JP2000273086A - Novel quinolone derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide the subject novel quinolone derivative that is a fermentation product obtained by culturing a specific microorganism in a culture medium, and can manifest excellent anti-Heliconbacter pylori activity. SOLUTION: This novel compound is 2-(2-nonenyl)-4(1H)-quinolone derivative represented by the formula or its salts. The derivative of the formula has the following physicochemical properties: Color and description: pale yellow or white amorphous, translucent solid; Reaction: neutral; Solubility: soluble in methanol and chloroform; Substantially insoluble in water and hexane; Molecular weight: 286.1805; Molecular formula: C18H23NO2; and the like. The derivative of the formula is obtained by culturing a microorganism in Atthrobacter, for example, Arthrobacter sp. YL-02729 strain and isolating and purifying the product from the culture mixture. The medicine including this derivative as an active ingredient can be expected as a therapeutic agent for diseases, for example, digestive ulcer, digestive inflammation as an anti-Helicobacter pylori-agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel quinolone derivative or a salt thereof which is a fermentation product, and a drug containing the derivative as an active ingredient, preferably a drug which is an anti-Helicobacter pylori agent.

[0002]

2. Description of the Related Art Helicobacter pylori
pylori) is a pathogenic bacterium discovered in 1983, and has peptic ulcers (eg, gastric or duodenal ulcers),
It is said to be a cause of inflammation (eg, gastritis) or diseases of the upper gastrointestinal tract such as gastric cancer, or chronic heart disease. Current,
Research on the treatment of Helicobacter pylori infection has been actively conducted, and many treatments have been reported as follows, including those for the purpose of eradication and those for the prevention of recurrence. For example, single drug administration such as bismuth, antibiotics, proton pump inhibitor (PPI), and anti-ulcer drug, or a multi-drug combination method (drug combination, triple-drug combination) combining the above drugs and the like (internal medicine, special feature) Vol. 78, No. 1 (199
6), Nankodo). However, the above-mentioned treatment method, for example, the frequency of the number of times of administration, the fact that it may be necessary to administer a large amount of normal dose or more, the onset of diarrhea / constipation due to drug administration,
There are still many points that need to be resolved, such as the emergence of resistant bacteria.

JP-A-7-189 reports antibiotics which are active against various Gram-positive bacteria and are produced by microorganisms belonging to the genus Arthrobacter.
No anti-Helicobacter pylori action is described. JP-A-11-29479 discloses 2-
An anti-Helicobacter pylori agent containing a (2-nonenyl) -3-methyl-4 (1H) -quinolone derivative as an active ingredient has been reported.

[0004]

Embedded image (The symbol R1 in the formula means a hydrogen atom or a hydroxyl group.)

[0005]

An object of the present invention is to provide a fermentation product having excellent anti-Helicobacter pylori activity,
Furthermore, it aims at providing a medicine containing the fermentation product as an active ingredient.

[0006]

Under the above circumstances, the present inventors have conducted intensive studies on substances produced by many naturally occurring microorganisms, and as a result, have found that Arthrobacter
By culturing microorganisms belonging to the genus in a medium, it was found that a novel substance having anti-Helicobacter pylori activity was produced in the medium. The present invention has been completed by further isolating the substance. That is, the present invention provides 2- (2-nonenyl) -4 represented by the following general formula (I).
The present invention relates to a (1H) -quinolone derivative or a salt thereof, a drug containing the quinolone derivative as an active ingredient, and a drug that is an anti-Helicobacter pylori agent.

[0007]

Embedded image

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The salt of the substance of the present invention is an acid addition salt with an inorganic or organic acid, or a salt with an inorganic or organic base, and a pharmaceutically acceptable salt is preferable. These salts include:
Specifically, a mineral acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid or phosphoric acid, or formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid Acid addition salts with organic acids such as lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid or ethanesulfonic acid, or acidic amino acids such as aspartic acid or glutamic acid, inorganic bases such as sodium, potassium, magnesium, calcium, aluminum And salts with organic bases such as methylamine, ethylamine and ethanolamine, and basic amino acids such as lysine and ornithine.

