1-(6-amino-3,5-differencein-2-yl)-8-bromo-7(3-ethyl - aminotetralin-1-yl)-6 - fluoro-4-oxo-1,4-dihydroquinoline-3 - carboxylic acid, pharmaceutical composition and method of treatment based on this connection

 

(57) Abstract:

The invention relates to 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihyd-rhinolin-3-carboxylic acid or its salt, as well as to antimicrobial drug and compositions on the basis of this compound or its salts. The technical result - obtaining a new 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihyd-rhinolin-3-carboxylic acid or its salts and medicines in the prevention and treatment of various infectious diseases of humans and animals. 4 N. p. F.-ly, 4 PL.

The scope of the invention

This invention relates to derivatives of quinoline-carboxylic acids and their salts, which exhibit excellent antimicrobial activity and oral absorption and antimicrobial agents, including them.

Background of the invention

It is known that compounds having a basic skeleton quinoline-carboxylic acid, include many compounds which are useful as synthetic antimicrobial agents due to their excellent antimicrobial activity and a broad spectra of antimicrobial activity. Among ofloxacin (JP 60-228479) and similar widely used in clinical practice as therapeutic agents against infectious diseases.

However, these compounds still have insufficient antimicrobial activity, absorption in the gut and metabolic stability and cause a lot of problems that need to be resolved, such as the reduction of phototoxicity and cytotoxicity characteristic quinoline-carboxylic acid and its derivatives. Recently there was also the problem with the emergence of bacteria resistant to these medicines.

Description of the invention

Therefore, the present invention is the provision of an antimicrobial agent that is clinically applicable, has excellent antimicrobial activity, absorption in the gut and metabolic stability, and exhibits low side effects.

When the above-mentioned circumstances, the present inventors have conducted extensive studies to provide clinically excellent medicinal agents. The result found that derivatives pyridonecarboxylic acid represented by the following formula (I):

in which R1denotes a hydrogen atom or carboxylate group, R2denotes a hydroxyl group, a lower alkoxygroup or substituted Dorada or halogen atom, R5denotes a halogen atom or a substituted or unsubstituted saturated cyclic amino group, R6denotes a hydrogen atom, a halogen atom, a nitro-group or a protected or unprotected amino group, X, Y, and Z may be the same or different and each independently represents a nitrogen atom, -CH= or-CR7= in which R7denotes a lower alkyl group, halogen atom or cyano, provided that at least one of X, Y and Z denotes a nitrogen atom and W represents a nitrogen atom or-CR8= in which R8denotes a hydrogen atom, halogen atom or lower alkyl group, and their salts have excellent antimicrobial activity and are useful as synthetic antimicrobial agents, and they filed an international PCT application (WO 97/11068 A).

The inventors conducted further research. In the result it was found that among the above derivative pyridonecarboxylic acid (I) 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-ethylamine-ortho-azetidin-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which has a 6-amino-3,5-differencialnoe group in position 1, ethylaminomethyl group in position 7, and the bromine atom in position 8 and presents SCHOU antimicrobial activity and a broad spectrum of antimicrobial action, covering resistant bacteria do not show phototoxicity, which is characteristic of the quinolone, and have a lesser antihypertensive effect and side effects on the skin, such as rashes, than known compounds of similar structures, and, in addition, have a great half-life in blood is extremely high bioavailability and is extremely useful as prophylactic and therapeutic agents of various infectious diseases, which has led to completion of the present invention.

Specifically, the present invention provides 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (hereinafter referred to as “compound 1”), or its salt.

The present invention also provides a drug comprising as an active ingredient the compound 1 or its salt.

The present invention is also a pharmaceutical composition comprising compound 1 or its salt and a pharmaceutically acceptable carrier.

In addition, the present invention provides the use of compound 1 or its salts as a drug.

Nastawienie compound 1 or its salt.

The best ways of carrying out the invention

Connection 1 of the present invention can be obtained in the form of additive salts of acids and in the form of additive salts of the bases. It should be noted that the compounds that form chelates with boron compounds are also included in these salts.

