Quinolone derivatives and salts thereof, preparation process es thereof, and antibacterial agents containing the same

Abstract: Antibacterial quinolone derivatives represented by the following formula and salts thereof are disclosed. wherein R¹ means a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted lower alkenyl group or a sub­ stituted or unsubstituted phenyl group, R² denotes a hydrogen atom or a carboxyl-protecting group, R³ represents a hydrogen or halogen atom or an amino, mono- or di-(lower alkyl)amino, hydroxyl or lower alkoxyl group, X is a hydrogen or halogen atom, Y means a nitrogen atom or a group C-R⁴ in which R⁴ is a hydrogen or halogen atom or a lower alkyl or lower alkoxyl group or is a group which forms a ring together with R¹ (i.e., the asterisked carbon atoms are linked to the N(1) atom of the quinolone skeleton), and A denotes a specific N-containing group. Preparation pro­ cesses of the quinolone derivatives and antibacterial agents containing the same are also disclosed.

Description: The present invention relates to novel quinolone derivatives and salts thereof, which are useful as synthetic antibacterial agents, to preparation processes thereof and also to antibacterial agents containing the same. Many of compounds having pyridonecarboxylic acid as a basic skeleton are known to be useful as synthetic antibacterial agents for their excellent antibacterial activities and broad antibacterial spectrum. Among these, norfloxacin [Japanese Patent Application Laid-Open (Kokai) No. 141286/1978], enoxacin [Japanese Patent Application Laid-Open (Kokai) No. 31042/1980], ofloxacin [Japanese Patent Application Laid-Open (Kokai) No. 46986/1982], ciprofloxacin [Japanese Patent Application Laid-Open (Kokai) No. 76667/1983] and the like have already found wide-spread clinical utility as therapeutic agents for infectious diseases. Principal features of these compounds reside in that the quinoline skeleton or naphthyridine skeleton is substituted on position 6 with a fluorine atom and a secondary amino group is contained at position 7. In particular, the introduction of a piperazine ring or pyrrolidine ring to position 7 is considered to play a significant role in the enhancement of antibacterial activities. Chemical Abstracts 106, 1987, p. 595, no. 67134x describes the use of 4-oxoquinoline-3-carboxylic acid derivatives as antibacterial agents. EP-A-339 406 relates to quinoline-3-carboxylic acid derivatives, processes for preparing the same and their use as antibacterial agents. However, both of the last-mentioned prior art documents fail to describe heterocyclic rings to be directly bonded to the position 7 of the 4-oxoquinolone-3-carboxylic acid skeleton. However, these compounds are still not fully satisfactory in antibacterial activities, intestinal absorption, metabolic stability, or side effects, etc. There is an outstanding desire for the preparation of novel compounds which can satisfy these requirements. With the foregoing in view, the present inventors have conducted an extensive investigation with a view toward providing clinically excellent synthetic antibacterial agents improved in the requirements described above. As a result, it has been found that compounds with a specific heterocyclic ring introduced on position 7 of the quinoline or naphthylidine skeleton can show superb antibacterial activities against gram-negative and gram-positive bacteria and can also satisfy other requirements and are hence useful as synthetic antibacterial agents, leading to the completion of the present invention. The present invention therefore provides quinolone derivatives represented by the below-described formula [I] and salts thereof, their preparation processes and antibacterial agents containing them. The compounds [I] and their salts according to the present invention are extremely valuable as antibacterial agents. They can therefore be used as drugs for human being and animals and also as drugs for fish diseases, agricultural chemicals and food preservatives. In the present invention, the term "C₁-C₇" or "C₃-C₇" employed in the definition for some substituent groups in formula [I] means that the group referred to has 1-7, preferably 1-5 carbon atoms when the substituent group is a linear or branched group but has 3-7 carbon atoms when the substituent group is a cyclic group. Illustrative of the C₁-C₇ alkyl group represented by R¹ includes methyl, ethyl, isopropyl, t-butyl and t-pentyl. Examples of the substituted or unsubstituted C₁-C₇ alkyl group include those substituted by one or more halogen atoms or hydroxyl groups. Specific examples include 2-fluoroethyl, 2-hydroxyethyl and difluoromethyl. Exemplary substituted or unsubstituted alkenyl groups include vinyl, isopropenyl, allyl and 2-butenyl. Exemplary substituted or unsubstituted cycloalkyl groups include cyclopropyl, 1-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Illustrative of the substituted or unsubstituted phenyl group include phenyl or phenyl groups substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro groups. Specific examples include phenyl, 2-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 2-fluoro-4-hydroxyphenyl, 4-methylphenyl, 4-acetyloxyphenyl, 4-aminophenyl and 4-nitrophenyl. Specific examples of the carboxyl-protecting group R² include those removable upon treatment under mild conditions, such as hydrolysis or catalytic reduction, such as C₁-C₇ alkyl groups (e.g., methyl, ethyl, n-propyl, t-butyl, etc.), benzyl, and phenyl or phenyl groups substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro groups; and those readily removable in vivo, such as C₁-C₇ alkanoyloxy- C₁-C₇ alkyl groups (e.g., acetoxymethyl, pivaloyloxymethyl, etc.), C₁-C₇ alkoxycarbonyloxy-C₁-C₇ alkyl groups (e.g., methoxycarbonyloxymethyl, 1-ethoxycarbonyloxyethyl, etc.), C₁-C₇ alkoxymethyl groups (e.g., methoxymethyl, etc.), lactonyl groups (phthalidyl, etc.), di(C₁-C₇ alkyl)amino- C₁-C₇ alkyl groups (e.g., 1-dimethylaminoethyl, etc.), (5-methyl-2-oxol-4-yl)methyl group, and the like. Illustrative of the halogen atom represented by R³ include F, Cl and Br, with F and cl being preferred. Examples of the C₁-C₇ alkoxyl group represented by R³ include methoxy, ethoxy and isopropyloxy. Examples of the mono- or di-(C₁-C₇ alkyl)amino group represented by R³ include methylamino, ethylamino and dimethylamino. Exemplary halogen atoms indicated by X include those exemplified as R³, preferably F and Cl, and more preferably F. Illustrative of the halogen atom represented by R⁴ when Y is C-R⁴ include F and Br, with F being preferred. Exemplary C₁-C₇ alkyl groups represented by R⁴ include linear or branched alkyl groups having 1-4 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl and t-butyl. Illustrative of the C₁-C₇ alkoxyl group indicated by R⁴ include those referred to above as R³. A denotes the following substituted 3-oxazolidinyl groups: 5-methyl-3-oxazolidinyl, 5-ethyl-3-oxazolidinyl, 5-propyl-3-oxazolidinyl, 5-hydroxymethyl-3-oxazolidinyl, 5-(1-hydroxyethyl)-3-oxazolidinyl, 5-(2-hydroxyethyl)-3-oxazolidinyl, 5-methoxymethyl-3-oxazolidinyl, 5-ethoxymethyl-3-oxazolidinyl, 5-aminomethyl-3-oxazolidinyl, 5-(1-aminoethyl-3-oxazolidinyl, 5-(2-aminoethyl)-3-oxazolidinyl, 5-(1-aminopropyl)-3-oxazolidinyl, 5-(2-aminopropyl)-3-oxazolidinyl, 5-(3-aminopropyl)-3-oxazolidinyl, 5-methylaminomethyl-3-oxazolidinyl, 5-dimethylaminomethyl-3-oxazolidinyl, 5-(1-methylaminoethyl)-3-oxazolidinyl, 5-(2-methylaminoethyl)-3-oxazolidinyl, 5-(1-dimethylaminoethyl)-3-oxazolidinyl, 5-(2-dimethylaminoethyl)-3-oxazolidinyl, 5-ethylmethylaminomethyl-3-oxazolidinyl, 5-diethylaminomethyl-3-oxazolidinyl, 4-methyl-3-oxazolidinyl, 2-methyl-3-oxazolidinyl, 4-methyl-5-hydroxymethyl-3-oxazolidinyl, 4-methyl-5-dimethylaminomethyl-3-oxazolidinyl, 2-methyl-5-aminomethyl-3-oxazolidinyl, and 2-methyl-5-ethylmethylaminomethyl-3-oxazolidinyl or substituted (tetrahydro-1,3-oxazin)-3-yl groups; 6-methyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethyl(tetrahydro-1,3-oxazin)-3-yl, 6-propyl-(tetrahydro-1,3-oxazin)-3-yl, 6-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl , 