JPH07228593A - Steroid derivative - Google Patents

Abstract

PURPOSE:To obtain a new compound useful as an antibacterial or anti- inflammatory agent. CONSTITUTION:This new compound as a steroid derivative has the structure expressed by formula I (R is H, methyl or OH), where the carboxyl group of a quinolonecarboxylic acid and the 21-site alcoholic hydroxyl group of a steroid compound are linked to each other by esterification {e.g. 11beta,17,21- trihydroxy-4-piperazinyl)-4-oxo-3-quinolinecarboxylatel }. The compound of formula I is obtained by reaction between a quinolonecarboxylic acid of formula II and a steroid-21-halogen of formula III (X is a halogen).

Description

Detailed Description of the Invention

[0001]

The present invention relates to a novel and useful ester compound of quinolonecarboxylic acid and a steroid compound,
It relates to its manufacturing method and its use. For more details,
The present invention relates to a compound having a structure in which a carboxyl group of quinolonecarboxylic acid and an alcoholic hydroxyl group at position 21 of a steroid compound are esterified and bonded, or a pharmaceutically acceptable salt thereof, a method for producing the same and an active ingredient thereof. As an antibacterial agent and an anti-inflammatory agent.

[0002]

2. Description of the Related Art In bacterial infection, the first condition is to kill the bacteria with antibiotics or antibacterial agents. Conventional antibiotics have almost no effect on MRSA bacteria (resistant staphylococci), and synthetic antibacterial agents, especially quinolonecarboxylic acid, are promising, and intensive studies are currently underway. In addition, since bacterial infection is often clinically accompanied by inflammation, it is usually used together with a non-steroidal anti-inflammatory drug or a steroidal anti-inflammatory drug. Of these, steroidal anti-inflammatory agents have excellent anti-inflammatory effects, but have side effects such as a decrease in immunity, and therefore have the drawback that they tend to cause bacterial infection. In any case, the current situation is that the administration of the steroidal anti-inflammatory drug is carefully performed while paying attention to the bacterial infection of the patient.

[0003]

Under these circumstances, the inventors of the present invention have focused their attention on solving the above problems with a novel compound having both an antibacterial action and an anti-inflammatory action, and have conducted diligent research. It was As a result, a compound having a structure in which a carboxyl group of quinolonecarboxylic acid, which is a synthetic antibacterial agent, and an alcoholic hydroxyl group at 21-position of a steroid agent are esterified and bonded, and a pharmacologically acceptable salt thereof have been successfully synthesized. Moreover, it was discovered that these compounds fulfill the above-mentioned objects. Based on these new findings,
After further study, the present invention has been completed.

[0004]

The present invention is based on the formula (1) (I)

[Chemical 2] [In formula, R shows a hydrogen atom, a methyl group, or a hydroxyl group. ] The compound having a structure in which the carboxyl group of quinolonecarboxylic acid and the alcoholic hydroxyl group at 21-position of the steroid agent are esterified and bonded, or a pharmaceutically acceptable salt thereof (hereinafter referred to as the present compound) ), (2) its production method (3), and an antibacterial and anti-inflammatory agent containing the same as an active ingredient.

The steroid compound, which is one of the constituents of the present compound, is an adrenocortical hormone (also called corticoid) secreted from the adrenal cortex, and is divided into a mineralocorticoid and a glucocorticoid depending on its physiological activity. Broadly classified, for the purposes of the present invention, any type of corticoid is used as appropriate. Besides, even synthetic steroids can be appropriately used for the purpose of the present invention as long as they have an alcoholic hydroxyl group or a halogen atom at the 21st position.

Examples of the mineralocorticoid used as a constituent element of the present compound include aldosterone, desoxycorticosterone, corticosterone and the like.
Mineralocorticoids are hormones that have a mineral metabolism effect, are involved in the metabolism of inorganic salts, moderately suppress the excretion of sodium chloride and water, and are retained in the interstitium of tissues, and potassium and phosphate from the kidneys are retained. Has the effect of promoting excretion,
It is a substance that is essential for maintaining the life of animals.

