JPH0770110A - 5,8-dimethylquinoline-3-carboxylic acid derivative - Google Patents

Abstract

PURPOSE:To obtain the subject new derivative containing methyl groups at both the 5- and the 8-positions and 5-azaspiro[2,4]hept-5-yl at the 7-position and its pharmacologically permissible salt useful as an antimicrobial agent. CONSTITUTION:A 5,8-dimethylquinoline-3-carboxylic acid derivative of formula I [R<1> is H or a lower alkyl; R<2> is H, a lower alkyl, a lower alkanoyl, a halogeno lower alkanoyl or ester type protecting group; R<3> is H or lower alkyl] and its pharmacologically permissible salt such as 7-(7-amino-5- azaspiro[2,4]hept-5-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethy l-4- oxoquinoline-3-carboxylic acid. The compound of formula I, for example, is obtained by reacting a 7-halogenoquinoline-3-carboxylic acid derivative of formula II (X is halogen) with a 7-amino-5-azaspiro[2,4]heptane derivative of formula III and optionally hydrolyzing.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel 5,8-dimethylquinoline-3-carboxylic acid derivative useful as an antibacterial agent, a pharmacologically acceptable salt thereof, and an antibacterial agent containing the same as an active ingredient. It is about.

[0002]

As an antibacterial agent having a cyclopropyl group at the 1-position of the quinoline skeleton, ciprofloxacin (The Merck Index 11th edition, 231
5) is well known. A large number of 5,7,8-position substitution products have been synthesized for the purpose of improving this ciprofloxacin, but the 5-position at the 7-position of the quinoline skeleton having a methyl group at the 5-position and 8-position as in the present invention has been No compound having an azaspiro [2.4] hept-5-yl group has been known so far.

The compound having the same skeleton as the compound of the present invention includes 7- (3-amino-1-pyrrolidinyl) -1-cyclopropyl-5,8- having a 3-amino-1-pyrrolidinyl group at the 7-position. Dimethyl-6-fluoro-1,4
-Dihydro-4-oxoquinoline-3-carboxylic acid and 1-cyclopropyl-5,8-dimethyl-6-fluoro-1,4-dihydro-4-oxo-7- (having a 1-piperazinyl group at the 7-position 1-piperazinyl) quinoline-3
-Carboxylic acids are only disclosed in JP-A-1-230558.

[0004]

The conventional quinolone synthetic antibacterial agents are not sufficient in terms of antibacterial activity or have strong antibacterial activity, but on the other hand, they are phototoxic, induce chromosomal abnormalities, induce convulsions, etc. It had a drawback in that there was a problem in safety due to the side effect of. The characteristics of each substituent are described below.

That is, as the 8-position substituent of the quinoline skeleton, it is known that a somewhat bulky substituent such as a chlorine atom or a methyl group is preferable from the viewpoint of antibacterial activity. Many of these compounds have strong side effects such as phototoxicity and induction of chromosomal aberrations, and compounds having a methyl group have strong drawbacks such as strong induction of chromosomal aberrations and safety problems. In addition, 5 of the quinoline skeleton
Amino groups, halogen atoms, methyl groups and the like are known as position substituents, but these substituents have the drawbacks of weakening antibacterial activity and safety. On the other hand, piperazines known as the 7-position substituent of the quinoline skeleton do not have sufficient antibacterial activity, and 3-aminopyrrolidines have strong antibacterial activity but often have problems in terms of side effects.

[0006]

Means for Solving the Problems As a result of intensive studies aimed at solving such problems, the present inventors have found that methyl groups are present at both the 5- and 8-positions and 5-azaspiro [2.4] at the 7-position. ] 1-Cyclopropyl-6 having a hept-5-yl group at the same time
-Fluoro-1,4-dihydro-4-oxoquinoline-
A 3-carboxylic acid derivative was found.

That is, 5-azaspiro [2.4] hept- at the 7-position of the quinoline skeleton having a methyl group at the 5- and 8-positions.
The compound of the present invention having a 5-yl group has a strong antibacterial activity, and is a highly safe compound that cannot be predicted from the findings so far, that is, it has few side effects such as phototoxicity, chromosomal abnormality induction, and convulsion induction. The present invention has been completed by finding that it is a highly safe compound.

