KR20050079152A - 4-[butylsulfiny)methyl]-1,2-benzenediol (1,3-benxodioxol-5-ylmethyl methyl sulfone) and its derivatives, preparation method thereof and whitening composition containing the same - Google Patents

Abstract

The present invention relates to a novel compound 4-[(butylsulfinyl) methyl] -1,2-benzenediol (1,3-benzodioxol-5-ylmethyl methyl sulfone) and derivatives thereof, and a method for preparing the same. More specifically, 4-[(butylsulfinyl) methyl] -1,2-benzenediol represented by the following Chemical Formula 1, its derivatives have excellent antioxidant activity, low density lipoprotein (LDL) antioxidant activity and Due to the excellent HMG-CoA reductase inhibitory activity it can control the blood cholesterol concentration.

[Formula 1]

In the above formula, R is a C ₃ to C ₄ alkyl group.

The present invention also relates to a cholesterol lowering agent composition containing 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives as an active ingredient.

Description

4-[(butylsulfinyl) methyl] -1,2-benzenediol and derivatives thereof, preparation method thereof and cholesterol lowering agent composition containing same {4- [butylsulfiny) methyl] -1,2-benzenediol (1,3- benxodioxol-5-ylmethyl methyl sulfone) and its derivatives, preparation method pretty and whitening composition containing the same}

The present invention relates to a novel compound 4-[(butylsulfinyl) methyl] -1,2-benzenediol and derivatives thereof, and a method for preparing the same, and more particularly to 4-[(butylsulfinyl) Nyl) methyl] -1,2-benzenediol and its derivatives have cholesterol lowering effects due to excellent antioxidant activity, antioxidant activity of low density lipoprotein (LDL) and excellent HMG-CoA reductase inhibitory activity.

[Formula 1]

In the above formula, R is a C ₃ to C ₄ alkyl group.

The present invention also relates to a cholesterol lowering agent composition containing 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives as an active ingredient.

The incidence of atherosclerosis in humans is due to the ideal differentiation of endothelial wall cells and is highly correlated with blood cholesterol levels (Casteli, W. P. et al., JAMA., 256, 2835-2845 (1986)). The amount of cholesterol delivered to the artery wall by low-density lipoproteins, the main substance that carries blood cholesterol, is dependent on blood concentration. Oxidation of low-density lipoproteins that have migrated to the arterial wall is regarded as an inflammatory response, which causes monocytes to migrate to this site and is stimulated by monocyte-colony stimulating factor (M-CSF), which is secreted by vascular endothelial cells. Differentiate into macrophage. The macrophages further promote low-density lipoprotein oxidation, and the oxidized low-density lipoproteins accumulate in macrophages by scavenger receptors, thereby losing a high level of cholesterol by the macrophages' loss of the rubbing mechanism. Will accumulate. At this time, the smooth muscle cells in the middle layer of the artery wall are transferred to the vascular wall endothelial layer, and together with the macrophages, they become fat cells having fat, which forms a fat streak and becomes an initial state of arteriosclerosis. The resulting foam cells secrete extracellular matrix to form a fibrous cover. When plaque is formed in the arterial wall by repeating the formation and rupture process, myocardial infarction, heart attack or angina occur. It is known that oxidative modification of low-density lipoproteins plays an important role in the mechanism of cholesterol-induced endothelial dysfunction (Aviram, M. et al., J. Cardiovascular Pharmacology, 31, 39-45 (1998). )]. Therefore, there is a high incidence of atherosclerosis in the vascular system in which low-density lipoprotein oxidation is active [Miesenock, G. et al., Leaf, A. and Webber, PC (ed), Raven Press, New York, vol. 21, p. 119-123 (1990). Oxidation of low density lipoproteins increases lipid peroxide and oxygen free radicals, or oxygen free radicals, and these molecules are toxic to endothelial cells. Easily adheres, damages blood vessel cells, deforms vascular tissues, and promotes the division of deformed cells, making peripheral oxidized low-density lipoproteins, platelets, and macrophages more easily adhere to blood vessel walls [Noguchi, N. et al. . Archiv. Biochem. Biophys., 3347, 141-147 (1997).

