Benzofurylpyrone derivatives

Abstract

There is provided benzofuryl-α-pyrone derivative represented by the following structural formula (I): wherein R 1 represents a hydrogen atom or an alkyl group of 1 to 5 carbons; R 2 represents hydrogen, —CO—R 5 or —SO 2 R 6 ; R 3 represents hydrogen, an alkyl group of 1 to 5 carbons, etc.; and R 4 is a substituent attached to the 4-carbon, 5-carbon, 6-carbon or 7 carbon of the benzofuran ring; and their salts. The compounds are useful as therapeutic agent for hypertriglyceridemia, lipid metabolism enhancers, or prophylactic and/or therapeutic agents for arteriosclerosis.

1 . A benzofuryl-α-pyrone derivative represented by the following structural formula (I)  
       
         
           
           
               
               
           
         
         wherein R 1  represents hydrogen or an alkyl group of 1 to 5 carbons;  
         R 2  represents hydrogen, —CO—R 5  (wherein R 5  represents hydrogen, an alkyl group of 1 to 5 carbons with optional substituents, a cycloalkyl group of 3 to 7 carbons, an aryl group of 6 to 10 carbons or a heterocycle), or —SO 2 R 6  (wherein R 6  represents an optionally halogen-substituted alkyl group of 1 to 5 carbons or aryl group of 6 to 10 carbons);  
         R 3  represents hydrogen, an alkyl group of 1 to 5 carbons, an alkenyl group of 2 to 5 carbons, an alkynyl group of 2 to 5 carbons, a cycloalkyl group of 3 to 7 carbons, a cycloalkyl group of 3 to 7 carbons-alkyl group of 1 to 5 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons, an alkoxy group of 1 to 5 carbons or an aryloxy group of 6 to 10 carbons;  
         R 4  is a substituent at the c-4 position, c-5 position, c-6 position or c-7 position of the benzofuran ring and represents: 
 R 4a  which represents hydrogen, a nitro group, a cyano group, a halogen atom, a heterocycle, an alkenyl group of 2 to 5 carbons, an alkynyl group of 2 to 5 carbons, an aryl group of 6 to 10 carbons, A=CH(CH 2 ) n — (wherein A represents an alicyclic heterocycle, “═” represents a double bond and n represents 0, 1 or 2), A=CH(CH 2 ) m O— (wherein A represents an alicyclic heterocycle, “═” represents a double bond and m represents 1, 2 or 3), A-SO 2 —(CH 2 ) m — (wherein A represents an alicyclic heterocycle and m represents 1, 2 or 3), —OR 7  (wherein R 7  represents hydrogen, a cycloalkyl group of 3 to 7 carbons, an aryl group of 6 to 10 carbons, a heterocycle or an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons or arylsulfonyl group of 6 to 10 carbons), —O—CO—R 8  (wherein R 8  represents hydrogen, an alkyl group of 1 to 4 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons or a heterocycle), —NR 9 R 10  (wherein R 9  and R 10  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, an aralkyl group of 7 to 20 carbons, a heterocycle, a phenyl group, —SO 2 —R 11  (wherein R 11  represents an optionally halogen-substituted alkyl group of 1 to 12 carbons, a heterocycle-substituted alkyl group of 1 to 6 carbons, an aryl group of 6 to 10 carbons, a heterocycle or an aralkyl group of 7 to 20 carbons) or —CO—R 12  (wherein R 12  represents hydrogen, an alkyl group of 1 to 12 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons, a heterocycle, an alkoxy group of 1 to 10 carbons, a heterocycle-substituted alkyl group of 1 to 6 carbons, an aryloxy group of 6 to 10 carbons, a heteroaryloxy group or an aralkyloxy group of 7 to 20 carbons)), —CO—R 13  (wherein R 13  represents hydrogen, —OH, an alkyl group of 1 to 4 carbons, an aryl group of 6 to 10 carbons, a heterocycle, an alkoxy group of 1 to 4 carbons, an aryloxy group of 6 to 10 carbons or an aralkyloxy group of 7 to 20 carbons) or —CO—NR 14 R 15  (wherein R 14  and R 15  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a cycloalkyl group of 3 to 7 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons, a heterocycle or a heterocycle-substituted alkyl group of 1 to 4 carbons);  