Examples of the glucocorticoid used as a constituent element of the present compound include cortisone, hydrocortisone, triamcinolone acetonide, prezonisolone, methylprezonisolone, triamcinolone, dexamethasone, parameterzone, clocortron, fluocinolone, clometazone, betamethasone and the like. It is illustrated.
Glucocorticoid is a corticoid having a glucose metabolism action. That is, glucocorticoids have the effect of metabolizing proteins in the body to carbohydrates, increase the storage of glycogen deposited in the liver, shock, cold,
It has the effect of exerting the resistance of the animal body against trauma, poisoning and the like.

Examples of the quinolonecarboxylic acid used as the other constituent element of the present compound include, but are not limited to, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin, fleroxacin, tosufloxacin and the like. For example, the 1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7- [4-
(4-Aminobenzenesulfonyl) -1-piperazinyl] -3-quinolinecarboxylic acid and the like can also be used for the purpose of the present invention.

The present compound, whether it is a free compound or a pharmacologically acceptable salt thereof, can be appropriately used for the purpose of the present invention. Examples of the salts include inorganic salts such as hydrochlorides, sulfates and nitrates or acetates, and organic salts such as maleates and tartrates, but other salts are also pharmacologically acceptable. Any salt can be used as appropriate as long as it is possible.

This compound can be appropriately synthesized by the following two methods or in accordance with them.

First, the production formula for obtaining this compound by reacting quinolonecarboxylic acid (II) with steroid-21-halogen (III) is shown below. In the formula, X represents a halogen atom, and R has the same meaning as above.

[0012]

[Chemical 3]

Quinolonecarboxylic acid (II) and steroid-21-halogen (III) are used in the same moles in a solvent such as acetone or methyl ethyl ketone.
The present compound (I) can be obtained by heating under reflux in the presence of a base (deoxidizing agent). The solvent used in this reaction may be any solvent other than those mentioned above, as long as it does not inhibit this reaction. This reaction is
It will be completed in about 1 to 24 hours. As the base (deoxidizing agent) used in this reaction, organic amines such as pyridine and triethylamine are preferable. The halogen atom at the 21st position of the steroid compound includes a chlorine atom, a bromine atom and an iodine atom, and the halogenation at the 21st position of the steroid compound can be appropriately performed by a known method (Pharmaceutical Journal, Vol. 81). , Pp. 373 (1961)). The compound (I) thus obtained is recrystallized from an appropriate solvent such as a mixed solvent of water and alcohol or acetone, dimethylformamide (DMF), alcohol, ethyl acetate alone or a mixed solvent thereof. Can be purified. Further, if necessary, the corresponding salt form may be formed by an inorganic acid such as hydrochloric acid, sulfuric acid or nitric acid, or an organic acid such as acetic acid, maleic acid or tartrate.

Next, quinolonecarboxylic acid (II) and 21
Compound having an alcoholic hydroxyl group at the position (V
The formula for producing the present compound (I) by the mixed acid anhydride method with I) is shown. In formulas (IV) and (V), R ₁ represents an alkyl group, and in formula (VI), R has the same meaning as described above.

[0015]

[Chemical 4]