The present invention has the following general formula (I):

[Chemical 3] (In the formula, R ¹ represents a hydrogen atom or a lower alkyl group, R ² represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a halogeno lower alkanoyl group or an ester-type protecting group, R ³
Represents a hydrogen atom or a lower alkyl group. The present invention relates to a 5,8-dimethylquinoline-3-carboxylic acid derivative represented by), a pharmacologically acceptable salt thereof, and an antibacterial agent containing the same as an active ingredient.

In the above general formula (I) of the present invention, examples of the lower alkyl group represented by R ¹ , R ² and R ³ include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-
Examples thereof include a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, and the lower alkanoyl group represented by R ² includes, for example, a formyl group, an acetyl group, a propanoyl group, a butyroyl group and a trimethylacetyl group. , Halogeno lower alkanoyl groups include, for example, fluoroacetyl group, difluoroacetyl group, trifluoroacetyl group, chloroacetyl group, dichloroacetyl group, trichloroacetyl group, and the like, ester type protecting groups include, for example, benzyloxycarbonyl group. , Ethoxycarbonyl group, methoxycarbonyl group, tert-butoxycarbonyl group and the like.

The compound represented by the above general formula (I) of the present invention can be converted into a pharmacologically acceptable salt, or a base or an acid can be liberated from the produced salt, if desired. .

Examples of the pharmacologically acceptable salt of the compound represented by the general formula (I) of the present invention include acid addition salts and alkali addition salts. Examples of the acid addition salt include:
Hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid and other mineral salts, or acetic acid, maleic acid, fumaric acid, citric acid, oxalic acid, malic acid, methanesulfonic acid, p-toluene sulfone Organic acid salts such as acids, mandelic acid, 10-camphorsulfonic acid, tartaric acid, etc., such as sodium, potassium, calcium, silver,
Examples thereof include inorganic alkali salts such as zinc, lead and ammonium, and salts of organic bases such as ethanolamine and N, N-dialkylethanolamine.

The compound represented by the general formula (I) of the present invention has an asymmetric carbon atom, and optical isomers may exist, but the present invention also includes these isomers and mixtures thereof. It

5,8-Dimethylquinoline-3-of the present invention
The following compounds may be mentioned as preferred embodiments of the carboxylic acid derivative, but the present invention is not limited to these examples. (1) 7- (7-Amino-5-azaspiro [2.4] hept-5-yl) -1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-4-oxoquinoline -3-Carboxylic acid (2) 7-((S) -7-amino-5-azaspiro [2.4] hept-5-yl) -1-cyclopropyl-
6-fluoro-1,4-dihydro-5,8-dimethyl-
4-oxoquinoline-3-carboxylic acid (3) 7-((R) -7-amino-5-azaspiro [2.4] hept-5-yl) -1-cyclopropyl-
6-fluoro-1,4-dihydro-5,8-dimethyl-
4-oxoquinoline-3-carboxylic acid (4) 1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-7- (7-methylamino-
5-Azaspiro [2.4] hept-5-yl) -4-oxoquinoline-3-carboxylic acid (5) 1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-7- ((S) -7-Methylamino-5-azaspiro [2.4] hept-5-yl)
-4-oxoquinoline-3-carboxylic acid (6) 1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-7-((R) -7-methylamino-5-azaspiro [ 2.4] hept-5-yl)
-4-oxoquinoline-3-carboxylic acid (7) 1-cyclopropyl-7- (7-dimethylamino-5-azaspiro [2.4] hept-5-yl) -6-
Fluoro-1,4-dihydro-5,8-dimethyl-4-
Oxoquinoline-3-carboxylic acid (8) 1-cyclopropyl-7-((S) -7-dimethylamino-5-azaspiro [2.4] hept-5-yl) -6-fluoro-1,4- Dihydro-5,8-dimethyl-4-oxoquinoline-3-carboxylic acid (9) 1-cyclopropyl-7-((R) -7-dimethylamino-5-azaspiro [2.4] hept-5-yl ) -6-Fluoro-1,4-dihydro-5,8-dimethyl-4-oxoquinoline-3-carboxylic acid

The novel 5,8-dimethylquinoline-3-carboxylic acid derivative represented by the above general formula (I) of the present invention can be produced by the following method. The production method of the compound is these methods. It is not limited to.

