EP1000066A1 - Fused 1,2,4-thiadiazine derivatives, their preparation and use - Google Patents
Fused 1,2,4-thiadiazine derivatives, their preparation and useInfo
- Publication number
- EP1000066A1 EP1000066A1 EP98930653A EP98930653A EP1000066A1 EP 1000066 A1 EP1000066 A1 EP 1000066A1 EP 98930653 A EP98930653 A EP 98930653A EP 98930653 A EP98930653 A EP 98930653A EP 1000066 A1 EP1000066 A1 EP 1000066A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- thiadiazine
- dioxide
- thieno
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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
Definitions
- the present invention relates to fused 1 ,2,4-thiadiazine derivatives, to methods for their preparation, to compositions comprising the compounds, to the use of these compounds as medicaments and their use in therapy e.g. in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.
- potassium channel openers which comprise a heterogeneous group of compounds, have been found to be able to relax vascular smooth muscles and have therefore been used for the treatment of hypertension.
- potassium channel openers can be used as bronchodilators in the treatment of asthma and various other diseases.
- Compounds of the present invention which inhibit insulin secretion by activating potassium channels of the beta-cell can be used in combination with other compounds which may be used to treat non-insulin dependent diabetes mellitus and insulin dependent diabetes mellitus.
- examples of such compounds are insulin, insulin sensitizers, such as thiazolidinediones, insulin secretagogues, such as repaglinide, tolbutamide, glibenclamide and glucagon like peptide ( GLP1), inhibitors of ⁇ -glucosidases and hepatic enzymes responsible for the biosynthesis of glucose.
- R 5 and R 4 together represent one of the bonds in a double bond between the atoms 2 and 3 of formula I;
- R 1 is hydrogen; hydroxy; C 1-6 -alkoxy; or C ⁇ -alkyl, C ⁇ -cycloalkyl, C 2 . 6 - alkenyl or C 2-6 - alkynyl optionally mono- or polysubstituted with halogen and R 4 is hydrogen; or R 4 together with R 5 represent one of the bonds in a double bond between the atoms 2 and 3 of formula I; or R 1 together with R 4 represent one of the bonds in a double bond between the atoms 3 and 4 of formula I;
- R 2 is hydrogen; hydroxy; C 1-6 -alkoxy; or C 1-6 -alkyl, C ⁇ -cycloalkyl, C 2 . 6 - alkenyl or C 2 . 6 - alkynyl optionally mono- or polysubstituted with halogen;
- a together with carbon atoms 5 and 6 of formula I represents a 5 or 6 membered heterocyclic system comprising one or more nitrogen-, oxygen- or sulfur atoms, the heterocyclic systems optionally being mono- or polysubstituted with halogen; C 1-12 -alkyl; C ⁇ -cycloalkyl; hydroxy; C 1-6 -alkoxy; C ⁇ -alkoxy-C L ⁇ -alkyl; nitro; amino; cyano; cyanomethyl; perhalome- thyl; C 1-6 -monoalkyl- or dialkylamino; sulfamoyl; C 1-6 -alkylthio; C 1-6 -alkylsulfonyl; C 1-6 - alkylsulfinyl; C 1-6 -alkylcarbonylamino; arylthio, arylsulfinyl, arylsulfonyl, the aryl group optionally being mono- or polysub
- the invention includes all optical isomers of compounds of formula I, some of which are optically active, and also their mixtures including racemic mixture thereof.
- C e-alkylthio refers to a straight or branched monovalent substituent comprising a lower alkyl group linked through a divalent sulfur atom having its free valence bond from the sulfur atom and having 1 to 6 carbon atoms e.g. methylthio, ethylthio, propylthio, butylthio, pentylthio.
- C 2 . 6 -alkenyl refers to an unsaturated hydrocarbon chain having 2-6 carbon atoms and one double bond such as e.g. vinyl, 1-propenyl, allyl, isopropenyl, n-butenyl, n-pentenyl and n-hexenyl.
- C 1-18 -alkyl as used herein also includes secondary C ⁇ -alkyl and tertiary C ⁇ -alkyl.
- C L g-dialkylamino refers to an amino group wherein the two hydrogen atoms independently are substituted with a straight or branched, saturated hydrocarbon chain having the indicated number of carbon atoms; such as dimethylamino, N-ethyl-N-methylamino, diethylamino, dipropylamino, N-(n-butyl)-N-methyiamino, di(n- pentyl)amino, and the like.