Examples of the additive salts of the acids may include (a) salts with mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, (b) salts with organic carboxylic acids such as formic acid, acetic acid, citric acid, trichloroacetic acid, triperoxonane acid, fumaric and maleic acid, and (C) salts with sulfonic acids such as methanesulfonate acid, benzolsulfonat acid, paratoluenesulfonyl acid, mesitylenesulfonic acid and naphthalenesulfonate acid, while examples of the additive salts of the bases may include (a’) salts with alkali metals, such as sodium and potassium, (b’) salts with alkaline-earth metals such as calcium and magnesium, (C’) ammonium salts (a’) salts with nitrogen-containing organic bases such as trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, IER is P CLASS="ptx2">Illustrations of boron compounds are the halides of boron, such as boron fluoride, and the lower allocable, such as acetoxylation. Of them preferred additive, acid salts, and particularly preferred maleate, methanesulfonate, paratoluenesulfonyl and hydrochloride.

Connection 1 or their salts according to the present invention can exist not only in resolutional form, but also in the form of hydrate or solvate. Accordingly, each of the compounds of the present invention covers all its crystalline form, hydrate and salt wool.

Compound 1, or a salt, according to the present invention, each, it is possible to obtain the desired way.

The approximate method can be illustrated as follows:

where R1and R2denote lower alkyl groups, and R3denotes a hydrogen atom or aminosidine group (for example, tert-butyl, benzyl, parametersjpanel or 1,1,3,3-TETRAMETHYLBUTYL).

Connection 1 of the present invention can be obtained by the reaction of the ether orthomorphisms acid, such as utilitarian or meteorophobia, with the compound (A) with the formation of a derivative of acrylic ester (B), reaction of a derivative of acrylic is soedineniya (E), hydrolysis of the compound (E) in the compound (F) and the subsequent interaction of the compound (F) with 3-ethylaminoethanol.

The reaction between the compound (A) and the ether orthomorphisms acid is usually carried out at 0-160S, preferably at 50-150C, and the reaction time usually ranges from 10 minutes to 48 hours, preferably 1-10 hours. Ether of orthomorphisms acid can preferably be used in an equimolar or greater amount relative to the compound (A), especially in a molar amount of about 1-10 times relative to the compound (A). It is preferable to add as a promoter of the reaction, the carboxylic acid anhydride such as acetic anhydride. The carboxylic acid anhydride can be preferably used in equimolar or greater amount relative to the compound (A), especially in a molar amount of about 1-10 times relative to the compound (A).

The reaction with compound (C) is carried out without solvent or in a suitable solvent. In this reaction it is possible to use any solvent, while it does not affect the reaction. Examples are aromatic hydrocarbons, such as benzene, toluene and xylene; ethers such as diethyl ether, tetrahydrofuran, dioxane, Uglevodorody, such as methylene chloride, chloroform and carbon tetrachloride; aprotic polar solvents such as dimethylformamide and dimethyl sulfoxide; alcohols such as methanol, ethanol and propanol. This reaction is usually carried out at 0-150C, preferably at 0-100C, and the reaction time is usually from 10 minutes to 48 hours. Connection (s) can be used in equimolar or greater amount relative to the compound (A), especially in the molar quantity, 1-2 times relative to the compound (A).

In an alternative method, an acetal such as N,N-dimethylformamidine or N,N-dimethylformamidine, is subjected to the interaction with the compound (A) with subsequent interaction with the compound (C) obtaining the compound (D). In the reaction it is possible to use any solvent, if only it does not affect the reaction. Examples are solvents listed above. This reaction is usually carried out at 0-150C, preferably at room temperature and up to 100C, and the reaction time is usually from 10 minutes to 48 hours, preferably from 1 to 10 hours.

