IE43256B1

IE43256B1 - 8-oxo-2,3,5,8-tetrahydrofuro /2,3-g/ quinoline-7-carboxylic acid derivatives

Info

Publication number: IE43256B1
Application number: IE1476/76A
Authority: IE
Original assignee: Schering Ag
Priority date: 1975-07-04
Filing date: 1976-07-05
Publication date: 1981-01-14
Also published as: FR2315932B1; DK142949C; PT65299A; DE2530412A1; JPS5223096A; IE43256L; FR2315932A1; IL49967A0; CA1071209A; BE843738A; CH626894A5; NL7607417A; DK142949B; SE7607515L; DK300076A; LU75294A1; PT65299B

Abstract

The invention provides quinoline carboxylic acid derivatives of the general formula where R1 is an alkenyl group containing 2 to 4 carbon atoms or an alkynyl group containing 2 to 4 carbon atoms and R2 is hydrogen; an alkenyl group containing 2 to 4 carbon atoms or an alkynyl containing 2 to 4 carbon atoms and physiologically tolerable salts of such compounds. Such quinoline carboxylic acid derivatives and their salts are useful as urinary antiseptics.

Description

The present invention is concerned with new quinoline carboxylic acid derivatives having valuable pharmacological properties as urinary antiseptics, with a process for their manufacture and v/ith their use.

The present invention provides quinoline carboxylic acid derivatives of the in which £ R1 R^ represents an unsaturated aliphatic hydrocarbon group containing up to 6 carbon atoms (which may be a straight chained or branched group), and R2 represents a hydrogen atom or a saturated or unsaturated aliphatic hydrocarbon group containing up to 6 carbon atoms (which may be a straight chained or branched group), and also, when Rg represents a hydrogen atom, physiologically tolerable salts thereof with inorganic or organic bases.

As the aforesaid straight chained or branched unsaturated aliphatic hydrocarbon groups containing up to 6 carbon atoms there may be mentioned, for example, vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 1-hexenyl, allenyl, 1,3-butadienyl, 1,3-hexadienyl, isopropenyl, 1-methylpropenyl, 2-methylpropenyl, 2-methallyl, isopentenyl, 3,3,-dimethylallyl, ethynyl, propargyl, 1-butynyl, 1-hexynyl, 1-methyl-2-propynyl, 2-methyl-3-pentynyl, 2-penten-4-ynyl, 1-methyl-2-penten-4-ynyl and 2-methyl-l,3-butadienyl groups, those groups containing up to 4 carbon atoms being preferred.

As the aforesaid straight chained or branched saturated aliphatic hydrocarbon groups, in other words alkyl groups, there may be mentioned, for example, methyl, - 2 43256 ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, tert-butyl, isobutyl, n-pentyl, isopentyl, neopentyl and n-hexyl groups, those groups containing 1 to 4 carbon atoms being preferred.

When R2 represents a hydrogen atom, the new compounds may be used in the form of physiologically tolerable water-soluble salts thereof with inorganic or organic bases.

For salt formation there come into consideration inorganic and organic bases of the type that are customarily used by the expert in the art.

As bases that are preferably used in a known manner for salt formation, there come into consideration, for example, potassium hydroxide, sodium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, glucamine, N-methylglucamine, Ν,Ν-dimethylglucamine, ethanol amine, diethanolamine, morpholine, N-methylmorpholine and tris-(hydroxymethyl) methylamine.

From United Kingdom Patent Specification No. 1,357,449 it has been known that 2,3-dihydrofuro [2,3-g] quinoline-7-carboxylic acids exhibit good inhibiting values against gram-positive and gram-negative bacteria and are thus suitable as urinary tract therapeutical agents. Compounds for this indication must exhibit an adequate elimination via the urine, because the dosage depends on this. Only with an increase in the urine level can the administration of an active substance be effected in a lower dosage.

It has now been found that the new compounds of the general formula I coupled with a good inhibiting action against gram-positive and gramnegative bacteria exhibit as compared, for example, with 5-ethyl-2,3 5,7-tetrahydro-8-oxofuro [2,3-g] quinoline-7-carboxylic acid (of United Kingdom Patent Specification No. 1,357,499), an increased urine elimination, as is shown in the following Table by way of example with reference to the compounds of Example 2 and Example 4 as compared with 5,ethyl-2,3,5,8-tetrahydro-8-oxo-furo fe,3-gJ quinoline-7-carboxylic acid. The numerical values give the percentage content of an - 3 administered dose which is eliminated in the urine during the course of 6 hours in the case of rats at a dosage of 100 mg/kg per os.