- acyl refers to a monovalent substituent comprising a C 1-6 -alkyl group linked through a carbonyl group; such as e.g. acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, and the like.
- arylalkyl refers to a straight or branched saturated carbon chain containing from 1 to 6 carbons substituted with an aromatic carbohydride; such as benzyl, phenethyl, 3-phenylpropyl, 1-naphtylmethyl, 2-(1-naphtyl)ethyl and the like.
- C ⁇ -dialkylaminocarbonylamino refers to an amino group wherein one of the hydrogen atoms is substituted with a C ⁇ -dialkylaminocarbonyl group, such as dimethylaminocarbonylamino, N-ethyl-N-methylaminocarbonylamino, diethyla- minocarbonylamino, dipropylaminocarbonylamino, N-(n-butyl)-N- methylaminocarbonylamino, di(n-pentyl)aminocarbonylamino, and the like.
- R 1 and R 5 independently are hydrogen; hydroxy; C 1-6 -alkoxy; or C ⁇ -alkyl, C ⁇ -cycloalkyl, C 2-6 -alkenyi or C 2 . 6 -alkynyl optionally mono- or polysubstituted with halogen and R 4 is hydrogen; or
- R is hydrogen; hydroxy; C 1-6 -alkoxy; or C ⁇ -alkyl, C ⁇ -cycloalkyl, C 2 . 6 -alkenyl or C 2 . 6 - alkynyl optionally mono- or polysubstituted with halogen and R 4 is hydrogen; or
- R 7 is C 1-6 -alkyl; or aryl or heteroaryl optionally mono- or polysubstituted with halogen, hydroxy, C 1-6 -alkoxy, aryloxy, arylalkoxy, nitro, amino, C ⁇ -monoalkyl- or dialkylamino, cyano, acyl or C ⁇ -alkoxycarbonyl.
- the general formula of formula I is (la).
- R 1 together with R 4 represent one of the bonds in a double bond between the atoms 3 and 4 of formula I.
- R 3 is selected from secondary C ⁇ - alkyl, tertiary C ⁇ -alkyl, C ⁇ -cycloalkyl or (C ⁇ -cycloalky methyl optionally mono- or polysubstituted with C 1-6 -alkyl, halogen, hydroxy or C 1-6 -alkoxy.
- A forms together with carbon atoms 5 and 6 a thieno[3,2-e]- or pyrrolo[3,2-e]- ring, thiophene, imidazole, thiazole, pyrazole, isoxazole or isothiazole, a pyrazino[2,3-e]-, a pyrimido[4,5-e]-, a pyrimido[5,4-e]-, a pyridazino[4,5-e]- or a pyridazino[4,3-e]-ring, thiopyran, piperidine, dioxane , oxazine or dithiane.
- the compounds of the present invention interact with the potassium channels and hence act as openers or blockers of the ATP-regulated potassium channels, which make them useful in the treatment of various diseases of the cardiovascular system, e.g. cerebral ischemia, hypertension, ischemic heart diseases, angina pectoris and coronary heart diseases; the pulmonary system; the gastrointestinal system; the central nervous system and the endocrinological system.
- the present compounds could also be used for treatment of conditions associated with disturbances in gastrointestinal mobility such as irritable bowel syndrome. Additionally these compounds can be used for the treatment of premature labour and dysmenorrhea.
- Potassium channel openers also relax urinary bladder smooth muscle, thus, the compounds of the present invention can be used for the treatment of urinary incontinence.
- potassium channel openers and hence the present compounds can be used to induce pancreatic cell rest which may prevent the progression of the autoimmune disease.
- Insulin requiring or Type 1 diabetes (IDDM) as well as late onset IDDM also known as type 1.5.
- IDDM Insulin requiring or Type 1 diabetes
- late onset IDDM also known as type 1.5.
- NIDM non-insulin-requiring Type 2 patients with autoreactivity against beta-cell epitopes that later turns insulin requiring
- NIDM non-insulin-requiring Type 2 patients with autoreactivity against beta-cell epitopes that later turns insulin requiring
- cytokines e.g.
- interleukin-1b IL-lb
- TNFa tumour necrosis factor a
- IFNg interferon g
- Nicotinamide belongs to the B-vitamin family and is derived from nicotinic acid by amidation of the carboxyl group. It processes none of nicotine's pharmacological properties.
- the compounds of the present invention may be used for treatment or prevention of diseases of the endocrinological system such as hyperinsulinaemia and diabetes.
