7148246B2 (en) | 2003-02-27 | 2006-12-12 | Sanofi-Aventis Deutschland Gmbh | Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals |
US7501440B2 (en) | 2003-03-07 | 2009-03-10 | Sanofi-Aventis Deutschland Gmbh | Substituted benzoylureidopyridylpiperidine-and-pyrrolidinecarboxylic acid derivatives, processes for preparing them and their use |
DE10314610A1 (de) | 2003-04-01 | 2004-11-04 | Aventis Pharma Deutschland Gmbh | Neues Diphenylazetidinon mit verbesserten physiologischen Eigenschaften, Verfahren zu dessen Herstellung, diese Verbindungen enthaltende Arzneimittel und dessen Verwendung |
ATE467616T1 (de) | 2003-04-11 | 2010-05-15 | High Point Pharmaceuticals Llc | Verbindungen mit aktivität an der 11beta- hydroxasteroiddehydrogenase |
FR2854634B1 (fr) * | 2003-05-05 | 2005-07-08 | Servier Lab | Nouveaux derives de thiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
US7008957B2 (en) | 2003-07-25 | 2006-03-07 | Sanofi-Aventis Deutschland Gmbh | Bicyclic cyanoheterocycles, process for their preparation and their use as medicaments |
US7094800B2 (en) | 2003-07-25 | 2006-08-22 | Sanofi-Aventis Deutschland Gmbh | Cyanopyrrolidides, process for their preparation and their use as medicaments |
US7094794B2 (en) | 2003-07-28 | 2006-08-22 | Sanofi-Aventis Deutschland Gmbh | Substituted thiazole-benzoisothiazole dioxide derivatives, process for their preparation and their use |
DE10335092B3 (de) | 2003-08-01 | 2005-02-03 | Aventis Pharma Deutschland Gmbh | Substituierte Benzoylureido-o-benzoylamide, Verfahren zu deren Herstellung und deren Verwendung |
JP2007532471A (ja) | 2003-09-30 | 2007-11-15 | ノボ ノルディスク アクティーゼルスカブ | 新規メラノコルチンレセプターアゴニスト |
EP2298337B1 (en) | 2003-12-09 | 2017-02-22 | Novo Nordisk A/S | Regulation of food preference using GLP-1 agonists |
BRPI0506662B8 (pt) | 2004-01-06 | 2021-05-25 | Novo Nordisk As | compostos ativadores de glucoquinase |
US7241787B2 (en) | 2004-01-25 | 2007-07-10 | Sanofi-Aventis Deutschland Gmbh | Substituted N-cycloexylimidazolinones, process for their preparation and their use as medicaments |
US7498341B2 (en) | 2004-01-31 | 2009-03-03 | Sanofi Aventis Deutschland Gmbh | Heterocyclically substituted 7-amino-4-quinolone-3-carboxylic acid derivatives, process for their preparation and their use as medicaments |
US7470706B2 (en) | 2004-01-31 | 2008-12-30 | Sanofi-Aventis Deutschland Gmbh | Cycloalkyl-substituted 7-amino-4-quinolone-3-carboxylic acid derivatives, process for their preparation and their use as medicaments |
US7402674B2 (en) | 2004-01-31 | 2008-07-22 | Sanofi-Aventis Deutschland Gmbh, | 7-Phenylamino-4-quinolone-3-carboxylic acid derivatives, process for their preparation and their use as medicaments |
DE102004005172A1 (de) | 2004-02-02 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Indazolderivate als Inhibitoren der Hormon Sensitiven Lipase |
GT200500063A (es) | 2004-04-01 | 2005-10-14 | Metodo para tratar la esquizofrenia y/o anormalidades glucoregulatorias | |
EP1586573B1 (en) | 2004-04-01 | 2007-02-07 | Sanofi-Aventis Deutschland GmbH | Oxadiazolones, processes for their preparation and their use as pharmaceuticals |
EP1604988A1 (en) | 2004-05-18 | 2005-12-14 | Sanofi-Aventis Deutschland GmbH | Pyridazinone derivatives, methods for producing them and their use as pharmaceuticals |