Compound 5-Ethy1-2,3,5,8-tetrahvdro-8-oxo-furo|2,3-<0 quinoline-7carboxyiic acid 8-0xo-5-(1-propenyl)2,3,5,8-tetrahydrofuro £2,3-gJquinoline7-carboxylic acid (Example 2) 8-oxo-2,3,5,8-tetrahydro-5-vinyl-furo£2,3-gJ quinoline-7carboxylic acid (Example 4) Elimination (2) 0.48’/ 2.1/ 3.4/ The new compounds may be administered in the pharmaceutically usual forms of application, for example tablets, dragees, capsules, pills, solutions and suspensions.

The present invention also provides a process for the manufacture of a compound of the general formula I, or a physiologically tolerable salt with an inorganic or organic base of such a compound in which Rz represents in which Rz has the meaning given above, is reacted in the presence of an inorganic base with a compound of the general formula RX in which R has the meaning given above for Ri or represents an alkyl group containing 2 to 6 carbon atoms which may be straight chained or branched and which is substituted by 1 or 2 substituents selected from halogen atoms, hydroxyl : groups, acyloxy groups containing 1 to 6 carbon atoms, benzoyloxy groups, alkane-sulphonyloxy groups containing 1 to 4 carbon atoms in the alkane part and aryl-sulphony!oxy groups (especially benzene-sulphonyloxy groups) which _ 4 .. 4325θ may be substituted in the aryl part by one of more substituents selected from halogen atoms and alkyl groups containing 1 to 4 carbon atoms, and X represents a halogen atom, an alkane-sulphonyloxy group containing 1 5 to 4 carbon atoms in the alkane part or an aryl-sulphonyloxy group (especially a benzene-sulphonyloxy group) which may be substituted in the aryl part by one or more substituents selected from halogen atoms and alkyl groups containing 1 to 4 carbon atoms, and, when R represents a substituted alkyl group, the substituent(s) on this group is/are split off to form an unsaturated aliphatic hydrocarbon group, and then, if desired, in any order of succession, in the resulting compound any free carboxyl group is esterified to form an esterified carboxyl group of the formula -C00R2, in which R2 represents a saturated or unsaturated aliphatic hydrocarbon group containing up to 6 carbon atoms, and/or any esterified carboxyl group is hydrolysed and/or a carbonto-carbon multiple bond in the group represented by Ri is rearranged and/ or, when R2 represents a hydrogen atom, the resulting compound is converted into a physiologically tolerable salt thereof with an inorganic or organic base.

When R represents a straight chained or branched C2-C6-alkyl group containing 1 or 2 substituents that is/are split off with the formation of multiple bond(s), the alkyl group may have one of the meanings given above for straight chained or branched alkyl groups (excluding of course a methyl group). As substituents there come into consideration the halogen atoms fluorine, chlorine, bromine and iodine, fluorine, chlorine and bromine being especially preferred, hydroxyl groups, the acyloxy groups formyloxy, aeetoxy, propionyloxy, butyryloxy,pentanoyloxyand - 5 hexanoyloxy, acyloxy groups containing 1 to 4 carbon atoms being especially preferred, alkane-sulphonyloxy groups, for example methaneand ethane-sulphonyToxy groups, the methane-sulphonyloxy groups being preferred, ortho-, meta- and para-halogenobenzene-sulphonyloxy groups, the para-positioned halogenobenzene-sulphony!oxy groups being especially preferred, (and as the halogen substituents fluorine, chlorine, bromine and iodine, the halogens chlorine and bromine being especially preferred), and ortho-, meta- and para-alkylbenzene-sulphonyloxy groups, the parapositioned alkylbenzene-sulphonyloxy groups being especially preferred, (and as the alkyl substituents methyl, ethyl, propyl and butyl, those containing 1 to 2 carbon atoms having precedence). As to the number of It substituents, one substituent on the alkyl group represented by R is preferred.