Since the substance of the present invention has a double bond, cis and trans geometric isomers and tautomers exist. The present invention includes all of these various isomers, and further includes hydrates, various solvates, and the like. Further, the present invention includes some having polymorphism, and includes all of these crystal forms.

(Production method) As a microorganism producing the substance of the present invention, there can be mentioned a bacterium belonging to the genus Arthrobacter, the properties of which are described in JP-A-7-189. Typical production methods include the production method disclosed in Japanese Patent Application Laid-Open No. 7-189. Specifically, bacteria belonging to the genus Arthrobacter, for example, Using Arthrobacter sp. Strain YL-02729 deposited under the deposit number FERM BP-6326 and isolating and purifying the strain from the culture.

The medium used for the culture may be any medium capable of growing the microorganism to be used, and a synthetic medium, a semi-synthetic medium or a natural medium can be used. As nutrients to be added to the medium, known nutrients for bacteria can be used. For example, as a nitrogen source (carbon source), commercially available peptones, meat extracts, corn steep liquor, cottonseed meal, peanut powder, soybean powder, yeast extract, NZ-amine, wheat germ, casein, fish meal, Starches, oats, and inorganic or organic substances such as sodium nitrate and ammonium nitrate, and carbohydrates such as molasses, glucose, maltose, fructose, mannitol, potato starch, corn starch, dextrin, soluble starch and the like, fats and oils as carbon sources Can be used.

The metal salts include Na, K, Mg, C
a, Zn, Fe, Mn, Co, Cu, and other lead sulfates, hydrochlorides, nitrates, phosphates, carbonates, and the like can be added as necessary. If necessary, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine,
Amino acids such as lysine, arginine, glutamic acid and aspartic acid, and secondary metabolite production promoting substances such as vitamins, oleic acid, methyl oleate, lard oil, silicone oil, and surfactants, or defoamers can be used as appropriate. In addition to these, any additive can be used as long as it is utilized by the present compound-producing bacterium and is useful for producing the present substance.

The culturing method may be the same as that of a general antibiotic or the like, and the culturing method may be solid culture or liquid culture. In the case of liquid culture, any of stationary culture, shaking culture, and stirring culture may be performed, but aeration and stirring culture is particularly desirable. As a culture condition, the culture temperature is a temperature at which a producing bacterium can grow and produce the antibiotic of the present invention, that is, a temperature in a range of 15 ° C to 37 ° C.
Is preferred. The pH can be appropriately applied in the range of pH 4 to 9, but pH 6 to 8 is preferable. The culturing time varies depending on various conditions, and is 10 hours to 168 hours.
The substance of the present invention accumulated in the culture solution in about 4 to 120 hours reaches the highest titer.

In order to isolate the desired compound from the culture, conventional extraction and purification means used for isolating metabolites produced by microorganisms can be appropriately used. The substance in the culture may be a culture solution as it is, or a culture filtrate obtained by centrifuging or adding a filter aid to the culture to obtain a culture filtrate, which is an organic compound that is immiscible with water such as ethyl acetate, chloroform, benzene, and toluene. Add solvent and extract. Further, the culture solution is brought into contact with an appropriate carrier, the produced substance in the filtrate is adsorbed, and then the substance is extracted by eluting with a suitable solvent. For example, the substance is adsorbed by contacting a porous adsorption resin such as Amberlite XAD-2, Diaion HP-20, Diaion CHP-20, or Diaion SP-900. Next, the substance is eluted using a mixture of water and an organic solvent such as methanol, ethanol, acetone and acetonitrile. By increasing the mixing ratio of the organic solvent to a high concentration stepwise or continuously from a low concentration at this time, a fraction having a higher ratio of the substance can be obtained. Next, the substance-containing fraction obtained using each of the above-mentioned procedures was applied to silica gel, ODS
And the like, and can be separated and purified further by a conventional method such as column chromatography using HPLC or the like, centrifugal liquid partition chromatography, or high performance liquid chromatography (HPLC) using ODS.