Atherosclerosis is the leading cause of death in Western society, and the incidence of cardiovascular disease in Korea is increasing, and attention is being paid to the development of substances that prevent atherosclerosis. Such substances include simvastatin, which lowers plasma cholesterol levels [Aki Nakai et al. : Biol. Pharm. Bull. 19 (9). 1231-1233 (1996)], lovastatin and the like are used as a therapeutic agent for hyperlipidemia, and probucol for inhibiting low-density lipoprotein oxidation has also been developed and used as a therapeutic agent.

Accordingly, the present inventors have tried to develop an antioxidant substance that can effectively control the harmful oxygen active species, and as a result, a novel substance, 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives, is a harmful oxygen active species. The present invention has been completed by discovering that it can be used as a cholesterol lowering agent due to oxidation inhibition and excellent HMG-CoA reductase inhibitory activity of low density lipoprotein.

Accordingly, it is an object of the present invention to provide 4-[(butylsulfinyl) methyl] -1,2-benzenediol and derivatives thereof, which are excellent in cholesterol lowering effects, and methods for preparing the same.

It is also an object of the present invention to provide a cholesterol lowering agent composition containing the 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives as an active ingredient.

In order to achieve the above object, the present invention provides 4-[(butylsulfinyl) methyl] -1,2-benzenediol and derivatives thereof represented by the following Chemical Formula 1.

In the above formula, R is a C ₃ to C ₄ alkyl group.

Preferred examples of the compound represented by Formula 1 include the following compounds:

4-[(propylsulfinyl) methyl] -1,2-benzenediol of Formula 1a;

4-[(isopropyl) sulfinyl] methyl-1,2-benzenediol of Formula 1b;

4-[(butylsulfinyl) methyl] -1,2-benzenediol of Formula 1c;

The present invention also relates to a process for producing 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives.

The process for preparing 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives according to the present invention comprises the following steps, which is shown in Scheme 1 below:

1) Reacting 1,3-benzodioxol-5-ylmethanol of formula 2 with thiol having an alkyl group in the presence of aluminum chloride to give 4-[(alkylsulfanyl) methyl] Preparing -1,2-benzenediol; And

In the above formula, R is a C ₃ to C ₄ alkyl group.

2) 4-[(alkylsulfanyl) methyl] -1,2-benzenediol of Chemical Formula 3 by reacting hydrogen peroxide with 4-[(alkylsulfinyl) methyl] -1,2-benzenediol of Chemical Formula 1 and its Preparing a derivative;

The present invention also relates to a cholesterol lowering agent composition containing 4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives as an active ingredient.

The cholesterol lowering composition of the present invention may be formulated in an oral dosage form such as a dry powder which is in the form of a solution, a suspension or an emulsion in an oil or an aqueous medium, or dissolved in sterile, water-free water before use. It may also be formulated into parenteral formulations such as subcutaneous, intravenous or intramuscular injection.

In the case of oral dosage forms, for example, tablets, troches, sugar-containing tablets, aqueous or oily suspensions, dispersible powders, etc., in a known manner using a pharmaceutically acceptable carrier or forming agent. Or in the form of oral dosage forms in the form of particles, emulsions, soft or hard capsules, syrups, elixirs, which may be suitably prepared according to unit dosages, forms and the like.