 R 4b  which represents a saturated or unsaturated alkoxy group of 1 to 6 carbons optionally substituted with 1 to 3 groups selected from the group consisting of halogens, cycloalkyl groups of 3 to 7 carbons, phenyl, naphthyl, heterocycles, —OR 16  (wherein R 16  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a naphthyl group, a benzyl group or a heterocycle), —O—CO—R 16  (wherein R 16  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a naphthyl group, a benzyl group or a heterocycle), —NR 17 R 18  (wherein R 17  and R 18  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a heterocycle, an alkylsulfonyl group of 1 to 4 carbons, a phenylsulfonyl group, —SO 2 -Het (wherein Het represents a heterocycle), an aminosulfonyl group, a methylaminosulfonyl group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, or an alkyl group of 1 to 4 carbons substituted with 1 or 2 groups selected from among phenyl, heterocycles, phenoxy, —O-Het (wherein Het represents a heterocycle) and hydroxyl, —NH—CO—R 19  (wherein R 19  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a naphthyl group, a benzyl group, a heterocycle, an alkoxy group of 1 to 4 carbons or a benzyloxy group), —CO—R 20  (wherein R 20  represents hydrogen, a heterocycle, an alkoxy group of 1 to 4 carbons, a phenoxy group, a benzyloxy group or —OR 21  (wherein R 21  represents hydrogen or a heterocycle)) and —CO—NR 22 R 23  (wherein R 22  and R 23  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a benzyl group or a heterocycle); or  
 R 4C  which represents an alkyl group of 1 to 4 carbons optionally substituted with 1 to 3 groups selected from the group consisting of halogens, cycloalkyl groups of 3 to 7 carbons, phenyl, naphthyl, heterocycles, —SH, —OR 16  (wherein R 16  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a naphthyl group, a benzyl group or a heterocycle), —O—CO—R 16  (wherein R 16  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a naphthyl group, a benzyl group or a heterocycle), —NR 17 R 18  (wherein R 17  and R 18  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a heterocycle, an alkylsulfonyl group of 1 to 4 carbons, a phenylsulfonyl group, —SO 2 -Het (wherein Het represents a heterocycle), an aminosulfonyl group, a methylaminosulfonyl group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, or an alkyl group of 1 to 4 carbons substituted with 1 or 2 groups selected from among phenyl, heterocycles, phenoxy, —O-Het (wherein Het represents a heterocycle) and hydroxyl, —NH—CO—R 19  (wherein R 19  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a naphthyl group, a benzyl group, a heterocycle, an alkoxy group of 1 to 4 carbons or a benzyloxy group), —CO—R 20  (wherein R 20  represents hydrogen, a heterocycle, an alkoxy group of 1 to 4 carbons, a phenoxy group, a benzyloxy group or —OR 21  (wherein R 21  represents hydrogen or a heterocycle)) and —CO—NR 22 R 23  (wherein R 22  and R 23 each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a benzyl group or a heterocycle); and  
 the numbers in italics represents the positions on the benzofuran ring;  
 or a salt thereof.  
 