Hereinafter, a method of formulating and administering a drug containing the substance of the present invention as an active ingredient will be described in detail. Pharmaceutical compositions containing one or more of the substance of the present invention or a salt thereof as an active ingredient include tablets, powders, and the like using carriers and excipients for pharmaceutical preparations and other additives that are commonly used. It is prepared into fine granules, granules, capsules, pills, solutions, injections, suppositories, ointments, patches and the like, and is orally or parenterally administered. The clinical dose of the substance of the present invention to humans is appropriately determined in consideration of the symptoms, weight, age, sex and the like of the patient to which the substance is applied. Usually, the dose is 0.1 to 500 mg orally and 0.01 to 100 mg parenterally per day for an adult, and these are administered once or in several divided doses. Since the dose varies under various conditions, a dose smaller than the above dose range may be sufficient.

As the solid composition for oral administration according to the present invention, tablets, powders, granules and the like are used. In such a solid composition, the one or more active substances comprise at least one inert diluent, such as lactose,
It is mixed with mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, metasilicic acid, magnesium aluminate. The composition may contain, in a conventional manner, additives other than an inert diluent, for example, a lubricant such as magnesium stearate, a disintegrant such as calcium cellulose glycolate, a stabilizer such as lactose, glutamic acid or asparagine. A solubilizing or solubilizing agent such as an acid may be contained. The tablets or pills may be coated with a film of a gastric or enteric substance such as sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, if necessary.

Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like, commonly used inert diluents, For example, it contains purified water and ethyl alcohol. This composition contains, in addition to an inert diluent, solubilizing or solubilizing agents, wetting agents, auxiliary agents such as suspending agents, sweetening agents, flavoring agents, flavoring agents,
Preservatives may be included. Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions,
Emulsifying agents. Diluents for aqueous solutions and suspensions include, for example, distilled water for injections and physiological saline. Examples of diluents for non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethyl alcohol, polysorbate 80 (trade name: polyoxyethylene sorbitan higher fatty acid ester) ). Such compositions may further comprise a tonicity agent, a preservative, a wetting agent,
Additives such as emulsifiers, dispersants, stabilizers (eg, lactose), solubilizing or solubilizing agents may be included. These are sterilized by, for example, filtration through a bacteria retaining filter, blending of a bactericide or irradiation. These can also be used by preparing a sterile solid composition and dissolving in sterile water or a sterile injection solvent before use.

When the solubility of the substance of the present invention is low, a solubilization treatment may be performed. As the solubilization treatment, known methods applicable to pharmaceutical preparations, for example, surfactants (polyoxyethylene hydrogenated castor oils, polyoxyethylene sorbitan higher fatty acid esters, polyoxyethylene polyoxypropylene glycols, sucrose fatty acid esters) ), A drug and a solubilizing agent, for example, a polymer [a water-soluble polymer such as hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), or polyethylene glycol (PEG); carboxymethylethylcellulose (CMEC); Propyl methylcellulose phthalate (HPMCP), methyl methacrylate-methacrylic acid copolymer {Eudragit L, Eudragit S, (trade name); ROHM &
And enteric polymers such as those manufactured by Haas Co., Ltd.]. If necessary, a method of forming a soluble salt, a method of forming an inclusion compound using cyclodextrin, or the like can also be employed. The means of solubilization can be appropriately changed according to the target drug ["Recent formulation technology and its application", Isamu Utsumi, Pharmaceutical Journal 157-1
59 (1983) and "Pharmaceutical Monograph No. 1, Bioavailability", Tsuneji Nagai et al., Soft Science, 78
-82 (1988)]. Of these, a method of improving the solubility by forming a solid dispersion of the drug and the solubilizer is preferably used (Japanese Patent Application Laid-Open No. 56-49314, FR24).
No. 60667).