- the invention relates to a compound of the general formula I or a pharmaceutically acceptable acid addition salt thereof for use as a therapeutically acceptable substance, preferably for use as a therapeutically acceptable substance in the treatment of hyperinsulinaemia and treatment or prevention of diabetes. Furthermore, the invention also relates to the use of the inventive compounds of formula I as medicaments useful for treating hyperinsulinaemia and treating or preventing diabetes
- the present invention relates to methods of preparing the above mentioned compounds.
- the methods comprises:
- R 1 is hydrogen and A, B, D and X are as defined above, or B is NH and R 1 , A, D and X are as defined above, with the compound of formula III, or a suitable salt thereof in the presence of P 2 O 5 and a high boiling tertiary amine or a suitable salt thereof, to form a compound of the general formula I;
- R 3 is as defined, to form a compound of the general formula I wherein D is SO 2 , B is >NR 5 , R 2 is H, and R 4 and R 5 together form a bond;
- Y is NH or S, or a suitable salt thereof, to form a compound of the general formula I, wherein D is SO 2 , B is >NR 5 , R 4 and R 5 together form a bond, and R 2 and R 3 are H;
- the opening of the K ATP -channels can be determined by measuring the subsequent change in the concentration of cytoplasmic free Ca 2+ concentration according to the method of Arkhammar P. et al. , J. Biol. Chem., 2g2, 5448-5454 (1987).
- the plates were washed 4 times with Ringer buffer (150 mM NaCI, 10 M Hepes, 3.0 mM KCI, 1.0 mM CaCI 2 , 20 mM Sucrose, pH 7.1). Eighty ⁇ l Ringer buffer and 1 ⁇ l control- or test compound dissolved in DMSO was added. After incubation 1 h at room temperature with a lid, 50 ⁇ l of the supernatant was transferred to PicoPlates (Packard Instrument Company, CT, USA) and 100 ⁇ l MicroScint40 (Packard Instrument Company, CT, USA) added. The plates were counted in TopCount (Packard Instrument Company, CT, USA) for 1 min/well at the 32 P program.
- Ringer buffer 150 mM NaCI, 10 M Hepes, 3.0 mM KCI, 1.0 mM CaCI 2 , 20 mM Sucrose, pH 7.1.
- the route of administration may be any route, which effectively transports the active compound to the appropriate or desired site of action, such as oral or parenteral e.g. rectal, transdermal, subcutaneous, intravenous, intramuscular or intranasal, the oral route being preferred.
- oral or parenteral e.g. rectal, transdermal, subcutaneous, intravenous, intramuscular or intranasal, the oral route being preferred.
- compositions include a compound of formula I or a pharmaceutically acceptable acid addition salt thereof, associated with a pharmaceutically acceptable excipient which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier which can be in form of a capsule, sachet, paper or other container.
- a pharmaceutically acceptable excipient which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier which can be in form of a capsule, sachet, paper or other container.
- a pharmaceutically acceptable excipient which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier which can be in form of a capsule, sachet, paper or other container.
- the formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents.
- the formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art.
- injectable solutions or suspensions preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.
- Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application.
- Preferable carriers for tablets, dragees, or capsules include lactose, corn starch, and/or potato starch.
- a syrup or elixir can be used in cases where a sweetened vehicle can be employed.
- the compounds are dispensed in unit form comprising from about 1 to about 100 mg in a pharmaceutically acceptable carrier per unit dosage.
- a typical tablet appropriate for use in this method, may be prepared by conventional tabletting techniques and contains:
- Phosgene (0.242 ml, 20 % in toluene) was added dropwise to a solution of ⁇ /-(3-amino-5- chloro-2-thienylsulfonyl)- ⁇ /'-(3-methylbutyl)thiourea (0.153 g, 0.42 mmol) and dry triethylamine (0.118 ml, 0.85 mmol) in dry tetrahydrofuran (3 ml) with stirring at 0°C. The mixture was stirred for 2 h at 0°C, and evaporated to dryness.
- Ethyl 3-(6-chloro-1 ,4-dihydro-1 ,1-dioxothieno[3,2-e]-1 ⁇ 6 ,2,4-thiadiazin-3- ylamino)butanoate (0.5 g. 1.42 mmol) was hydrolyzed to the acid by stirring in 5 ml of 2 N sodium hydroxide for 2 h at room temperature. The solution was treated with decolorising charcoal, filtered and acidified with 4 M hydrochloric acid to pH 2.