The symbol X in the compound of the general formula RX may represent the halogen atom fluorine, chlorine, bromine or iodine, fluorine, bromine or iodine being preferred, an alkanesulphony!oxy group with alkane having the meaning methane or ethane, methane being preferred, or an arylsulphonyloxy group with aryl having the meaning, for example, phenyl, ortho-, meta- or para-alkylphenyl (alkyl = methyl or ethyl), ortho-, meta-or para-ha1ogenophenyl or naphthyl.

The alkylation in accordance with the process of the present invention is carried out in an alkaline medium, preferable in water or in an organic solvent, for example alcohol, dimethyl sulphoxide, dioxan or tetrahydrofuran, or a mixture thereof with water, at a temperature within the range of from 0 to 150°C, preferably from 0 to 100°C, for a reaction period of 0.5 hour to 5 days. As an alkaline medium there is used, for example, 1 to 10 equivalents of an alkali, preferably - 6 sodium hydroxide or potassium hydroxide, calculated on the alkylating agent used, especially 2 to 6 equivalents, in an aqueous alcohol or dimethyl sulphoxide.

The N-alkylation may be carried out with an alkylating agent of the general formula RX, in which R is present in the meaning finally desired for the symbol Ri in the general formula I, or also-which is advantageous for experimental reasons (for example when Ri represents a vinyl group) - carried out with an alkylating agent of the general formula RX, in which R represents an alkyl group that is substituted by a group that can easily be split off with the formation of the finally desired unsaturated carbon-to-carbon bond. Starting from such substituted RX-alkylating agents the splitting off generally takes place spontaneously under the alkylating conditions to form the desired end products of the general formula Γ. If the substituents present in the group represented by R11 do not split off simultaneously under the conditions of the alkylation, the subsequent splitting off may be carried out in a known manner with a basic reagent, for example NaOH, KOH, K-tert.-butylate, NaH, K2CO3. pyidine or another amine, in a solvent, for example water, alcohol, dimethylformamide or dimethyl sulphoxide, at a temperature within the range of from 0 to 150°C, preferably from 20 to 100°C, during the course of 0.5.to 10 hours, preferably 0.5.to 5 hours.

When the primary product of the process of the present invention does not yet contain the unsaturated carbon-to-carbon bond in the finally desired position in the group represented by Rx, it can be shifted by a method generally known to the expert for such rearrangement reactions. - 7 The reaction can be carried out under alkaline or also acid reaction conditions. As basic rearrangement catalysts there come into consideration, for example, alkalies, for example NaOH, KOH or K-tert.butylate, and as an acid catalyst, for example, trifluoroacetic acid.

The basic rearrangement is preferable. It is carried out, for example, at a temperature within the range of from 0 to 180°C, preferably from 0 to 130°C, during the course of 0.5 to 24 hours, preferably 2 to 4 hours, with 3N to 7N-NaOH or KOH in a solvent, for example water, ethylene glycol or dimethylformamide.

The -COOR,, group in the 7-position in the product of the process of the present invention may be a free or esterified carboxy! group. When Rg represents a hydrogen atom in the starting compound, esterification of the free carboxyl group may also take place simultaneously under the alkylating conditions, especially when R in the alkylating agent has the same meaning as R-j.

When -COORg in the starting compound is an esterified carboxyl group, the stability of this ester group depends on the conditions of the alkylating and/or substituent-splitting off reaction(s). If these reactions are carried out at an especially high reaction temperature, the ester group is wholly or at least partially hydrolysed. Depending on the finally desired meaning of Rg, by a method known per se a free carboxyl group may be esterified or re-esterified and art esterified carboxyl group may be hydrolysed.

Salt formation may be carried out in a manner known per se, for example, with a suitable amount of a 1-hormal solution of the appropriate inorgahic or organic base, and the‘solution so obtained is evaporated,and the - 8 4 3 2 5 6 residue remaining behind is recrystallized, for example, from an alcohol/ water mixture (5-9:5-1).

Usually the reaction products areobtained, owing to the multiple bonds in R-| and optionally also in R2, in the form of their cis/trans-isomeric mixtures, which may be separated in the usual manner into the cis-and trans-forms, for example, by fractional crystallization or chromatography.

As stated above, the new compounds of the present invention may be administered in the usual pharmaceutical forms of application, for example tablets, dragees, capsules, pills, solutions and suspensions.