First, the compound (I) can be obtained by producing a mixed acid anhydride (V) of quinolonecarboxylic acid and reacting it with a steroid compound (VI) having an alcoholic hydroxyl group at the 21-position. it can. More specifically, the quinolonecarboxylic acid (II) is reacted with, for example, an alkyl (IV) chlorocarbonate (such as ethyl chlorocarbonate or butyl chlorocarbonate) in a solvent such as chloroform or tetrahydrofuran (THF) in the presence of a base. A mixed acid anhydride (V) of quinolonecarboxylic acid is obtained. The solvent used in the step of producing the mixed acid anhydride may be any solvent other than those mentioned above, as long as it does not inhibit this reaction. This reaction is about -5 ° C to 0
It completes in about 1 to 15 minutes at 0 ° C. The base used in this reaction is preferably an organic amine such as triethylamine or tributylamine. Next, the mixed acid anhydride (V) of quinolonecarboxylic acid thus obtained is reacted with a steroid compound (VI) having an alcoholic hydroxyl group at the 21-position to esterify the compound (I). ) Can be obtained. The solvent used in the present esterification reaction may be any solvent other than the above solvents as long as it does not inhibit the present esterification reaction. This reaction is about 3 at below 0 ° C.
After proceeding for 0 minutes, further proceeding for about 1 hour at room temperature ends. The compound (I) thus obtained can be purified as described above, and may be in the form of a salt if necessary.

The present compound (I) thus obtained
Is a novel compound that has not been published in the literature and has both an antibacterial action and an anti-inflammatory action. Therefore, it exhibits both an antibacterial and anti-inflammatory effect when administered alone, and is therefore extremely useful. It is a compound.

Examples of the anti-inflammatory diseases which can be treated by the anti-inflammatory agent of the present invention include hemorrhoids, rheumatoid arthritis, rheumatoid arthritis, osteomyelosis, osteoarthritis, low back pain,
Gout attack, pleurisy, acute otitis media, cystitis, prostatitis,
Toothache, uveitis, sinusitis and the like.

The antibacterial agent of the present invention is advantageously used for various bacterial infectious diseases caused by Gram-negative bacteria and Gram-positive bacteria.

The drug of the present invention is appropriately used orally or parenterally as an antibacterial agent and an anti-inflammatory agent. Examples of the form of the preparation include solid preparations such as tablets, granules, powders, capsules, ointments and suppositories, or eye drops,
Any form of liquid such as injection and syrup can be appropriately prepared by a known method. These formulations include commonly used excipients, binders, disintegrants, thickeners,
Dispersant, reabsorption promoter, buffer, surfactant, preservative,
Various additives such as an isotonicity agent, a stabilizer and a pH adjuster may be appropriately used.

The drug of the present invention contains
One kind or two or more kinds of the present compound may be contained in an appropriate combination.

When the present compound is used as an antibacterial agent or an anti-inflammatory agent, the dose of the present compound may vary depending on the kind of the compound used, the kind of target disease, the weight of the patient, the age and the indication symptoms and the administration method. Different, for example
In the case of injection, adults about 0.1 mg to about 30 mg once a day,
In the case of oral preparations, for adults, several times a day, 1 dose to about 1 mg
It is recommended to administer about 00 mg. In the case of an ointment, the concentration is about 0.01 to about 1 (w / w)%, preferably about 0.0.
It is preferable that the amount is adjusted to 5 to about 0.5 (w / w)% and applied once to several times a day.

The drug of the present invention may optionally contain other antibacterial agents, anti-inflammatory agents and / or other types of medicinal components as long as the object of the present invention is not impaired.

[0024]

EXAMPLES The present invention will be described in more detail with reference to examples.

[Example 1] Norfloxacin-hydro
Process for producing cortisone ester hydrochloride 11β, 17,21-trihydroxy-4-pregnene-3,20-dione-21- [1-ethyl-6-fluoro-1,4-dihydro-7- (1-piperazinyl) -4
-Oxo-3-quinolinecarboxylate] hydrochloride Hydrocortisone-21-iodo (1.0 g) and norfloxacin (0.68 g) are added with acetone (40 ml), and further with triethylamine (1 ml), and the mixture is heated under reflux for 3 hours. Norfloxacin dissolves as the reaction proceeds. After cooling, the precipitated crystals are collected by filtration, suspended in a mixed solution of ethanol and water, dissolved in this with a 3% sodium hydrogen carbonate solution to be weakly alkaline, and further acidified with hydrochloric acid to collect precipitated white crystals. This is recrystallized from ethanol-water to obtain 0.75 g of the desired compound. Melting point 218
~ 220 ° C (decomposition). Elemental analysis C ₃₇ H ₄₆ FN ₃ O ₇
Theoretical value (%) as HCl · 3 / 2H ₂ O: C, 61.11; H, 6.93;
N ,; 5.78 Found (%): C, 61.17; H, 7.14;
N ,; 5.74