According to the present invention, the substance of the present invention is used not only alone but also in combination with other antibacterial agents (preferably 1 to 3).
Species) can be used. Such other antibacterial agents include, for example, nitroimidazole antibiotics (eg, tinidazole and metronidazole), tetracyclines (eg, tetracycline, minocycline, doxycycline), penicillins (eg, amoxicillin, ampicillin, tarampicillin, bacampicillin, lenampicillin) , Mezlocillin, sultamicillin), cephalosporins (eg, cefaclor, cefadroxil, cephalexin, cefpodoxime proxetil, cefixime, cefdinir, ceftibutene, cefotiamhexetil, cefmetmet pivoxil, cefuroxime axetil), Drugs (eg, fopenem, lipipenem akoxyl), macrolide drugs (eg, erythromycin, oleandomycin) Josamycin, midecamycin, rokitamicin, clarithromycin, roxithromycin, azithromycin), lincomycins (eg, lincomycin, clindamycin), aminoglycosides (eg, paromomycin), quinolones (eg, ofloxacin, levofloxacin) , Norfloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosfloxacin, fleloxacin, spafloxacin, temafloxacin, nadifoxacin, grepafloxacin, pazufoxacin) and nitrofurantoin. Also, pharmaceutical compounds used in the treatment of acid-related diseases {eg, acid pump inhibitors (omeprazole and lansoprazole)) or H
Combinations of two antagonists (eg, ranitidine, cimetidine, and famotidine) with a substance of the present invention are also included within the scope of the present invention.

[0020]

EXAMPLES The present invention will be described in more detail below, but the present invention is of course not limited to these examples.

Example 1 Glucose 1.0%, potato starch 2.0%, yeast extract 0.
Prepare a seed medium (pH 7.0) containing 5%, 0.5% polypeptone and 0.4% calcium carbonate, and place 100ml in a 500ml Erlenmeyer flask.
Was dispensed. After sterilizing this medium at 121 ° C for 20 minutes,
Arthrobacter (Arthr) described in JP-A-7-189.
Bacteria of the genus (obacter) were grown well on Bennett agar, scraped, inoculated, and cultured at 28 ° C. for 48 hours with shaking to obtain a seed culture solution. Next, a medium (pH 7.0) containing 1.0% glucose, 2.0% potato starch, 0.5% yeast extract, 0.5% polypeptone, and 0.4% calcium carbonate was prepared and 2,000ml.
400 ml was dispensed into an Erlenmeyer flask. Keep this medium at 121 ° C
After sterilization for 20 minutes, the culture obtained with the seed culture
% And inoculated at 28 ° C. for 48 hours with shaking. next,
Glucose 1.0%, potato starch 2.0%, yeast extract 0.
A medium (pH 7.0) containing 5%, 0.5% polypeptone and 0.4% calcium carbonate was prepared, and 18L was dispensed into 30L Jar.
After sterilizing this medium at 121 ° C. for 20 minutes, a culture obtained from the above seed culture solution was inoculated at a rate of 2%, and cultured with stirring at 28 ° C. for 72 hours. Next, glycerol 5.0%, yeast extract 0.25
%, Polypeptone 1.0%, and calcium carbonate 0.4%, a seed medium (pH 7.0) was prepared, and 200 L was dispensed into a 300 L Jar.
After sterilizing this medium at 121 ° C. for 20 minutes, a culture obtained from the above seed culture solution was inoculated at a rate of 2%, and cultured with stirring at 28 ° C. for 48 hours.

[0022] 200 L of the culture solution thus cultivated is p
Adjust to H3.0 and filter to separate into supernatant and cells. The obtained supernatant was subjected to Diaion HP-20 (manufactured by Mitsubishi Chemical Corporation) 20
Adsorbed on L, washed with 60L of water, washed with 60L of 30% acetone water, eluted with 100% acetone water, concentrated under reduced pressure to remove acetone, and adjusted to pH 8.5. And
Extracted twice with 20 L of ethyl acetate. One of the cells was added with 50 L of 80% acetone water, stirred and left overnight, and then filtered to separate into a supernatant and a precipitate. After the supernatant was concentrated under reduced pressure to remove acetone, the resulting concentrated solution was adjusted to pH 8.
Adjusted to 5 and extracted twice with 20 L of ethyl acetate. The supernatant and the ethyl acetate layer obtained from the cells were mixed and concentrated to dryness under reduced pressure to obtain a crude extract. This crude extract was subjected to silica gel column chromatography (Wako-Gel C-300: manufactured by Wako Pure Chemical Industries, Ltd.), and first chloroform, then chloroform: ethyl acetate (20: 1), and then chloroform:
Ethyl acetate (9: 1), then chloroform: ethyl acetate (4: 1), then chloroform: ethyl acetate (2: 1),
Subsequently, fractionation was performed by elution with chloroform: ethyl acetate (1: 2) in order to obtain an active fraction containing the target substance (hereinafter referred to as YM-176005). Finally, purification was performed by HPLC, and the active fraction YM-17600 eluted at 19.5 minutes
53.8mg of 5 were isolated. HPLC conditions are as follows. Column: SUPELCOSIL LC-ABZ + PLU
S (manufactured by Spelco, 21.2φ × 250 mm) Elution solvent: mixed solution of tetrahydrafuran / acetonitrile / water (10/80/10) Outflow rate: 6 ml / min Detection wavelength: 210 nm