6-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-propyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-hydroxyethyl)-tetrahydro-1,3-oxazin)-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(ethylmethylaminomethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxy-(tetrahydro-1,3-oxazin)-3-yl, 5-methoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-amino-(tetrahydro-1,3-oxazin)-3-yl, 5-methylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylmethylamino(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-6-methylamiomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-5-amino-(tetrahydro-1,3-oxazin)-3-yl, and 4-methyl-6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl. The compounds [I] of the present invention can be converted into both acid addition salts and base addition salts. Exemplary acid addition salts include (a) the salts with mineral acids such as hydrochloric acid and sulfuric acid, (b) the salts with organic carboxylic acids such as formic acid, citric acid, trichloroacetic acid and trifluoroacetic acid, and (c) the salts with sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, mesitylenesulfonic acid and naphthalenesulfonic acid. On the other hand, illustrative base addition salts include (a) the salts with alkali metals such as sodium and potassium, (b) the salts with alkaline earth metals such as calcium and magnesium, (c) the ammonium salt, (d) the salts with nitrogen-containing organic bases such as trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, procaine, dibenzylamine, N-benzyl-β-phenethylamine, 1-ephenamine and N,N'-dibenzylethylenediamine. The compounds [I] of the present invention may be not only in unsolvated forms but also in hydrated or solvated forms. The present invention therefore embraces the compounds [I] in any crystalline forms and their hydrated and solvated products. Further, the compounds [I] of the present invention include those containing an asymmetric carbon atom in a substituent group on position 7. They can exist as optically active substances. These optically active substances are also embraced in the compounds of the present invention. The compounds [I] of the present invention also include those containing two asymmetric carbon atoms in a substituent group on position 7. They can exist as different stereoisomers (cis-form, trans-form). These stereoisomers are also included in the compounds of the present invention. Each compound [I] of the present invention can be prepared by a process suited for the types of its substituent groups. Preferred preparation processes are as follows: [Process 1] wherein R¹, R², R³, X, Y and A have the same meanings as defined above, X¹ means a halogen atom, and A' denotes the same group as A or when the group A contains an amino, imino, hydroxyl or carboxyl group, the amino, imino, hydroxyl or carboxyl group may be protected. Namely, the compound [I] of the present invention can be prepared by condensing the compound [II] and the compound [III] and if necessary, removing the protecting group and/or conducting hydrolysis. The above condensation reaction is conducted in a solvent which does not give influence to the reaction, for example, an aromatic hydrocarbon such as benzene, toluene or xylene, an ether such as diethyl ether, tetrahydrofuran or monoglyme, a dipolar aprotic solvent such as dimethylformamide, dimethylsulfoxide, HMPA or sulfolane, acetonitrile, or pyridine, preferably in the presence of an acid-neutralizing agent, for example, a metal hydride such as sodium hydride or calcium hydride, an alkali metal such as sodium or potassium, an inorganic base such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, or an organic base such as triethylamine, diisopropylethylamine or 1,8-diazabicyclo[5.4.0]undecene (DBU). This reaction proceeds normally at 0-150°C, preferably about 0-110°C and is completed in 10 minutes to 24 hours or so. The compound [III] may be used in at least an equimolar amount, preferably in a molar amount 1-5 times relative to the compound [II]. When the compound [III] employed in the above reaction contains an amino, imino, hydroxyl or carboxyl group in the group A', the compound [III] may preferably be used in a form with such a group being protected, followed by the removal of the protecting group by a method known per se after completion of the reaction. Any protecting group can be used as long as it can be removed without destroying the structure of the compound of the present invention to be formed by the reaction. Protecting groups usually employed in the chemical field of peptides, aminosaccharides and nucleic acids can be used. Exemplary protecting groups for amino and imino groups include acetyl, t-butoxycarbonyl, benzyloxycarbonyl, trifluoroacetyl and benzyl. Illustrative protecting groups for a hydroxyl group include acetyl, benzoyl, benzyl and t-butyldimethylsilyl. Exemplary carboxyl-protecting groups include those exemplified above. When R² is a carboxyl-protecting group in the compound [I] obtained by the above reaction, the compound can be converted by usual hydrolysis, hydrogenolysis or the like into a compound in which R² is a hydrogen atom. The hydrolysis is conducted, for example, in the presence of a basic compound such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, a mineral acid such as hydrochloric acid, sulfuric acid, hydrobromic acid, or an organic sulfonic acid such as p-toluenesulfonic acid; in a solvent, e.g., water, an alcohol such as methanol, ethanol or propanol, an ether such as tetrahydrofuran or dioxane, a ketone such as acetone or methyl ethyl ketone, or an organic acid such as acetic acid or propionic acid, or a mixed solvent thereof. The starting compound [II] can be prepared by the process disclosed in any one of the following publications or by a similar process thereto: 1) J. Med. Chem., 23 , 1358(1980) 2) J. Med. Chem., 27 , 292(1984) 3) J. Med. Chem., 28 , 1558(1985) 4) J. Med. Chem., 30 , 504(1987) 5) J. Med. Chem., 29 , 2363(1986) 6) Liebigs Ann. Chem., 29 (1987) 7) Chem. Pharm. Bull., 34 , 4098(1986) 8) J. Med. Chem., 31 , 503(1988) 9) J. Med. Chem., 30 , 465(1987) 10) Japanese Pat. Appln. Laid-Open (Kokai) No. 47658/1980 11) Japanese Pat. Appln. Laid-Open (Kokai) No. 30964/1981 12) Japanese Pat. Appln. Laid-Open (Kokai) No. 130594/1988 13) Japanese Pat. Appln. Laid-Open (Kokai) No. 145268/1988 14) Japanese Pat. Appln. Laid-Open (Kokai) No. 59263/1987 15) Japanese Pat. Appln. Laid-Open (Kokai) No. 277362/1987 16) Japanese Pat. Appln. Laid-Open (Kokai) No. 145268/1988 17) Japanese Pat. Appln. Laid-Open (Kokai) No. 187459/1987 18) Japanese Pat. Appln. Laid-Open (Kokai) No. 264461/1988 19) Japanese Pat. Appln. Laid-Open (Kokai) No. 226962/1987 20) Japanese Pat. Appln. Laid-Open (Kokai) No. 228063/1987 21) Japanese Pat. Appln. Laid-Open (Kokai) No. 297366/1988 22) Japanese Pat. Appln. Laid-Open (Kokai) No. 28157/1990 [Process 2] Among the compounds represented by the formula [I], those containing a carboxyl-protecting group as R² can be prepared, for example, by the reaction step shown by the following reaction formula (2). wherein R¹, R³, X, Y and A have the same meanings as defined above, R 2a means a carboxyl-protecting group, and X² denotes a halogen atom. The compound [Ib] can be obtained by reacting the halide [IV] with the compound [Ia]. Exemplary solvents usable in the reaction include inert solvents, for example, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as methylene chloride and chloroform, dipolar aprotic solvents such as dimethylformamide and dimethylsulfoxide, and ethers such as diethyl ether and tetrahydrofuran. The reaction temperature generally ranges from room temperature to about 100°C. Preferably, this reaction is carried out in the presence of a basic compounds such as triethylamine, diisopropylethylamine, dicyclohexylamine, DBU, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide. [Process 3] Among the compounds of the present invention represented by the formula [I], those containing C-R⁴ as Y, R⁴ being a C₁-C₇ alkoxy group, can be prepared, for example, by the reaction step shown by the following reaction formula (3). wherein R¹, R², R³, X, A and A' have the same meanings as defined above, X³ means a halogen atom, and R⁹ denotes a lower alkyl group, M represents an alkali or alkaline earth metal atom, and n'' stands for an integer of 