Example 2 Norfloxacin-Dexame
Method for producing sazone ester hydrochloride 9-fluoro-11β, 17,21-trihydroxy-
16α-methyl-1,4-pregnadiene-3,20-
Dione-21- [1-ethyl-6-fluoro-1,4-
Dihydro-7- (1-piperazinyl) -4-oxo-3
-Quinolinecarboxylate] hydrochloride Dexamethasone-21-iodo 0.79 g and norfloxacin 0.5 g, triethylamine 1 ml and acetone 40 ml were reacted in the same manner as in Example 1, the solvent was distilled off, and the precipitated crystals were collected by filtration and washed with water. The crystals of iodohydrochloride obtained later are treated in the same manner as in Example 1 to give the hydrochloride.
This is recrystallized from ethanol to give the target compound 0.55 g.
To get Melting point 214-216 [deg.] C (decomposition). Elemental analysis C ₃₈ H ₄₅ F ₂ N ₃ O ₇ · HCl · 3 / 2H ₂
Theoretical value (%) as O: C, 60.27; H, 6.52;
N, 5.55 Found (%): C, 60.56; H, 6.76;
N, 5.23

[Example 3] Norfloxacin-cortisol
Method for producing ester hydrochloride. 17,21-Dihydroxy-4-pregnene-3,1
1,20-trione-21- [1-ethyl-6-fluoro-1,4-dihydro-7- (1-piperazinyl) -4
-Oxo-3-quinolinecarboxylate] hydrochloride Cortisone-21-iodo 1.0 g, norfloxacin 0.6 g, triethylamine 2 ml, acetone 10 ml
Then, using 10 ml of DMF and DMF, the reaction is carried out in the same manner as in Example 1, the solvent is distilled off, water is added, and the precipitated crystals are collected by filtration. The obtained crystal of iodohydrogen salt is treated in the same manner as in Example 1 to obtain the hydrochloride. This is recrystallized from DMF-ethyl acetate to obtain 0.3 g of the objective compound as white crystals. Melting point 202-204 ° C (decomposition). Elemental analysis C ₃₇ H ₄₄ FN ₃ O ₇ · HCl · 3 / 4H ₂ O
As a theoretical value (%): C, 62.44; H, 6.59;
N, 5.90 Found (%): C, 62.42; H, 6.41;
N, 5.69

Example 4 Lomefloxacin-hydro
Process for producing cortisone ester hydrochloride 11β, 17,21-trihydroxy-4-pregnene-3,20-dione-21-[(±) -1-ethyl-
6,8-Difluoro-1,4-dihydro-7- (3-methyl-1-piperazinyl) -4-oxo-3-quinolinecarboxylate] hydrochloride Hydrocortisone-21-iodo 0.47 g, lomefloxacin 0.39 g Example 1 using 3 ml of triethylamine, 50 ml of acetone and 10 ml of DMF.
The reaction is performed in the same manner as in (1), the solvent is distilled off, water is added, and the precipitated crystals are collected by filtration. The obtained crystal of iodohydrogen salt is treated in the same manner as in Example 1 to obtain the hydrochloride. This is recrystallized from ethanol-water to obtain 0.15 g of the desired compound. Melting point 2
18-220 ° C (decomposition). Elemental analysis _{C 38 H 47 F 2 N 3} O 7 · HCl · 2H 2 O theoretically (%): C, 59.41; H, 6.82;
N, 5.47 Found (%): C, 59.35; H, 6.92;
N, 5.51

