JP2518497B2 - Antilipemic agent - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an antilipemic agent.

[0002]

2. Description of the Related Art Hyperlipidemia is a condition in which blood lipid levels such as serum total cholesterol and serum triglyceride are increased, and is considered to be one of the major causes of various adult diseases such as arteriosclerosis. Conventionally, antilipemic agents such as clofibrate and probucol have been used as therapeutic / preventive agents for hyperlipidemia. By the way, cholesterol is present in the blood in the form of very low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, etc. Among these, VLDL and LDL are arteries. HDL promotes the deposition of cholesterol on the wall and causes arteriosclerosis
Is known to prevent the deposition of cholesterol on the arterial wall and exert a therapeutic / preventive effect on arteriosclerosis [Annals of Internal Medicine (Annals o
fInternal Medicine), Volume 90,
85-91 (1979)]. Therefore, in recent years, it has been desired to develop an antilipemic agent capable of decreasing the amount of blood lipids such as serum total cholesterol and serum triglyceride while increasing the amount of HDL-cholesterol.

[0003]

DISCLOSURE OF THE INVENTION The present invention provides an antilipemic agent containing a benzoxazole derivative as an active ingredient.

[0004]

The present invention has the general formula (I)

[0005]

Embedded image

(However, R has a phenyl group which may have a substituent, a 1,3-oxazol-4-yl group or a pyridyl group, and Alk has a single bond, a lower alkenylene group, a lower alkynylene group or a substituent. Sometimes, a lower alkylene group and a dotted line indicate that the bond at the site may be a double bond.) An antilipemic agent containing a benzoxazole derivative or a pharmaceutically acceptable salt thereof as an active ingredient. Regarding agents.

Specific examples of the benzoxazole derivative which is the active ingredient of the antilipemic agent of the present invention include R in the general formula (I) in which R is a phenyl group and 1,3-oxazole-4-.
Is an yl group or a pyridyl group, or these groups are (lower alkoxy) carbonyl group, lower alkoxy group,
Lower alkyl group, trihalogeno lower alkyl group, lower alkylthio group, lower alkylsulfinyl group, lower alkylsulfonyl group, phenyl group, phenoxy group, phenyl group-substituted lower alkoxy group, hydroxyl group, halogen atom, nitro group, amino group, lower alkanoylamino group Examples thereof include compounds substituted with a group selected from a group, a di (lower alkyl) amino group, a cycloalkyl group, a pyrrolidino group, a piperidino group, a morpholino group and a pyrrolyl group. Another specific example of the benzoxazole derivative (I) is Al.
k is a single bond, a linear or branched lower alkylene group, a lower alkenylene group or a lower alkynylene group,
Alternatively, there are compounds having a lower alkylene group substituted with an oxo group, a phenyl group or a cycloalkyl group.

As a compound exhibiting a particularly excellent therapeutic effect, R in the general formula (I) is a lower alkoxy group, a lower alkyl group, a trihalogeno lower alkyl group, a phenyl group, a halogen atom, a nitro group or di (lower alkyl) amino. Examples thereof include compounds having a phenyl group, a pyridyl group or a 1,3-oxazol-4-yl group which may be substituted with 1 to 2 groups selected from the group, and especially R
Compounds in which is a di (lower alkyl) aminophenyl group are preferred. In addition, other compounds that exhibit particularly excellent therapeutic effects include Alk as a single bond or a lower alkylene group and a 2,4-dioxothiazolidin-5-yl (or ylidene) methyl group at the 5-position of the benzoxazole ring. Is a compound bound to.

In the benzoxazole derivative (I) which is the active ingredient of the present invention, the lower alkoxy group, the lower alkyl group, the lower alkanoyl group, the lower alkylene group, the lower alkenylene group and the lower alkynylene group have 6 or less carbon atoms. In particular, those having 4 or less carbon atoms are preferable, and the cycloalkyl group has 3 to 3 carbon atoms.
It is preferably 9, especially 4 to 7. These benzoxazole derivatives (I) can be used for the purpose of the present invention either in a free form or in the form of a pharmaceutically acceptable salt thereof. Examples of the salt include alkali metal salts such as sodium salt and potassium salt, calcium salt,
Alkaline earth metal salts such as magnesium salts, acid addition salts such as hydrochlorides, sulfates and the like can be used.