1 or 2. Namely, the compound [Id] can be prepared by reacting the metal alkoxide [V] with the compound [Ic]. Exemplary solvents usable in this reaction include those exemplified above under [Process 1]. This reaction proceeds normally at 0-150°C, preferably about 0-110°C and is completed in 10 minutes to 24 hours or so. The compound [V] may be used in at least an equimolar amount, preferably in a molar amount 1-5 times relative to the compound [Ic]. When an amino, imino, hydroxy or carboxyl group exists in the group A in the above reaction, it is preferable to use the compound [Ic] in a form with such a group being protected, followed by the removal of the protecting group by a method known per se after completion of the reaction. When R² is a carboxyl-protecting group in the compound [I] obtained by the above reaction, the compound can be converted by usual hydrolysis or hydrogenolysis into a compound in which R² is a hydrogen atom. The hydrolysis is conducted under similar conditions to those described above under [Process 1]. [Process 4] Among the compounds of the present invention represented by the formula [I], those containing a substituted or unsubstituted 3-oxazolidinyl group or a substituted or unsubstituted (tetrahydro-1,3-oxazin)-3-yl group as A, can be prepared, for example, by the reaction step shown by the following reaction formula (4). wherein R¹, R², R³, X and Y have the same meanings as defined above, X⁴ means a reactive leaving group, R¹² denotes a substituted or unsubstituted ethylene or substituted or unsubstituted propylene group, R¹³ represents a hydrogen atom or a group capable of being converted to a substituted group on the 3-oxazolidinyl or the (tetrahydro1,3-oxazin)-3-yl group as A¹, R¹⁴ is a C₁-C₇ alkyl group, and A¹ means a substituted or unsubstituted 3-oxazolidinyl group or a substituted or unsubstituted (tetrahydro-1,3-oxazin)-3-yl group. Namely, the compound [Ig] of the present invention can be prepared by reacting the compound [VII] with the alkanolamine derivative [VIII] to obtain the compound [IX] and then reacting the dialkoxymethane derivative [X] with the compound [IX]. The reactive quinolone derivative [VII] can be prepared by any one of the processes described in the publications referred to above and the following publications and similar processes thereto. 1) J. Med. Chem., 27 , 1103(1984) 2) Yakugaku Zasshi, 106 , 802(1986) 3) Yakugaku Zasshi, 106 , 795(1986) 4) J. Med. Chem., 29 , 1531(1986) 5) Japanese Pat. Appln. Laid-Open (Kokai) No. 157068/1984 6) Japanese Pat. Appln. Laid-Open (Kokai) No. 212474/1984 7) Japanese Pat. Appln. Laid-open (Kokai) No. 72885/1985 8) Japanese Pat. Appln. Laid-Open (Kokai) No. 260577/1985 9) Japanese Pat. Appln. Laid-Open (Kokai) No. 469/1987 10) Japanese Pat. Appln. Laid-Open (Kokai) No. 490/1987 11) Japanese Pat. Appln. Laid-open (Kokai) No. 26272/1987 12) Japanese Pat. Appln. Laid-Open (Kokai) No. 53987/1987 13) Japanese Pat. Appln. Laid-Open (Kokai) No. 84085/1987 14) Japanese Pat. Appln. Laid-Open (Kokai) No. 155282/1987 15) Japanese Pat. Appln. Laid-Open (Kokai) No. 167768/1987 16) Japanese Pat. Appln. Laid-Open (Kokai) No. 174054/1987 17) Japanese Pat. Appln. Laid-Open (Kokai) No. 175482/1987 18) Japanese Pat. Appln. Laid-Open (Kokai) No. 175484/1987 19) Japanese Pat. Appln. Laid-Open (Kokai) No. 175485/1987 20) Japanese Pat. Appln. Laid-Open (Kokai) No. 187472/1987 21) Japanese Pat. Appln. Laid-Open (Kokai) No. 187459/1987 22) Japanese Pat. Appln. Laid-Open (Kokai) No. 201869/1987 23) Japanese Pat. Appln. Laid-Open (Kokai) No. 205060/1987 24) Japanese Pat. Appln. Laid-Open (Kokai) No. 215572/1987 25) Japanese Pat. Appln. Laid-Open (Kokai) No. 226962/1987 26) Japanese Pat. Appln. Laid-Open (Kokai) No. 228063/1987 27) Japanese Pat. Appln. Laid-Open (Kokai) No. 39880/1988 28) Japanese Pat. Appln. Laid-Open (Kokai) No. 60990/1988 Illustrative of the reactive leaving group designated by X⁴ in the formula [VII] include halogen atoms (e.g., F, I), arylsulfonyl groups (e.g., phenylsulfonyl), and arylsulfonyloxy groups (phenylsulfonyloxy). The condensation reaction between the compound [VII] and the alkanolamine derivative [VIII] can be practiced by reacting them in an inert solvent and if necessary, in the presence of an acid-neutralizing agent, at 20-160°C for several minutes to several tens hours, preferably 10-24 hours. Exemplary inert solvents usable in the above reaction include aromatic hydrocarbons such as benzene, toluene and xylene, alcohols such as methanol and ethanol, tetrahydrofuran, acetonitrile, pyridine, dimethylformamide, dimethylsulfoxide, and N-methylpyrrolidone. Illustrative of the acid-neutralizing agent include sodium carbonate, sodium hydrogencarbonate, potassium carbonate, triethylamine, and 1,8-diazabicyclo[5.4.0]-7-undecene. When the starting compound [VIII] employed in the above reaction contains one or more amino groups which do not take part in the reaction, the starting compound is used in a form with the amino groups being protected. Any protecting groups can be used as long as they can be removed without destroying the structure of the compound of the present invention to be formed by the reaction. Protecting groups usually employed in the chemical field of peptides, aminosaccharides and nucleic acids can be used. The reaction between the compound [IX] and the dialkoxymethane derivative [X] can be practiced by reacting them at 20-160°C under solventless conditions or in a solvent while using an acid catalyst. Any solvent can be used in the reaction as long as it does not impede the reaction. Exemplary solvents include inert solvents, for example, aromatic hydrocarbons such as benzene, toluene and xylene, tetrahydrofuran, acetonitrile, dimethylformamide, and dimethylsulfoxide. Illustrative of the acid catalyst includes mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid and phosphoric acid as well as organic acids such as acetic acid, citric acid and p-toluenesulfonic acid. Of these, p-toluenesulfonic acid is particularly preferred. When the compound [IX] employed in the above reaction contains one or more amino and/or hydroxyl groups which do not take part in the reaction, the compound may be used in a form with the amino and/or hydroxyl groups being protected, followed by the removal of the protecting groups after the completion of the reaction. Any protecting groups can be used as long as they can be removed without destroying the structure of the compound of the present invention to be formed by the reaction. Protecting groups usually employed in the chemical field of peptides, aminosaccharides and nucleic acids can be used. The thus-obtained compounds of the present invention can be isolated and purified by methods known per se in the art. They are obtained in the form of salts, carboxylic acid esters, free carboxylic acids or free amines, depending on the conditions for isolation and purification. However, they can be converted mutually from one of these forms into another one, whereby the compounds of the present invention can be prepared in a desired form. [Action] (1) Antibacterial activities: With respect to certain representative compounds among the compounds [I] of the present invention, their minimum inhibitory concentrations (MIC; µg/mℓ) were measured in accordance with the standard method established by the Japan Society of Chemotherapy [CHEMOTHERAPY, 29 (1), 76-79 (1981)]. The results are summarized in Table 1, in which the compound numbers are as shown in examples. Compound No. Minimum inhibitory concentration (µg/mℓ) E. coli NIH JC-2 (IFO 12734) S. aureus 209 P (IFO 12732) P. aeruginosa (IFO 3445) 5 0.2 0.1 0.78 14 0.2 0.2 1.56 20 0.39 0.2 3.13 6 0.78 0.39 6.25 7 0.2 0.1 0.78 15 0.2 0.1 0.78 16 0.78 0.2 3.13 8 0.2 0.2 1.56 17 0.2 0.2 1.56 22 0.1 0.1 0.78 24 0.39 0.39 3.13 (2) Partition coefficient: Following the method proposed by Akira Tsuji et al. in Antimicrob. Agents Chemother., 32 , 190-194 (1988), 50 mM phosphate buffer (pH 7.4, µ=0.15)/n-octanol partition coefficients were measured. The measurement results of representative compounds are shown in Table 2. Compound No. Partition coefficient 12 0.483 As has been described above, the compounds [I] and their salts according to the present invention are all