The present invention accordingly further provides a pharmaceutical preparation which comprises a compound of the present invention, in admixture or conjuction with a pharmaceutically suitable carrier.

The new compounds may be used in combination with the additives normally used in galenical pharmacy, for example, for making preparations active against infections of the urinary tract.

The use of the new compounds may be carried out by means of the usual pharmaceutical forms of application. The compounds of the invention are especially suitable for oral administration; thus, the pharmaceutical preparations of the present invention may be in a form suitable for oral administration, for example as tablets, dragees, capsules, pills, solutions or suspensions. Tablets contain, for example, 0.1 to 1 gram of active substance and 0.1 to 5 grams of a pharmacologically inert auxiliary substance. As auxiliary substances there are used, for example, for tablets, lactose, starches, talcum, gelatine and magnesium stearate. - 9 The compounds of the present invention can be used in the field both of human and veterinary medicine.

The new active substances are used for human beings in quantities between 0.1 to 4.0 grams per patient per day.

The present invention accordingly also provides a method for the treatment of a urinary traGt infections wherein a compound of the present invention is administered to a living being. A living being is understood herein to exclude a human being.

Example 1 -Allyl-8-oxo-2s3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid. (a) 5-Allyl-8-oxo-2,335s8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid allyl ester. 3.8 Grams of pulverized sodium hydroxide were suspended in 27 ml of dimethyl sulphoxides then 3.1 grams of 8-hydroxy-2,3-dihydro-furo [2,3-g] quinoline-7-carboxylic acid were introduced, and the whole was stirred for 10 minutes at room temperature. Then 5.67 ml of allyl bromide were added, and the mixture was stirred for 2 hours at room temperature, and then poured into water. The solid product was filtered off and recrystallized from ethanol to yield the compound identified in the sub-heading above. Melting point: !00°C. Yield: 2.5 grams. (b) 5-Allyl-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid. 1.0 Gram of 5-allyl-8-oxo-2,3,5,8"tetrahydro-furo [2,3,-tj] quinoline7~carboxylic acid allyl ester was boiled under reflux for 10 minutes - 10 43256 with 10 ml of a 2N sodium hydroxide solution. The solution was filtered and acidified. The precipitated product was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 264-279°C. Yield: 0.55 gram.

Example 2 8-0xo-5-(l-propenyl)-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7carboxylic acid. 500 mg of 5-allyl-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid were heated in 5 ml of a 5N sodium hydroxide solution and 2.5 ml of ethylene glycol for 3 hours at 130°C. Water and concentrated hydrochloric acid were added, and the precipitated material was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 263°C.

Yield 0.30 gram.

Example 3 The sodium salt of 8-oxo-5-(l-propenyl)-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid. 0.30 Gram of 8-oxo-5-(l-propenyl)-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid was dissolved in 1.1 ml of a IN sodium hydroxide solution. The mixture was evaporated and the residue was recrystallized from ispropanol/water 8:2 to yield the compound identified in the heading above. Melting point: 235°C. Yield: 0.20 grams.

Example 4 8-0xo-2,3,5,8-tetrahydro-5-vinyl-furo [2,3-g] quinoline-7-carboxylic acid. - 11 13256 (a) 6.0 Grams of pulverized sodium hydroxide were suspended in 45 ml of dimethyl sulphoxide, 5.0 grams of 8-hydroxy-2.3-dihydro-furo [2,3-gJ quinoline-7-carboxylic acid were introduced, and the whole was stirred for 10 minutes at room temperature. 8.2. grams of l-bromo-2-fluoroethane were added, and then the mixture was stirred for 2 hours. The mixture was poured into water and acidified with concentrated hydrochloric acid. The resulting solid product was chromatographed over 200 grams of silica gel with dioxan/conc. NH^OH/water 8:1:2, and the resulting purified substance was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 300-304°C (with decomposition). Yield: 0.3 gram. (b) 2.8 Grams of pulverized sodium hydroxide were suspended in 20 ml of dimethyl sulphoxide, 2.3 grams of 8-hydroxy-2,3-furo [2,3-g] quinoline7-carboxylic acid were introduced, and the whole was stirred for 10 minutes at room temperature. 2.6 ml of 1,2-dibromomethane were added, and the mixture was stirred for 24 hours at room temperature. The mixture was poured into water and acidified with concentrated hydrochloric acid. The resulting solid product was chromatographed over silica gel with dioxan/conc. NH^OH/water 8:12, and the purified substance was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 300-304°C (with decomposition). Yield: 0.04 gram. (c) 2.3 Grams of 8-hydroxy-2,3-dihydro-furo 2,3-g quino1ine-7carboxylic acid were added to a mixture of 2.04 grams of potassium hydroxide, 14.8 ml of water, 46 ml of ethanol and 7.5 grams of 1,2bromofluorethane, and the whole was boiled under reflux for 5 days.