JP2008501765A (ja) | 2004-06-11 | 2008-01-24 | ノボ ノルディスク アクティーゼルスカブ | Glp−1アゴニストを用いた薬剤誘発性肥満の中和 |
WO2006028970A1 (en) | 2004-09-02 | 2006-03-16 | Cengent Therapeutics, Inc. | Derivatives of thiazole and thiadiazole inhibitors of tyrosine phosphatases |
DE102004042607A1 (de) | 2004-09-03 | 2006-03-09 | Bayer Healthcare Ag | Substituierte Phenylaminothiazole und ihre Verwendung |
CN101060856B (zh) | 2004-11-22 | 2011-01-19 | 诺和诺德公司 | 可溶、稳定的含胰岛素制剂 |
BRPI0518798A2 (pt) | 2004-12-03 | 2008-12-09 | Transtech Pharma Inc | composto, composiÇço farmacÊutica, e, mÉtodos para tratar diabete tipo ii e para tratar uma condiÇço ou distérbio |
ES2490243T3 (es) | 2005-02-02 | 2014-09-03 | Novo Nordisk A/S | Derivados de insulina |
JP4933455B2 (ja) | 2005-02-02 | 2012-05-16 | ノヴォ ノルディスク アー/エス | 新規のインスリン誘導体 |
DE102005026762A1 (de) | 2005-06-09 | 2006-12-21 | Sanofi-Aventis Deutschland Gmbh | Azolopyridin-2-on-derivate als Inhibitoren von Lipasen und Phospholipasen |
ATE529404T1 (de) | 2005-06-30 | 2011-11-15 | High Point Pharmaceuticals Llc | Phenoxyessigsäuren als ppar-delta-aktivatoren |
EP2233470B1 (en) | 2005-07-04 | 2011-12-07 | High Point Pharmaceuticals, LLC | Histamine H3 receptor antagonists |
MX2008000255A (es) | 2005-07-14 | 2008-04-02 | Novo Nordisk As | Activadores de urea glucocinasa. |
WO2007009462A2 (en) * | 2005-07-15 | 2007-01-25 | Region Hovedstaden V/Glostrup Hospital | Treatment of migraine and headaches |
US8106090B2 (en) | 2005-07-20 | 2012-01-31 | Eli Lilly And Company | 1-amino linked compounds |
WO2007123581A1 (en) | 2005-11-17 | 2007-11-01 | Eli Lilly And Company | Glucagon receptor antagonists, preparation and therapeutic uses |
EP1979311B1 (en) | 2005-12-22 | 2012-06-13 | High Point Pharmaceuticals, LLC | Phenoxy acetic acids as ppar delta activators |
AU2007225088B2 (en) | 2006-03-13 | 2012-09-13 | Kyorin Pharmaceutical Co., Ltd | Aminoquinolones as GSK-3 inhibitors |
CN101410385B (zh) | 2006-03-28 | 2011-08-24 | 高点制药有限责任公司 | 具有组胺h3受体活性的苯并噻唑类 |
SG163547A1 (en) | 2006-05-29 | 2010-08-30 | High Point Pharmaceuticals Llc | 3- (1, 3-benz0di0x0l-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine h3 receptor antagonist |
DE102006028862A1 (de) | 2006-06-23 | 2007-12-27 | Merck Patent Gmbh | 3-Amino-imidazo[1,2-a]pyridinderivate |
WO2008017381A1 (de) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituierte imidazolidin-2,4-dione, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und ihre verwendung |
DE102006042143A1 (de) | 2006-09-08 | 2008-03-27 | Bayer Healthcare Aktiengesellschaft | Neue substituierte Bipyridin-Derivate und ihre Verwendung |
ATE538109T1 (de) | 2006-11-15 | 2012-01-15 | High Point Pharmaceuticals Llc | Neue für die behandlung von obesitas und diabetes geeignete 2-(2-hydroxyphenyl)benzothiadiazine |
DE102006056740A1 (de) | 2006-12-01 | 2008-06-05 | Bayer Healthcare Ag | Cyclisch substituierte 3,5-Dicyano-2-thiopyridine und ihre Verwendung |
DE102006056739A1 (de) | 2006-12-01 | 2008-06-05 | Bayer Healthcare Ag | Substituierte 4-Amino-3,5-dicyano-2-thiopyridine und ihre Verwendung |
US8318778B2 (en) | 2007-01-11 | 2012-11-27 | Novo Nordisk A/S | Urea glucokinase activators |
DE102007002260A1 (de) | 2007-01-16 | 2008-07-31 | Sanofi-Aventis | Verwendung von substituierten Pyranonsäurederivaten zur Herstellung von Medikamenten zur Behandlung des Metabolischen Syndroms |