       
     
     
         2 . A benzofuryl-α-pyrone derivative according to  claim 1  wherein R 1  is hydrogen, methyl, ethyl or isopropyl; or a salt thereof.  
     
     
         3 . A benzofuryl-α-pyrone derivative according to  claim 1  wherein R 1  is methyl; or a salt thereof.  
     
     
         4 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  3 , wherein R 5  is (1) an alkyl group of 1 to 5 carbons optionally substituted with 1 to 4 substituents selected from the group consisting of halogens, —OR 8  (wherein R 8  represents hydrogen, an alkyl group of 1 to 4 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons or a heterocycle), —O—CO—R 8  (wherein R 8  represents hydrogen, an alkyl group of 1 to 4 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons or a heterocycle), —NR 9 R 10  (wherein R 9  and R 10  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, an aralkyl group of 7 to 20 carbons, a heterocycle, an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons or an arylsulfonyl group of 6 to 10 carbons), —NH—CO—R 24  (wherein R 24  represents hydrogen, an alkyl group of 1 to 4 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons, a heterocycle, an alkoxy group of 1 to 4 carbons or an aralkyloxy group of 7 to 20 carbons), cycloalkyl groups of 3 to 7 carbons, aryl groups of 6 to 10 carbons, heterocycles and —CO—R 25  (wherein R 25  represents hydrogen, an alkyl group of 1 to 4 carbons, a heterocycle, —OR 8  (wherein R 8  represents hydrogen, an alkyl group of 1 to 4 carbons, an aryl group of 6 to 10 carbons, an aralkyl group of 7 to 20 carbons or a heterocycle) or —NR 26 R 27  (wherein R 26  and R 27  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, an aralkyl group of 7 to 20 carbons or a heterocycle)), (2) a hydrogen atom, (3) a cycloalkyl group of 3 to 7 carbons, (4) an aryl group of 6 to 10 carbons, or (5) a heterocycle;  
       or a salt thereof.  
     
     
         5 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  3 , wherein R 5  is (1) an alkyl group of 1 to 5 carbons optionally substituted with 1 to 3 substituents selected from the group consisting of —OH, alkoxy groups of 1 to 4 carbons, phenoxy, benzyloxy, —O—CO—R 28  (wherein R 28  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group or a heterocycle), —NR 29 R 30  (wherein R 29  and R 30  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a benzyl group, a heterocycle or an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons), —NH—CO—R 31  (wherein R 31  represents hydrogen, an alkyl group of 1 to 4 carbons, a heterocycle, an alkoxy group of 1 to 4 carbons or a benzyloxy group), aryl groups of 6 to 10 carbons, heterocycles and —CO—R 32  (wherein R 32  represents hydrogen, —OR 32  (wherein R 32  represents hydrogen, an alkyl group of 1 to 4 carbons, a benzyl group or a heterocycle), —NR 33 R 34  (wherein R 33  and R 34  each independently represents hydrogen, methyl, ethyl, benzyl or a heterocycle) or a heterocycle), (2) a cycloalkyl group of 3 to 7 carbons, (3) an aryl group of 6 to 10 carbons, or (4) a heterocycle;  
       or a salt thereof.  
     
     
         6 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  3 , wherein R 5  is (1) an alkyl group of 1 to 5 carbons optionally substituted with 1 to 3 substituents selected from the group consisting of phenoxy, —NR 29 R 30  (wherein R 29  and R 30  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a benzyl group, a heterocycle or an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons), —NH—CO—R 31  (wherein R 31  represents hydrogen, an alkyl group of 1 to 4 carbons, a heterocycle, an alkoxy group of 1 to 4 carbons or a benzyloxy group), phenyl and —CO—R 35  (wherein R 35  represents —OH, an alkoxy group of 1 to 4 carbons, a benzyloxy group, —NR 33 R 34  (wherein R 33  and R 34  each independently represents hydrogen, methyl, ethyl, benzyl or a heterocycle) or a heterocycle), (2) an aryl group of 6 to 10 carbons, or (3) a heterocycle;  
       or a salt thereof.  
     
     
         7 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  3 , wherein R 5  is (1) an alkyl group of 1 to 5 carbons optionally substituted with 1 or 2 substituents selected from the group consisting of phenoxy, —NR 36 R 37  (wherein R 36  and R 37  each independently represents hydrogen or methyl), —NH—CO—R 38  (wherein R 38  represents hydrogen, methyl, a heterocycle, t-butoxy or benzyloxy), phenyl and —CO—R 39  (wherein R 39  represents a heterocycle), (2) a phenyl group, or (3) a heterocycle;  
       or a salt thereof.  
     
     
         8 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  7 , wherein R 2  is hydrogen or —CO—R 5 ; or a salt thereof.  
     