novel compounds, exhibit extremely high antibacterial activities against gram-negative bacteria and gram-positive bacteria, and have high safety. When the compounds [I] and their salts according to the present invention are used as antibacterial agents, they can be formulated into preparations along with a pharmaceutically-acceptable carrier for parenteral administration such as injection or rectal administration or for oral administration in the form of a solid or a liquid. Preparations of this invention for use as injections can take the form of solutions, suspensions or emulsions in pharmaceutically-acceptable germ-free water or non-aqueous liquid. Exemplary suitable non-aqueous carriers, diluents, solvents and vehicles include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. These preparations can contain one or more auxiliary agents, for example, antiseptics, wetting agents, emulsifiers and dispersants. These formulations can be sterilized, for example, by filtering them through a bacterial filter or by mixing, immediately before use, a sterilizing agent in the form of a germ-free solid composition soluble in sterilized water or one of some other media which can be sterilized and injected. Exemplary solid preparations for oral administration include capsules, tablets, pills, powders, granules, etc. Upon formulation of these solid preparations, the compounds and their salts according to the present invention are generally mixed with at least one inert extender such as sucrose, lactose or starch. One or more materials other than inert extenders, for example, a lubricant such as magnesium stearate can also be incorporated in the preparations upon formulation of the latter in a usual manner. A buffer can also be incorporated in the case of capsules, tablets and pills. Tablets and pills can be applied with an enteric coating. Illustrative liquid preparations includes pharmaceutically-acceptable emulsions, solutions, suspensions, syrups and elixirs, which contain an inert diluent employed commonly by those skilled in the art, for example, water. In addition to such an inert diluent, the liquid preparations can also be added with one or more auxiliary agents, for example, wetting agents, emulsifiers, suspending agents, sweetening agents, seasoning agents and perfumes. Preparations for rectal administration are preferably suppositories which may contain an excipient such as cacao butter or suppository wax in addition to a compound or its salt according to the present invention. The dosage of the compounds [I] and their salts according to the present invention generally ranges from about 0.1 mg/kg to 1,000 mg/kg per day, with about 1-100 mg/kg per day being preferred especially. If desired, this daily dosage can be administered in 2-4 portions. The present invention will hereinafter be described by the following examples. Example 1 Ethyl 1-cyclopropyl-6-fluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate (Compound NO. 1) 1) A mixture of 2.94 g of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 1.83 g of monoethanolamine and 20 mℓ of dimethylformamide was heated at 90-100°C for 1 hour under stirring. The reaction mixture was concentrated to dryness under reduced pressure. To the residue was added 100 mℓ of chloroform, so that the residue was dissolved. The chloroform solution thus obtained was washed successively with 5% acetic acid and saturated saline, dried over anhydrous magnesium sulfate and then concentrated. The residue was recrystallized from a mixed solvent of diethyl ether and ethanol, whereby 3.0 g of ethyl 1-cyclopropyl-6-fluoro-7-(2-hydroxyethylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained. Melting point: 228-230°C. 2) A mixture of 0.67 g of ethyl 1-cyclopropyl-6-fluoro-7-(2-hydroxyethylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 0.08 g of p-toluenesulfonic acid, 2.08 g of diethoxymethane and 20 mℓ of acetonitrile was stirred for 3 hours under reflux. After the reaction mixture was allowed to cool down, 100 mℓ of chloroform was added to the reaction mixture. The resultant mixture was successively washed with 5% aq. sodium carbonate solution and saturated saline, dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by columnchromatography on silica gel, whereby 0.39 g of the title compound was obtained. Melting point: 221-224°C. ¹H-NMR (CDCl₃) δ: 1.12-1.30(m,4H), 1.40(t,3H,J=7.1Hz), 3.39(m,1H), 3.60(t,2H,J=6.0Hz), 4.19(q,2H,J=7.1Hz), 4.19(t,2H,J=6.0Hz), 4.38(d,2H,J=7.1Hz), 6.82(d,1H,J=7.1Hz), 7.98(d,1H,J=13.7Hz), 8.45(s,1H). Example 2 Compound Nos. 2-4 shown in Table 3 were synthesized in a similar manner to Example 1. Example 3 1-Cyclopropyl-6-fluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound No. 5) A mixture of 173 mg of ethyl 1-cyclopropyl-6-fluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 1 mℓ of ethanol and 5 mℓ of a 10% aq. sodium carbonate solution was stirred for 1 hour under reflux. The reaction mixture was allowed to cool down and then acidified with acetic acid. Crystals thus precipitated were collected by filtration, washed with water and ethanol, and then dried, whereby 140 mg of the title compound was obtained. Melting point: 293-295°C (decomposed). ¹H-NMR (DMSO-d₆) δ: 1.12-1.31(m,4H), 3.68(m,3H), 4.17(m,2H), 5.12(m,2H), 7.12(d,1H,J=6.0Hz), 7.87(d,1H,J=13.2Hz), 8.60(s,1H). Example 4 Compound Nos. 6-8 shown in Table 4 were synthesized in a similar manner to Example 3. Example 5 Ethyl 1-cyclopropyl-6,8-difluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate (Compound No. 9) 1) A mixture of 9.33 g of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 5.49 g of monoethanolamine and 50 mℓ of dimethylformamide was heated at 90-100°C for 1 hour under stirring. The reaction mixture was concentrated to dryness under reduced pressure. To the residue thus obtained was added 150 mℓ of chloroorm, so that the residue was dissolved. The chloroform solution was successively washed with 5% acetic acid and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated. The residue was recrystallized from a mixed solvent of diethyl ether and ethanol, whereby 6.42 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(2-hydroxyethylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained. Melting point: 171-173°C. 2) A mixture of 0.70 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(2-hydroxyethylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 0.08 g of p-toluenesulfonic acid, 2.08 g of diethoxymethane and 20 mℓ of acetonitrile was stirred for 3 hours under reflux. The reaction mixture was allowed to cool down, followed by the addition of 100 mℓ of chloroform. The resultant mixture was washed successively with 5% aq. sodium carbonate solution and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated. The residue was purified by columnchromatography on silica gel, whereby 0.30 g of the title compound was obtained. Melting point: 178-181°C. ¹H-NMR (CDCl₃) δ: 1.10-1.23(m,4H), 1.40(t,3H), 3.82(m,3H), 4.09(t,2H,J=6.0Hz), 4.38(q,2H,J=7.1Hz), 5.09(s,2H), 7.89(d,1H,J=13.7Hz), 8.50(s,1H). Example 6 Compound Nos.10-13 shown in Table 5 were synthesized in a similar manner to Example 5. Example 7 1-Cyclopropyl-6,8-difluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound No. 14) A mixture of 182 mg of ethyl 1-cyclopropyl-6,8-difluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 5 mℓ of ethanol and 10 mℓ of 10% aq. sodium carbonate solution was stirred for 1 hour under reflux. The reaction mixture was allowed to cool down and then acidified with acetic acid. Crystals thus precipitated were collected by filtration. They were washed with water and ethanol and then dried, whereby 112 mg of the title compound was obtained. Melting point: 261-264°C (decomposed). ¹H-NMR (DMSO-d₆) δ: 1.18(m,4H), 3.80(m,2H), 4.05(m,3H), 5.10(m,2H), 7.76(d,1H,J=13.7Hz), 8.62(s,1H). Example 8 Compound Nos. 15-18 shown in Table 6 were synthesized in a similar manner to Example 7. Example 9 Ethyl 1-cyclopropyl-5,6,8-trifluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate (Compound No. 19) 1) A mixture of 9.87 g of ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 5.49 g of monoethanolamine and 60 mℓ of dimethylformamide was heated at 90-100°C for 1 hour under stirring. The reaction