DE102007005045B4 (de) | 2007-01-26 | 2008-12-18 | Sanofi-Aventis | Phenothiazin Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE102007008420A1 (de) | 2007-02-21 | 2008-08-28 | Merck Patent Gmbh | Benzimidazolderivate |
US20080319221A1 (en) | 2007-06-22 | 2008-12-25 | Bernd Junker | Esters of Pentahydroxyhexylcarbamoyl Alkanoic Acids |
DE102007035367A1 (de) | 2007-07-27 | 2009-01-29 | Bayer Healthcare Ag | Substituierte Aryloxazole und ihre Verwendung |
DE102007036076A1 (de) | 2007-08-01 | 2009-02-05 | Bayer Healthcare Aktiengesellschaft | Dipeptoid-Produgs und ihre Verwendung |
EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE102007042754A1 (de) | 2007-09-07 | 2009-03-12 | Bayer Healthcare Ag | Substituierte 6-Phenylnikotinsäuren und ihre Verwendung |
CN101855228B (zh) | 2007-09-11 | 2012-10-24 | 杏林制药株式会社 | 作为gsk-3抑制剂的氰基氨基喹诺酮和四唑并氨基喹诺酮 |
CA2699152C (en) | 2007-09-12 | 2015-11-24 | Activx Biosciences, Inc. | Spirocyclic aminoquinolones as gsk-3 inhibitors |
DE102007048716A1 (de) | 2007-10-11 | 2009-04-23 | Merck Patent Gmbh | Imidazo[1,2-a]pyrimidinderivate |
DE102007054497B3 (de) | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
DE102007061763A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Substituierte azabicyclische Verbindungen und ihre Verwendung |
DE102007061757A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Substituierte 2-Phenylpyrimidin-5-carbonsäuren und ihre Verwendung |
DE102007061756A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Substituierte 4-Aminopyrimidin-5-carbonsäuren und ihre Verwendung |
DE102007061764A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Anellierte Cyanopyridine und ihre Verwendung |
DE102008008838A1 (de) | 2008-02-13 | 2009-08-20 | Bayer Healthcare Ag | Cycloalkoxy-substituierte 4-Phenyl-3,5-dicyanopyridine und ihre Verwendung |
DE102008013587A1 (de) | 2008-03-11 | 2009-09-17 | Bayer Schering Pharma Aktiengesellschaft | Heteroaryl-substituierte Dicyanopyridine und ihre Verwendung |
DE102008017590A1 (de) | 2008-04-07 | 2009-10-08 | Merck Patent Gmbh | Glucopyranosidderivate |
CN101555214B (zh) | 2008-04-08 | 2012-07-11 | 北京嘉事联博医药科技有限公司 | 苯基环丁基酰胺衍生物及其光学异构体、制备方法和用途 |
US8791146B2 (en) | 2008-05-29 | 2014-07-29 | Bayer Intellectual Property Gmbh | 2-alkoxy-substituted dicyanopyridines and their use |
EP2310372B1 (en) | 2008-07-09 | 2012-05-23 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
EP2362730A4 (en) | 2008-11-21 | 2012-08-29 | High Point Pharmaceuticals Llc | Adamantyl BENZAMIDE CONNECTIONS |
WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
DE102008062567A1 (de) | 2008-12-16 | 2010-06-17 | Bayer Schering Pharma Aktiengesellschaft | Dipeptoid-Prodrugs und ihre Verwendung |
DE102008062566A1 (de) | 2008-12-16 | 2010-06-17 | Bayer Schering Pharma Aktiengesellschaft | Aminosäureester-Prodrugs und ihre Verwendung |
DE102009006602A1 (de) | 2009-01-29 | 2010-08-05 | Bayer Schering Pharma Aktiengesellschaft | Alkylamino-substituierte Dicyanopyridine und deren Aminosäureester-Prodrugs |
EP2470552B1 (en) | 2009-08-26 | 2013-11-13 | Sanofi | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
US20120270819A1 (en) | 2009-10-02 | 2012-10-25 | Sanofi | Use of compounds with sglt-1/sglt-2 inhibitor activity for producing medicaments for treatment of bone disease |