Parenteral formulations may be injected as a sterile injectable solution or as a suspension in which the active ingredient is suspended in a solvent such as a non-toxic usable diluent or 1,3-butanediol. Excipients or solvents that may be used include water, Ringer's solution, and isotonic saline solution. Cosolvents such as ethanol, polyethylene glycol, and polypropylene glycol may be used. In addition, sterile, nonvolatile oils can be customarily used as solvents or suspending solvents. The suppository form is formulated by mixing the drug with a suitable non-irritating excipient, such as cocoa butter or polyethylene glycol, which is solid at room temperature but liquid at the rectal temperature and will melt in the rectum to release the drug and then enter the rectum. Administration.

When treating a disease using the composition of the present invention, the dose of the compound of formula 1 as an active ingredient is determined by the age, weight, general state of health, sex, meal, time of administration, rate of excretion, combination of drugs, during treatment. Depending on the severity of the disease, depending on the disease can be used every day up to 0.01 ~ 140mg / kg body weight, 0.5mg ~ 7g can be used per day per patient.

On the other hand, the amount of the compound of the present invention mixed with the carrier material to determine one formulation depends on the mode of administration and the patient being treated. For example, formulations intended for application to oral dermal application to humans will contain from 5 to 95% by weight of carrier materials and 0.5 mg to 5 g of active ingredient in the total composition, and parenteral administration to humans will be possible. The desired formulation will contain from 5 to 99% of the carrier material and from 0.1 mg to 2.5 g of active ingredient.

Hereinafter, the present invention will be described in detail by examples. However, the examples are only to illustrate the invention and the present invention is not limited by the following examples.

Example 1 Synthesis of 4-[(propylsulfinyl) methyl] -1,2-benzenediol

(Step 1) Preparation of 4-[(propylsulfanyl) methyl] -1,2-benzenediol

After dissolving 149 ml of propane thiol and 22 g of aluminum chloride in methylene chloride, 5 g of 1,3-benzodioxol-5-ylmethanol dissolved in 10 ml of methylene chloride was added at 0 ° C. After stirring for 5 hours at room temperature, water was added to remove the remaining aluminum chloride, extracted with methylene chloride and water, dried over anhydrous magnesium sulfate, and the solvent was removed. Column chromatography using 2% methanol of methylene chloride as eluent gave 5.3 g of the title compound of formula 3a (Rf: 0.35, yield: 82%).

[Formula 3a]

Dissolved in CDCl ₃ and TMS and measured by ¹ H NMR were as follows;

¹ H NMR δ: 0.987 (t, 3H), 1.48-1.66 (m, 2H), 2.43 (t, 2H), 3.60 (s, 2H), 6.7-6.79 (m, 2H), 6.85 (s, 1H) .

(Step 2) Preparation of 4-[(propylsulfinyl) methyl] -1,2-benzenediol

0.2 g of 4-[(propylsulfanyl) methyl] -1,2-benzenediol was dissolved in 5 ml of methanol, and 0.09 ml of 35% aqueous hydrogen peroxide solution was added thereto, followed by heating to 60 ° C. for 3 hours. Column chromatography using 5% methanol of methylene chloride as the eluent gave 0.1 g of the title compound of formula 1a (Rf: 0.35, yield: 48%).

[Formula 1a]

Dissolved in CDCl ₃ and TMS and measured by ¹ H NMR were as follows;

¹ H NMR δ: 0.88-0.96 (t, 3H), 1.52-1.56 (m, 2H), 2.46-2.59 (m, 2H), 3.68-3.90 (q, 2H), 6.52-6.66 (m, 3H).

Example 2 Preparation of 4-[(isopropylsulfinyl) methyl] -1,2-benzenediol

(Step 1) Preparation of 4-[(isopropylsulfanyl) methyl] -1,2-benzenediol

152 ml of isopropanethiol and 22 g of aluminum chloride were dissolved in methylene chloride, and then 5 g of 1,3-benzodioxol-5-ylmethanol dissolved in 10 ml of methylene chloride was added at 0 ° C. After stirring for 5 hours at room temperature, water was added to remove the remaining aluminum chloride, extracted with methylene chloride and water, dried over anhydrous magnesium sulfate, and the solvent was removed. Column chromatography using 2% methanol of methylene chloride as the eluent gave 4.78 g of the title compound of the general formula 3b (Rf: 0.35, yield: 73%).