     
         9 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  3 , wherein R 2  is hydrogen, acetyl, isobutyryl, benzoyl, 4-methoxybenzoyl, 2,4-dimethoxybenzoyl, 4-hydroxymethylbenzoyl, 3-dimethylaminobenzoyl, 4-acetylaminobenzoyl, phenylacetyl, 3-phenylpropionyl, phenoxyacetyl, furan-2-carbonyl, pyridine-4-carbonyl, pyridine-3-carbonyl, pyridine-2-carbonyl, 6-hydroxypyridine-3-carbonyl, 2-aminoacetyl, 2-(t-butoxycarbonylamino)acetyl, 2-(N-carbobenzyloxy-N-methylamino)acetyl, 1-carbobenzyloxy-2-pyrrolidone-5-carbonyl, 2-pyrrolidone-5-carbonyl, 3-acetylamino-4-morpholinyl-4-oxobutyryl, trifluoromethanesulfonyl or methanesulfonyl;  
       or a salt thereof.  
     
     
         10 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  3 , wherein R 2  is hydrogen or acetyl; or a salt thereof.  
     
     
         11 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  10 , wherein R 3  is hydrogen, an alkyl group of 1 to 5 carbons, an alkenyl group of 2 to 5 carbons, an alkynyl group of 2 to 5 carbons, 2-cycloalkylmethyl group of 4 to 8 carbons, a cycloalkylethyl group of 5 to 9 carbons, a phenyl group, a benzyl group, a phenethyl group, a methoxy group or a phenoxy group;  
       or a salt thereof.  
     
     
         12 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  10 , wherein R 3  is hydrogen, an alkyl group of 1 to 5 carbons, an alkenyl group of 2 to 4 carbons, a cycloalkylmethyl group of 6 to 7 carbons, 2-cycloalkylethyl group of 7 to 8 carbons, a phenyl group, a benzyl group, a methoxy group or a phenoxy group;  
       or a salt thereof.  
     
     
         13 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  10  wherein R 3  is an alkyl group of 1 to 5 carbons; or a salt thereof.  
     
     
         14 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  10  wherein R 3  is methyl or ethyl; or a salt thereof.  
     
     
         15 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  14 , wherein R 4c  is an alkyl group of 1 to 3 carbons optionally substituted with 1 to 3 substituents selected from the group consisting of heterocycles, —SH, —OH, alkoxy groups of 1 to 4 carbons, acyloxy groups of 1 to 4 carbons, —NR 4 OR 41  (wherein R 40  and R 41  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons, or an alkyl group of 1 or 2 carbons substituted with 1 or 2 substituents selected from among phenyl, heterocycles, phenoxy, —O-Het (wherein Het represents a heterocycle) and hydroxyl), —NH—CO—R 42  (wherein R 42  represents hydrogen, phenyl, an alkyl group of 1 to 4 carbons or an alkoxy group of 1 to 4 carbons), —CO—R 43  (wherein R 43  represents hydrogen, a heterocycle, an alkoxy group of 1 to 4 carbons or —OR 21  (wherein R 21  represents hydrogen or a heterocycle)) and —CO—NR 44 R 45  (wherein R 44  and R 45  each independently represents hydrogen, an alkyl group of 1 to 4 carbons or a heterocycle);  
       or a salt thereof.  
     
     
         16 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  14 , wherein R 4c  is an alkyl group of 1 to 3 carbons substituted with a heterocycle, —SH, benzoylamino, an acylamino group of 1 to 5 carbons or —NR 40 R 41  (wherein R 40  and R 41  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons, or an alkyl group of 1 or 2 carbons substituted with 1 or 2 substituents selected from among phenyl, heterocycles, phenoxy, —O-Het (wherein Het represents a heterocycle) and hydroxyl);  
       or a salt thereof.  
     
     
         17 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  14 , wherein R 4c  is (3,5-dioxo-2,4-thiazolidinyl)methyl, (3,5-dioxo-2,4-oxazolidinyl)methyl, (2,5-dioxoimidazolidin-4-yl)methyl or (5-oxo-3-thioxo-2,4-thiazolidinyl)methyl; or a salt thereof.  
     
     
         18 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  14 , wherein R 4c  is (3,5-dioxo-2,4-thiazolidinyl)methyl; or a salt thereof.  
     