The antilipemic agent of the present invention can be administered orally or parenterally, and can be administered in an appropriate pharmaceutical preparation such as tablets, granules, capsules, powders and injections by a conventional method. Used as. Although the dose of the active ingredient compound of the present invention varies depending on the administration method, age, weight and condition of the patient, it is usually about 5 to 200 mg / kg, preferably about 10 to 20 mg / kg per day. As the benzoxazole derivative (I), any of geometric isomers, optically active isomers and mixtures thereof can be used as the active ingredient of the present invention. The benzoxazole derivative (I), which is the active ingredient of the present invention, is (I) the general formula (II)

[0011]

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(Wherein R ¹ represents a hydroxyl group, a lower alkoxy group or a reactive residue, Y represents an oxygen atom or an imino group,
R and Alk have the same meanings as described above. ) And a compound represented by the general formula (III)

[0013]

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(Where the symbols have the same meanings as described above) and the dioxothiazolidine compound is subjected to a condensation reaction in the presence or absence of a condensing agent (eg, polyphosphoric acid trimethylsilyl ester), or (2 ) General formula (IV)

[0015]

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The amide compound represented by (where the symbols have the same meanings as described above) is subjected to an intramolecular condensation reaction in the presence or absence of a condensing agent (eg, polyphosphoric acid trimethylsilyl ester), or ( 3) General formula (V)

[0017]

[Chemical 6]

(However, the symbols have the same meanings as described above.) The azomethine compound can be produced by subjecting it to a dehydrogenation reaction in the presence of a dehydrogenating agent (eg lead tetraacetate). Further, among the benzoxazole derivatives (I), which are the active ingredients of the present invention, the general formula (I-
a)

[0019]

[Chemical 7]

The compounds represented by the formulas (where the symbols have the same meanings as described above) are represented by the general formula (VI)

[0021]

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(However, the symbols have the same meanings as described above.) The imine compound represented by the above can also be produced by hydrolysis. In the benzoxazole derivative (I), which is the active ingredient of the present invention, the compound (I) in which R is a lower alkylthiophenyl group is oxidized to a compound in which R is a lower alkylsulfinylphenyl group or a lower alkylsulfonylphenyl group. And R is a benzyloxyphenyl group (I)
Can be debenzylated to give a compound in which R is a hydroxyphenyl group.

Experimental Example (Serum cholesterol level lowering action, HDL-cholesterol level raising action and serum triglyceride level lowering action) S
Male D strain rats (body weight: 120-140 g, 1 group 5)
The diet containing 2 W / W% of cholesterol and 0.5 W / W% of sodium cholate was freely ingested for 4 days. After that, the control group was allowed to freely ingest the above feed, and the sample administration group was allowed to freely ingest the diet in which 100 mg% of the sample was added to the above feed. After 3 days, the rat was anesthetized with ether,
Body weight was measured and blood was collected from the abdominal aorta. The blood was allowed to stand at room temperature for 1 hour and then centrifuged to obtain serum, from which the amount of serum cholesterol and the amount of triglyceride were measured by the enzymatic method. In addition, a lipoprotein precipitation method using dextran sulfate from a portion of the serum [Canadian Journal of Biochemistry (Can. J. Bioc
hem. ), Vol. 47, p. 1043 (1969)], and separated HDL-cholesterol from
The amount of L-cholesterol was measured by the above enzymatic method. From this result, the serum cholesterol level lowering rate according to the following formula,
The HDL-cholesterol level increase rate and serum triglyceride level decrease rate were determined.

[0024]

[Equation 1]

[0025]

[Equation 2]

[0026]

(Equation 3)

The results are shown in Table 1 below.

[0028]

[Table 1]