[Formula 3b]

Dissolved in CDCl ₃ and TMS and measured by ¹ H NMR were as follows;

¹ H NMR δ: 1.30 (d, 6H, J = 6.6 Hz), 2.77 2.83 (m, 1H), 3.64 (s, 2H), 6.7-6.79 (m, 2H), 6.85 (s, 1H)

(Step 2) Preparation of 4-[(isopropylsulfinyl) methyl] -1,2-benzenediol

0.2 g of 4-[(isopropylsulfanyl) methyl] -1,2-benzenediol was dissolved in 3 ml of methanol, and then 0.09 ml of 35% aqueous hydrogen peroxide solution was added and heated to 60 ° C. for 3 hours. The reaction was concentrated under reduced pressure, and then column chromatography was performed using 5% methanol of methylene chloride as the eluent to obtain 0.08 g of the title compound of the following Chemical Formula 1b (Rf: 0.38, yield: 40%).

[Formula 1b]

Dissolved in CDCl ₃ and TMS and measured by ¹ H NMR were as follows;

¹ H NMR δ: 1.19-1.23 (d, 6H, J = 6.6 Hz), 3.76-3.79 (q, 1H, 8.0 Hz), 4.77 (s, 2H), 6.58-6.71 (m, 3H)

Example 3 Preparation of 4-[(butylsulfinyl) methyl] -1,2-benzenediol

(Step 1) Preparation of 4-[(butylsulfanyl) methyl] -1,2-benzenediol

176 ml of butanethiol and 22 g of aluminum chloride were dissolved in methylene chloride, and then 5 g of 1,3-benzodioxol-5-ylmethanol dissolved in 10 ml of methylene chloride was added at 0 ° C. After stirring for 5 hours at room temperature, water was added to remove the remaining aluminum chloride, extracted with methylene chloride and water, dried over anhydrous magnesium sulfate, and the solvent was removed. Column chromatography using 2% methanol of methylene chloride as eluent gave 4.85 g of the title compound of the general formula (3c) (Rf: 0.35, yield: 67%).

[Formula 3c]

Dissolved in CDCl ₃ and TMS and measured by ¹ H NMR were as follows;

¹ H NMR δ: 0.96 (t, 3H, J = 5.8 Hz), 1.29-1.60 (m, 4H), 2.47 (t, 2H, J = 5.8 Hz), 3.63 (s, 2H), 6.7-6.79 (m , 2H), 6.85 (s, 1H).

(Step 2) Preparation of 4-[(butylsulfinyl) methyl] -1,2-benzenediol

0.2 g of 4-[(butylsulfanyl) methyl] -1,2-benzenediol was dissolved in 3 ml of methanol, and then 0.09 ml of 35% aqueous hydrogen peroxide solution was added and heated to 60 ° C. for 3 hours. Column chromatography using 5% methanol of methylene chloride as the eluent gave 0.12 g of the title compound of the following Chemical Formula 1b (Rf: 0.30, Yield: 58%).

[Formula 1c]

Dissolved in CDCl ₃ and TMS and measured by ¹ H NMR were as follows;

¹ H NMR δ: 0.81-0.88 (t, 3H, J = 7.4 Hz), 1.32-1.38 (m, 2H), 1.60-1.66 (m, 2H, J = 7.2 Hz), 2.52-2.58 (m, 2H, J = 5.8 Hz), 3.83 (s, 2 H), 6.53-6.71 (m, 3 H).

