JPS611666A - Novel 2(1h)-quinolone derivative - Google Patents

Abstract

NEW MATERIAL:3,6-Dihydroxy-3-methoxycarbonyl-3,4-dihydro-2(1H)-quinolone of the formula and its salt. USE:Immune regulator, antiallergic and anti-inflammatory analgesic. PREPARATION:Dried rice bran is dipped in a lower alcohol to obtain a primary extract, when needed, the extract is combined with a lower alcohol, further mixed with a hydrophobic solvent such as n-hexane and water. After thoroughly stirring, the mixture is separated into the aqueous phase and the solvent phase and the aqueous phase which contains alcohol, but no lipids is collected, concentrated under reduced pressure to dryness, then a lower alcohol is added to the residue to obtain the secondary extract containing substances soluble in alcohol. The extract is concentrated under reduced pressure and mixed with a mixed solvent of a lower alcohol and chloroform. Then, the supernatant is subjected to column chromatography or thin-film chromatography to give the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to novel 2(1·H)-quinolone derivatives having immunomodulatory, antiallergic, and antiinflammatory and analgesic effects, and more specifically to 3,6-hydroxy-3-quinolone derivatives. This invention relates to methoxycarzenyl-3,4-dihydro-2(IH)-quinolone (hereinafter referred to as compound [1]) and its salification.

OBJECTS OF THE INVENTION The object of the present invention is to provide compound (13) and its salts which can be used as an ingredient of immunomodulators, anti-allergy agents, anti-inflammatory analgesics.

1. 'Compound CI]t-1 of the present invention has the above chemical structural formula,
□ At the hydroxyl group at the 3rd and/or 6th position, a pharmaceutically acceptable strong basic compound such as sodium hydroxide,
Potassium hydroxide, a salt of hydroxide (1), can be obtained from Yoshima. The compound CI) of the present invention and its salts have immunomodulatory, anti-inflammatory, anti-inflammatory and analgesic effects.
Therefore, it is extremely useful as a medicinal ingredient for immunomodulators, anti-allergy agents, and anti-inflammatory analgesics.

In addition, the compound [I] of the present invention also includes its racemate and optical isomer.

Compound CI) of the invention can be easily isolated from rice bran, for example. As the isolation means, known separation methods such as solvent extraction, column chromatography, and thin layer chromatography are employed. An example of a method for isolating compound CI) from rice bran is to soak rice bran in a dry state in a lower alcohol such as methanol, ethanol, isopropanol, etc. at room temperature to 50"C. The soluble matter is extracted from the rice bran to obtain a first extract. If necessary, lower alcohol is added to this first extract, and a hydrophobic solvent (e.g. n-hexane) and water are added and mixed thoroughly. The mixture is allowed to stand still or centrifuged to separate the layers, and an aqueous solution containing lower alcohols and no lipids is collected.Next, this aqueous solution is concentrated under reduced pressure or dried under reduced pressure, and then the lower alcohols are separated again. Alcohol is added to dissolve alcohol-soluble substances therein, and alcohol-insoluble substances (carbohydrates) are removed from the 'tl-alcohol solution to obtain a second extract.

After the secondary extract thus obtained is preferably concentrated under reduced pressure, a mixture of lower alcohol and chloroform is added and mixed, the resulting tar-like substance is precipitated, and the supernatant is collected. Next, the substance obtained by drying this supernatant under reduced pressure is dissolved in a lower alcohol, and the alcohol solution is subjected to column chromatography or thin layer chromatography to isolate the target compound, compound CI). can.

For example, silica gel, activated alumina, silver nitrate silica gel, etc. can be used as a carrier for column chromatography, and examples of eluents include tban-bexane, konzene, diethyl ether, chloroform, ethyl acetate, acetone, and methanol. , ethanol and mixtures thereof-
is available.

The present invention will be further explained below with reference to Examples.

Example 10 kf1i of dried rice bran was extracted by immersing it in 5 ol of methanol heated to 40°C for 1 hour.
The extract is then concentrated at 511 under reduced pressure. This concentrate contains n
- After adding 10 parts of hexane and 10 parts of water and shaking at 40°C, when this is left to stand, an aqueous solution containing methanol is separated into a lower layer, and this is separated to obtain an aqueous solution. Next, this aqueous solution is evaporated to dryness under reduced pressure, pure methanol 51 is added to the dried product to precipitate carbohydrates, and the precipitate is removed by filtration to obtain a methanol solution (secondary extract). obtain. After evaporating this methanol solution to dryness, methanol/chloroform mixed solvent (volume ratio 2:8) 51
is added to precipitate the resulting tar-like substance, and the supernatant liquid is separated. Next, this supernatant liquid is evaporated to dryness, and then methanol is added thereto again to prepare a methanol solution.

On the other hand, a thin layer with a thickness Q of 5 mm is made with Kiesel Satsuel 60G manufactured by Merck and activated at 120° C. for 1 hour. On this thin layer, the previously prepared methanol solution was spotted linearly, and developed for 10 cm with a mixed solvent of metamer and chloroform (volume ratio 1:9) to determine the Rf value -
Collect parts ○ and 26 and extract with methanol. Thereafter, by distilling off methanol from this methanol extract, 3,6-cyhydroxy-3-methoxycarboxylic acid
Nilu-3,4-dihydro-2(IH)-quinolone 500
mg was obtained.

The physical and chemical properties of the compound are as follows.

Appearance: Yellow-brown crystalline powder Melting point: 67-68°C Specific rotation: [α]D--3.8° (C1, OMeOH)
Solubility: Easily soluble in water and lower alcohols. S dissolved in ethyl acetate, chloroform, and benzene.

Taste: The aqueous solution has a bitter taste.

Elemental analysis values (as C,, H,, NO) Ultraviolet absorption Nuclear magnetic resonance absorption (See Figures 1 and 2) 'HNMR
CD5OD, 400BJ)Is) to WLd 2.
97 (IH,d, J-15,4)-3,03(IH
,d, J-15,4)-' 3.49 (3H,8) ,,,=6.67(IH,dd, Jm 8.3.2
．． 3) = 6.70 (IH, dd, J == s, a
, o, e ), = 6.84 (IH, dd, Jm
2.3. 0.6) (CD, OD signal 3.30
ppm)”CNMR (DM80-d, ,
tlMHz)1',,y1=-41,5,50,7
, 72,9, 109,6.

112.1, 115.0, 131.7
, 133.8.

152.3, 168.8, 177.4 (D
M90-d, as 39.5') mass (see Figure 3) Z 237 (M'', C,, Hl, NO,).

219(M-)1. (1).

185, 177 (MC, H40,).

164, 135 (MC, H, O,) infrared spectrum (see Figure 4...KBr tablet method)

[Brief explanation of drawings]

Figure 1141 shows 1H of the compound [l] of the present invention obtained in Example.
Figure 2 shows the nuclear magnetic resonance spectrum of compound (1).
130 nuclear magnetic resonance spectrum of gold. FIG. 3 shows the mass spectrum of the compound (1) of the present invention obtained in the example, and FIG. 4 similarly shows the infrared spectrum of the compound (I). Complete 1 diagram

Claims (1)

[Claims] 1. 3,6-dihydroxy-3-methoxycarbonyl-3,4-dihydro-2(1H)-quinolone or its salt.