According to the first mode of the method for producing a compound according to the present invention, the compound represented by the general formula (I) has the following general formula (II):

[Chemical 4] (In the formula, R ¹ has the same meaning as described above, and X represents a halogen atom.), And a 7-halogenoquinoline-3-carboxylic acid derivative represented by the following general formula (III)

[Chemical 5] (Wherein R ² and R ³ have the same meanings as described above) and the 7-amino-5-azaspiro [2.4] heptane derivative is reacted in a solvent in the presence or absence of a base. And hydrolyzing as needed, and can manufacture.

The solvent used in the reaction between the compound represented by the general formula (II) and the compound represented by the general formula (III) in the present production method may be any solvent as long as it does not inhibit the reaction, for example, methanol. , Ethanol, alcohol solvents such as n-propanol, isopropanol, n-butanol, aprotic substances such as acetonitrile, N, N-dimethylformamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, hexamethylphosphoric triamide, etc. Examples of the solvent include polar solvents, aromatic hydrocarbon solvents such as benzene and toluene, organic bases such as pyridine, picoline, lutidine and collidine, and mixed solvents thereof. Examples of the base used include triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] -7 Undecene, 1, 2, 2,
6,6-pentamethylpiperidine, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like can be mentioned. The reaction is carried out in the range from ice cooling to the solvent reflux temperature.

The hydrolysis is carried out by a method known per se using an acid or an alkali. For the acidic hydrolysis, hydrochloric acid,
Acids such as sulfuric acid are used for alkaline hydrolysis, and alkalis such as sodium hydroxide and potassium hydroxide are used. These acids or alkalis are aqueous solutions or methanol, ethanol, n-butanol, sec-butanol, tert-butanol, etc. It can be used in the reaction as a solution with an organic solvent or a water-containing organic solvent, and the reaction is carried out from room temperature to the heating reflux temperature of the solvent.

According to the second mode of the method for producing a compound according to the present invention, the compound represented by the above general formula (I) has the following general formula (IV)

[Chemical 6] (In the formula, X has the same meaning as described above, and R ⁴ represents a halogen atom, an aliphatic acyloxy group, an aliphatic acyloxy group optionally substituted with a halogen atom, or an aromatic acyloxy group.) Derivatives and the general formula (II
7-amino-5-azaspiro [2.4] represented by I)
After reacting with a heptane derivative in a solvent in the presence or absence of a base, further dechelation by treatment with a protic polar solvent in the presence or absence of a base, if necessary. It can be manufactured by carrying out.

In the present production method, the solvent used for the reaction between the compound represented by the general formula (IV) and the compound represented by the general formula (III) may be any solvent as long as it does not inhibit the reaction. Alcohol solvents such as methanol, ethanol, n-propanol, isopropanol, n-butanol, aprotons such as acetonitrile, N, N-dimethylformamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, hexamethylphosphoric triamide, etc. Polar solvents, aromatic hydrocarbon solvents such as benzene and toluene, organic bases such as pyridine, picoline, lutidine and collidine, halogen-containing hydrocarbon solvents such as dichloromethane, 1,2-dichloroethane and chloroform, or mixed solvents thereof. Etc.

Examples of the base used in the present production method include triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] -7-
Undecene, 1,2,2,6,6-pentamethylpiperidine, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate and the like can be mentioned, and the reaction is carried out in the range from under ice cooling to the reflux temperature of the solvent. .

The protic polar solvent used in the dechelation reaction is, for example, methanol,
Alcohol solvents such as ethanol, n-propanol, isopropanol, n-butanol, etc., or water, and mixed solvents thereof, or acetonitrile, N, N-dimethylformamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphine. For example, a mixed solvent of a solvent such as folic triamide, benzene, toluene, pyridine, picoline, lutidine, collidine, dichloromethane, 1,2-dichloroethane, chloroform and methanol or water may be used. It is carried out up to the reflux temperature.