Test Example 1 DPPH Scavenging Activity

1,1-Diphenyl-2-picrylhydrazyl (abbreviated as "DPPH") is a purple dye that can measure the antioxidant activity of phenols and aromatic amines. It is a widely used substance [Blois, MS Antioxidant determinations by the use of a stable free radical. Nature, 181, 1990-1200 (1958). DPPH exhibits a strong absorption band due to its odd number of electrons at 520 nm, but when reacted with hydrogen or an electron donor like phenol, it receives electrons or hydrogen radicals from a donor to generate phenoxy radicals. At this time, the absorption disappears and is stabilized to change from the original progressive color to yellow to reduce the absorbance. That is, the radical scavenging activity can be known by measuring the decrease in absorbance of the reaction solution [Yokozawa, T. et al., Biochemical Pharmacology, 56, 213-222 (1998); Hatano, T. et al., Chem. Pharm. Bull., 37 (8), 2016-2021 (1989)].

Determination of the scavenging effect on DPPH radicals of each sample is as follows [Blois, M. S. Nature, 181, 1990-1200 (1958)].

Samples of 0.1 μg / mL concentration were dissolved in methanol, and 4 mL of each sample was mixed with 1 mL of DPPH solution dissolved in methanol at a concentration of 1.5x10-4 M. After leaving this reaction liquid at room temperature for 30 minutes, absorbance was measured at 520 nm. Free radical scavenging activity was expressed as a percentage compared to the control without the sample. The measured values are expressed as mean ± standard deviation of the results obtained from three replicates [Yoshida et al., Chem. Pharm. Bull., 37 (7), 1919-1921 (1989).

Table 1 shows the results of measuring the DPPH radical scavenging effect of the synthetic compounds. As a result, the free radical scavenging activity of Example 1-3 was about 6-7 times higher than that of vitamin C known as an antioxidant.

Test subject DPPH elimination effect (%) Example 1 0.84 ± 0.91 Example 2 0.91 ± 0.17 Example 3 0.84 ± 0.36 Vitamin c 0.14 ± 0.11

Test Example 2 Measurement of LDL Oxidation Inhibition Rate

LDL (Sigma No. L-5402) was purchased and dialyzed with PBS for 24 hours, and then sterilized by passing through a 0.45 μm sterile filter-mounted syringe. Protein concentration of LDL was quantified by Lowry method using bovine serum albumin (hereinafter abbreviated as "BSA") as a standard.

To the reaction solution containing 0.1 mg protein / ml LDL and the compound prepared in Example 1-3 was added so that the final concentration of Cu ²⁺ to 5M and oxidized at 40 ℃ for 4 hours. 1% oxidized LDL reaction solution and malondialdehyde (hereinafter abbreviated as "MDA") prepared by concentration in 0.4% thiobarbituric acid (hereinafter abbreviated as "TBA") standard reaction solution, 15 1 ml of a solution of thiobarbituric acid reactive substances (TBARS) containing 2.5% trichloroacetic acid (hereinafter abbreviated as "TCA") and 2.5% HCl was mixed, and the reaction mixture was reacted for 20 minutes in a 95-100 ° C water bath. The hot sample was vortexed to remove bubbles, cooled in cold water, centrifuged at 2000 rpm for 10 minutes, and the supernatant was measured for absorbance at 532 nm. The results are shown in Table 2 below. The concentration of TBARS in the sample was obtained from the standard curve of MDA made of MDA and expressed as nmole of MDA.

In order to examine the inhibitory effect on the LDL oxidation of the compounds prepared in Examples 1-3, the concentrations of the compounds were added to the LDL reaction solution at 0.5, 1, and 5 µg / mL, respectively. Compared with the effect of. The TBARS concentration of oxidized LDL (40 ° C., 4hrs) was 30.35 ± 5.60 nmole MDA / mg protein LDL. The results were repeated three times with the mean ± standard deviation. Samples were repeated three times per experiment.