     
         19 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  18 , wherein R 4b  is an alkoxy group of 1 to 6 carbons optionally substituted with 1 to 3 substituents selected from the group consisting of halogens, cycloalkyl groups of 3 to 7 carbons, phenyl, naphthyl, heterocycles, acyloxy groups of 1 to 4 carbons, —CHO, —CO 2 H, alkoxycarbonyl groups of 2 to 5 carbons, —OR 46  (wherein R 46  represents hydrogen, an alkyl group of 1 to 4 carbons, a phenyl group, a benzyl group or a heterocycle) and —NR 47 R 48  (wherein R 47  and R 48  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, an alkoxycarbonyl group of 2 to 5 carbons, a heterocycle, an alkylsulfonyl group of 1 to 4 carbons, a phenylsulfonyl group, —SO 2 -Het (wherein Het represents a heterocycle), an aminosulfonyl group, a methylaminosulfonyl group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, an acyl group of 1 to 5 carbons, a benzoyl group, —CO-Het (wherein Het represents a heterocycle), a benzyloxycarbonyl group, or an alkyl group of 1 to 4 carbons substituted with 1 or 2 groups selected from among phenyl, heterocycles, phenoxy, —O-Het (wherein Het represents a heterocycle) and hydroxyl) or an unsaturated alkoxy group of 3 to 6 carbons;  
       or a salt thereof.  
     
     
         20 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  18 , wherein R 4b  is methoxy, 2-propynyloxy, 2,2-dimethylpropoxy, cyclopentylmethoxy, 2-bromoethoxy, benzyloxy, chlorobenzyloxy, fluorobenzyloxy, (trifluoromethyl)benzyloxy, dichlorobenzyloxy, dimethylbenzyloxy, methoxybenzyloxy, sulfamoylbenzyloxy, (methylenedioxy)benzyloxy, carboxybenzyloxy, (methoxycarbonyl)benzyloxy, n-butoxybenzyloxy, aminobenzyloxy, (t-butoxycarbonylamino)benzyloxy, 3-phenylpropoxy, di(methoxyphenyl)methoxy, 1-methyl-1-phenylethoxy, naphthylmethoxy, thienylmethoxy, 2-(morpholinesulfonyl)thienylmethoxy, pyridylmethoxy, (2-methoxypyridyl)methoxy, 2-(pyridyl)ethoxy, pyrazinylmethoxy, pyrimidinylmethoxy, oxazolylmethoxy, 4-phenyloxazolylmethoxy, imidazolylmethoxy, 3-tosyl-5-methylimidazolylmethoxy, thiazolylmethoxy, 4-methylthiazolylmethoxy, 2-(morpholinesulfonyl)thiazolylmethoxy, 2,4-dichlorothiazolylmethoxy, 2-(5-thiazolyl)ethoxy, 2-(4-methyl-5-thiazolyl)ethoxy, (3,5-dioxo-2,4-thiazolidinyl)methoxy, N-methylpiperidylmethoxy, (4-oxachroman-2-yl)methoxy, (3,3-dimethyl-2,4-dioxolanyl)methoxy, methoxymethyl, 2-(acetyloxy)ethoxy, bis(dimethylaminomethyl)methoxy, 4-(t-butoxycarbonylamino)butoxy, ethoxycarbonylmethoxy, 2-(methoxycarbonyl)ethoxy, 5-(ethoxycarbonyl)pentyloxy or 2-(benzyloxy)ethoxy;  
       or a salt thereof.  
     
     
         21 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  18 , wherein R 4b  is methoxy, 2-propynyloxy, benzyloxy, chlorobenzyloxy, fluorobenzyloxy, (trifluoromethyl)benzyloxy, dichlorobenzyloxy, dimethylbenzyloxy, methoxybenzyloxy, sulfamoylbenzyloxy, (methylenedioxy)benzyloxy, carboxybenzyloxy, (methoxycarbonyl)benzyloxy, n-butoxybenzyloxy, aminobenzyloxy, (t-butoxycarbonylamino)benzyloxy, thienylmethoxy, 2-(morpholinesulfonyl)thienylmethoxy, pyridylmethoxy, (2-methoxypyridyl)methoxy, 2-(pyridyl)ethoxy, pyrazinylmethoxy, pyrimidinylmethoxy, oxazolylmethoxy, 4-phenyloxazolylmethoxy, imidazolylmethoxy, 3-tosyl-5-methylimidazolylmethoxy, thiazolylmethoxy, 4-methylthiazolylmethoxy, 2-(morpholinesulfonyl)thiazolylmethoxy, 2,4-dichlorothiazolylmethoxy, 2-(5-thiazolyl)ethoxy, 2-(4-methyl-5-thiazolyl)ethoxy, (3,5-dioxo-2,4-thiazolidinyl)methoxy, N-methylpiperidylmethoxy or methoxymethyl;  
       or a salt thereof.  
     