This is followed by a reaction in which compound (D) is subjected to cyclization with obtaining compound (E), in the presence or in the absence of the and reaction. Examples are aromatic hydrocarbons, such as benzene, toluene and xylene; ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme; halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride; aprotic polar solvents such as dimethylformamide and dimethyl sulfoxide; alcohols such as methanol, ethanol and propanol. The compounds used as the primary connection may include, for example, alkali metals such as metallic sodium and metallic potassium; metal hydrides such as sodium hydride and calcium hydride; inorganic salts such as sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate; an alcoholate such as sodium methylate, sodium ethylate, trebuchet sodium; metal fluorides such as sodium fluoride and potassium fluoride; and organic bases such as triethylamine and 1,8-diazabicyclo[5.4.0]undecene (DBU). The reaction temperature is usually from 0 to 200C, preferably from room temperature to 180C, and the reaction can be completed in time from 5 minutes to 24 hours. The basic compound can be used in equimolar or greater amount relative to the compound (D), especially in the molar is minatomirai group, R3hydrolysis of the compound (E) gives the possibility to obtain compound (F).

For hydrolysis of all applicable conditions of reactions, usually used in the hydrolysis. The hydrolysis can be carried out, for example, in the presence of a basic compound such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, mineral acids such as hydrochloric, sulfuric or Hydrobromic acid, or organic acids such as para-toluensulfonate acid, in a solvent, for example water, alcohol such as methanol, ethanol or propanol, simple ether, such as tetrahydrofuran or dioxane, a ketone such as acetone or methyl ethyl ketone, acetic acid or mixtures of these solvents. Usually, the reaction can be conducted at a temperature from room temperature up to 180C, preferably from room temperature to 140 C, and the reaction time may usually be from 1 to 24 hours.

Further, the compound (F) is subjected to interaction with 3-ethylaminoethanol, to obtain the compound 1 of the present invention.

This reaction can be carried out in a solvent which does not affect the reaction, for example in an aromatic hydrocarbon such as benzene, toluene or xylene, alcohol such as methanol or ethanol, a simple EF is, chloroform or carbon tetrachloride, an aprotic polar solvent such as dimethylformamide, dimethylsulfoxide or N-organic, acetonitrile or pyridine, in the presence of, if necessary, agent, neutralizing the acid, for example sodium carbonate, calcium carbonate, triethylamine or 1,8-diazabicyclo[5.4,0]undecene (DBU), at a temperature from room temperature up to 160S. The reaction time may range from several minutes to 48 hours, preferably from 10 minutes to 24 hours. 3-Acylaminoacyl can be used in equimolar or greater amount relative to the compound (F), preferably in a molar amount of 1-5 times relative to the compound (F).

Compound 1 can be converted to additive salt of the acid or additive salt of the base with the methods known in this field.

This reaction can be carried out in a polar solvent, for example, alcohol such as methanol or ethanol, or water in the presence of mineral acids such as hydrochloric, sulphuric or phosphoric acid, organic acids such as formic acid, acetic acid, citric acid, trichloroacetic acid, triperoxonane acid, fumaric or maleic acid, organic sulfonic acid is Lifanova acid or naphthalenesulfonate acid, basic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide or magnesium hydroxide, or organic nitrogen-containing bases, such as ammonia, trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, cyclohexylamine, procaine, dibenzylamine, N-benzyl-phenethylamine, 1-fenamin or N,N’-dibenziletilendiaminom, at room temperature or under heating, if necessary.

The original compound (A) can be obtained, for example, by the way, opened in any of the following publications, or in the same way.

(1) J. Heterocyclic Chem., 22, 1033 (1985)

(2) Liebigs Ann. Chem., 29 (1987)

(3) J. Med. Chem., 31, 991 (1988)

(4) J. Org. Chem., 35, 930 (1970)

(5) JP 62-246541 AND

(6) JP 63-26272 AND

(7) JP 63-145268 AND

(8) J. Med. Chem., 29, 2363 (1986)

(9) J. Fluorin. Chem., 28, 361 (1985)

(10) JP 63-198664 AND

(11) JP 63-264461 AND

(12) JP 63-104974 AND

On the other hand, reacting the compound (C) can be obtained in a desired way. For example, it can be obtained by substitution of the amino derivatives of the halogen atom attached to the carbon atom of the 6-membered cycle in accordance with the known reaction of substitution of the halogen-amine described in WO 97/11068 a or WO 97/38971 A.