The resulting solid product was filtered off and chromatographed over 200 - 12 43256 grams of silica gel with dioxan/cone.NH^OH/water 8:12, and was then recrystallized from ethanol. 0.36 Gram of 5-{2-fluoroethyl)8-oxo-2,3,5,8;tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid was obtained with a decomposition point of 308-314°C. 0.36 Gram of 5-(2-fluorethyl)j8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7- carboxylic acid was introduced into a mixture of 4.8 grams of sodium hydroxide and 3.5 ml of dimethyl sulphoxide, and the whole was stirred for 2 hours at 25°C. The mixture was then poured into water, and acidified with concentrated hydrochloric acid, and the resulting solid product was chromatographed over silica gel with dioxan/conc.NH^OH/water 8:12. 0.20 Gram of 8-oxo-2,3,5,8-tetrahydro-5-vinyl-furo [2,3-g] quinoline-7-carboxylic acid melting at 300-304°C (with decomposition) was obtained.

Example 5 8- oxo-5-propargyl-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7carboxylic acid. 2.31 Grams of 8-hydroxy-2,3-dihydro-furo [2,3-g] quinoline-7-carboxylic acid and 4.7 ml of 3-bromopropyne were boiled under reflux for 5 days in solution of 1.96 grams of potassium hydroxide in 14.2 ml of water and 40 ml of ethanol. The product that crystallized out after cooling was recrystallized from acetic acid to yield the compound identified in the heading above. Melting point: 308-310°C. Yield 1.7 grams.

Example 6 8-0xo-5-propadienyl-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7carboxylic acid. (a) 0.54 Gram of 8-oxo-5-propargyl-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid was introduced into a suspension of 0.56 gram of pulverised potassium hydroxide and - 13 43256 Π ml of dimethylformamide at 0°C. The mixture was stirred for 2 hours at 0°C, poured into water, and acidified with hydrochloric acid, and the resulting solid product was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 257-261°C. Yield: 0.16 gram. (b) 0.20 Gram of 8-oxo-5-propargyl-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxy!ic acid was stirred in 10 ml of trifluoroacetic acid for 20 hours at room temperature, and the mixture was poured into water, and the resulting solid product was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 257-261°C. Yield: 0.10 gram.

Example 7 -(2-Butenyl)-B-oxo-2,3,5,8-tetrahydro-furo [2,3-g] qui noli ne-7carboxylic acid. (a) 5-(2-Butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid 2-butenyl ester. 2.5 Grams of 8-hydroxy-2,3-dihydro-furo [2,3-g] quinoline-7carboxylic acid were introduced at room temperature into a suspension of 3.0 grams of sodium hydroxide in 21.8 ml of dimethyl sulphoxide, and then 4.4 grams of crotyl bromide were added. The mixture was stirred for 2 hours at room temperature, and poured into water, and the resulting solid product was recrystallized from ethanol to yield the compound identified in the sub-heading above. Melting point: m°C. Yield: 0.85 gram. (b) 5-(2-Butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid. - 14 ^3256 0.75 Gram of 5-(2-butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid 2-butenyl ester was boiled under reflux in 10 ml of a 2N sodium hydroxide solution for 10 minutes. The mixture was filtered, and acidified with hydrochloric acid, and the resulting solid product was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 276-286°C. Yield 0.43 gram.

Example 8 -(1-Butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7carboxylic acid. 0.30 Gram of 5-(2-butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid was heated in 3 ml of a 5N sodium hydroxide solution and 1.5 ml of ethylene glycol for 4 hours at 130°C. The mixture was diluted with some water, and acidified with hydrochloric acid, and the resulting solid product was recrystallized from dimethyl sulphoxide/water to yield the compound identified in the heading above. Melting point: 27O-271°C.