- Potassium terf-butoxide (135 mg, 1.2 mmol) was added to a solution of N-(5-chloro-3- sulfamoylthiophen-2-yi)-acetamide(255 mg, 1.0 mmol) in dry ⁇ /, ⁇ -dimethylformamide (5 ml) with stirring on an ice bath. After 5 min, isopropyl isothiocyanate (0.128 ml, 1.2 mmol) was added dropwise and the solution was stirred for 30 min at 0°C and then at room temperature for 3 h. A further amount of potassium tert-butoxide (135 mg, 1.2 mmol) was added to the solution and stirring was continued at room temperature for 1 h.
- Phosgene (0.416 ml, 20 % in toluene) was added dropwise to a solution of N-[5-chloro-3- (isopropylthiocarbamoyl)sulfamoylthiophen-2-yl]acetamide(261 mg, 0.73 mmol) and dry triethylamine (0.209 ml, 1.5 mmol) in dry tetrahydrofuran (5 ml) with stirring at 0°C. The mixture was stirred for 1 h at 0°C, and evaporated to dryness.
- Powdered potassium hydroxide (128 mg, 2.28 mmol) was added to a solution of 6-chloro- 3-isopropylamino-4H-thieno[3,2-e]-1 ,2,4-thiadiazine 1 ,1-dioxide (319 mg, 1.14 mmol) in 25 ml of methanol and the mixture was hydrogenated at room temperature and atmospheric pressure for 3 days with 150 mg of 10 % palladium on carbon. The catalyst was removed by filtration and washed with ethanol and water. The combined filtrate was acidified with 4 M hydrochloric acid and evaporated to dryness.
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)
- Heart & Thoracic Surgery (AREA)
- Cardiology (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 (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK87297 | 1997-07-16 | ||
DK87297 | 1997-07-16 | ||
DK36898 | 1998-03-17 | ||
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 (1)
Publication Number | Publication Date |
---|---|
EP1000066A1 true EP1000066A1 (en) | 2000-05-17 |
Family
ID=26063863
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98930653A Withdrawn EP1000066A1 (en) | 1997-07-16 | 1998-06-30 | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP1000066A1 (pt) |
JP (1) | JP2001510195A (pt) |
KR (1) | KR20010021936A (pt) |
CN (1) | CN1264384A (pt) |
AU (1) | AU757693B2 (pt) |
BR (1) | BR9810592A (pt) |
CA (1) | CA2294830A1 (pt) |
HU (1) | HUP0003999A3 (pt) |
IL (1) | IL133604A0 (pt) |
NO (1) | NO315470B1 (pt) |
PL (1) | PL338013A1 (pt) |
RU (1) | RU2215004C2 (pt) |
WO (1) | WO1999003861A1 (pt) |
Families Citing this family (169)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1751299A (en) * | 1997-12-19 | 1999-07-12 | Novo Nordisk A/S | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
EP1140945B1 (en) * | 1998-12-18 | 2003-06-04 | 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 |
EP1194430A1 (en) * | 1999-06-30 | 2002-04-10 | Novo Nordisk A/S | Novel process |
WO2002000223A1 (en) * | 2000-06-26 | 2002-01-03 | Novo Nordisk A/S | Use of potassium channel agonists for reducing fat food comsumption |
AU2002221577A1 (en) * | 2000-12-21 | 2002-07-01 | Novo-Nordisk A/S | A new process for preparing fused 1,2,4-thiadiazine derivatives |
CN1221546C (zh) | 2000-12-21 | 2005-10-05 | 阿文蒂斯药物德国有限公司 | 二苯基氮杂环丁酮衍生物、它们的制备方法、含有这些化合物的药物和它们的用途 |
KR100833089B1 (ko) | 2000-12-21 | 2008-05-29 | 사노피-아벤티스 도이칠란트 게엠베하 | 신규한 1,2-디페닐아제티딘온 및 당해 화합물을 함유하는 지질 대사 장애를 치료하기 위한 약제학적 조성물 |
DE10110747A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte 2,6-Diamino-3,5-dicyano-4-aryl-pyridine und ihre Verwendung |
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 |
PE20021091A1 (es) | 2001-05-25 | 2003-02-04 | Aventis Pharma Gmbh | Derivados de fenilurea sustituidos con carbonamida y procedimiento para su preparacion |
NZ531293A (en) | 2001-08-22 | 2005-08-26 | Aventis Pharma Gmbh | Pharamceuticals containing 1,4-benzothiepine-1,1-dioxide derivatives and another active substances such as ezetimibe, pamaqueside or tiqueside for treating lipid metabolism and atherosclerotic disorders |
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 |
DE10142662B4 (de) | 2001-08-31 | 2004-07-08 | Aventis Pharma Deutschland Gmbh | Derivate von C2-substituierten Indan-1-ol-Systemen und ihre Verwendung als Arzneimittel |