According to the third mode of the method for producing a compound according to the present invention, among the compounds represented by the general formula (I), the compound in which R ² is a hydrogen atom is the compound represented by the general formula (I).
Wherein R ² is a lower alkanoyl group,
It is produced by hydrolyzing a compound which is a halogeno lower alkanoyl group or by deprotecting a compound where R ² is an ester type protecting group with an acid in the presence or absence of a cationic scavenger in the absence or presence of a cationic scavenger. be able to.

This hydrolysis is carried out by a method known per se using an acid or an alkali. For the acidic hydrolysis, hydrochloric acid,
Acids such as sulfuric acid are used for alkaline hydrolysis, and alkalis such as sodium hydroxide and potassium hydroxide are used. These acids or alkalis are aqueous solutions or methanol, ethanol, n-butanol, sec-butanol, tert-butanol, etc. It can be used in the reaction as a solution with an organic solvent or a water-containing organic solvent, and the reaction is carried out from room temperature to the heating reflux temperature of the solvent.

Examples of the solvent used in the deprotection reaction of the ester-type protecting group include acetic acid, ethyl acetate, dioxane, water, methanol, ethanol, and mixed solvents thereof, and the cation scavenger includes Examples thereof include anisole and thioanisole, and examples of the acid include hydrochloric acid, hydrobromic acid, trifluoroacetic acid, and the like, and the reaction is performed under ice-cooling to a solvent heating reflux temperature range.

According to the fourth mode of the method for producing a compound of the present invention, the compound of the formula (I) wherein R ² and / or R ³ is a lower alkyl group is:
In the above general formula (I), a compound in which R ² or / and R ³ is a hydrogen atom is reacted with a halogeno lower alkyl in a solvent in the presence or absence of a base, or (V)

[Chemical 7] (In the formula, R ⁵ represents a hydrogen atom or a lower alkyl group.)
It can be produced by reacting with an aldehyde compound represented by: in the presence of formic acid.

In the present production method, when the halogeno lower alkyl is used, examples of the solvent include N, N-dimethylformamide, acetone, ethanol, tetrahydrofuran, benzene, chloroform and the like, and examples of the base include hydrogenation. Sodium, sodium amide,
Examples include triethylamine and potassium carbonate.

The aldehyde compound represented by the general formula (V) when an aldehyde compound is used in the present production method includes formaldehyde, acetaldehyde,
Propionaldehyde and the like can be mentioned. Formaldehyde is preferably used as an aqueous formaldehyde solution (formalin), and when acetaldehyde and propionaldehyde are used, nitrobenzene is preferably used as a solvent. Both reactions are carried out in the temperature range from room temperature to the reflux temperature of the solvent.

In the present production method, among the compounds used as starting materials, the compound represented by the general formula (II) is a compound of the journal of heterocyclic chemistry [(Jou
rnalof Heterocyclic Chemistry) 27, 1609 (1990)].

The above-mentioned general formula (I) produced in this manner
The pharmaceuticals containing the novel 5,8-dimethylquinoline-3-carboxylic acid derivative represented by and the pharmacologically acceptable salt thereof as active ingredients are usually capsules, tablets, fine granules,
It is administered as an oral administration agent such as granules, powders, syrups, etc., or as an injection, a suppository, an eye drop, an eye ointment, an ear drop or an external skin preparation. These preparations can be manufactured by a conventional method by adding pharmacologically and pharmaceutically acceptable additives. That is, for oral agents and suppositories, excipients (lactose, D-mannitol, corn starch, crystalline cellulose, etc.), disintegrants (carboxymethyl cellulose, carboxymethyl cellulose calcium, etc.), binders (hydroxypropyl cellulose, hydroxypropyl) Pharmaceutical ingredients such as methylcellulose, polyvinylpyrrolidone, etc., lubricants (magnesium stearate, talc, etc.), coating agents (hydroxypropylmethylcellulose, sucrose, titanium oxide, etc.), bases (polyethylene glycol, hard fat, etc.), For injections, eye drops, and ear drops, solubilizers or solubilizers (water for injection, physiological saline, propylene glycol, etc.) that can form a water-based or dissolution-in-use dosage form, pH adjusters (inorganic) Or organic acids or bases), isotonic Formulation components such as agents (salt, glucose, glycerin, etc.), stabilizers, etc. are suitable for ointments, skin preparations, ointments, creams, and patches (white petrolatum). , Macrogol, glycerin, cotton cloth, etc.) are used.