The media in this area. Depending on the conditions of extraction and purification of the compound obtained as salts or in the form of the free carboxylic acid or free amine. These two forms can be transformed one into the other, if desired, the compound of the present invention can be obtained in the desired form.

Connection 1 which is 6-amino-3,5-differencialnoe group in position 1, ethylaminomethyl group in position 7, and the bromine atom in position 8, and salts thereof obtained by the method described above, as will be demonstrated in tests 1-4, show action, unpredictable, based on the correlation of structure-activity taken today in relation to derivatives pyridonecarboxylic acid represented by the formula (I), that is, have a great half-life in the blood when administered orally and show an extremely high value (78%) bioavailability, calculated from the AUC, up to the 24th hour after injection, while maintaining excellent properties, such as extremely good antimicrobial activity and lack of phototoxicity characteristic of the quinolone. In addition, compound 1 and its salts also possess excellent properties, with a lesser antihypertensive action and side effects in the tion 1 and its salts, according to the present invention, each can be formed as an antimicrobial agent together with pharmaceutically acceptable carriers in compositions for parenteral administration, e.g. by injection, rectal administration, instillation or oral administration in solid or liquid form.

Examples of drugs for injection may include pharmaceutically acceptable sterile aqueous or nonaqueous solutions, suspensions and emulsions. Illustrations nonaqueous carriers, diluents, solvents and fillers are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters, for example etiloleat. Such solutions, if necessary, may also contain additives such as preservatives, moisturizing agents, emulsifiers and dispersing agents. Injectable preparations can be sterilized, for example, by filtration through a bacterial filter or added immediately before use sterilizing agents, alone or in the form of sterile solid compositions, soluble in any other sterile environment for injection.

The preparations for introduction via instillation, if you think is you, isotonic agents, thickeners and similar.

Examples of solid preparations for oral administration may include capsules, tablets, pills, powders and granules. After making such solid preparations of the compounds of the present invention are usually mixed, with at least one inert extenders such as sucrose, lactose or starch. In the preparation of conventional drugs can also use materials other than inert extenders such as lubricants (e.g. magnesium stearate). Capsules, tablets and pills, you can use the buffers. Tablets and pills may be coated with intersolubility shell.

Examples of liquid preparations for oral administration can include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing commonly used inert diluents, for example water. In addition to the inert diluents can also be added additives such as wetting agents, emulsifiers or suspendresume agents, sweetening agents, spices and flavorings.

Preparations for rectal application in addition to the compounds of the present invention may contain fillers, tarium depending on the properties of the connection the method of application, the required period of treatment and other factors. However, the daily dose is preferably from about 0.1 to 1000 mg/kg, particularly preferably from about 0.5 to 100 mg/kg, alternatively, the daily dose can be administered 2 or 4 portions, as desired.

Examples

Hereinafter the present invention will be described in more detail using examples and reference examples.

Referential example 1. Synthesis of ethyl 8-bromo-1-[6-(tert-butylamino)-3,5-differencein-2-yl]-6,7-debtor-4-oxo-1,4-dihydroquinoline-3-carboxylate.

To a solution in chloroform (5 ml), which was dissolved ethyl 3-ethoxy-2-(3-bromo-2,4,5-triftorbyenzola) acrylate obtained well-known in this field by way of ethyl 3-bromo-2,4,5-tripersonality (1,32 g), is added 2-amino-6-(tert-butylamino)-3,5-giftability, when TLC monitoring of the reaction until, until becoming aminoacylation derived. The reaction mixture was concentrated under reduced pressure, obtaining a yellow solid residue. To the residue is added anhydrous potassium carbonate (1.2 g) and N,N-dimethylformamide (2 ml), and the mixture was stirred at 90 ° C for 15 minutes. The mixture is allowed to cool. Add chloroform (30 ml) and distilled water (300 ml) and allow the mixture section is ω magnesium, concentrate under reduced pressure and put aside. The precipitate is collected by filtration and washed successively with ethanol and diisopropyl ether in that order, receiving specified in the header connection (1,41 g) as colorless powder.