Production Example 1 (1) A mixture of 5-amino-2-phenylbenzoxazole (4.87 g), concentrated hydrochloric acid (6 ml) and acetone (50 ml) under ice-cooling under ice-cooling, sodium nitrite (1.76 g) in water (5 m).
1 is added dropwise. The mixture is stirred at the same temperature for 10 minutes, 12.1 g of acrylic acid methyl ester is further added, and 150 mg of cuprous oxide is gradually added while heating to 40 ° C. After the generation of nitrogen gas is finished, it is heated to 35 ° C. for 20 minutes, the reaction solution is diluted with water and extracted with ethyl acetate. After washing the extract with water and drying, the solvent is distilled off, and the residue is purified by silica gel column chromatography (solvent: chloroform) to give 3-
(2-Phenylbenzoxazol-5-yl) -2-
5.13 g of chloropropionic acid methyl ester are obtained as a light brown oil. IR ^Neat ν _max (cm ⁻¹ ): 1740 (2) A mixture of 5.13 g of this product, 2.30 g of thiourea, 1.50 g of sodium acetate and 35 ml of ethylene glycol monomethyl ether is heated at 100 ° C. for 8 hours. The solvent was distilled off from the reaction solution, water and n-hexane were added to the residue, and the precipitated crystals were collected by filtration, washed and dried to give 5-[(2-imino-4-oxothiazolidine-5).
4.35 g of -yl) methyl] -2-phenylbenzoxazole are obtained as colorless powder. M. p. 281 to 283 ° C (decomposition) (3) 3.18 g of this product is dissolved in 50 ml of ethylene glycol monomethyl ether, 2.05 g of toluenesulfonic acid monohydrate and 6 ml of water are added, and the mixture is refluxed for 1 hour and 45 minutes. The solvent is distilled off from the reaction solution, water is added to the residue, the mixture is extracted with ethyl acetate, washed and dried, and then the solvent is distilled off. By purifying the residue by silica gel column chromatography [solvent: chloroform-methanol (20: 1)],
1.83 g of 5-[(2,4-dioxothiazolidin-5-yl) methyl] -2-phenylbenzoxazole are obtained. M. p. 192-194 degreeC Mass (m / e): 324 (M ^<+> ) IR ^Nujol (nu) _max (cm < ^-1 >): 3180,17.
45,1680

Production Examples 2-3 By treating corresponding raw material compounds in the same manner as in Production Example 1, compounds shown in Table 2 below are obtained.

[0031]

[Table 2]

Production Example 4 (1) 2-phenyl-4-oxazoleacetic acid 2.03
g, 5- (3-amino-4-hydroxybenzyl)-
A mixture of 2.38 g of 2,4-dioxothiazolidine, 2.06 g of dicyclohexylcarbodiimide, 2 ml of dimethylformamide and 20 ml of tetrahydrofuran is stirred at room temperature for 18 hours. After the reaction, the insoluble matter is removed and the mixture is poured into ice water, extracted with ethyl acetate, washed with water and dried, and then the solvent is distilled off. The residue was purified by silica gel column chromatography (solvent; chloroform: methanol = 10: 1) and crystallized from ethyl acetate to give N- [5- (2,4-dioxothiazolidin-5-yl) methyl-. 2.83 g of 2-hydroxyphenyl] -2-phenyloxazole-4-acetamide are obtained. M. p. 197.5 to 199.5 ° C (2) 635 mg of this product is heated at 230 ° C for 40 minutes.
After cooling, it was purified by silica gel column chromatography (solvent; chloroform: methanol = 10: 1) and recrystallized from acetonitrile to give 5-[(2,4-dioxothiazolidin-5-yl) methyl] -2- [. 383 mg of (2-phenyl-1,3-oxazol-4-yl) methyl] benzoxazole are obtained. Yield 63% M. p. 174 to 177.5 ° C. IR ^Nujol ν _max (cm ⁻¹ ): 1730,17
10, Mass (m / e): 405 (M ⁺ ), 289

Production Examples 5 to 19 The corresponding starting material compounds are treated in the same manner as in Production Example 4 to obtain the compounds shown in Table 3 below.

[0034]

[Table 3]

[0035]

[Table 4]

[0036]

[Table 5]

[0037]

[Table 6]

Production Example 20 4.0 g of phosphorus pentoxide and 10 of hexamethyldisiloxane
5 ml of a mixture of 20 ml of 1,2-dichlorobenzene.
A trimethylsilyl ester polyphosphate solution is prepared by heating under reflux for a minute. Then 2-phenyl-5-methyl-4
-1.52 g of oxazole acetic acid and 5- (3-amino-
4-Hydroxybenzyl) -2,4-dioxothiazolidine 2.17 is added and heated at 150 ° C. for 2 hours.
After the reaction, the mixture is poured into ice water, extracted with ethyl acetate, washed with water, dried and the solvent is distilled off. The residue was purified by silica gel column chromatography (solvent; chloroform: methanol = 100: 1) and recrystallized from a mixed solution of ethyl acetate-n-hexane to give 5-[(2,4-dioxothiazolidin-5-yl). ) Methyl] -2-[(2-phenyl-5-methyl-
1.99 g of 1,3-oxazol-4-yl) methyl] benzoxazole are obtained. Yield 68% M. p. 175-178 ° C IR ^Nujol ν _max (cm ^-1 ): 1745,17
00, 1640 Mass (m / e): 419 (M ⁺ ), 348, 303

Production Examples 21 to 51 Corresponding raw material compounds were treated in the same manner as in Production Example 20 to give the following 4th
The compounds listed are obtained.

