JPH03161440A - Antibacterial agent - Google Patents

Abstract

PURPOSE:To provide an antibacterial agent containing a condensed imidazole derivative, exhibiting excellent antibacterial activity against microaerophils, especially bacterial of genus Campylobacter and useful for the prevention and remedy of infectious diseases. CONSTITUTION:The objective agent can be prepared by mixing a compound of formula [ring A is (substituted) benzopyran ring, tetrahydroquinoline ring, indoline ring, etc.; R is (substituted) phenyl or pyridyl; n is 0 or 1] or its acid addition salt with a pharmacologically allowable additives such as carrier, excipient, diluent and solubilizer and forming in the form of medicine by conventional method. It can be used in the form of capsule, tablet, granule, injection, drops, etc. The daily dose of the compound is 0.1-30mg/kg for adult in the case of oral administration. An example of the compound of formula is 2-[(3- methyl-2-pyridyl)methylthio]pyrano[2,3-e]benzimidazole.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an antibacterial agent, particularly an antibacterial agent having excellent antibacterial activity against Campyostobacter bacteria.

[Conventional technology]

JP-A-62-145083 discloses anti-ulcer agents, analgesics and
Fused imidazur compounds are disclosed that are useful as pharmaceuticals such as anti-inflammatory agents.

[Problem to be solved by the invention]

Durham-negative microaerobic bacteria, Cannibalacter (
Bacteria of the genus Campylobacter were discovered as bacteria that cause diarrhea and miscarriage in livestock. In humans, Campylobacter jejuni causes bacterial enteritis.
), Campylobacter coli (Campyloba
cter colt), etc. are known. On the other hand, 19
In 1983, Warren and Marshall
Many studies and reports have been made since the association between gastritis and Campylobacter pylori (Campylobacter pylori) infection was reported. In fact, Campobacter pylori is frequently detected in antral gastritis tissue associated with chronic gastritis and gastric/duodenal ulcers. At present, the relationship between the above lesions and Campylobacter pylori infection has not been clarified, but attempts have been made to administer antibiotics such as ofloxan and bacampicillin hydrochloride to patients in order to eliminate this bacterium. ing.
However, the eradication effect of vacambicillin hydrochloride is only 50%, and as it is said that this bacterium tends to acquire resistance to ofloxacin, sufficient efficacy has not yet been achieved. Under these circumstances, it is desired to develop a useful antibacterial agent that can be used against bacterial infections caused by Canbyobacter pylori and the like.

[Means to solve the problem]

the above! I! In order to solve this problem, the present inventors have conducted various studies and found that the group of compounds described in the above publication, which are known as anti-ulcer agents or analgesic/anti-inflammatory agents, are effective against Campylobacter bacteria. It was discovered that it has excellent antibacterial activity, and the present invention was completed.

That is, the present invention relates to an antibacterial agent characterized by containing a condensed imidazole compound represented by the general formula H (I) or an acid addition salt thereof.

In the formula, NA condensed with the imidazole ring has lower alkyl (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, etc.), lower alkanoyl (acetyl, propionyl, butyryl, pivaloyl, valeryl, etc.) as a substituent. etc.), a penzopyran ring, a penzothiopyran ring, a tetrahydroquinoline ring, or an indoline ring which may have at least one of oxo, and R is a substituent of halogen (chlorine, bromine, fluorine, etc.), lower alkyl (same as above). ), lower alkoxy (methoxy, ethoxy, proboxy, isobroboxy, butoxy,
n is 0 or 1; show. The compound of general formula (+) of the present invention may exist in various isomers. The present invention includes one of these isomers or a mixture of these isomers.

Acid addition salts of compounds of formula 1a (r) include hydrochloride, hydrobromide, sulfate, fumarate, maleate, citrate, malate, tartrate, methanesulfonate. etc.

The compound of general formula (T) or its acid addition salt can be produced by a known method, for example, the method described in JP-A-62-145083.