Yield: 0.11 gram.

Example 9 -(2-Methyl-2-propenyl) - 8 -oxo-2,3,5,8-tetrahydro-furo [2,3-g] -quinoline-7-carboxylic acid. (a) 5-(2-Methyl-2-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid (2-methyl-2-propenyl) ester. 2.3 Grams of 8-hydroxy-2,3-dihydro-furo [2,3-g] quinoline-7-carboxylic acid were introduced into a suspension of 3.0 grams of sodium hydroxide and 20 ml of dimethyl sulphoxide, and then 6.0 - 15 43350 grams of methallyl bromide were added. The mixture was stirred for 2 hours at room temperature, and poured into water, and the resulting solid product was recrystallized from ethanol to yield the compound identified in the sub-heading above. Melting point: 169-172°C. Yield: 0.80 gram. (b) 5-(2-Methyl-2-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2, 3-g] quinoline-7-carboxylic acid. 0.75Qram of 5-(2-methyl-2-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid (2-methyl-2-propenyl) ester vias suspended in 10 ml of a 2N aqueous sodium hydroxide solution and boiled under reflux for 10 minutes. The mixture was filtered, and acidified with hydrochloric acid, and the resulting solid product was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 265-272°C. Yield: 0.30 gram.

Example 10 - (2-Methyl-l-propenyl.)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid. 0.25 Gram of 5-(2-methyl-2-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinolipe-7-carboxylic acid was heated in 3 ml of a 5N sodium hydroxide solution and 1.5. ml of ethylene glycol for 3 hours at 130°C. The mixture was diluted with some water, and acidified with hydrochloric acid, and the resulting solid product was recrystallized from dimethylformamide to yield the compound identified in the heading above. Melting point: 293-295°C. Yield: 0.16 gram. - 16 EXAMPLE 11 The sodium salt of 8-oxo-2,3,5,8-tetrahydro-5-vinyl-furo [2,3-g] quinoline-7-carboxylic acid. 0.23 Gram of 8-oxo-2,3,5,8-tetrahydro-5-vinyl-furo [2,3-g] quinoline 7-carboxylic acid was dissolved in 0.9 ml of IN sodium hydroxide solution. The mixture was concentrated in vacuo, and the residue was recrystallized from isopropanol/water 8:2 to yield the compound identified in the heading above. Melting point: 253-257°C. Yield: 0.13 gram.

Claims

1. WHAT HE CLAIM IS:1. A quinoline carboxylic acid derivative of the general formula 1 0 in which R x represents an unsaturated aliphatic hydrocarbon group containing up to 6 carbon atoms, and R 2 represents a hydrogen atom or a saturated or unsaturated aliphatic hydrocarbon group containing up to 6 carbon atoms.

2. A physiologically tolerable salt with an inorganic or organic base of a compound as claimed in claim 1 in which R 2 represents a hydrogen atom.

3. A compound as claimed in claim 1, wherein R x represents an unsaturated aliphatic hydrocarbon group containing up to 4 carbon atoms.

4. A compound as claimed in claim T or 3, wherein R 2 represents a saturated or unsaturated aliphatic hydrocarbon group containing up to 4 carbon atoms.

5. A physiologically tolerable salt with an inorganic or organic base of a compound as claimed in claim 3 in which R 2 represents a hydrogen atom.

6. 5-Allyl-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7carboxylic acid allyl ester. - 18 43256

7. 5-Allyl-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7carboxylic acid.

8. 8-0xo-5-(l-propenyl)-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid. 5

9. The sodium salt of 8-oxo-5-(l-propenyl)-2,3,5,8-tetrahydrofuro- [2,3-g] quinoline-7-carboxylic acid.

10. 8-0xo-2,3,5,8-tetrahydro-5-vinyl-furo [2,3-gj quinoline-7carboxylic acid.

11. 8-0xo-5-propargyl-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-710 carboxylic acid.

12. 8-0xo-propadienyl-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid.

13. 5-(2-Butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid 2-butenyl ester.

14. 15 14. 5-(2-Butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid. 15. 5-(l-Butenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline7-carboxylic acid.

15. 16. 5-(2-Methyl-2-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] 20 quinoline-7-carboxylic acid(2-roethyl-2-propenyl) ester.