mixture was concentrated to dryness under reduced pressure. To the residue thus obtained was added 300 mℓ of chloroform so that the residue was dissolved. The chloroform solution was washed successively with 5% acetic acid and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated. The residue was purified by columnchromatography on silica gel, whereby 3.20 g of ethyl 1-cyclopropyl-5,6,8-trifluoro-7-(2-hydroxyethylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained. Melting point: 193-195°C. 2) A mixture of 0.74 g of ethyl 1-cyclopropyl-5,6,8-trifluoro-7-(2-hydroxyethylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 0.08 g of p-toluenesulfonic acid, 2.08 g of diethoxymethane and 20 mℓ of acetonitrile was stirred for 3 hours under reflux. The reaction mixture was allowed to cool down, followed by the addition of 100 mℓ of chloroform. The resultant mixture was washed successively with 5% aq. sodium carbonate solution and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated. The residue was purified by columnchromatography on silica gel, whereby 0.32 g of the title compound was obtained. Melting point: 182-185°C. ¹H-NMR (CDCl₃) δ: 1.06-1.22(m,4H), 1.38(t,3H,J=7.1Hz), 3.83(m,3H), 4.11(t,2H,J=6.0Hz), 4.35(q,2H,J=7.1Hz), 5.11(t,2H,J=2.8Hz), 8.39(s,1H). Example 10 1-Cyclopropyl-5,6,8-trifluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound No. 20) A mixture of 191 mg of ethyl 1-cyclopropyl-5,6,8-trifluoro-7-(3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 1 mℓ of ethanol and 5 mℓ of 10% aq. sodium carbonate solution was stirred for 1 hour under reflux. The reaction mixture was allowed to cool down and then acidified with acetic acid. Crystals thus precipitated were collected by filtration. They were washed with water and ethanol and then dried, whereby 163 mg of the title compound was obtained. Melting point: 290-293°C (decomposed). ¹H-NMR (DMSO-d₆) δ: 1.13(m,4H), 3.83(m,1H), 4.70(m,2H), 5.13(m,2H), 8.60(s,1H). Example 11 Ethyl 1-cyclopropyl-6,8-difluoro-7-(5-benzoyloxymethyl-3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate (Compound No. 21) 1) A mixture of 6.22 g of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 5.46 g of 3-aminopropane-1,2-diol and 40 mℓ of dimethylformamide was heated at 90-100°C for 1 hour under stirring. The reaction mixture was concentrated to dryness under reduced pressure. To the residue was added 200 mℓ of chloroform, so that the residue was dissolved. The resultant chloroform solution was washed successively with 5% acetic acid and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated. The residue thus obtained was recrystallized from diethyl ether, whereby 5.40 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(2,3-dihydroxypropylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained. Melting point: 173-175°C. 2) A mixture of 3.82 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(2,3-dihydroxypropylamino)-1,4-dihydro-4- oxoquinoline-3-carboxylate, 2.30 g of benzoic anhydride. 0.12 g of 4-dimethylaminopyridine and 50 mℓ of dimethylformamide was reacted for 1 hour at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in 150 mℓ of chloroform. The resultant chloroform solution was washed successively with 5% acetic acid, water, saturated aq. sodium hydrogencarbonate solution and saturated saline, dried over anhydrous magnesium sulfate, and then evaporated. The residue thus obtained was purified by columnchromatography on silica gel, whereby 1.35 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(3-benzoyloxy-2-hydroxypropylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained. Melting point: 134-136°C. 3) A mixture of 1.22 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(3-benzoyloxy-2-hydroxypropylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 2.6 g of diethoxymethane, 100 mg of p-toluenesulfonic acid hydrate and 25 mℓ of acetonitrile was stirred for 4 hours under reflux. After the reaction mixture was allowed to cool down, 100 mℓ of chloroform was added to the reaction mixture. The resultant mixture was washed successively with 5% aq. sodium carbonate solution and saturated saline, dried over anhydrous magnesium sulfate, and then evaporated. The residue thus obtained was purified by columnchromatography on silica gel, whereby 0.57 g of the title compound was obtained. Melting point: 120-123°C. ¹H-NMR (CDCl₃) δ: 1.08-1.21(m,4H), 1.40(t,3H,J=7.1Hz), 3.75-3.96(m,3H), 4.38(q,2H,J=7.1Hz), 4.55(m,3H), 5.14(m,1H), 5.24(m,1H), 7.90(dd,1H,J=1.7Hz,13.7Hz), 7.40-8.05(m,5H), 8.50(s,1H). Example 12 1-Cyclopropyl-6,8-difluoro-(5-hydroxymethyl-3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound No. 22) A mixture of 250 mg of ethyl 1-cyclopropyl-6,8-difluoro-7-(5-benzoyloxymethyl-3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 2 mℓ of ethanol and 10 mℓ of 10% aq. sodium carbonate solution was stirred under reflux for 1 hour. The reaction mixture was allowed to cool down and then acidified with acetic acid. Crystals thus precipitated were collected by filtration. They were washed with water and ethanol and then dried, whereby 162 mg of the title compound was obtained. Melting point: 209-212°C (decomposed). ¹H-NMR (DMSO-d₆) δ: 1.17(m,4H), 3.62(m,2H), 3.81(m,1H), 4.06(m,1H), 4.16(m,1H), 4.96(m,1H), 5.11(m,1H), 5.21(m,1H), 7.71(d,1H,J=13.6Hz), 8.60(s,1H). Example 13 Ethyl 1-cyclopropyl-6,8-difluoro-7-(tetrahydro-1,3-oxazin)-3-yl-1,4-dihydro-4-oxoquinoline-3-carboxylate (Compound No. 23) 1) A mixture of 1.71 g of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 1.13 g of 3-aminopropanol and 10 mℓ of dimethylformamide was heated at 90-100°C for 1 hour under stirring. The reaction mixture was concentrated to dryness under reduced pressure. To the residue was added 50 mℓ of chloroform, so that the residue was dissolved. The resultant chloroform solution was washed successively with 5% acetic acid and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated. The residue thus obtained was recrystallized from diethyl ether, whereby 1.54 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(3-hydroxypropylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained. Melting point: 160-162°C. 2) A mixture of 0.37 g of ethyl 1-cyclopropyl-6,8-difluoro-7-(3-hydroxypropylamino)-1,4-dihydro-4-oxoquinoline-3-carboxylate, 0.04 g of p-toluenesulfonic acid, 1.04 g of diethoxymethane and 10 mℓ of acetonitrile was stirred for 3 hours under reflux. After the reaction mixture was allowed to cool down, 50 mℓ of chloroform was added to the reaction mixture. The resultant mixture was washed successively with 5% aq. sodium carbonate solution and saturated saline, dried over anhydrous magnesium sulfate, and then evaporated. The residue thus obtained was purified by columnchromatography on silica gel, whereby 0.20 g of the title compound was obtained. Melting point: 171-173°C. ¹H-NMR (CDCl₃) δ: 1.11-1.25(m,4H), 1.40(t,3H,J=7.1Hz), 1.89 (m,2H), 3.59(m,2H), 3.88(m,1H), 3.98(m,2H), 4.38(q,2H,J=7.1Hz), 4.85(s,2H), 7.91(dd,1H,J=1.7Hz,12.1Hz), 8.53(s,1H). Example 14 1-Cyclopropyl-6,8-difluoro-7-(tetrahydro-1,3-oxazin)-3-yl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound No. 24) A mixture of 170 mg of ethyl 1-cyclopropyl-6,8-difluoro-7-(tetrahydro-1,3-oxazin)-3-yl-1,4-dihydro-4-oxoquinoline-3-carboxylate, 1 mℓ of ethanol and 5 mℓ of 10% aq. sodium carbonate solution was stirred for 1 hour under reflux. The reaction mixture was allowed to cool down, followed by the addition of acetic acid to acidify the same. Crystals thus precipitated were collected by filtration, washed with water and ethanol, and then dried, whereby 81 mg of the title compound was obtained. Melting point: 215-218°C. ¹H-NMR (DMSO-d₆) δ: 1.20(m,4H), 1.78(m,2H), 3.61*m,2H), 3.91(m,2H), 4.13(m,1H), 4.84(s,2H), 7.83(d,1H,J=11.5Hz), 8.68(s,1H). Example 15 7-(1-Morpholinooxy)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound No. 25) In a manner similar to Example 9, the title compound was obtained using 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinolin-3-carboxylic acid, 1-hydroxymorpholine and sodium hydride. Melting point: 170-174°C (decomposed). ¹H-NMR (DMSO-d₆) δ: 1.22-1.34(m,4H), 3.00(m,2H), 3.41(m,2H), 3.71(m,2H), 3.87(m,1H), 4.02(m,2H), 8.03(d,1H,J=9Hz), 8.26(d,1H,J=12Hz), 8.72(s,1H).