[0040]

[Table 7]

[0041]

[Table 8]

[0042]

[Table 9]

[0043]

[Table 10]

[0044]

[Table 11]

[0045]

[Table 12]

[0046]

[Table 13]

Production Example 52 (1) N- (5-amino-2-hydroxyphenyl)-
By treating 9.47 g of 2- (4-chlorophenyl) acetamide in the same manner as in Production Example 1, N- [5- (2,
5.64 g of 4-dioxothiazolidin-5-yl) methyl-2-hydroxyphenyl] -2- (4-chlorophenyl) acetamide are obtained as a pale yellow powder. M. p. 207-209 ° C. (2) 50.64 g of the product of (1) above at 220 ° C.
After heating for 5 minutes, cooling, purification by silica gel column chromatography [solvent: chloroform-methanol (50: 1)], and recrystallization from ether to give 5-
4.0 g of [(2,4-dioxothiazolidin-5-yl) methyl] -2- (4-chlorobenzyl) benzoxazole are obtained. M. p. 169.5 to 170.5 ° C Mass (m / e): 374, 372 (M ⁺ ) IR ^Nujol ν _max (cm ^-1 ): 1750, 16
90

Production Example 53 N- (5-amino-2-hydroxyphenyl) -4-hydroxy-3,5-di (tert-butyl) benzamide was treated in the same manner as in Production Example 52 to give 5-
[(2,4-Dioxothiazolidin-5-yl) methyl] -2- [4-hydroxy-3,5-di (tert-
Butyl) phenyl] benzoxazole is obtained. M. p. 213-216 degreeC Mass (m / e): 452 (M ^<+> ) IR ^Nujol (nu) _max (cm < ^-1 >): 1750,17.
Production Example 54 N- (4-amino-2-hydroxyphenyl) -2-
By treating (4-chlorophenyl) acetamide in the same manner as in Production Example 52, 6-[(2,4-dioxothiazolidin-5-yl) methyl] -2- [4-chlorobenzyl] benzoxazole is obtained. M. p. 219.5 to 220.5 ° C Mass (m / e): 374, 372 (M ⁺ ) IR ^Nujol ν _max (cm ^-1 ): 1745, 16
95

Production Example 55 3.48 g of 5-[(2,4-dioxothiazolidin-5-yl) methyl] -2- (4-nitrobenzyl) benzoxazole was dissolved in a mixed solution of 70 ml of tetrahydrofuran and 70 ml of methanol, 2.5 g of 10% palladium-carbon is added and subjected to a reduction reaction in hydrogen at atmospheric pressure. The insoluble material was removed from the reaction solution by filtration, and the filtrate was concentrated and purified by silica gel column chromatography [(solvent: chloroform-methanol (20: 1)] and recrystallized from ethyl acetate to give 5-[(2 , 4-dioxothiazolidine-5
1.86 g of -yl) methyl] -2- (4-aminobenzyl) benzoxazole are obtained. M. p. 180-1
83 ° C Mass (m / e): 353 (M ⁺ ) IR ^Nujol ν _max (cm ^-1 ): 1735, 17
Production Example 56 A mixture of 5-[(2,4-dioxothiazolidin-5-yl) methyl] -2- (4-aminobenzyl) benzoxazole 0.99 g, acetic anhydride 2 ml and pyridine 10 ml was stirred overnight at room temperature. Thereafter, 10% hydrochloric acid is added, the mixture is extracted with ethyl acetate, washed with water, dried and the solvent is distilled off. By recrystallizing the residue from ethyl acetate, 5-[(2,4-
Dioxothiazolidin-5-yl) methyl] -2- (4
-Acetamidobenzyl) benzoxazole 0.56 g
Get. M. p. 233-236 degreeC Mass (m / e): 395 (M ^<+> ) IR ^Nujol (nu) _max (cm < ^-1 >): 1745,16.
90