The above extracted, separated and purified YM-176
005 has the following physicochemical properties. (1) Color and shape: a slightly yellow or white amorphous translucent solid. (2) Classification of acidic, neutral and basic: neutral. (3) Solubility: soluble in methanol and chloroform, but hardly soluble in water and hexane. (4) Ultraviolet absorption spectrum: shows an absorption maximum at 214, 242, 330 and 337 nm (FIG. 1). (5) Molecular weight: 286.1805 (6) Molecular formula: C ₁₈ H ₂₃ NO ₂ (7) Infrared absorption spectrum (KBr): (FIG. 2) (8) ¹ H-NMR spectrum (500 MHz, CDCl ₃ ): ( 3
(9) ¹³ C-NMR spectrum (125 MHz, CDCl ₃ ): (FIG. 4) From the above physicochemical properties, the chemical structural formula of YM-176005 was determined as follows.

[0024]

Embedded image

Example 2 In vitro activity of YM-176005 was measured by the following method. Measurement of antibacterial activity Preparation of antibacterial substance-containing agar plate 100% dimethyl sulfoxide (DMS)
O) and serially diluted 2-fold. Put the diluted solution into a sterile round petri dish, and sterilize it and keep it warm at 50 ° C.
Was added to a Brucella agar medium (0.1% β-cyclodextrin), mixed and solidified. The final concentration of DMSO is 1
% Or less. Preparation of inoculum and results judged Brucella agar medium (5% fetal calf serum-containing) multi-gas incubator with _{(N 2: 80%, CO} 2: 15%, O 2: 5
%) At 37 ° C. for 3 days, for example, Helicobacter pylori ATCC 43504.
It was prepared using Brucella broth to be about 10 ^8/1 ml by turbidity. A solution obtained by diluting this bacterial solution 100-fold with brucella broth was inoculated on agar surface containing about 5 μl of the drug-containing agar medium using a microplanter. The inoculated agar plate was cultured in the above multigas incubator at 37 ° C. for 3 days (72 hours). The agar plate after completion of the culture was observed, and the drug concentration at which no growth was observed was defined as the MIC. As a result, the MI of YM-176005
C was 0.013 μg / ml.

Example 3 In vitro activities against facultative anaerobic bacteria and aerobic bacteria were measured by the following method. Preparation of antibacterial substance-containing agar plate 100% dimethyl sulfoxide (DMS)
O) and serially diluted 2-fold. Put the diluted solution into a sterile round petri dish, and sterilize it and keep it warm at 50 ° C.
Was added to the Mueller Hinton agar medium, mixed, and hardened. The final concentration of DMSO will be less than 1%. With the preparation of inoculum and results determined Mueller Hinton broth, the bacterial solution cultured overnight at incubator set at 37 ° C., diluted prepared to be about 10 ⁶ cells / 1 ml using Muller Hinton broth. About 5 μl of the bacterial solution was inoculated on the agar surface containing the drug using a microplanter. The inoculated agar plate was cultured for 18 hours in a 37 ° C furan apparatus. The agar plate after completion of the culture was observed, and the drug concentration at which no growth was observed was defined as the MIC. As a result, YM-176005 shows that Staphylococcus oureus F
DA209A, Escherichiacoli O
-1, Pseudomonasaerugin
osa) representative facultative anaerobic bacteria such as NCTC10490,
The MIC against aerobic bacteria showed a value larger than 50 μg / ml.