DE10142666A1 (de) | 2001-08-31 | 2003-03-20 | Aventis Pharma Gmbh | Verwendung von C2-substituierten Indan-1-ol-Systemen zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Obesitas |
DE10142661B4 (de) | 2001-08-31 | 2004-06-09 | Aventis Pharma Deutschland Gmbh | Mehrfach substituierte Indan-1-ol-Systeme und ihre Verwendung als Arzneimittel |
DE10142659A1 (de) | 2001-08-31 | 2003-03-20 | Aventis Pharma Gmbh | Verwendung von mehrfach substituierten Indan-1-ol. Systemen zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Obesitas |
US7399777B2 (en) | 2001-08-31 | 2008-07-15 | Sanofi-Aventis Deutschland Gmbh | Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmceuticals |
US6884812B2 (en) | 2001-08-31 | 2005-04-26 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmaceuticals |
DE10142663B4 (de) | 2001-08-31 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | C2-Disubstituierte Indan-1-ol-Systeme |
EP1425014B1 (de) | 2001-08-31 | 2006-12-13 | Sanofi-Aventis Deutschland GmbH | Diarylcycloalkylderivate, verfahren zu ihrer herstellung und ihre verwendung als ppar-aktivatoren |
DE10142665B4 (de) | 2001-08-31 | 2004-05-06 | Aventis Pharma Deutschland Gmbh | C2-Disubstituierte Indan-1-one und ihre Derivate |
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 |
DE10142722A1 (de) | 2001-08-31 | 2003-03-27 | Aventis Pharma Gmbh | C2-substituierte Indan-1-one und ihre Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
EP2243776A1 (en) | 2001-10-12 | 2010-10-27 | High Point Pharmaceuticals, LLC | Substituted piperidines and their use for the treatment of diseases related to the histamine H3 receptor |
AU2002365289A1 (en) * | 2001-11-30 | 2003-06-10 | Novo Nordisk A/S | Use of selective potassium channel openers |
WO2003045954A1 (en) * | 2001-11-30 | 2003-06-05 | Novo Nordisk A/S | Use of selective potassium channel openers |
PL370989A1 (en) | 2001-12-21 | 2005-06-13 | Novo Nordisk A/S | Amide derivatives as gk activators |
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 |
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 |
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 |
KR101116627B1 (ko) | 2002-06-27 | 2012-10-09 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
DE10231370B4 (de) | 2002-07-11 | 2006-04-06 | Sanofi-Aventis Deutschland Gmbh | Thiophenglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
US7262220B2 (en) | 2002-07-11 | 2007-08-28 | Sanofi-Aventis Deutschland Gmbh | Urea- and urethane-substituted acylureas, process for their preparation and their use |
OA12881A (en) | 2002-07-12 | 2006-09-15 | Aventis Pharma Gmbh | Heterocyclially 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 |
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 |
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 |
DE10306250A1 (de) | 2003-02-14 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Substituierte N-Arylheterozyklen, 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 |
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 |
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 |
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 |
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 |
JP4629657B2 (ja) | 2003-04-11 | 2011-02-09 | ハイ・ポイント・ファーマスーティカルズ、エルエルシー | 11β−ヒドロキシステロイドデヒドロゲナーゼ1型化活性化合物 |
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 |
US7094800B2 (en) | 2003-07-25 | 2006-08-22 | Sanofi-Aventis Deutschland Gmbh | Cyanopyrrolidides, process for their preparation and their use as medicaments |
US7008957B2 (en) | 2003-07-25 | 2006-03-07 | Sanofi-Aventis Deutschland Gmbh | Bicyclic cyanoheterocycles, 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 |
EP1670815A2 (en) | 2003-09-30 | 2006-06-21 | Novo Nordisk A/S | Melanocortin receptor agonists |
DE602004031455D1 (de) | 2003-12-09 | 2011-03-31 | Novo Nordisk As | Regulierung der nahrungspräferenz mit glp-1-agonisten |
MXPA06007667A (es) | 2004-01-06 | 2006-09-01 | Novo Nordisk As | Heteroaril-ureas y su uso como activadores de glucocinasa. |