EP2539364A1 (en) | 2010-02-26 | 2013-01-02 | Novo Nordisk A/S | Peptides for treatment of obesity |
BR112012021231A2 (pt) | 2010-02-26 | 2015-09-08 | Basf Plant Science Co Gmbh | método para acentuar o rendimento em plantas, planta, construto, uso de um construto, método para a produção de uma planta transgênica, partes coletáveis de uma planta, produtos derivados de uma planta, uso de um ácido nucleíco e método para a produção de um produto |
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
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DE102010015123A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi-Aventis Deutschland Gmbh | Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
EP2585055A1 (de) | 2010-06-25 | 2013-05-01 | Bayer Intellectual Property GmbH | Verwendung von stimulatoren und aktivatoren der löslichen guanylatzyklase zur behandlung von sichelzellanämie und konservierung von blutersatzstoffen |
DE102010030688A1 (de) | 2010-06-30 | 2012-01-05 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Dicyanopyridine und ihre Verwendung |
TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
US20120058983A1 (en) | 2010-09-02 | 2012-03-08 | Bayer Pharma Aktiengesellschaft | Adenosine A1 agonists for the treatment of glaucoma and ocular hypertension |
EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
WO2012120057A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
US8710050B2 (en) | 2011-03-08 | 2014-04-29 | Sanofi | Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
US8809325B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Benzyl-oxathiazine derivatives substituted with adamantane and noradamantane, medicaments containing said compounds and use thereof |
US8846666B2 (en) | 2011-03-08 | 2014-09-30 | Sanofi | Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
EP2683702B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
US8828994B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
EP2691108A1 (en) | 2011-03-28 | 2014-02-05 | Novo Nordisk A/S | Novel glucagon analogues |
MX2014000031A (es) | 2011-07-01 | 2014-07-09 | Bayer Ip Gmbh | Polipeptidos de fusion de relaxina y usos de los mismos. |
AU2012283235A1 (en) | 2011-07-08 | 2014-01-09 | Bayer Intellectual Property Gmbh | Fusion proteins releasing Relaxin and uses thereof |
WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
CA2849673A1 (en) | 2011-09-23 | 2013-03-28 | Novo Nordisk A/S | Novel glucagon analogues |
EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
WO2013144191A1 (de) | 2012-03-29 | 2013-10-03 | Bayer Intellectual Property Gmbh | Substituierte 2 -amino - 3 - cyanopyridine als inhibitoren des natrium calcium austausches und ihre verwendung bei kardiovaskulären erkrankungen |
WO2014093696A2 (en) | 2012-12-12 | 2014-06-19 | Massachusetts Institute Of Technology | Insulin derivatives for diabetes treatment |
MX362275B (es) | 2013-04-18 | 2019-01-10 | Novo Nordisk As | Co-agonista de peptido similar a glucagon tipo 1 (glp-1) receptor de glucagon de larga duracion, estables para uso medico. |
JP6378685B2 (ja) | 2013-09-04 | 2018-08-22 | 国立大学法人京都大学 | レプチン抵抗性を改善する医薬組成物 |
JOP20200052A1 (ar) | 2013-12-19 | 2017-06-16 | Bayer Pharma AG | بيبريدينيل تتراهيدرو كوينولينات مستبدلة واستخدامها كمعضدات مستقبل أدريني ألفا- 2c |