Example 4 The in vitro activity of anaerobic bacteria was measured by the following method. Preparation of antibacterial substance-containing agar plate 100% dimethyl sulfoxide (DMS)
O) and serially diluted 2-fold. Put the diluted solution into a sterile round petri dish, and sterilize it and keep it warm at 50 ° C.
Was added to a GAM agar medium, mixed, and hardened. The final concentration of DMSO will be less than 1%. Preparation of Inoculum and Judgment of Result Using a GAM broth, a mixed gas (N ₂ : 80%, CO ₂ : 1)
0%, H _2: 10%) bacterial liquid cultured overnight at 37 ° C. using a gas replacement anaerobic bacteria culture device in, to be about 10 ⁶ cells / 1 ml using the same GAM broth prepared did. About 5 μl of the bacterial solution was inoculated on the agar surface containing the drug using a microplanter. The inoculated agar plate was cultured for 18 hours in the anaerobic bacterium culture device set at 37 ° C. as described above. The agar plate after completion of the culture was observed, and the drug concentration at which no growth was observed was defined as the MIC. As a result, YM
-176005 is Bifidobacterium bifidum (B
ifidobacterium bifidum) CAYA21-1, Peptostreptococcusproctus
MIC against obligate anaerobic bacteria such as CAYA12-2 and Bacteroides fragilis GA15562 showed values greater than 50 μg / ml.

[0028]

Industrial Applicability The present invention has an antibacterial activity against Helicobacter pylori and is effective in treating bacterial infection belonging to the genus Helicobacter pylori in humans and related Helicobacter species in animals. In addition, the anti-Helicobacter pylori agent of the present invention is also effective for treating peptic ulcers (eg, gastric and duodenal ulcers), inflammation (gastritis, duodenitis), diseases of the upper gastrointestinal tract such as gastric cancer, and chronic heart disease. is there.

[0029]

[Brief description of the drawings]

FIG. 1 shows an ultraviolet absorption spectrum of YM-176005 (solvent: methanol).

FIG. 2: Infrared absorption spectrum of YM-176005 (KB
r).

FIG. 3 ¹ H-NMR spectrum of YM-176005
(500 MHz, CDCl ₃ ).

FIG. 4 ¹³ C-NMR spectrum of YM-176005
(125 MHz, CDCl ₃ ).

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // C12P 17/12 C12P 17/12 (C12P 17/12 C12R 1:06) (72) Inventor Koichi Tanaka 1-1-8 Shozuzawa, Itabashi-ku, Tokyo Yamanouchi Seiyaku Co., Ltd. (72) Inventor Masato Watanabe 1-1-8 Shozuzawa, Itabashi-ku, Tokyo Yamanouchi Seiyaku Co., Ltd. (72) Inventor Masayuki Komiya Itabashi-ku, Tokyo 1-1-8 Shodosawa Yamanouchi Pharmaceutical Co., Ltd. (72) Inventor Yoji Yamaguchi 1-1-8 Shozusawa, Itabashi-ku, Tokyo Tokyo, Japan Inside (72) Inventor Mitsuo Amase 1-1 Shodosawa, Itabashi-ku, Tokyo, Japan -8 Yamanouchi Pharmaceutical Co., Ltd. (72) Inventor Pre-Agusta Shinwatro Indonesia Bekasi 17550 Kawasan Industry Delta Silicon Re Posikaran Jalan Muhammat Husuni Samlin Block A3-1 (No address) (72) Inventor Boen Setiawan Indonesia Bekasi 17550 Kawasan Industry Delta Silicon Riposikaran Jalan Muhammat Husuni Samlin Block A3-1 (No address) F-term (Reference) 4B064 AE49 BA03 BD02 BE07 BE09 BG01 BG02 BG09 BH02 BH04 BH05 BH06 CA02 DA02 4C031 QA01 QA04 4C086 AA01 AA02 BC28 GA16 MA01 MA04 NA14 ZA36 ZA66 ZA68 ZB11 ZB26 ZB35

Claims (3)

[Claims] 1. A compound represented by the following general formula (I) A 2- (2-nonenyl) -4 (1H) -quinolone derivative represented by or a salt thereof. 2. A medicament comprising the quinolone derivative according to claim 1 as an active ingredient. 3. The medicament according to claim 2, which is an anti-Helicobacter pylori agent.