Claims: Claims for the following Contracting States : AT, BE, CH, DE, DK, FR, GB, IT, LI, LU, NL, SE A quinolone derivative represented by the following formula [I] or a salt thereof: wherein R¹ means a C₁-C₇ alkyl group optionally substituted by one or more halogen atoms or hydroxyl groups, a C₃-C₇ cycloalkyl group optionally substituted by methyl, a C₂-C₇ alkenyl group or a phenyl group optionally substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro groups, R² denotes a hydrogen atom or C₁-C₇ alkyl groups, a benzyl group, phenyl or phenyl groups substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro group, C₁-C₇ alkanoyloxy-C₁-C₇ alkyl groups, C₁-C₇ alkoxycarbonyloxy-C₁-C₇ alkyl groups, C₁-C₇ alkoxymethyl groups, phthalidyl, di(C₁-C₇ alkyl)amino-C₁-C₇ alkyl groups, (5-methyl-2-oxol-4-yl)methyl group, R³ represents a hydrogen or halogen atom or an amino, mono- or di-(C₁-C₇ alkyl)amino, hydroxyl or C₁-C₇ alkoxyl group, X is a hydrogen or halogen atom, Y means a nitrogen atom or a group C-R⁴ in which R⁴ is a hydrogen or halogen atom other than Cl or a C₁-C₇ alkyl or C₁-C₇ alkoxyl group or is a group which forms a ring together with R¹ (i.e., the asterisked carbon atoms are linked through R¹ to the N(1) atom of the quinolone skeleton), A denotes 3-oxazolidinyl, 5-methyl-3-oxazolidinyl, 5-ethyl-3-oxazolidinyl, 5-propyl-3-oxazolidinyl, 5-hydroxymethyl-3-oxazolidinyl, 5-(1-hydroxyethyl)-3-oxazolidinyl, 5-(2-hydroxyethyl)-3-oxazolidinyl, 5-methoxymethyl-3-oxazolidinyl, 5-ethoxymethyl-3-oxazolidinyl, 5-aminomethyl-3-oxazolidinyl, 5-(1-aminoethyl-3-oxazolidinyl, 5-(2-aminoethyl)-3-oxazolidinyl, 5-(1-aminopropyl)-3-oxazolidinyl, 5-(2-aminopropyl)-3-oxazolidinyl, 5-(3-aminopropyl)-3-oxazolidinyl, 5-methylaminomethyl-3-oxazolidinyl, 5-dimethylaminomethyl-3-oxazolidinyl, 5-(1-methylaminoethyl)-3-oxazolidinyl, 5-(2-methylaminoethyl)-3-oxazolidinyl, 5-(1-dimethylaminoethyl)-3-oxazolidinyl, 5-(2-dimethylaminoethyl)-3-oxazolidinyl, 5-ethylmethylaminomethyl-3-oxazolidinyl, 5-diethylaminomethyl-3-oxazolidinyl, 4-methyl-3-oxazolidinyl, 2-methyl-3-oxazolidinyl, 4-methyl-5-hydroxymethyl-3-oxazolidinyl, 4-methyl-5-dimethylaminomethyl-3-oxazolidinyl, 2-methyl-5-aminomethyl-3-oxazolidinyl, and 2-methyl-5-ethylmethylaminomethyl-3-oxazolidinyl, or (tetrahydro-1,3-oxazin)-3-yl, 6-methyl-(tetrahydro-1,3-oxazin)-3-yl , 6-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-propyl-(tetrahydro-1,3-oxazin)-3-yl, 6-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-methyl-(tetrahydro1,3-oxazin)-3-yl, 5-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-propyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-hydroxyethyl)-tetrahydro-1,3-oxazin)-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(ethylmethylaminomethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxy-(tetrahydro-1,3-oxazin)-3-yl, 5-methoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-amino-(tetrahydro-1,3-oxazin)-3-yl, 5-methylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylmethylamino(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-6-methylamiomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-5-amino-(tetrahydro-1,3-oxazin)-3-yl, and 4-methyl-6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl. A process for the preparation of a quinolone derivative represented by the following formula [I] or a salt thereof: wherein R¹, R², R³, X, Y and A are defined as in claim 1, which comprises reacting a compound represented by the following formula [III]: A-H [III] with a compound represented by the following formula [II]: wherein R¹, R², R³, X and Y have the same meanings as defined above and X¹ means a halogen atom; and optionally subjecting the reaction product to hydrolysis; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Ib] or a salt thereof: wherein R¹, R³, X, Y and A are defined as in claim 1 and R 2a is defined as R² in claim 1 provided that R 2a is not a hydrogen atom, which comprises reacting a compound represented by the following formula [IV]: R 2a -X² [IV] wherein R 2a has the same meaning as defined above and X² denotes a halogen atom, with a compound represented by the following formula [Ia]: wherein R¹, R³, X, Y and A have the same meanings as defined above; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Id] or a salt thereof: wherein R¹, R², R³, A and X are defined as in claim 1 and R⁹ means a C₁-C₇ alkyl group, which comprises reacting a metal alkoxide represented by the following formula [V]: (R⁹O) n'' M [V] wherein R⁹ has the same meaning as defined above, M denotes an alkali or alkaline earth metal atom and n'' stands for a value of 1 or 2, with a compound represented by the following formula [Ic]: wherein R¹, R², R³ and X have the same meanings as defined above, and X³ means a halogen atom; and optionally subjecting the reaction product to hydrolysis; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Ig] or a salt thereof: wherein R¹, R², R³, X, Y and A are defined as in claim 1, which comprises reacting an alkanolamine represented by the following formula [VIII]: H₂N-R¹²-OH [VIII] wherein R¹² means a substituted or unsubstituted ethylene or substituted or unsubstituted propylene group, with a compound represented by the following formula [VII]: wherein R¹, R², R³, X and Y have the same meanings as defined above and X⁴ denotes a reactive leaving group, thereby obtaining a compound represented by the following formula [IX]: wherein R¹, R², R³, R¹², X and Y have the same meanings as defined above; and then reacting the compound [IX] with a dialkoxymethane derivative represented by the following formula [X]: wherein R¹³ means a hydrogen atom or a group capable of being converted to a substituted group on the oxazolidinyl or the (tetrahydro-1,3-oxazin)-3-yl group and R¹⁴ denotes a C₁-C₇ alkyl group; and when the salt is desired, converting the reaction product [Ig] into the salt by a method known per se in the art. An antibacterial agent comprising as an active ingredient the quinolone derivative or the salt thereof according to claim 1. Claims for the following Contracting State : ES A process for the preparation of a quinolone derivative represented by the following formula [I] or a salt thereof: wherein R¹ means a C₁-C₇ alkyl group optionally substituted by one or more halogen atoms or hydroxyl groups, a C₃-C₇ cycloalkyl group optionally substituted by methyl, a C₂-C₇ alkenyl group or a phenyl group optionally substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro