Glucopyranosyl-substituerede benzol-derivater, lægemiddel indeholdende disse forbindelser, deres anvendelse og fremgangsmåder til deres fremstilling
申请公布号:DK1730131(T3)
申请号:DK20050715979T
申请日期:2005.03.11
申请公布日期:2012.08.13
发明人:HIMMELSBACH, FRANK;ECKHARDT, MATTHIAS;EICKELMANN, PETER;BARSOUMIAN, EDWARD LEON;THOMAS, LEO
分类号:C07D309/10;A61K31/351;A61K31/70;A61K31/7004;A61P3/00;C07H15/04;C07H15/20;C07H15/26
主分类号:C07D309/10
摘要:<p>Glucopyranosyl-substituted benzene derivatives (I) and their tautomers, sterioisomers andsalts are new. Glucopyranosyl-substituted benzene derivatives of formula (I) and their tautomers, stereoisomers and salts are new. R 1> : definitions of the group A; R 2> : H, F, Cl, Br, OH, 1-4C alkyl, 1-4C alkoxy, CN or NO 2 (while the alkyl or alkoxy group mono- or polysubstituted by F); R 3> : definitions of the group B 1>; R 4>, R 5> : H, F, Cl, Br, I, CN, NO 2, 1-3C alkyl, 1-3C alkoxy, methyl or methoxy (substituted by 1-3 F atoms); A : e.g. 2-6C alkyn-1-yl, 2-6C alken-1-yl or 3-7C cycloalkyl; B 1> : e.g. tri-(1-4C alkyl)silyl-1-6C alkyl, 2-6C alkyn-1-yl or 2-6C alken-1-yl; R-N : H, 1-4C alkyl, 1-4C alkylcarbonyl or 1-4C alkylsulfonyl; L1 : OH, CN, NO 2, 3-7C cycloalkyl, (hetero)aryl, 1-4C alkylcarbonyl, (hetero)arylcarbonyl, aminocarbonyl, 1-4C alkylaminocarbonyl, di-(1-3C alkyl)-aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, (hetero)arylaminocarbonyl, 1-4C alkoxycarbonyl, (hetero)aryl-1-3C alkoxycarbonyl, 1-4C alkyloxy, (hetero)aryloxy, 1-4C alkylsulfanyl, (hetero)arylsulfanyl, 1-4C alkylsulfinyl, (hetero)arylsulfinyl, 1-4C alkylsulfonyl or (hetero)arylsulfonyl; L2 : F, Cl, Br, I, 1-3C alkyl, difluoromethyl, trifluoromethyl, 1-3C alkoxy, difluoromethoxy, OCF 3 or CN; and R 6>, R-7a, R-7b, R-7c : H, (1-18C alkyl)carbonyl, (1-18C alkyl)oxycarbonyl, arylcarbonyl or aryl-(1-3C alkyl)-carbonyl (while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups which mono- or disubstituted of one another by identical or different groups L2 and by the heteroaryl groups mentioned in the definition of the above groups are meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl, isoquinolinyl or tetrazolyl group or is meant a pyrrolyl, furanyl, thienyl or pyridyl group where 1-2 methyne groups are replaced by nitrogen atoms or meant an indolyl, benzofuranyl, benzothiophenyl or (iso)quinolinyl group, where 1-3 methyne groups are replaced by nitrogen atoms, while the above-mentioned heteroaryl groups of one another may be mono- or disubstituted by identical or different groups L2. Provisos are given. Full definitions are given in the "Definitions" section. Independent claims are also included for: (1) physiologically acceptable salts of (I) with inorganic or organic acids; (2) a glucopyranosyl-substituted benzene derivatives of formula (II); (3) composition containing (I) or a physiologically acceptable salt optionally together with one or more inert carriers and/or diluents; (4) process for preparing a composition comprising the step of incorporating one or more inert carriers and/or diluents into the composition by a non-chemical method. (5) a benzene derivatives of formula (IV); (6) the preparation of (I); (7) the preparation of (II) comprises an organometallic compound (V) which may be obtained by halogen-metal exchange or by the insertion of a metal in the carbon-halogen bond of (IV) and optionally subsequent transmetallation, is added to a gluconolactone of formula (VI) then reacting the adduct obtained with water or an alcohol of formula (R-a-OH), in the presence of an acid and optionally the product obtained in the reaction with water is converted in a subsequent reaction with an acylating agent to give (II); and (8) a pharmaceutical composition for use as a diuretic or hypertensive, the composition comprising (I). R-s : H, 1-4C alkyl, (1-8Calkyl)carbonyl, (1-18C-alkyl)oxycarbonyl, arylcarbonyl or aryl-(C1 3-alkyl)-carbonyl (where the alkyl or aryl groups may be mono- or polysubstituted by halo); either R-8a-R-8d : R 6>, R-7a-R-7c or denote a benzyl group or a R-aR-bR-cSi group or a ketal or acetal group; or R-8a-R-8d : may form a cyclic ketal or acetal group or a 1,2-di(1-3C-alkoxy)-1,2-di(13C-alkyl)-ethylene bridge, (while the above-mentioned ethylene bridge forms, together with two oxygen atoms and the two associated carbon atoms of the pyranose ring, a substituted dioxane ring and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or 13C-alkoxy and benzyl groups may also be substituted by a di-(1-3C-alkyl)amino group); R-a, R-b, R-c : 1-4C alkyl, aryl or aryl-1-3C-alkyl; and aryl : phenyl (preferred) or naphthyl groups. [Image] [Image] ACTIVITY : Antidiabetic; Vasotropic; Analgesic; Antianginal; Antilipemic; Antiarteriosclerotic; Anorectic; Cardiant; Antiinflammatory. MECHANISM OF ACTION : Sodium-dependent glucose cotransporter inhibitor. The ability of (I) to inhibit sodium-dependent glucose cotransporter was tested in biological assays. The results showed that (I) exhibits a median effective concentration value of less than 50 nM.</p>
CORROSION PREVENTION SYSTEM FOR REINFORCED CONCRETE
HIGH-RISE HORIZONTAL MEMBER JACK-DOWN METHOD, AND JACK TO BE USED FOR THE SAME
REINFORCING CONSTRUCTION METHOD OF STEEL STRUCTURE
DOOR SCOPE FOR APARTMENT DOOR OR THE LIKE
BLEACHED KRAFT PULP HAVING IMPROVED THERMAL COLOR FADING RESISTANCE
METHOD OF GRANULATING SINTERING RAW MATERIAL FOR IRON MANUFACTURE
PARTICULATE WATER-ABSORBING RESIN COMPOSITION
PROCESS FOR PRODUCING SURFACE-TREATED PARTICULATE WATER-ABSORBING RESIN
METHOD FOR MANUFACTURING THREE-DIMENSIONALLY SHAPED ARTICLE AND APPARATUS FOR THE SAME