Melting point: 198-S.

1H NMR (Dl3) :

to 1.38 (s, N), of 1.40 (t, J=1 Hz, 3H), Android 4.04 (q, J=7 Hz, 2H), 4,71 (sh.S., 1H), 7,20 (DD, J=8 Hz, 10 Hz, 1H), at 8.36 (DD, J=9 Hz, 10 Hz, 1H), 8,54 (s, 1H).

Referential example 2. Synthesis of 1-(6-amino-3,5-differencein-2-yl)-8-bromo-6,7-debtor-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

Ethyl 8-bromo-1-[6-(tert-butylamino)-3,5-differencein-2-yl]-6,7-debtor-4-oxo-1,4-dihydroquinoline-3-carboxylate (1,38 g) is added to a liquid mixture of 12% hydrochloric acid (3.5 ml) and acetic acid (3.5 ml) and the mixture is heated for 5 hours under stirring and boiling under reflux. After adding distilled water (5 ml) the mixture is allowed to cool. The precipitate is collected by filtration and washed successively with ethanol and diisopropyl ether in that order, getting mentioned in the title compound (1.10 g) as colorless powder.

Melting point: 272-S.

1H-NMR (D6-DMSO) :

to 6.80 (s, 2H), 7,99 (t, J=9 Hz, 1H), scored 8.38 (t, J=9 Hz, the-1,4-dihydroquinoline-3-carboxylic acid (compound 1).

3-Acylaminoalkyl (700 mg), 1-(6-amino-3,5-differencein-2-yl)-8-bromo-6,7-debtor-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (1.5 g), N-methylpyrrolidone (2.0 g) and dimethyl sulfoxide (4.5 g) are combined and the mixture is heated under stirring at 40C for 24 hours. After the mixture is allowed to cool, add isopropyl ether (10 ml), the mixture is stirred and remove the transparent layer with the surface of the mixture. Repeat the same procedure and the residue concentrated under reduced pressure. Add ethanol (5 ml) and the mixture is heated under stirring at 70 C for 30 minutes. Precipitated precipitated solid is collected by filtration. Get listed in the title compound (1.38 in).

Appearance: colorless powder.

Melting point: 195-S.

1H NMR (D6-DMSO) :

0,99 (t, J=7 Hz, 3H), 2,48 (kV, J=7 Hz, 2H), 4,05-to 4.15 (m, 2H), 4,35 was 4.42 (m, 1H), 4,60-4,69 (m, 2H), 6,74 (sh.with. 2H), 7,88 (d, J=14 Hz, 1H), to 7.93 (t, J=9 Hz, 1H), 8,69 (s, 1H).

Example 2. Synthesis maleate of 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound 2).

1-(6-Amino-3,5-differencein-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (1,38 g) are added to ethanol (13 ml) to the mixture and gradually add the art is allowed to cool, the solid is collected by filtration. The solid is washed with ethanol. Get listed in the title compound (1,33 g).

Appearance: colorless powder.

Melting point: 196-S.

1H NMR (D6-DMSO) :

of 1.16 (t, J=7 Hz, 3H), of 2.93 (q, J=7 Hz,2H), 3,99-4,06 (m, 1H), to 4.41-4,48 (m, 1H), 4,50-4,56 (m, 1H), 4,67-4,74 (m, 1H), 4,74-4,82 (m, 1H), 6,02 (s, 2H), 6,76 (sh.with. 2H), 7,95 (t, J=9 Hz, 1H), of 7.97 (d, J=14 Hz, 1H), up 8.75 (s, 1H).