The following compounds are exemplified as compound proboscises included in the present invention, but the present invention is not limited thereto. 2-8) Benzidiξdazole, melting point 1
77-181'C (212-C(3-methyl-2-pyridyl)methylsulfinyl)pyrano (3.2-e) Benzyl and dazole, melting point 168-170°C (decomposed) (3+2-((3-methyl- 2-pyridyl)methylthio]pyrano (2,3-r)penzimidazole, melting point 1
41-145℃ f412-((3-methyl-2-pyridyl)methylsulfinyl)pyrano (2,3-f)benzidazole, melting point 149-152℃CminM) (512-((3-methyl-2-pyridyl) -pyridyl)methylthio]-5-methyl-6-oxo56.7.8-tetrahydro-3H-imidazo (4.5-g)quinoline, mp 1
01-104°C 2<(3-methyl-2-pyridyl)methylsulfinyl]-5-methyl-6-oxo5.6,7.8-tetrahydro-3H imidazo(4,5-g)quinoline, melting point 1
74-179°C 2-((3.5-dimethyl-4-methoxy=2-pyridyl)methylthio]-5-methyl-6-oxo5.6,
7.8-Tetrahydro-3H-imidazo (4,51 g)
Quinoline, melting point 120-12.3°C 2-((3.5-dimethyl-4-methoxy-2-biridyl)methylsulfinyl) 5-methyl-6-oxo 5,67.8 tetrahydride
3H-Imidazo [4.5g]quinoline, melting point 196-1
99°C (decomposition) 2-((3-methyl-2-pyridyl)methylthio)-8
．． 8-Dimethyl-6-oxo-5.6,7.8-tetrahydro-3H-imidazo(4,5-g)quinoline, melting point 119-122°C 2-[(3-methyl-2-pyridyl)methylsulfinyl )-8,8-dimethyl-6oxo5,6,7.8-
Tetrahydride port 3 H-imidazo C4.5-g) Quinoline, melting point 224-228゛C 2-(2-chloropendylthio)-8.8 dimethyl-6
-Oxo5.6,7.8tetrahydride-3H-imidazo [4.5g]quinoline, melting point 229-230°C 5-acetyl-2-((3-methyl-2pyridyl)methylthio)-6.7-dihydrobi- (2,3-f)benzidandazole, melting point 235-238°C
f) Penzimidazole, melting point 201-203°C (decomposition) 2-((3,5-dimethyl-4-methoxy2-pyridyl〉methylthio)-6-oxo5.6,7.8-tetrahydro-3H-imidazo( 4,5-g) Quinoline 2-((3,5-dimethyl-4-methoxy2-biridyl)methylsulfinyl) 6-oxo5.6.7.8-tetrahydro-3H-imidazo(4,5 -g) Quinoline 2-(2-dimethylaminobenzylthio)thiopyrano
(2,3-f)penzimidazole2-(2-dimethylaminobenzylsulfinyl)thiopyrano (2,3-f)penzimidazole(112-(4-dimethylaminohenzylthio)5-methyl-6-oxo5 .6,7.8-tetrahydride-3
H-Imidazo [4.5g] Quinoline (lgl 2-(4-dimethylaminohendylsulfinyl)-5-methyl-6-oxo 5,6,7.8-tetrahydro-3 H-Imidazo C4.5 -g) Quinoline [Action and Effect] The compound of the general formula (+) of the present invention is particularly suitable for Durum-negative bacteria,
It is particularly effective against microaerophilic bacteria, especially Campylobacter genus bacteria represented by Campylobacter pylori. Therefore, the antibacterial agent of the present invention can be used for the prevention and treatment of infectious diseases in mammals including humans.

When the antibacterial agent of the present invention is used, for example, as a bacterial infection treatment/prevention agent, the compound ([) itself (i.e., free base), or a salt thereof, or a salt thereof is usually used together with a pharmaceutically acceptable carrier. In the form of pharmaceutical preparations containing as an excipient, carrier, diluent, solubilizer, etc., it can be mixed with additives such as capsules, tablets (including sugar-coated tablets and film-coated tablets), granules, injections, It can be administered in a dosage form such as an intravenous solution. In the case of oral administration, the dosage is about 0.1 to 30 μ/kg per Kaito I day, preferably 0.1
~4■/kg, but it goes without saying that this can vary depending on the patient's symptoms, age, drug tolerance, etc.

Experimental Example 1 The in vitro antibacterial activity of the effective precepts of the present invention against C. pylori was determined by the agar plate dilution method described below.

Using 5% horse serum, the test bacteria were cultured for 72 hours under microaerophilic conditions at 37°C and diluted with Brucella broth to obtain a bacterial count of approximately 10.
A bacterial solution of h bacteria/ml was prepared. Using a microplanter, the diluted bacterial solution was spot-inoculated onto an agar plate containing a 2-fold diluted concentration series of the test compound, and after culturing for 2 days at 37°C under 10% carbon dioxide, the minimum growth inhibition level was reached. (MIC) was measured.

The results are shown in Table 1.

Table 1 Test Compound MIC (μg/ml) Compound (11) 25 From the above pharmacological data, the compound of the present invention has excellent antibacterial activity and is useful as a medicine such as an antibacterial agent.

〔Example〕

Examples of the antibacterial agent of the present invention are shown below, but the present invention is not limited to these Examples.

Formulation example compound (1) 30. 0
■Lactose 50.0■Corn starch 15.5■Microcrystalline cellulose 20.0■Talc
4. O mg magnesium stearate
0.5■120.0nv Compound (1), lactose, cornstarch and microcrystalline cellulose are mixed in a kneading machine, then 5% cornstarch paste is added, granulated and dried. The mixture is sieved through a 24 mesh sieve, mixed with talc and magnesium stearate, and made into 120 square tablets using a pestle with a diameter of 7 mm.

Claims (1)

[Claims] (1) An antibacterial agent characterized by containing a fused imidazole derivative or its acid addition salt represented by the general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼. In the formula, ring A condensed with the imidazole ring is a benzopyran ring, benzothiopyran ring, tetrahydroquinoline ring, or indoline ring which may have at least one of lower alkyl, lower alkanoyl, and oxo as a substituent, and R is n represents phenyl or pyridyl which may have halogen, lower alkyl, lower alkoxy or di-lower alkylamino as a substituent; n represents 0 or 1;