US7241787B2 (en) | 2004-01-25 | 2007-07-10 | Sanofi-Aventis Deutschland Gmbh | Substituted N-cycloexylimidazolinones, 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 |
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 |
DE102004005172A1 (de) | 2004-02-02 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Indazolderivate als Inhibitoren der Hormon Sensitiven Lipase |
EP1586573B1 (en) | 2004-04-01 | 2007-02-07 | Sanofi-Aventis Deutschland GmbH | Oxadiazolones, processes for their preparation and their use as pharmaceuticals |
GT200500063A (es) | 2004-04-01 | 2005-10-14 | Metodo para tratar la esquizofrenia y/o anormalidades glucoregulatorias | |
EP1604988A1 (en) | 2004-05-18 | 2005-12-14 | Sanofi-Aventis Deutschland GmbH | Pyridazinone derivatives, methods for producing them and their use as pharmaceuticals |
CN1950078A (zh) | 2004-06-11 | 2007-04-18 | 诺和诺德公司 | 使用glp-1激动剂抵抗药物诱发的肥胖 |
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 |
US8263551B2 (en) | 2004-11-22 | 2012-09-11 | Novo Nordisk A/S | Soluble, stable insulin-containing formulations with a protamine salt |
AU2005311269B2 (en) | 2004-12-03 | 2011-11-10 | Transtech Pharma, Inc. | Heteroaromatic glucokinase activators |
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 |
ES2490243T3 (es) | 2005-02-02 | 2014-09-03 | Novo Nordisk A/S | Derivados de insulina |
DE102005026762A1 (de) | 2005-06-09 | 2006-12-21 | Sanofi-Aventis Deutschland Gmbh | Azolopyridin-2-on-derivate als Inhibitoren von Lipasen und Phospholipasen |
ES2372617T3 (es) | 2005-06-30 | 2012-01-24 | High Point Pharmaceuticals, Llc | Ácidos fenoxiacéticos como activadores de ppar-delta. |
CN103110635A (zh) | 2005-07-04 | 2013-05-22 | 海波因特制药有限责任公司 | 组胺h3受体拮抗剂 |
AU2006268589B2 (en) | 2005-07-14 | 2011-09-29 | Vtv Therapeutics Llc | Urea glucokinase activators |
WO2007009462A2 (en) * | 2005-07-15 | 2007-01-25 | Region Hovedstaden V/Glostrup Hospital | Treatment of migraine and headaches |
EP1910317B1 (en) | 2005-07-20 | 2013-07-03 | Eli Lilly And Company | 1-amino linked compounds |
PT1951658E (pt) | 2005-11-17 | 2012-11-12 | Lilly Co Eli | Antagonistas do receptor do glucagon, preparação e utilizações terapêuticas |
WO2007071766A2 (en) | 2005-12-22 | 2007-06-28 | Transtech Pharma | Phenoxy acetic acids as ppar delta activators |
EP2383271B1 (en) | 2006-03-13 | 2013-07-10 | Kyorin Pharmaceutical Co., Ltd. | Aminoquinolones as GSK-3 Inhibitors |
EA015569B1 (ru) | 2006-03-28 | 2011-10-31 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Бензотиазолы, обладающие антагонистической активностью по отношению к h3-рецептору гистамина, и фармацевтические композиции, включающие эти соединения |
SI2079732T1 (sl) | 2006-05-29 | 2012-03-30 | High Point Pharmaceuticals Llc | benzodioksol il ciklopropilpiperazin il piridazin njegove soli in solvati in njegova uporaba kot antagonist histaminskega receptorja H |
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 |
CA2669874A1 (en) | 2006-11-15 | 2008-05-22 | High Point Pharmaceuticals, Llc | Novel 2-(2-hydroxyphenyl) benzothiadiazines useful for treating obesity and diabetes |
DE102006056739A1 (de) | 2006-12-01 | 2008-06-05 | Bayer Healthcare Ag | Substituierte 4-Amino-3,5-dicyano-2-thiopyridine und ihre Verwendung |
DE102006056740A1 (de) | 2006-12-01 | 2008-06-05 | Bayer Healthcare Ag | Cyclisch substituierte 3,5-Dicyano-2-thiopyridine und ihre Verwendung |
WO2008084044A1 (en) | 2007-01-11 | 2008-07-17 | 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 |
KR101563018B1 (ko) | 2007-09-11 | 2015-10-23 | 교린 세이야꾸 가부시키 가이샤 | Gsk-3 억제제로서의 시아노아미노퀴놀론 및 테트라졸로아미노퀴놀론 |
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 |
DE102007063671A1 (de) | 2007-11-13 | 2009-06-25 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
DE102007061757A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Substituierte 2-Phenylpyrimidin-5-carbonsäuren und ihre Verwendung |
DE102007061763A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Substituierte azabicyclische Verbindungen 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 |