16. 17. 5-(2-methyl-2-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [*2,3-g] quinoline-7-carboxylic acid.

17. 18. 5-(2-Methyl-l-propenyl)-8-oxo-2,3,5,8-tetrahydro-furo [2,3-g] quinoline-7-carboxylic acid. - 19 43256

18. 19. The sodium salt of 8-oxo-2,3,5,8-tetrahydro-5-vinyl-furo [2,3-g] quinoline-7-carboxyTic acid.

19. 20. A pharmaceutical preparation which comprises a compound as claimed in any one of claims 1, 3 and 4, in admixture or conjunction with a pharmaceutically suitable carrier.

20. 21. A pharmaceutical preparation which comprises a salt as claimed in claim 2 or 5, in admixture or conjunction with a pharmaceutically suitable carrier.

21. 22. A pharmaceutical preparation which comprises the compound claimed in any one of claims 6 to 8 and 10 to 18, in admixture or conjunction with a pharmaceutically suitable carrier.

22. 23. A pharmaceutical preparation which comprises the salt claimed in claim 9 or T9, in admixture or conjunction with a pharmaceutically suitable carrier.

23. 24. A preparation as claimed in any one of claims 20 to 23, which is in a form suitable for oral administration,

24. 25. A preparation as claimed in claim 24, which is in the form of a tablet, dragee, capsule, pill, solution or suspension.

25. 26. A preparation as claimed in claim 24, which is in the form of a tablet containing 0.1 to 1 gram of active substance.

26. 27. A method for the treatment of a urinary tract infection, wherein a compound as claimed in any one of. claims 1, 3 and 4 is administered to a living being, as hereinbefore defined. -2043256

27. 28. A method for the treatment of a urinary tract infection, wherein a salt as claimed in claim 2 or 5 is administered to a living being, as hereinbefore defined.

28. 29. A method for the treatment of a urinary tract infection, 5 wherein the compound claimed in any one of claims 6 to 8 and 10 to 18 is administered to a living being, as hereinbefore defined.

29. 30. A method for the treatment of a urinary tract infection, wherein the salt claimed in claim 9 or 19 is administered to a living being, as hereinbefore defined.

30.

31. A process for the manufacture of a quinoline carboxylic acid derivative of the general formula I given in claim 1, in which and R 2 have the meanings given in claim 1, or a physiologically tolerable salt with an inorganic base of such a compound of the general formula II, which may be in the tautomeric form of the general formula II A or II B, in which R 2 has the meaning given above, is reacted in the presence of an inorganic Dase with a compound of the general formula RX in which R has the meaning given above for or represents an alkyl group containing 2 to 6 carbon atoms which is substituted by 1 or 2 substituents selected from halogen atoms, hydroxyl groups, acyloxy groups containing 1 to 6 carbon atoms, benzyloxy groups, alkanesulphonyl oxy groups containing 1 to 4 carbon atoms in the alkane - 21 43256 part and aryl-sulphony!oxy groups, which may be substituted in the aryl part by one or more substituents selected from halogen atoms and alkyl groups containing 1 to 4 carbon atoms, and X represents a halogen atom, an alkane-sulphonyloxy group containing 1 to 4 carbon atoms in the alkane part of an aryl-sulphonyloxy group which may be substituted in the aryl part by one or more substituents selected from halogen atoms and alkyl groups containing 1 to 4 carbon atoms, and, when R B represents a substituted alkyl group, the substituent(s) on this group is/are split off to form an unsaturated aliphatic hydrocarbon group, and then, if desired, in any order of succession, in the resulting compound any free carboxyl group is esterified to form an esterified carboxyl group of the formula-C00R 2 in which R 2 represents a saturated or unsaturated aliphatic hydrocarbon group containing up to 6 carbon atoms, and/or any esterified carboxyl group is hydrolysed and/or a carbon-to-carbon multiple bond in the group represented by R^ is rearranged and/or, when R 2 represents a hydrogen atom, the resulting compound is converted into a physiologically tolerable salt thereof with an inorganic or organic base,

32. A process as claimed in claim 31, wherein the reaction with the compound of the general formula RX is carried out at a temperature within the range of from 0 to 1DO°C.

33. A process as claimed in claim 31, conducted substantially as described herein.

34. A process as claimed in claim 31, conducted substantially as described in any one of Examples 1 to 11 herein.