groups, R² denotes a hydrogen atom or C₁-C₇ alkyl groups, a benzyl group, phenyl or phenyl groups substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro group, C₁-C₇ alkanoyloxy-C₁-C₇ alkyl groups, C₁-C₇ alkoxycarbonyloxy-C₁-C₇ alkyl groups, C₁-C₇ alkoxymethyl groups, phthalidyl, di(C₁-C₇ alkyl)amino-C₁-C₇ alkyl groups, (5-methyl-2-oxol-4-yl)methyl group, R³ represents a hydrogen or halogen atom or an amino, mono- or di-(C₁-C₇ alkyl)amino, hydroxyl or C₁-C₇ alkoxyl group, X is a hydrogen or halogen atom, Y means a nitrogen atom or a group C-R⁴ in which R⁴ is a hydrogen or halogen atom other than Cl or a C₁-C₇ alkyl or C₁-C₇ alkoxyl group or is a group which forms a ring together with R¹ (i.e., the asterisked carbon atoms are linked through R¹ to the N(1) atom of the quinolone skeleton), A denotes 3-oxazolidinyl, 5-methyl-3-oxazolidinyl, 5-ethyl-3-oxazolidinyl, 5-propyl-3-oxazolidinyl, 5-hydroxymethyl-3-oxazolidinyl, 5-(1-hydroxyethyl)-3-oxazolidinyl, 5-(2-hydroxyethyl)-3-oxazolidinyl, 5-methoxymethyl-3-oxazolidinyl , 5-ethoxymethyl-3-oxazolidinyl, 5-aminomethyl-3-oxazolidinyl, 5-(1-aminoethyl-3-oxazolidinyl, 5-(2-aminoethyl)-3-oxazolidinyl, 5-(1-aminopropyl)-3-oxazolidinyl, 5-(2-aminopropyl)-3-oxazolidinyl, 5-(3-aminopropyl)-3-oxazolidinyl, 5-methylaminomethyl-3-oxazolidinyl, 5-dimethylaminomethyl-3-oxazolidinyl, 5-(1-methylaminoethyl)-3-oxazolidinyl, 5-(2-methylaminoethyl)-3-oxazolidinyl, 5-(1-dimethylaminoethyl)-3-oxazolidinyl, 5-(2-dimethylaminoethyl)-3-oxazolidinyl, 5-ethylmethylaminomethyl-3-oxazolidinyl, 5-diethylaminomethyl-3-oxazolidinyl, 4-methyl-3-oxazolidinyl, 2-methyl-3-oxazolidinyl, 4-methyl-5-hydroxymethyl-3-oxazolidinyl, 4-methyl-5-dimethylaminomethyl-3-oxazolidinyl, 2-methyl-5-aminomethyl-3-oxazolidinyl, and 2-methyl-5-ethylmethylaminomethyl-3-oxazolidinyl, or (tetrahydro-1,3-oxazin)-3-yl, 6-methyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-propyl-(tetrahydro-1,3-oxazin)-3-yl, 6-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-propyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-hydroxyethyl)-tetrahydro-1,3-oxazin)-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(ethylmethylaminomethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxy-(tetrahydro-1,3-oxazin)-3-yl, 5-methoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-amino-(tetrahydro-1,3-oxazin)-3-yl, 5-methylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylmethylamino(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-6-methylamiomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-5-amino-(tetrahydro-1,3-oxazin)-3-yl, and 4-methyl-6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, which comprises reacting a compound represented by the following formula [III]: A-H [III] with a compound represented by the following formula [II]: wherein R¹, R², R³, X and Y have the same meanings as defined above and X¹ means a halogen atom; and optionally subjecting the reaction product to hydrolysis; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Ib] or a salt thereof: wherein R¹, R³, X, Y and A are defined as in claim 1 and R 2a is defined as R² in claim 1 provided that R 2a is not a hydrogen atom, which comprises reacting a compound represented by the following formula [IV]: R 2a -X² [IV] wherein R 2a has the same meaning as defined above and X² denotes a halogen atom, with a compound represented by the following formula [Ia]: wherein R¹, R³, X, Y and A have the same meanings as defined above; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Id] or a salt thereof: wherein R¹, R², R³, A and X are defined as in claim 1 and R⁹ means a C₁-C₇ alkyl group, which comprises reacting a metal alkoxide represented by the following formula [V]: (R⁹O) n'' M [V] wherein R⁹ has the same meaning as defined above, M denotes an alkali or alkaline earth metal atom and n'' stands for a value of 1 or 2, with a compound represented by the following formula [Ic]: wherein R¹, R², R³ and X have the same meanings as defined above, and X³ means a halogen atom; and optionally subjecting the reaction product to hydrolysis; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Ig] or a salt thereof: wherein R¹, R², R³, X, Y and A are defined as in claim 1, which comprises reacting an alkanolamine represented by the following formula [VIII]: H₂N-R¹²-OH [VIII] wherein R¹² means a substituted or unsubstituted ethylene or substituted or unsubstituted propylene group, with a compound represented by the following formula [VII]: wherein R¹, R², R³, X and Y have the same meanings as defined above and X⁴ denotes a reactive leaving group, thereby obtaining a compound represented by the following formula [IX]: wherein R¹, R², R³, R¹², X and Y have the same meanings as defined above; and then reacting the compound [IX] with a dialkoxymethane derivative represented by the following formula [X]: wherein R¹³ means a hydrogen atom or a group capable of being converted to a substituted group on the oxazolidinyl or the (tetrahydro-1,3-oxazin)-3-yl group and R¹⁴ denotes a C₁-C₇ alkyl group; and when the salt is desired, converting the reaction product [Ig] into the salt by a method known per se in the art. Claims for the following Contracting State : GR A quinolone derivative represented by the following formula [I] or a salt thereof: wherein R¹ means a C₁-C₇ alkyl group optionally substituted by one or more halogen atoms or hydroxyl groups, a C₃-C₇ cycloalkyl group optionally substituted by methyl, a C₂-C₇ alkenyl group or a phenyl group optionally substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro groups, R² denotes a hydrogen atom or C₁-C₇ alkyl groups, a benzyl group, phenyl or phenyl groups substituted by one or more substituents such as halogen atoms, C₁-C₇ alkoxyl, C₁-C₇ acyloxy, hydroxyl, amino, C₁-C₇ alkyl and/or nitro group, C₁-C₇ alkanoyloxy-C₁-C₇ alkyl groups, C₁-C₇ alkoxycarbonyloxy-C₁-C₇ alkyl groups, C₁-C₇ alkoxymethyl groups, phthalidyl, di(C₁-C₇ alkyl)amino-C₁-C₇ alkyl groups, (5-methyl-2-oxol-4-yl)methyl group, R³ represents a hydrogen or halogen atom or an amino, mono- or di-(C₁-C₇ alkyl)amino, hydroxyl or C₁-C₇ alkoxyl group, X is a hydrogen or halogen atom, Y means a nitrogen atom or a group C-R⁴ in which R⁴ is a hydrogen or halogen atom other than Cl or a C₁-C₇ alkyl or C₁-C₇ alkoxyl group or is a group which forms a ring together with R¹ (i.e., the asterisked carbon atoms are linked through R¹ to the N(1) atom of the quinolone skeleton), A denotes 3-oxazolidinyl, 5-methyl-3-oxazolidinyl, 