Test

In tests 1-4 will be described results of testing the compounds of the present invention to antimicrobial activity, toxicity and in vivo distribution. As comparative compounds using the following compounds disclosed in WO 97/11068 and industrially available, ciprofloxacin (CPFX) and levofloxacin (LVFX).

Comparative compound 1:

1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-methylaminomethyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

Comparative compound 2:

1-(6-amino-3,5-differencein-2-yl)-8-chloro-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

CPFX:

1-cyclopropyl-6-fluoro-7-(1-piperazinil)-1,4-dihydro-4-oxoindole-3-carboxylic acid.

LVFX:

S(-)-9-fluoro-2,3-dihydro-3-IU is the amount of action

Determine the minimum inhibiting the growth concentration (MIC: μg/ml) in accordance with the standard method of Japan Society of Chemotherapy [Chemotherapy, 29(1), 76 (1981)].

The results are presented in table.1.

(2) Test for phototoxicity

Test for phototoxicity carried out by the following method. The ICR female mice (5-6 weeks of age) administered intravenously tested compound (40 mg/kg/10 ml) and subjected them within 4 hours of UV radiation (320 to 400 nm, and 1.8 mV/cm2/s). See anomalies in their ears at time 0 h (immediately after exposure) and after 24 and 48 hours.

Anomalies in the ears is classified according to the following standards:

no anomalies (0 units), mild erythema (1 unit), the average erythema (2 units) and severe erythema or edema (3 units).

The results are presented in table.2.

(3) Antibacterial effect on clinically selected resistant chinolone pneumococci(pneumococci)

Using tablets with agar with 5% defibrinating sheep blood, determine the minimum inhibiting the growth concentration (MIC: μg/ml) relative to some pneumococci in accordance with standartnym method of Japan Society of Chemotherapy [Chemothera the unity of the present invention show antimicrobial activity, comparable to the activities of the comparative compounds or above, and are not any phototoxic.

(4) Pharmacokinetic study in vivo

The study was conducted in absorption and excretion of the compounds of the present invention in dogs.

a 0.5% Suspension of one of the investigated compounds in the methyl cellulose (10 mg/ml/kg) was forcibly administered orally 2-4-year-old male hound dogs, kept in conditions of starvation for 16-17 hours. After the introduction of taking samples of blood through 0,25, 0,5, 1, 2, 4, 6, 8 and 24 hours and get the serum samples. To determine the rate of excretion with urine also collect urine samples until the 24th hour after injection. Concentrations of the studied compounds in samples of serum and urine was measured by the method using paper disks, using as the test bacteria, Bacillus subtilis ATCC6633, and classify the absorption and excretion. Thus obtained results are presented in table.4.

The data table.4 confirm that the compounds of the present invention possess in vivo pharmacokinetic characteristics are significantly improved relative to comparative compounds.

Industrial applicability

Compound 1 and its salts according to the shape of a long half-life in blood and exceptionally high bioavailability while maintaining properties such as an exceptionally high antimicrobial effects and low toxicity. Compound 1 and its salts also possess excellent properties, providing low antihypertensive effect and adverse effect on the skin, such as rashes, compared to known compounds of similar structures. Therefore, compound 1 and its salts can be widely used as prophylactic and therapeutic agents against various infectious diseases of humans and animals, as well as medicines for fish, agricultural chemicals, food preservatives and similar. In addition, it is expected that the compound 1 and its salts have antiviral activity, especially against HIV (human immunodeficiency virus), and it is believed that they are effective for the prevention and treatment of AIDS.

1. 1-(6-Amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or its salt.

2. Antimicrobial drug, representing 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or its salt.

3. Antimicrobial pharmaceutical composition comprising 1-(6-amino-3 the salt and a pharmaceutically acceptable carrier.

4. A method of treating infectious diseases, including the introduction of 1-(6-amino-3,5-differencein-2-yl)-8-bromo-7-(3-acylaminoalkyl-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a salt thereof.

 

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