Production Example 57 5-[(2,4-dioxothiazolidin-5-yl) methyl] -2- (4-methylthiobenzyl) benzoxazole 1.0 g, 80% m-chloroperbenzoic acid 0.58
g and 25 ml of methylene chloride are stirred at room temperature for 10 minutes. The solvent was distilled off, ethyl acetate was added, and washing was performed.
After drying, the solvent was distilled off, and the residue was purified by silica gel column chromatography (solvent; chloroform: methanol = 20: 1) and 5-[(2,4-dioxothiazolidin-5-yl) methyl] -2- (4- 0.67 g of methylsulfinylbenzyl) benzoxazole is obtained as a colorless foam. Yield 64% Mass (m / e): 400 (M ⁺ ) IR ^Nujol ν _max (cm ⁻¹ ): 1750, 16
90 Production Example 58 5-[(2,4-Dioxothiazolidin-5-yl) methyl] -2- (4-methylthiobenzyl) benzoxazole 1.2 g, 80% m-chloroperbenzoic acid 2.1 g
And a mixture of 30 ml of methylene chloride are stirred for 20 minutes at room temperature. After the same treatment as in Production Example 57 was performed, the crystals were recrystallized from a tetrahydrofuran-n-hexane mixed solution to give 5-
1.2 g of [(2,4-dioxothiazolidin-5-yl) methyl] -2- (4-methylsulfonylbenzyl) benzoxazole are obtained as colorless powder. Yield 69% M. p. 168-169 ° C

Production Example 59 5-[(2,4-Dioxothiazolidin-5-yl) methyl] -2- (4-benzyloxybenzyl) benzoxazole 0.95 g, 25% hydrobromic acetic acid solution 10 m
A mixture of 1 and 10 ml of acetic acid is stirred overnight at room temperature. Ethyl acetate and water are added to the reaction solution, the ethyl acetate layer is washed with water and dried, and then the solvent is distilled off. The residue was crystallized from n-hexane and recrystallized from a mixed solution of ethyl acetate-n-hexane to give 5-[(2,4-dioxothiazolidine-5-
0.42 g of (yl) methyl] -2- (4-hydroxybenzyl) benzoxazole are obtained as colorless needles. Yield 55% p. 201-204 ° C

[Preparation of Raw Material Compound] Reference Example 1 (1) 2-amino-4-nitrophenol (6.16 g) and benzaldehyde (4.77 g) were condensed under heating to give 2-
After making benzylideneamino-4-nitrophenol,
This product was heated to ring closure in the presence of lead tetraacetate to give 5-nitro-2.
-5.08 g of phenylbenzoxazole are obtained. M. p. 169 to 171.5 ° C. (2) 8.85 g of the above product is catalytically reduced in the presence of a palladium-carbon catalyst to obtain 7.02 g of 5-amino-2-phenylbenzoxazole. M. p. 150.5 to 153 ° C. Reference Examples 2 and 3 The corresponding starting material compounds are treated in the same manner as in Reference Example 1 to obtain the compounds shown in Table 5 below.

[0053]

[Table 14]

Reference Example 4 (1) 4-Chlorophenylacetic acid 8.55 g was chlorinated and then 2-amino-4-nitrophenol 7.70.
g in the presence of N, N-dimethylaniline to condense N
-(5-Nitro-2-hydroxyphenyl) -2- (4
14.2 g of -chlorophenyl) acetamide are obtained. M. p. 250-252 ° C (decomposition) (2) 13.93 g of this product is reduced with stannous chloride to give N-
(5-Amino-2-hydroxyphenyl) -2- (4-
9.86 g of chlorophenyl) acetamide are obtained. M. p. 164-167 ° C. Reference Example 5 4-hydroxy-3,5-di (tert-butyl) benzoic acid and 2-amino-4-nitrophenol were used as Reference Example 4.
-(1) and Reference Example 1- (2) were treated in the same manner as N-
(5-Amino-2-hydroxyphenyl) -4-hydroxy-3,5-di (tert-butyl) benzamide is obtained. M. p. 222-225 ° C (decomposition)