Example 5 9-Fluoro-11β, 1
7,21-trihydroxy-16α-methyl-1,4-
Pregnadien-3,20-dione-21- [1-shik
Ropropyl-6,8-difluoro-7- [4- (4-a
Minobenzenesulfonyl) -1-piperazinyl] -1,
4-dihydro-4-oxo-3-quinolinecarboxylate
Over preparative] of production method 1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-
1.85 g of quinolinecarboxylic acid was suspended in 100 ml of pyridine, 20 ml of a benzene solution of 4.95 g of 4-acetamidobenzenesulfonyl chloride was gradually added to this while stirring under ice-cooling, and the mixture was cooled under ice-cooling for 1 hour and then at room temperature. Stir for 3 hours. The reaction solution is concentrated under reduced pressure, and 1N aqueous sodium hydroxide solution is added to the residue to dissolve it.
This was adjusted to pH 4 with acetic acid, and the precipitated crystals were collected by filtration, washed with water, and recrystallized from DMF-ethanol to give 1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7- [. 2.71 g of 4- (4-acetamidobenzenesulfonyl) -1-piperazinyl] -3-quinolinecarboxylic acid are obtained. Melting point 288-290 [deg.] C (decomposition).

Compound 2.15 thus obtained
g, 2N hydrochloride 100 ml and ethanol 50 ml
The mixture is stirred at reflux for 2 hours. The reaction solution is concentrated under reduced pressure, and 1N aqueous sodium hydroxide solution is added to the solution to dissolve it. The pH of this is adjusted to 7.0 with acetic acid, and the precipitated crystals are collected by filtration and washed with water. Water was added to the crystals collected by filtration, the pH was adjusted to 4 with acetic acid, and the crystals were dissolved.
The pH is adjusted to 7.0 with regular sodium hydroxide, and the precipitated crystals are filtered and washed with water. This was recrystallized from dimethylformamide-ethanol to give 1-cyclopropyl-6,6.
8-difluoro-1,4-dihydro-4-oxo-7-
2.15 g of [4- (4-aminobenzenesulfonyl) -1-piperazinyl] -3-quinolinecarboxylic acid (*) are obtained. Melting point 280-282 [deg.] C. (decomposition). Elemental analysis _{C 23 H 22 F 2 N 4} O 5 S · 1 / 4H 2 O theoretically (%): C, 54.27; H, 4.46;
N, 11.01 Found (%): C, 54.29; H, 4.46;
N, 11.02

(*) The present compound is a novel quinolonecarboxylic acid which was synthesized by the present inventors.

Dexamethasone-21-iodo 0.76
g, 1-cyclopropyl-obtained by the above method
6,8-Difluoro-7- [4- (4-aminobenzenesulfonyl) -1-piperazinyl] -1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 0.75 g, triethylamine 1 ml, acetone 50 ml and DMF
Using 5 ml, heat reflux for 8 hours as in Example 1. After distilling off the solvent under reduced pressure, the precipitated crystals are collected by filtration and washed with water. This is dissolved in chloroform, washed with a 3% aqueous sodium hydrogen carbonate solution and water in this order, and then the solvent is distilled off.
The residual crystalline product is recrystallized from acetone-water to obtain 0.50 g of the objective compound. Melting point 198-200 ° C (decomposition). Elemental analysis Theoretical value (%) as C ₄₅ H ₄₉ F ₃ N ₄ O ₉ S.1 / 2H ₂ O: C, 60.87; H, 5.68;
N, 6.31 Found (%): C, 60.59; H, 5.62;
N, 6.22