The dose of this drug to a treated patient depends on the symptoms of the patient, but in the case of an adult, the daily dose is usually about 10 to 1000 mg by oral administration and about 1 to 500 mg by parenteral administration. .

[0031]

The results of the antibacterial spectra of standard bacteria and clinically isolated bacteria are shown in Tables 1 and 2 as an example showing the excellent effect of the compound of the present invention. The following compounds were used as control drugs. Control drug: Ciprofloxacin hydrochloride

1. Antibacterial spectrum The antibacterial test was carried out according to the method specified by the Japanese Society of Chemotherapy (Journal of the Japanese Society of Chemotherapy, 29 (1), 76 (1981)). The results are shown in Tables 1 and 2. The compound of the present invention showed an excellent antibacterial action as compared with the control drug.

[0033]

[Table 1]

[0034]

[Table 2]

2. Safety On the other hand, the compound of the present invention did not show a clear abnormality in the chromosome aberration test and the micronucleus test. Further, it did not induce convulsions even when used in combination with the anti-inflammatory drug fenbufen, and its toxicity was extremely weak in the phototoxicity test, and it was very excellent in terms of safety.

[0036]

The present invention will be described below with reference to reference examples and examples, but the present invention is not limited to these examples.

Reference Example 1 [1-Cyclopropyl-6,7-difluoro-1,4-
Dihydro-5,8-dimethyl-4-oxoquinoline-3
- carboxylic acid -O ^3, O ^4] Difluoro Boron 1-cyclopropyl-6,7-difluoro-1,4-dihydro-5,8-dimethyl-4-oxo-3-
A mixture of 3.00 g of carboxylic acid, 1.89 ml of boron trifluoride diethyl ether and 45 ml of methyl isobutyl ketone was heated under reflux for 2 hours. After cooling, the crystals were collected by filtration and washed with diethyl ether to obtain 3.20 g of colorless crystals. NMR spectrum δ (DMSO-d ₆ ) ppm: 1.10-1.15 (2
H, m), 1.28-1.33 (2H, m), 2.80 (3H, d, J = 3Hz), 2.85 (3H, d, J =
3.5Hz), 4.64-4.72 (1H, m), 9.28 (1H, s)

Reference Example 2 [1-Cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-4-oxo-7-((S) -7
-Trifluoroacetylamino-5-azaspiro [2.
4] hept-5-yl) quinoline-3-carboxylic acid-O
³ , O ⁴ ] difluoroboron [1-cyclopropyl-6,7-difluoro-1,4-
Dihydro-5,8-dimethyl-4-oxoquinoline-3
- carboxylic acid -O ^3, O ^4] difluoro boron 1.00
g, (S) -7-trifluoroacetylamino-5-azaspiro [2.4] heptane hydrochloride ([α] _D ²⁰ -56.
1 ° (c = 0.1, H ₂ O)) 0.86 g, triethylamine 1.
A mixture of 35 ml and 4 ml of dimethyl sulfoxide was heated at an external temperature of 3
The mixture was heated and stirred at 0 ° C for 5 days. (S) -7-Trifluoroacetylamino-5-azaspiro [2.4] heptane hydrochloride (0.36 g) and triethylamine (0.20 ml) were added, and the mixture was heated and stirred at an external temperature of 40 ° C for 1 day. Water was added to the reaction solution under ice cooling to adjust the pH to 3 to 4 with 10% hydrochloric acid, and the precipitated crystals were collected by filtration,
The crystals were washed with water to obtain 1.38 g of yellowish brown crystals. The crystals were purified by column chromatography [methylene chloride-methanol (70: 1 to 50: 1)] and washed with a mixed solution of acetone and diethyl ether to obtain 0.93 g of pale yellow crystals. NMR spectrum δ (DMSO-d ₆ ) ppm: 0.62-1.02 (6
H, m), 1.18-1.34 (2H, m), 2.56 (3H, s), 2.70 (3H, d, J = 3Hz),
3.32-3.42 (1H, m), 3.63-3.74 (1H, m), 4.00-4.28 (3H, m), 4.
48-4.58 (1H, m), 9.10 (1H, s), 9.63 (1H, d, J = 6Hz)