Reference Example 6 (1) 4-Hydroxy-3-nitrobenzaldehyde 1
8.0 g and 2,4-dioxothiazolidine 12.74 g
And are heated and condensed in the presence of piperidine to obtain 14.82 g of 5- (4-hydroxy-3-nitrobenzylidene) -2,4-dioxothiazolidine. Yield 52% p. 256.5-258 ° C (2) 12.85 g of this product was reduced with sodium hypophosphite in the presence of a palladium-carbon catalyst to give 5- (3-amino-
10.86 g of 4-hydroxybenzylidene) -2,4-dioxothiazolidine are obtained. Yield 95% M. p. 260.5-261.5 ° C (decomposition)

Reference Example 7 (1) L-3-Hydroxy-3-nitrophenylalanine (13.3 g) was treated with sodium nitrite in the presence of potassium bromide in 3N-sulfuric acid to prepare 2-bromo-3- (4). −
Hydroxy-3-nitrophenyl) propionic acid 15.
2 g are obtained as a brown solid. (2) 15.1 g of this product and 6.14 g of thiourea were heated and condensed in the presence of sodium acetate to give 12.2 g of 5- (4-hydroxy-3-nitrobenzyl) -2-imino-4-oxothiazolidine. Obtained as a yellow powder. M. p. 221-223 ° C (decomposition) (3) 12.1 g of this product was hydrolyzed in the presence of hydrochloric acid to give 5
-(4-Hydroxy-3-nitrobenzyl) -2,4-
10.4 g of dioxothiazolidine are obtained as a yellow powder. M. p. 141-143.5 ° C. (4) 10.3 g of this product was catalytically reduced in the presence of a palladium-carbon catalyst to give 8.77 g of 5- (3-amino-4-hydroxybenzyl) -2,4-dioxothiazolidine. Obtained as a pale yellow powder. M. p. 215-217.5 ° C

[0057]

INDUSTRIAL APPLICABILITY The benzoxazole derivative (I) and its salt, which are the active ingredients of the antilipemic agent of the present invention, are novel compounds, and have a serum cholesterol lowering effect and HD.
It has an excellent antilipemic action based on the action of increasing L-cholesterol level and / or the action of decreasing serum triglyceride level. Furthermore, this compound (I) has low toxicity, for example, 5
72 after oral administration (dose 3000 mg / kg) of CMC suspension of-[(2,4-dioxothiazolidin-5-yl) methyl] -2- [4- (dimethylamino) benzyl] benzoxazole to mice Observed over time, no deaths were observed. Therefore, the compound (I) or a pharmaceutically acceptable salt thereof is a compound useful as an antilipemic agent, for example, hyperlipidemia (eg, hypercholesterolemia), arteriosclerosis (eg, porridge). It can be used for the treatment and prevention of arteriosclerosis, Menkeberg arteriosclerosis, etc. Also,
HDL- while reducing serum total cholesterol
Since it has a characteristic of increasing cholesterol level, it can be used especially for the treatment and prevention of arteriosclerosis.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical display location C07D 417/14 213 C07D 417/14 213 215 215 263 263 (72) Inventor Masanori Inamasu Saio No. 407, No. 3, Building 3-4, Waseda, Misato City (56) References Japanese Patent Laid-Open No. 64-13088 (JP, A)

Claims (5)

(57) [Claims] 1. A compound of the general formula (I) (However, R is a phenyl group which may have a substituent,
A 1,3-oxazol-4-yl group or a pyridyl group,
Alk represents a single bond, a lower alkenylene group, a lower alkynylene group, or a lower alkylene group which may have a substituent, and a dotted line represents that the bond at the relevant site may be a double bond. ) An antilipemic agent comprising a benzoxazole derivative or a pharmacologically acceptable salt thereof as an active ingredient. 2. R is substituted with 1 to 2 groups selected from a lower alkoxy group, a lower alkyl group, a trihalogeno lower alkyl group, a phenyl group, a halogen atom, a nitro group and a di (lower alkyl) amino group. The antilipemic agent according to claim 1, which is a phenyl group, a pyridyl group or a 1,3-oxazol-4-yl group. 3. The antilipemic agent according to claim 1, wherein R is a di (lower alkyl) aminophenyl group. 4. Alk is a single bond or a lower alkylene group, and a 2,4-dioxothiazolidin-5-yl (or ylidene) methyl group is bonded to the 5-position of the benzoxazole ring. The antilipemic agent according to 2 or 3. 5. 5-[(2,4-Dioxothiazolidin-5-yl) methyl] -2- [4- (dimethylamino)
Benzyl] benzoxazole or an antilipemic agent comprising a pharmacologically acceptable salt thereof as an active ingredient.