As shown in Table 2, the compounds prepared in Examples 1-3 showed potent antioxidant capacity against LDL oxidation. Antioxidant effect of the compounds of the present invention was slightly lower than that of vitamin C in Examples 1 to 3 compared to the vitamin C showed about 21% LDL oxidation inhibitory effect when 1 μg / mL of the compound was added. Example 2-3 showed a higher effect. In particular, Example 3 showed about three times higher effect than vitamin C. At low concentrations, the antioxidant effect was significantly higher than that of vitamin C.

Test subject LDL oxidation inhibition rate (%) 0.5 μg / mL 1 μg / mL 5 μg / mL Vitamin c -36.67 ± 19.02 -20.56 ± 17.13 -38.99 ± 9.07 Example 1 -59.82 ± 5.65 -18.36 ± 13.54 -20.58 ± 9.15 Example 2 -61.87 ± 3.34 -34.65 ± 22.76 -57.18 ± 12.39 Example 3 -63.06 ± 3.13 -62.98 ± 1.61 -69.71 ± 17.85

Test Example 3 Measurement of Cholesterol Concentration Reducing Effect

Six rabbits per group were experimentally divided into the compound of Example 3, simvastatin group, the best LDL oxidation inhibitory effect among the examples. Simvastatin and the compound of Example 3 were administered to the posterior posterior vein at 2 mg / 2day / 3 kg based on the 20 mg / 60 kg / day dose in hyperlipidemic patients with a hypercholesterolemia diet. At this time, the experimental control group was administered the same amount of PBS. Body weights were measured at weekly intervals and blood was collected from the posterior forearm veins at four-day intervals. Blood was collected from rabbit's posterior ear vein, separated for 20 minutes at 3,000 rpm to obtain plasma, and stored frozen until analysis.

After breeding 30, fasting for 24 hours, and then anesthetized by injecting 2ml of keiran (Keiran, 50mg / ml, Korea Unite Pharmaceutical Co., Ltd.) per body in the posterior ear vein. After collecting blood from the heart with a heparinized syringe, the liver was extracted, washed with 0.9% saline solution, and stored frozen at -70 ° C, and cut to the bifurcation of the ileum from the arterial valve for measurement of lipid deposition of the aorta. The blood was washed off and stained immediately. After obtaining plasma from the collected blood, total cholesterol was analyzed by enzyme method with a cholesterol kit (Total Cholesterol Kit AM 202-K, Asan Pharmaceutical).

The results are shown in Tables 3 to 5 below, and the results obtained by measurement are expressed as mean ± standard deviation.

When looking at the blood cholesterol in Table 3, the compound of Example 3 was reduced by about 25% compared to the experimental control, which was higher than the lowering effect of 12% of the simvastatin group used as a cholesterol treatment. In addition, the compound of Example 3 in Table 4 in which LDL cholesterol was measured was decreased by 27.91% compared to the experimental control, and 13.89% was decreased when simvastatin was administered, showing the same tendency as plasma cholesterol. However, the HDL cholesterol was not significantly different from the experimental control in Table 5, but the compound of Example 3 can treat hypercholesterolemia, but the effect of increasing HDL cholesterol was not examined.

 Plasma Total Cholesterol Test subject Total Cholesterol (mg / dl) Control 1706.67 ± 321.66 Simvastatin 1493.33 ± 441.12 Example 3 1278.33 ± 173.02

LDL-cholesterol in the blood Test subject LDL-cholesterol (mg / dl) Control 1354.13 ± 285.81 Simvastatin 1166.07 ± 373.76 Example 3 976.20 ± 135.20

HDL-cholesterol in the blood Test subject HDL-cholesterol (mg / dl) Control 91.00 ± 71.06 Simvastatin 69.67 ± 39.57 Example 44.83 ± 24.81

Test Example 4 Measurement of HMG-CoA Reductase Activity in Liver Tissues

The operation for measuring HMG-CoA reductase activity in the liver was largely performed in the following three steps.