     
         22 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  21 , wherein R 4a  is hydrogen, a nitro group, a cyano group, a halogen atom, a heterocycle, A=CH(CH 2 ) n — (wherein A represents an alicyclic heterocycle, “═” represents a double bond and n represents 0, 1 or 2), A=CH(CH 2 ) m O— (wherein A represents an alicyclic heterocycle, “═” represents a double bond and m represents 1, 2 or 3), A-SO 2 —(CH 2 ) m — (wherein A represents an alicyclic heterocycle and m represents 1, 2 or 3), —OR 49  (wherein R 49  represents hydrogen, a heterocycle, an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons or a phenylsulfonyl group), —O—CO—R 50  (wherein R 50  represents hydrogen, an alkyl group of 1 to 4 carbons or phenyl), —NR 51 R 52  (wherein R 51  and R 52  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, phenyl, benzyl, —SO 2 —R 53  (wherein R 53  represents phenyl, naphthyl, a heterocycle or an alkyl group of 1 to 3 carbons optionally substituted with 1 to 3 substituents selected from the group consisting of halogen atoms, heterocycles and phenyl), or —CO—R 54  (wherein R 54  represents hydrogen, phenyl, naphthyl, a heterocycle, an alkoxy group of 1 to 4 carbons, a phenoxy group, a naphthyloxy group, a heteroaryloxy group, an aralkyloxy group of 7 to 11 carbons or an alkyl group of 1 to 3 carbons optionally substituted with phenyl or a heterocycle)), —CO—R 55  (wherein R 55  represents hydrogen, —OH, a heterocycle, an alkoxy group of 1 to 4 carbons or a phenoxy group), or —CO—NR 56 R 57  (wherein R 56  and R 57  each independently represent hydrogen, an alkyl group of 1 to 4 carbons, a cycloalkyl group of 3 to 7 carbons, a phenyl group, a benzyl group, a phenethyl group, a heterocycle or a heterocycle-substituted alkyl group of 1 to 4 carbons); or a salt thereof.  
     
     
         23 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  21 , wherein R 4a  is hydrogen, a nitro group, a cyano group, a halogen atom, a heterocycle, A=CH(CH 2 ) n — (wherein A represents an alicyclic heterocycle, “═” represents a double bond and n represents 0, 1 or 2), A=CH(CH 2 ) m O— (wherein A represents an alicyclic heterocycle, “═” represents a double bond and m represents 1, 2 or 3), A-SO 2 —(CH 2 ) m — (wherein A represents an alicyclic heterocycle and m represents 1, 2 or 3), —OR 58  (wherein R 58  represents hydrogen, an optionally halogen-substituted alkylsulfonyl group of 1 to 4 carbons or a phenylsulfonyl group), —O—CO—R 59  (wherein R 59  represents an alkyl group of 1 to 4 carbons or phenyl), —NR 60 R 61  (wherein R 60  and R 61  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, phenyl, benzyl, —SO 2 —R 62  (wherein R 62  represents an optionally halogen-substituted alkyl group of 1 to 3 carbons, a heterocycle-substituted alkyl group of 1 to 3 carbons, a phenyl group, a heterocycle, a benzyl group or a phenethyl group) or —CO—R 63  (wherein R 63  represents an alkyl group of 1 to 4 carbons, a phenyl group, an aralkyl group of 7 to 9 carbons, a heterocycle, an alkoxy group of 1 to 4 carbons, a heterocycle-substituted alkyl group of 1 to 3 carbons, a phenoxy group, a heteroaryloxy group or a benzyloxy group)), —CO—R 64  (wherein R 64  represents hydrogen, —OH or an alkoxy group of 1 to 4 carbons), or —CO—NR 65 R 66  (wherein R 65  and R 66  each independently represents hydrogen, an alkyl group of 1 to 4 carbons, a cycloalkyl group of 3 to 7 carbons, a phenyl group, a benzyl group, a phenethyl group, a heterocycle or a heterocycle-substituted alkyl group of 1 to 4 carbons); or a salt thereof.  
     