JP2011520997A (ja) | 2008-05-29 | 2011-07-21 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 2−アルコキシ置換ジシアノピリジン類およびそれらの使用 |
AR072707A1 (es) | 2008-07-09 | 2010-09-15 | Sanofi Aventis | Compuestos heterociclicos, procesos para su preparacion, medicamentos que comprenden estos compuestos y el uso de los mismos |
WO2010059618A1 (en) | 2008-11-21 | 2010-05-27 | High Point Pharmaceuticals, Llc | Adamantyl benzamide compounds |
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 |
DE102008062566A1 (de) | 2008-12-16 | 2010-06-17 | Bayer Schering Pharma Aktiengesellschaft | Aminosäureester-Prodrugs und ihre Verwendung |
DE102008062567A1 (de) | 2008-12-16 | 2010-06-17 | Bayer Schering Pharma Aktiengesellschaft | Dipeptoid-Prodrugs und ihre Verwendung |
DE102009006602A1 (de) | 2009-01-29 | 2010-08-05 | Bayer Schering Pharma Aktiengesellschaft | Alkylamino-substituierte Dicyanopyridine und deren Aminosäureester-Prodrugs |
CA2771278A1 (en) | 2009-08-26 | 2011-03-03 | 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 |
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 |
US20130012432A1 (en) | 2010-02-26 | 2013-01-10 | Novo Nordisk A/S | Peptides for Treatment of Obesity |
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
RU2559320C2 (ru) | 2010-03-26 | 2015-08-10 | Ново Нордиск А/С | Новые аналоги глюкагона |
DE102010015123A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi-Aventis Deutschland Gmbh | Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | 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 |
TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
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 |
TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
US20120058983A1 (en) | 2010-09-02 | 2012-03-08 | Bayer Pharma Aktiengesellschaft | Adenosine A1 agonists for the treatment of glaucoma and ocular hypertension |
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 |
US8809324B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
EP2683703B1 (de) | 2011-03-08 | 2015-05-27 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
WO2012120051A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit adamantan- oder noradamantan substituierte benzyl-oxathiazinderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes 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 |
JP2014510739A (ja) | 2011-03-28 | 2014-05-01 | ノヴォ ノルディスク アー/エス | 新規のグルカゴン類似体 |
KR20140054009A (ko) | 2011-07-01 | 2014-05-08 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 릴랙신 융합 폴리펩타이드 및 그의 용도 |
WO2013007563A1 (en) | 2011-07-08 | 2013-01-17 | 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 |
US8541368B2 (en) | 2011-09-23 | 2013-09-24 | Novo Nordisk A/S | Glucagon analogues |
WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | 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 |
US9867869B2 (en) | 2012-12-12 | 2018-01-16 | Massachusetts Institute Of Technology | Insulin derivatives for diabetes treatment |
MY174727A (en) | 2013-04-18 | 2020-05-11 | Novo Nordisk As | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
US9931351B2 (en) | 2013-09-04 | 2018-04-03 | Kyoto University | Method for improving leptin resistance |
MX2016008114A (es) | 2013-12-19 | 2017-01-20 | Bayer Pharma AG | Piperidiniltetrahidroquinolinas sustituidas. |
JOP20200052A1 (ar) | 2013-12-19 | 2017-06-16 | Bayer Pharma AG | بيبريدينيل تتراهيدرو كوينولينات مستبدلة واستخدامها كمعضدات مستقبل أدريني ألفا- 2c |
US20160318866A1 (en) | 2013-12-19 | 2016-11-03 | Bayer Pharma Aktiengesellschaft | Substituted bipiperidinyl derivatives |
CA2934134A1 (en) | 2013-12-19 | 2015-06-25 | Bayer Pharma Aktiengesellschaft | Substituted bipiperidinyl derivatives as adrenoreceptor alpha 2c antagonists |
US10570184B2 (en) | 2014-06-04 | 2020-02-25 | Novo Nordisk A/S | GLP-1/glucagon receptor co-agonists for medical use |