All steps were performed at 0 to 4 ° C. to prepare microsomes from liver tissue. The microsomes were separated from liver tissue and used as an enzyme source. The liver microsomal fraction used as an enzyme source was separated by 1 g of liver and contained ₄ ml homogeneous solution (pH7.4), that is, 50 mM KH ₂ PO ₄ and 0.2 M DTT. After pulverizing in a buffer solution prepared so as to centrifuged for 15 minutes at 15,000 × g of 4 ℃ to take the supernatant and repeated ultracentrifugation for 75 minutes at 100,000 × g at 4 ℃. The obtained precipitate was dissolved in a buffer and adjusted to a protein concentration of 8 to 10 µg / ml and stored in a freezer.

To solubilize the isolated microsomes, 5 µl of 0.1M NADPH and 55 µl of buffer A were added to 100-200 µg of microsomes, incubated at 37 ° C for 15 minutes, and 15 µl of 10N HCl was added again. The above culture was carried out. Centrifuge at 10,000 rpm for 5 minutes at 4 ° C, take 20 µl of the supernatant, and drop onto a TLC plate. Saturate a developing solvent of benzene: acetone: methyl alcohol = 3: 6: 1 in the development tank and saturate. And then deployed.

The developed thin layer chromatography (TLC) plate was left for one day, and then radioisotope was released on the image plate. And radioactivity meter was taken and radioactivity activity was calculated. The enzyme activity unit expressed the amount of mevalonate produced by 1 mg of microsomal protein per minute in pmol (pmole / min / mg microsome protein).

The results are shown in Table 6 below, and the results obtained by measurement are expressed as mean ± standard deviation.

In Table 6, when looking at the HMG-CoA reductase activity of the liver tissue, the compound of Example 3 was found to be 52% inhibited compared to the experimental control, which was remarkable compared to the 16% reduction of the simvastatin group.

HMG-CoA Reductase Activity in Liver Tissues Test subject HMG-CoA reductase activity (pmole / min / mg microsome protein) Control 52.44 ± 1.16 Simvastatin 43.77 ± 15.25 Example 3 24.7 ± 8.15

As described above, the novel compounds according to the present invention could be used as an excellent low-density lipoprotein oxidation inhibitor, and also have excellent cholesterol control ability as an excellent HMG-CoA reductase inhibitor, which can be used as an active ingredient of a cholesterol lowering agent composition. .

Claims (5)

4-[(butylsulfinyl) methyl] -1,2-benzenediol and its derivatives represented by the following formula: [Formula 1] In the above formula, R is a C ₃ to C ₄ alkyl group. According to claim 1, wherein the compound of Formula 1 4-[(propylsulfinyl) methyl] -1,2-benzenediol; 4-[(isopropylsulfinyl) methyl] -1,2-benzenediol; 4-[(butylsulfinyl) methyl] -1,2-benzenediol; and 4-[(butylsulfinyl) methyl] -1,2-benzenediol and 4-[(butylsulfinyl) methyl] -1,2-benzenediol and derivatives thereof. 1) 1,3-benzodioxol-5-ylmethanol of formula 2 is reacted with thiol having various alkyl groups in the presence of aluminum chloride to give 4-[(alkylsulfanyl) Preparing methyl] -1,2-benzenediol; And [Formula 2] [Formula 3] In the above formula, R is a C ₃ to C ₄ alkyl group. 2) 4-[(alkylsulfanyl) methyl] -1,2-benzenediol of formula 3 is dissolved in methanol and reacted with hydrogen peroxide to react 4-[(butylsulfinyl) methyl] -1, Preparing 2-benzenediol and its derivatives; 4-[(propylsulfinyl) methyl] -1,2-benzenediol and derivative thereof comprising the same. A composition for lowering cholesterol, comprising 4-[(butylsulfinyl) methyl] -1,2-benzenediol and derivatives thereof as an active ingredient. An HMG-CoA reductase inhibitor comprising, as an active ingredient, 4-[(butylsulfinyl) methyl] -1,2-benzenediol according to claim 1.