5-ethyl-3-oxazolidinyl, 5-propyl-3-oxazolidinyl, 5-hydroxymethyl-3-oxazolidinyl, 5-(1-hydroxyethyl)-3-oxazolidinyl, 5-(2-hydroxyethyl)-3-oxazolidinyl, 5-methoxymethyl-3-oxazolidinyl, 5-ethoxymethyl-3-oxazolidinyl, 5-aminomethyl-3-oxazolidinyl, 5-(1-aminoethyl-3-oxazolidinyl, 5-(2-aminoethyl)-3-oxazolidinyl, 5-(1-aminopropyl)-3-oxazolidinyl, 5-(2-aminopropyl)-3-oxazolidinyl, 5-(3-aminopropyl)-3-oxazolidinyl, 5-methylaminomethyl-3-oxazolidinyl, 5-dimethylaminomethyl-3-oxazolidinyl, 5-(1-methylaminoethyl)-3-oxazolidinyl, 5-(2-methylaminoethyl)-3-oxazolidinyl, 5-(1-dimethylaminoethyl)-3-oxazolidinyl, 5-(2-dimethylaminoethyl)-3-oxazolidinyl, 5-ethylmethylaminomethyl-3-oxazolidinyl, 5-diethylaminomethyl-3-oxazolidinyl, 4-methyl-3-oxazolidinyl, 2-methyl-3-oxazolidinyl, 4-methyl-5-hydroxymethyl-3-oxazolidinyl, 4-methyl-5-dimethylaminomethyl-3-oxazolidinyl, 2-methyl-5-aminomethyl-3-oxazolidinyl, and 2-methyl-5-ethylmethylaminomethyl-3-oxazolidinyl, or (tetrahydro-1,3-oxazin)-3-yl, 6-methyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-propyl-(tetrahydro-1,3-oxazin)-3-yl, 6-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminoethyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(1-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(2-aminopropyl)-tetrahydro-1,3-oxazin)-3-yl, 6-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 6-diethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-propyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-hydroxyethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-hydroxyethyl)-tetrahydro-1,3-oxazin)-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin-3-yl, 5-methoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxymethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(3-aminopropyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-methylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-methylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(1-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(2-dimethylaminoethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-(ethylmethylaminomethyl)-(tetrahydro-1,3-oxazin)-3-yl, 5-diethyl-aminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-(tetrahydro-1,3-oxazin)-3-yl, 5-hydroxy-(tetrahydro-1,3-oxazin)-3-yl, 5-methoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-ethoxy-(tetrahydro-1,3-oxazin)-3-yl, 5-amino-(tetrahydro-1,3-oxazin)-3-yl, 5-methylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-dimethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-diethylamino-(tetrahydro-1,3-oxazin)-3-yl, 5-ethylmethylamino(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-5-dimethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl, 2-methyl-6-methylamiomethyl-(tetrahydro-1,3-oxazin)-3-yl, 4-methyl-5-amino-(tetrahydro-1,3-oxazin)-3-yl, and 4-methyl-6-ethylmethylaminomethyl-(tetrahydro-1,3-oxazin)-3-yl. A process for the preparation of a quinolone derivative represented by the following formula [I] or a salt thereof: wherein R¹, R², R³, X, Y and A are defined as in claim 1, which comprises reacting a compound represented by the following formula [III]: A-H [III] with a compound represented by the following formula [II]: wherein R¹, R², R³, X and Y have the same meanings as defined above and X¹ means a halogen atom; and optionally subjecting the reaction product to hydrolysis; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Ib] or a salt thereof: wherein R¹, R³, X, Y and A are defined as in claim 1 and R 2a is defined as R² in claim 1 provided that R 2a is not a hydrogen atom, which comprises reacting a compound represented by the following formula [IV]: R 2a -X² [IV] wherein R 2a has the same meaning as defined above and X² denotes a halogen atom, with a compound represented by the following formula [Ia]: wherein R¹, R³, X, Y and A have the same meanings as defined above; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Id] or a salt thereof: wherein R¹, R², R³, A and X are defined as in claim 1 and R⁹ means a C₁-C₇ alkyl group, which comprises reacting a metal alkoxide represented by the following formula [V]: (R⁹O) n'' M [V] wherein R⁹ has the same meaning as defined above, M denotes an alkali or alkaline earth metal atom and n'' stands for a value of 1 or 2, with a compound represented by the following formula [Ic]: wherein R¹, R², R³ and X have the sane meanings as defined above, and X³ means a halogen atom; and optionally subjecting the reaction product to hydrolysis; and when the salt is desired, converting the reaction product into the salt by a method known per se in the art. A process for the preparation of a quinolone derivative represented by the following formula [Ig] or a salt thereof: wherein R¹, R², R³, X, Y and A are defined as in claim 1, which comprises reacting an alkanolamine represented by the following formula [VIII]: H₂N-R¹²-OH [VIII] wherein R¹² means a substituted or unsubstituted ethylene or substituted or unsubstituted propylene group, with a compound represented by the following formula [VII]: wherein R¹, R², R³, X and Y have the same meanings as defined above and X⁴ denotes a reactive leaving group, thereby obtaining a compound represented by the following formula [IX]: wherein R¹, R², R³, R¹², X and Y have the same meanings as defined above; and then reacting the compound [IX] with a dialkoxymethane derivative represented by the following formula [X]: wherein R¹³ means a hydrogen atom or a group capable of being converted to a substituted group on the oxazolidinyl or the (tetrahydro-1,3-oxazin)-3-yl group and R¹⁴ denotes a C₁-C₇ alkyl group; and when the salt is desired, converting the reaction product [Ig] into the salt by a method known per se in the art.

Inventors: AMANO HIROTAKA C O WAKUNAGA SE, HAYASHI NORIHIRO C O WAKUNAGA, INOUE SATOSHI C O WAKUNAGA SEI, KURAMOTO YASUHIRO C O WAKUNAGA, NODA SHUICHIRO C O WAKUNAGA SE, YAMAMOTO HITOSHI C O WAKUNAGA, YATSUNAMI TAKASHI C O WAKUNAGA, YAZAKI AKIRA C O WAKUNAGA SEIY, AMANO, HIROTAKA, C/O WAKUNAGA SEIYAKU, HAYASHI, NORIHIRO, C/O WAKUNAGA SEIYAKU, INOUE, SATOSHI C/O WAKUNAGA SEIYAKU, KURAMOTO, YASUHIRO, C/O WAKUNAGA SEIYAKU, NODA, SHUICHIRO, C/O WAKUNAGA SEIYAKU, YAMAMOTO, HITOSHI, C/O WAKUNAGA SEIYAKU, YATSUNAMI, TAKASHI, C/O WAKUNAGA SEIYAKU, YAZAKI, AKIRA, C/O WAKUNAGA SEIYAKU
Applicants: WAKUNAGA SEIYAKU KK, WAKUNAGA SEIYAKU KABUSHIKI KAISHA
Application year: 1990
Main classification: C07D413
IPC codes: C07D417, C07D471, C07D401, C07D413, C07D498, C07D453