WO2017081044A1 (en) | 2015-11-13 | 2017-05-18 | Bayer Pharma Aktiengesellschaft | 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 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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. |
AU727775B2 (en) * | 1996-01-17 | 2000-12-21 | Novo Nordisk A/S | Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their preparation and use |
-
1998
- 1998-06-30 RU RU2000103491/04A patent/RU2215004C2/ru not_active IP Right Cessation
- 1998-06-30 AU AU81018/98A patent/AU757693B2/en not_active Ceased
- 1998-06-30 CA CA002294830A patent/CA2294830A1/en not_active Abandoned
- 1998-06-30 KR KR1020007000501A patent/KR20010021936A/ko not_active Application Discontinuation
- 1998-06-30 IL IL13360498A patent/IL133604A0/xx unknown
- 1998-06-30 CN CN98807264A patent/CN1264384A/zh active Pending
- 1998-06-30 HU HU0003999A patent/HUP0003999A3/hu unknown
- 1998-06-30 PL PL98338013A patent/PL338013A1/xx unknown
- 1998-06-30 JP JP2000503085A patent/JP2001510195A/ja active Pending
- 1998-06-30 BR BR9810592-2A patent/BR9810592A/pt not_active IP Right Cessation
- 1998-06-30 EP EP98930653A patent/EP1000066A1/en not_active Withdrawn
- 1998-06-30 WO PCT/DK1998/000288 patent/WO1999003861A1/en not_active Application Discontinuation
-
2000
- 2000-01-14 NO NO20000185A patent/NO315470B1/no not_active IP Right Cessation
Non-Patent Citations (1)
Title |
---|
See references of WO9903861A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1999003861A1 (en) | 1999-01-28 |
AU8101898A (en) | 1999-02-10 |
CN1264384A (zh) | 2000-08-23 |
NO315470B1 (no) | 2003-09-08 |
HUP0003999A2 (hu) | 2001-08-28 |
CA2294830A1 (en) | 1999-01-28 |
JP2001510195A (ja) | 2001-07-31 |
PL338013A1 (en) | 2000-09-25 |
BR9810592A (pt) | 2000-09-12 |
HUP0003999A3 (en) | 2003-03-28 |
IL133604A0 (en) | 2001-04-30 |
KR20010021936A (ko) | 2001-03-15 |
NO20000185L (no) | 2000-01-14 |
AU757693B2 (en) | 2003-03-06 |
RU2215004C2 (ru) | 2003-10-27 |
NO20000185D0 (no) | 2000-01-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6225310B1 (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use | |
AU757693B2 (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use | |
AU727775B2 (en) | Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their preparation and use | |
EP1140945B1 (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use | |
US6242443B1 (en) | 1,2,4-benzothiadiazine derivatives, their preparation and use | |
AU727905B2 (en) | Pyrido-1,2,4-thiadiazine and pyrido-1,4-thiazine derivatives, their preparation and use | |
US6232310B1 (en) | Fused 1,4-thiazine-2-carbonitrile derivatives, their preparation and use | |
US6329367B1 (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use | |
WO1999032495A1 (en) | Pyrido 1,2,4-thiadiazine derivatives, their preparation and use | |
RU2199542C2 (ru) | Производные конденсированного 1,2,4-тиадиазина и конденсированного 1,4-тиазина, их получение и использование | |
WO1999032494A1 (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use | |
WO1999032467A1 (en) | 1,2,4-benzothiadiazine derivatives, their preparation and use | |
CZ200044A3 (cs) | Kondenzovaný 1,4-thiazinový derivát, způsob jeho výroby a farmaceutický prostředek ho f obsahující | |
WO2000055147A1 (en) | Fused 1,4-thiazine-2-carbonitrile derivatives, their preparation and use | |
MXPA00000223A (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use | |
MXPA01006224A (en) | Fused 1,2,4-thiadiazine derivatives, their preparation and use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20000216 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU NL PT SE |
|
AX | Request for extension of the european patent |
Free format text: LT PAYMENT 20000216;RO PAYMENT 20000216;SI PAYMENT 20000216 |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: MOGENSEN, JOHN, PATRICK Inventor name: TAGMOSE, TINA, M LLER Inventor name: HANSEN, HOLGER, CLAUS Inventor name: HANSEN, JOHN, BONDO Inventor name: NIELSEN, FLEMMING, ELMEDLUND |
|
17Q | First examination report despatched |
Effective date: 20020222 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20040129 |