     
         24 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  21  wherein R 4a  is hydrogen, nitro, cyano, bromine, thiazolyl, furyl, thienyl, morpholinyl, piperazinyl, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, phenylsulfonyloxy, acetyloxy, benzoyloxy, dimethylamino, dibenzylamino, phenylsulfonylamino, dimethylcarbamoyl, N-methyl-N-phenylcarbamoyl, N-benzyl-N-methylcarbamoyl, cyclohexylcarbamoyl, phenylcarbamoyl, imidazolylcarbamoyl, benzimidazolylcarbamoyl, thiazolylcarbamoyl, benzothiazolylcarbamoyl, isothiazolylcarbamoyl, pyrazolylcarbamoyl, triazolylcarbamoyl, pyridylcarbamoyl, pyrimidinylcarbamoyl, pyrazinylcarbamoyl, isoxazolylcarbamoyl, formyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, t-butoxycarbonyl, acetyl, benzoyl, 1,3,4-trihydroisoquinolin-2-ylcarbonyl, (3,5-dioxo-2,4-thiazolidinylidene)methyl, (3,5-dioxo-2,4-oxazolidinylidene)methyl, (2,5-dioxoimidazolidin-4-ylidene)methyl, (5-oxo-3-thioxo-2,4-thiazolidinylidene)methyl, ((3,5-dioxo-2,4-thiazolidinyl)sulfonyl)methyl, ((3,5-dioxo-2,4-oxazolidinyl)sulfonyl)methyl, ((2,5-dioxoimidazolidin-4-yl)sulfonyl)methyl, ((5-oxo-3-thioxo-2,4-thiazolidinyl)sulfonyl)methyl or —NR 67 —CO—R 68  (wherein R 67  represents an alkyl group of 1 to 4 carbons and R 68  represents an alkyl group of 1 to 3 carbons, a phenyl group, a heterocycle, an aralkyl group of 7 to 9 carbons or an alkoxy group of 1 to 4 carbons);  
       or a salt thereof.  
     
     
         25 . A benzofuryl-α-pyrone derivative according to any one of  claims 1  to  21 , wherein R 4a  is hydrogen, nitro, cyano, bromine, thienyl, piperazinyl, hydroxyl, trifluoromethanesulfonyloxy, phenylsulfonyloxy, acetyloxy, dimethylamino, dibenzylamino, tiazolylcarbamoyl, methoxycarbonyl, isopropoxycarbonyl, (3,5-dioxo-2,4-thiazolidinylidene)methyl, or —N(Me)—CO—R 69  (wherein R 69  represents an alkyl group of 1 to 3 carbons, a phenyl group, a heterocycle, a benzyl group or an alkoxy group of 1 to 4 carbons);  
       or a salt thereof.  
     
     
         26 . A pharmaceutical composition comprising a therapeutically effective dose of a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt, and a pharmaceutically acceptable carrier.  
     
     
         27 . A lipid metabolism enhancer comprising as an active ingredient a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt.  
     
     
         28 . A triglyceride biosynthesis inhibitor comprising as an active ingredient a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt.  
     
     
         29 . A blood triglyceride lowering agent comprising as an active ingredient a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt.  
     
     
         30 . A blood HDL elevating agent comprising as an active ingredient a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt.  
     
     
         31 . An arteriosclerosis prophylactic agent comprising as an active ingredient a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt.  
     
     
         32 . An arteriosclerosis treatment agent comprising as an active ingredient a benzofuryl-α-pyrone derivative according to any one of  claims 1  to  25  or its salt.