Patent EA-002477-B1 (EA)
Title: The use of 70(2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-quinolone carboxylic acid and naphthryidon carboxylic acid derivatives for the treatment of helicobaster pylori infections and associated gastroduodenal diseases
Inventor: MATZKE MICHAEL
IPC: A61P31/04
Filed: 1997-12-04
Abstract: 1. Use of compounds comprising quinoline carboxylic acid derivatives as an active agent of the general formula (I)   in which R<1> represents alkyl having 1 to 4 C atoms, which is optionally mono- or disubstituted by halogen, phenyl which is optionally substituted by 1 or 2 fluorine atoms or cyclopropyl which is optionally substituted by 1 or 2 fluorine atoms, R<2> represents hydrogen, alkyl having 1 to 4 carbon atoms, which is optionally substituted by hydroxyl, methoxy, amino, methylamino or dimethylamino, or (5-methyl-2-oxo-l,3-dioxol-4-yl)-methyl, A represents N or C-R<3>, where R<3> represents hydrogen, halogen, methyl, methoxy, difluoromethoxy or cyano alternatively, together with R<1> , can form a bridge of the structure -*O-CH2-CH-CH3 or -*O-CH2-N-CH3, where the atom marked by * is connected to the carbon atom of A, R<4> represents hydrogen, benzyl, C1-C3-alkyl, (5-methyl-2-oxo-l,3-dioxol-4-yl)-methyl, radicals of the structures -CH=CH-COOR<5>, -CH2CH2COOR<5>, -CH2CH2CN, -CH2CH2COCH3, -C2COCH3, in which R<5> represents methyl or ethyl, R<6> represents hydrogen, amino, hydroxyl, methyl or halogen, in the form of racemates, diastereomer mixtures or as enantiomerically pure or diastereomerically pure compounds, and their pharmaceutically utilizable hydrates and/or salts for the therapy of Helicobacter pylori infections and the gastroduodenal disorders associated therewith. 2. Use of compounds of the formula (I), in which R<1> represents tert-butyl which is optionally mono- or disubstituted by fluorine or cyclopropyl which is optionally substituted by 1 fluorine atom, R<2> represents hydrogen, alkyl having 1 to 4 carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl, A represents C-R<3>, where R<3> represents hydrogen, fluorine, methoxy, difluoromethoxy or cyano or alternatively, together with R<1>, can form a bridge of the structure -*O-CH2-CH-CH3 or -*O-CH2-N-CH3, where the atom marked by * is connected to the carbon atom of A, R<4> represents hydrogen, C1-C3-alkyl, radicals of the structures, -CH2CH2COOR<5>, -CH2C2CN, -CH2COCH3 in which R<5> represents methyl or ethyl, R<6> represents hydrogen, amino or methyl, and their pharmaceutically utilizable hydrates and/or salts for the therapy of Helicobacter pylori infections and the gastroduodenal disorders associated therewith. 3. Use a pharmaceutical compound of the formula (I), in which R<1> represents tert-butyl which is optionally mono- or disubstituted by fluorine, or cyclopropyl, R<2> represents hydrogen, methyl or ethyl, A represents C-R<3>, where R<3> represents hydrogen, methoxy, difluoromethoxy or cyano or alternatively, together with R<1>, can form a bridge of the structure -*O-CH2-CH-CH3 or -*O-CH2-N-CH3, where the atom marked by * is connected to the carbon atom of A, R<4> represents hydrogen or methyl  or pharmaceutically acceptable hydrate and/or a salt thereof. 4. Use a pharmaceutical compound according to Claims 1 to 3 for the therapy of Helicobacter pylon infections and the gastroduodenal disorders associated therewith. 5. Use a pharmaceutical compound according to Claim 1, comprising 8-cyano-l-cyclopropyl-6-fluoro-7-((1S,6S)-2-oxa-5,8-diazabicyclo-[4.3.0]non-8-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its pharmaceutically utilizable hydrates and/or salts. 6. Use a pharmaceutical compound according to Claim 1, comprising a diastereomerically pure and enantiomerically pure compounds from the group consisting of 8-cyano-1-cyclopropyl-6-fluoro-7-(2-oxa-5,8-diazabicyclo[4.3,0]non-8-yl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1-cyclopropyl-8-difluoromethoxy-6-fluoro-1,4-dihydro-7-(2-oxa-5,8-diaza-bicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid and their pharmaceutically utilizable hydrates and/or salts. 7. Use a pharmaceutical compound according to Claim 6, comprising 8-cyano-l-cyclopropyl-6-fluoro-7-((lS,6S)-2-oxa-5,8-diazabicyclo[4.3.0]-non-8-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its pharmaceutically utilizable hydrates and/or salts. 8. Quinolinecarboxylic acid derivatives of the general formula (II)   in which R represents cyano- or difluoromethoxy group, diastereomers, enanstomers thereof and pharmaceutically utilizable hydrates and/or salts 9. Quinolinecarboxylic acid derivatives according to Claim 8 of the general formula (II), comprising 8-cyano-l-cyclopropyl-6-fluoro-7-((lS,6S)-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-1,4-dihydro-4-oxo-3-qumolinecarboxylic acid and its phannaceutically utilizable hydrates and/or salts.