Example 6 Ofloxacin-Dexamesa
Method for producing zone ester 9-fluoro-11β, 17,21-trihydroxy-
16α-methyl-1,4-pregnadiene-3,20-
Dione-21-[(±) -9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyrido [1,2,3-d
e] [1,4] Benzoxazine-6-carboxylate] 0.57 g of ofloxacin is dissolved in 30 ml of chloroform, and 0.4 ml of triethylamine is added thereto, and the temperature is kept at 0 ° C or lower. To this, 0.2 ml of ethyl chlorocarbonate was gradually added dropwise, and after stirring for 5 minutes, a pyridine solution of 0.62 g of dexamethasone was added dropwise. Stir for 30 minutes as it is, and further for 1 hour at room temperature. Next, the solvent was distilled off under reduced pressure, water was added to the residue, and the precipitated crystals were collected by filtration and recrystallized from dimethylformamide-isopropyl ether to obtain 0.15 g of the desired compound as white crystals. Melting point 191-19
3 ° C (decomposition). Elemental analysis Theoretical value (%) as C ₄₀ H ₄₇ F ₂ N ₃ O ₈ .H ₂ O: C, 63.73; H, 6.55;
N, 5.57 Found (%): C, 63.69; H, 6.42;
N, 5.46

[Example 7] Ofloxacin-triamushi
Process for producing nolone acetonide ester 9-fluoro-11β, 21-dihydroxy-16α,
17-isopropylidenedioxy-1,4-pregnadiene-3,20-dione-21-[(±) -9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) ) -7-Oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6
-Carboxylate] 0.42 g of ofloxacin, 30 ml of chloroform, 0.3 ml of triethylamine and 0.5 g of triamcinolone acetonide were treated in the same manner as in Example 6, and the obtained crystals were regenerated from dimethylformamide-isopropyl ether. Crystallized white crystalline target compound 0.1
6 g are obtained. Melting point 206-208 ° C (decomposition). Elemental analysis _{C 42 H 49 F 2 N 3} O 9 · 3 / 2H 2 O theoretically (%): C, 62.67; H, 6.51;
N, 5.22 Found (%): C, 62.49; H, 6.33;
N, 5.03

[Experimental Example 8] Rat carrageenin against pleuritis
The inhibitory effect of the present compound was tested for the inhibitory effect of norfloxacin-dexamethasone ester hydrochloride on rat carrageenin pleurisy.

[Test substance] Norfloxacin-dexamethasone ester hydrochloride (abbreviation: NFLX-DX).

[Test Method] Wista weighing about 200 g
r strain rats were used. The group is (1) distilled water (5 ml / k
g) (2) NFLX-DX (13.4 mg / kg) was set. Under pentoparbital anesthesia into rat pleura 2
0.1 ml of% λ-carrageenin was injected to prepare pleurisy. Five hours after the creation of pleurisy, a 5% Pontamine Sky Blue aqueous solution (2 ml / kg) was intravenously injected, 20 minutes after that, the rat was sacrificed, and the exudate in the thoracic cavity was collected using a sonde. The amount of dye leakage (μg / site) in the thoracic cavity was calculated from the leached amount (ml) and the absorbance (625 nm) of the collected sample using a calibration curve. The test substance was orally administered (5 ml / kg) 30 minutes before the induction of inflammation.

[Test Results] The results are shown in Table 1.

[0039]

Table 1 Effect group of this compound on rat carrageenin pleurisy n Dye leakage (μg / site) Suppression rate (%) Control group (distilled water) 8 74.81 ± 10.70 ─ NFLX-DX 7 20.20 ± 3.80 * 73.0 Dye Leakage Value indicates the mean ± standard error. * Significantly different from control group; p <0.01.

As is clear from Table 1, this compound showed a significant inhibitory effect on rat carrageenin pleurisy.

[Formulation Example 1] Oral tablet Compound of Example 2 100 mg Lactose 80 mg Starch 17 mg Magnesium stearate 3 mg Using the above ingredients as ingredients for one tablet, tablets are formed by a conventional method. A sugar coating may be added if necessary.

[Formulation Example 2] Ophthalmic solution Compound of Example 6 200 mg Boric acid 700 mg Borax 300 mg Sodium chloride 500 mg Polyvinyl alcohol 100 mg Benzalkonium chloride 5 mg Sterilized purified water Total amount 100 ml The above ingredients were admixed by a conventional method. Use as liquid.