CA2934132A1 (en) | 2013-12-19 | 2015-06-25 | Bayer Pharma Aktiengesellschaft | Substituted bipiperidinyl derivatives as adrenoreceptor alpha 2c antagonists |
CN105980374A (zh) | 2013-12-19 | 2016-09-28 | 拜耳制药股份公司 | 取代的哌啶基四氢喹啉 |
JP2017503778A (ja) | 2013-12-19 | 2017-02-02 | バイエル ファーマ アクチエンゲゼルシャフト | アドレナリン受容体α2C拮抗薬としての置換されたビピペリジニル誘導体 |
WO2015185640A1 (en) | 2014-06-04 | 2015-12-10 | Novo Nordisk A/S | Glp-1/glucagon receptor co-agonists for medical use |
US20190008867A1 (en) | 2015-11-13 | 2019-01-10 | Ph Pharma Co., Ltd. | 4-(4-cyano-2-thioaryl)dihydropyrimidinones for treating chronic wounds |
JP2020514365A (ja) | 2017-03-15 | 2020-05-21 | ノヴォ ノルディスク アー/エス | メラノコルチン4受容体に結合可能な二環式化合物 |
WO2019219714A1 (en) | 2018-05-15 | 2019-11-21 | Novo Nordisk A/S | Compounds capable of binding to melanocortin 4 receptor |
WO2020053414A1 (en) | 2018-09-14 | 2020-03-19 | Novo Nordisk A/S | Bicyclic compounds capable of acting as melanocortin 4 receptor agonists |
WO2020165031A1 (de) | 2019-02-15 | 2020-08-20 | Bayer Aktiengesellschaft | Substituierte isochinolin-piperidinylmethanon-derivate |
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Publication number | Priority date | Publication date | Assignee | Title |
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GB1368948A (en) * | 1970-11-11 | 1974-10-02 | Manuf Prod Pharma | Pyridine derivatives |
FR2703051B1 (fr) * | 1993-03-26 | 1995-04-28 | Adir | Nouvelles pyridothiadiazines, leurs procédés de préparation, et les compositions pharmaceutiques qui les contiennent. |
WO1997026265A1 (en) * | 1996-01-17 | 1997-07-24 | Novo Nordisk A/S | Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their preparation and use |
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1998
- 1998-06-30 KR KR1020007000501A patent/KR20010021936A/ko not_active Application Discontinuation
- 1998-06-30 PL PL98338013A patent/PL338013A1/xx unknown
- 1998-06-30 AU AU81018/98A patent/AU757693B2/en not_active Ceased
- 1998-06-30 WO PCT/DK1998/000288 patent/WO1999003861A1/en not_active Application Discontinuation
- 1998-06-30 RU RU2000103491/04A patent/RU2215004C2/ru not_active IP Right Cessation
- 1998-06-30 EP EP98930653A patent/EP1000066A1/en not_active Withdrawn
- 1998-06-30 JP JP2000503085A patent/JP2001510195A/ja active Pending
- 1998-06-30 HU HU0003999A patent/HUP0003999A3/hu unknown
- 1998-06-30 CN CN98807264A patent/CN1264384A/zh active Pending
- 1998-06-30 IL IL13360498A patent/IL133604A0/xx unknown
- 1998-06-30 CA CA002294830A patent/CA2294830A1/en not_active Abandoned
- 1998-06-30 BR BR9810592-2A patent/BR9810592A/pt not_active IP Right Cessation
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2000
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HUP0003999A2 (hu) | 2001-08-28 |
WO1999003861A1 (en) | 1999-01-28 |
JP2001510195A (ja) | 2001-07-31 |
CN1264384A (zh) | 2000-08-23 |
BR9810592A (pt) | 2000-09-12 |
NO20000185D0 (no) | 2000-01-14 |
AU8101898A (en) | 1999-02-10 |
NO20000185L (no) | 2000-01-14 |
RU2215004C2 (ru) | 2003-10-27 |
HUP0003999A3 (en) | 2003-03-28 |
IL133604A0 (en) | 2001-04-30 |
EP1000066A1 (en) | 2000-05-17 |
AU757693B2 (en) | 2003-03-06 |
KR20010021936A (ko) | 2001-03-15 |
PL338013A1 (en) | 2000-09-25 |
CA2294830A1 (en) | 1999-01-28 |
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