Example 1 1-Cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-4-oxo-7-((S) -7-
Trifluoroacetylamino-5-azaspiro [2.
4] Hept-5-yl) quinoline-3-carboxylic acid [1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-4-oxo-7-((S) -7
-Trifluoroacetylamino-5-azaspiro [2.
4] hept-5-yl) quinoline-3-carboxylic acid-O
A mixture of 0.90 g of ³ , O ⁴ ] difluoroboron, 0.89 ml of triethylamine, 18 ml of methanol and 9 ml of 1,2-dichloroethane was heated under reflux for 8 hours. The reaction solution was concentrated under reduced pressure, water was added to the residue, and the crystals were collected by filtration and washed successively with water, isopropanol and diethyl ether to obtain 0.76 g of yellow crystals. This crystal was recrystallized from a mixed solution of methylene chloride and methanol to give a melting point of 226.5 to 227.
Pale yellow prism crystals at 5 ° C. were obtained. Elemental analysis C ₂₃ H ₂₃ F ₄ N ₃ O ₄ Theoretical value C _, 57.38; H, 4.82; N, 8.73 Experimental value C _, 57.03; H, 4.78; N, 8.61 Optical rotation [α] _D ²⁰ -132.0 ° ( c = 0.1, DMF)

Example 2 7-((S) -7-amino-5-azaspiro [2.4]]
Hept-5-yl) -1-cyclopropyl-6-fluoro-1,4-dihydro-5,8-dimethyl-4-oxoquinoline-3-carboxylic acid 1-cyclopropyl-6-fluoro-1,4- Dihydro-5,8-dimethyl-4-oxo-7-((S) -trifluoroacetylamino-5-azaspiro [2.4] hept-5-yl) quinoline-3-carboxylic acid 0.60
1 g of potassium hydroxide, 0.41 g of potassium hydroxide and 4 ml of water
Stir at room temperature for hours. The reaction solution was adjusted to pH 8 with 10% hydrochloric acid, and the precipitated crystals were collected by filtration and washed with water to obtain 0.41 g of slightly brown crystals. Recrystallized from acetonitrile, melting point 180-18
0.15 g of pale brown crystals at 1.5 ° C. were obtained. Elemental analysis C ₂₁ H ₂₄ FN ₃ O ₃ theory _{C, 65.44; H, 6.28;} N, 10.90 Found _{C, 65.30; H, 6.31;} N, 10.90 Optical rotation [α] _D ²⁰ - 59.0 ° (c = 0.1, DMF)

[0041]

INDUSTRIAL APPLICABILITY The novel 5,8-dimethylquinoline-3 represented by the above general formula (I) thus produced
-Carboxylic acid derivatives and their pharmacologically acceptable salts are extremely useful as antibacterial agents because they have excellent antibacterial activity and high safety.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Yoichi Yamamoto 72 U, Hatta-cho, Nanao City, Ishikawa Prefecture

Claims (2)

[Claims] 1. The following general formula: (In the formula, R ¹ represents a hydrogen atom or a lower alkyl group, R ² represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a halogeno lower alkanoyl group or an ester-type protecting group, R ³
Represents a hydrogen atom or a lower alkyl group. ) 5,8-dimethylquinoline-3-carboxylic acid derivative and a pharmacologically acceptable salt thereof. 2. The following general formula: (In the formula, R ¹ represents a hydrogen atom or a lower alkyl group, R ² represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a halogeno lower alkanoyl group or an ester-type protecting group, R ³
Represents a hydrogen atom or a lower alkyl group. ) An antibacterial agent containing the 5,8-dimethylquinoline-3-carboxylic acid derivative and the pharmacologically acceptable salt thereof as an active ingredient.