[Formulation Example 3] Ointment Compound of Example 7 100 mg Hydrophilic ointment Total amount 100 g The above components are mixed according to a conventional method to give an ointment.

[0044]

INDUSTRIAL APPLICABILITY The novel steroid derivative of the present invention has both an antibacterial action and an anti-inflammatory action, so that it exhibits both an antibacterial and anti-inflammatory effect when administered alone, and is therefore extremely useful. It is a compound.

[Brief description of drawings]

1 shows an infrared absorption spectrum (IR) of the compound synthesized in Example 1. FIG.

FIG. 2 shows an infrared absorption spectrum (IR) of the compound synthesized in Example 6.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Kazuhiko Ito 2-8-9 Honcho, Mukonosou, Amagasaki-shi, Hyogo Cube Kitamu-Kunosou I No. 105

Claims (12)

[Claims] 1. Formula (I): [In formula, R shows a hydrogen atom, a methyl group, or a hydroxyl group. ] The compound or its pharmacologically acceptable salt which has a structure represented by the above and which has a structure in which the carboxyl group of quinolonecarboxylic acid and the alcoholic hydroxyl group at 21-position of the steroid compound are esterified and bonded. 2. The chemical name is 11β, 17,21-trihydroxy-4-pregnene-3,20-dione-21-.
[1-ethyl-6-fluoro-1,4-dihydro-7-
(1-Piperazinyl) -4-oxo-3-quinolinecarboxylate], or a pharmaceutically acceptable salt thereof. 3. The chemical name is 9-fluoro-11β, 17,
21-trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione-21- [1-ethyl-
6-Fluoro-1,4-dihydro-7- (1-piperazinyl) -4-oxo-3-quinolinecarboxylate]
The compound according to claim 1 or a pharmaceutically acceptable salt thereof. 4. The chemical name is 17,21-dihydroxy-4.
-Pregnen-3,11,20-trione-21- [1
-Ethyl-6-fluoro-1,4-dihydro-7- (1
-Piperazinyl) -4-oxo-3-quinolinecarboxylate], or a pharmaceutically acceptable salt thereof. 5. The chemical name is 11β, 17,21-trihydroxy-4-pregnene-3,20-dione-21-.
[(±) -1-Ethyl-6,8-difluoro-1,4-
Dihydro-7- (3-methyl-1-piperazinyl) -4
-Oxo-3-quinolinecarboxylate]. The compound or pharmacologically acceptable salt thereof according to claim 1. 6. The chemical name is 9-fluoro-11β, 17,
21-trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione-21- [1-cyclopropyl-6,8-difluoro-7- [4- (4-aminobenzenesulfonyl) -1- Piperazinyl] -1,4-
Dihydro-4-oxo-3-quinolinecarboxylate], or a pharmaceutically acceptable salt thereof. 7. The chemical name is 9-fluoro-11β, 17,
21-trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione-21-[(±) -9-
Fluoro-2,3-dihydro-3-methyl-10- (4
-Methyl-1-piperazinyl) -7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylate] or a pharmacological compound thereof. Acceptable salt. 8. The chemical name is 9-fluoro-11β, 21-
Dihydroxy-16α, 17-isopropylidenedioxy-1,4-pregnadiene-3,20-dione-21
-[(±) -9-Fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-
Oxo-7H-pyrido [1,2,3-de] [1,4]
Benzoxazine-6-carboxylate], The compound according to claim 1, or a pharmaceutically acceptable salt thereof. 9. A process for producing a compound or a pharmaceutically acceptable salt thereof according to claim 1, which comprises reacting a quinolonecarboxylic acid with a compound obtained by halogenating the 21-position of a steroid compound in the presence of a base. . 10. The method for producing a compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the quinolonecarboxylic acid and the steroid compound are esterified by a mixed acid anhydride method. 11. An antibacterial agent comprising the compound according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient. 12. An anti-inflammatory agent comprising the compound according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient.