Patent DE-102004039096-A1 (DE)
Title: New D-xylopyranosyl-phenyl-substituted cycle compounds useful for treating e.g. diabetes mellitus, complications of diabetes, metabolic acidosis or ketosis
Inventor: ECKHARDT MATTHIAS
IPC: A61K31/70
Filed: 2004-08-11
Abstract: D-xylopyranosyl-phenyl-substituted cycle compounds, their tautomers, stereoisomers, mixtures and salts are new. D-xylopyranosyl-phenyl-substituted cycle compounds of formula (I), their tautomers, stereoisomers, mixtures and salts are new. X = e.g. H, 1-6C alkyl, 2-6C alkynyl, 2-6C alkenyl, 3-10C cycloalkyl, 5-10C cycloalkenyl, (hetero)aryl, arylcarbonyl, piperidin-1-ylcarbonyl, bromomethyl, iodomethyl or cyano (the alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl groups are optionally partly or totally fluorinated or mono- or disubstituted by chlorine, cyano, hydroxy, mercapto, 1-3C alkoxy or 1-3C alkyl, and in cycloalkyl and cycloalkenyl groups, one or two methylene groups are optionally replaced by O, S, CO, SO or SO2 and in N-heterocycloalkyl groups a methylene group is optionally replaced by CO or SO2); (MK#2) Cy = a 5- or 6-membered saturated or monounsaturated carbocyclic ring, optionally comprising 1 - 3 heteratoms of N, O and S, and is substituted by R4-R6 through a single bond and by R3 through a single or double bond, and one or two methylene groups are optionally replaced by CO or a sulfanyl group SO or SO2 and at least one H atom bound to carbon is optionally replaced by fluorine); Z = -O-, -CH2-, -CH=, -NRn-, -S-, -SO- or -SO2- (H atoms of the methylene or methanylylidene bridge is optionally substituted by CH3 or F); R1 = e.g. H, halogen, 1-6C alkyl, 2-6C alkynyl, 2-6C alkenyl, 3-10C cycloalkyl, 1-6C alkyloxy (the (cyclo)alkyl, (cyclo)alkenyl or alkynyl are partly or totally fluorinated or mono- or disubstituted by chlorine, hydroxy, 1-3C alkoxy or 1-3C alkyl, and in cycloalkyl and cycloalkenyl groups, 1 or 2 methylene groups are optionally replaced by O, S, CO, SO or SO2, and in N-heterocycloalkyl groups, a methylene group is optionally replaced by CO or SO2); R3 = e.g. H, halogen, 1-6C alkyl, 2-6C alkynyl, 2-6C alkenyl, 3-10C cycloalkyl, (hetero)aryl; R4 = e.g. H, F, Cl, cyano, nitro, amino, 1-3C alkyl-amino, di-(1-3C alkyl)amino, 1-3C alkylcarbonylamino, 1-3C alkyl, 1-3C alkoxy, hydroxycarbonyl, 1-3C alkoxycarbonyl or methyl or methoxy (mono-trisubstituted by fluorine atoms); R5 = e.g. H, F, Cl, cyano, 1-3C alkyl, 1-3C alkoxy or methyl or methoxy (mono--trisubstituted by fluorine atoms); R4+R5 = 1-4C alkylene or 2-4C alkenylene bridge which forms an anellated or bridged bicyclic group with 2-4 atoms of the Cy ring and optionally partly or wholly fluorinated or mono- or disubstituted by chlorine, hydroxy, 1-3C alkoxy or 1-3C alkyl, and 1 or 2 methylene groups are optionally replaced by O, S, CO, SO, SO2 or NRn; R6 = H, 1-3C alkyl or fluorine; R4+R5+R6 = 3-6C alkanetriyl bridge, which together with the Cy ring forms a bridged bicyclic or a tricyclic system (the alkanetriyl bridge is optionally mono or polyfluorinated or mono or disubstituted by chlorine, hydroxy, 1-3C alkoxy or 1-3C alkyl, and 1 or 2 methylene groups are optionally replaced by O, CO, SO2 or NRn); E = e.g. oxygen, (fluoro)methylidene, chloromethylidene, 1-6C alkylmethylidene; Rn = H or 1-4C alkyl; R7a-R7c = H, (1-18C alkyl)carbonyl, (1-18C alkyl)oxycarbonyl, arylcarbonyl or aryl-(1-3C alkyl)-carbonyl. The dotted line represents a single or double bond. Provided that X excludes hydroxymethyl. [Image] ACTIVITY : Vasotropic; Antidiabetic; Antilipemic; Antiarteriosclerotic; Anorectic; Hypotensive; Cardiant; Anti-inflammatory; Ophthalmological; Nephrotropic; Neuroprotective; Antiulcer. MECHANISM OF ACTION : Inhibitors of sodium-dependent glucose cotransporter SGLT (particularly SGLT2 and SGLT1).