TW200916098A - Agent for lowering uric acid level - Google Patents

Abstract

Disclosed is a novel agent for lowering an uric acid level or the like. Specifically disclosed is an agent for lowering an uric acid level or the like, which comprises a nitrogenated aromatic ring derivative represented by the formula (I) or a salt thereof as an active ingredient.

Description

200916098 IX. INSTRUCTIONS OF THE INVENTION [Technical Field to Be Invented by the Invention] The present invention relates to an agent for reducing uric acid bismuth. Specifically, it relates to a composition for reducing uric acid bismuth containing the nitrogen-containing aromatic ring derivative represented by the formula (I) or a salt thereof as an active ingredient. [Prior Art] Uric acid is present in the body depending on the pH to form uric acid or a salt thereof, and is mainly excreted by the kidney. With hyperuricemia, the uric acid strontium in the blood exceeds the solubility, and sodium urate crystals will precipitate in the joints and the like, and gout will occur. The symptoms include gout arthritis (gout attack), gout nodules, renal disorders of urinary calculi, and other gout patients with complex obesity, hypertension, hyperlipidemia, and glucose tolerance. The integration of the complication is considered to be related to the prognosis of gout (Non-Patent Document 1). Unadjusted serum uric acid sputum will gradually cause gout arthritis, which will gradually form chronic gout arthritis, leading to gout nodules. Moreover, if hyperuricemia persists for a long time, kidney stones, urinary calculi, and renal medulla interstitial nephritis produce a disease called sore gout. More highly known serum uric acid sputum will increase the risk of ischemic heart disease, and hyperuricemia shows risk factors for cardiovascular disease and cerebrovascular disease. The uric acid in the blood is filtered by the renal spheroid, and most of the urinary tract is reabsorbed. Therefore, it is usually only slightly excreted in the urine. In recent years, UR AT i has been shown to act as a central transporter of uric acid reabsorption in the proximal urinary tract of the kidney. The probenecid or the 200916098 benzbromarone that interferes with URAT1 is disclosed as a therapeutic or preventive agent for gout. Medicine (Non-Patent Document 2). Further, the compound used in the present invention is disclosed in Patent Documents 1 to 4 as a compound having a compound which inhibits the activity of an enzyme preparation. The chymase is a neutral protease present in the mast cell granules, which is closely related to various biological reactions related to the mast cell. For example, the conversion of Angiotensin (Ang) I to Ang II, the activation of promatrix metalloprotease, the conversion from Endothelin to Endothelin (1~31), and the conversion of growth factors (Transformation growth factor-stone, TGF-; (S) activation, interleukin-1 - /3 (Interl eukin-1 β, IL-1 β), interleukin-18 (

Interleunation-18, IL-18) activation, fibrin, hyalin, and type I collagen, Substance P, Vasoactive intestinal polypeptide (VIP), inhibition Various effects such as activation of tissue factor pathway inhibitors are revealed. From the above, it is considered to have a compound which hinders the activity of an enzyme preparation, for heart disease such as cardiac hypertrophy, heart failure, or myocardial infarction; kidney disease such as diabetic nephropathy, renal failure, kidney disease, or nephritis; allergic Patients, such as: Atopy dermatitis, can be used as effective prophylactic and / or therapeutic agents. [Non-Patent Document 1] Related to Gout and Glucose Metabolism Related to Lifestyle-related Diseases and Abnormal Glucose Metabolism in Usimi Mihopurine-6 - 200916098 2000; 24: 139-151 [Non-Patent Document 2] Protein Nucleic Acid Enzyme Vol. 48, No. 1 (2003) [Patent Document 1] International Publication No. 2001 1/5329 No. 1 Manual [Patent Document 2] International Publication No. 2000/03 997 Manual [Patent Document 3] International Publication No. 2007/ 06 8 62 No. 1 Manual [Patent Document 4] International Publication No. 2008/045 68 No. 8 [Invention] The object of the present invention is to provide a novel UR AT 1 inhibitor or a urate-reducing agent. The invention further provides an effective treatment and prevention of novel gout 'hyperuricemia, gout arthritis, gout nodules, urinary calculi, kidney stones, kidney disorders, gout kidney, cardiovascular diseases, or cerebrovascular diseases, etc. A good uric acid-lowering agent for uric acid-related diseases for its purpose. The present invention further provides a prophylactic or therapeutic agent for heart disease accompanied by gout or hyperuricemia. That is, the present invention is a u RAT 1 inhibitor containing the nitrogen-containing aromatic ring derivative represented by the formula (I) or a salt thereof as an active ingredient; and a urate-reducing agent: gout, hyperuricemia, or uric acid-related a preventive or therapeutic agent for diseases such as gout arthritis, gout nodules, urinary calculi, kidney stones, kidney disorders, gout kidneys, cardiovascular diseases, or cerebrovascular diseases; the heart with gout or hyperuricemia A prophylactic or therapeutic agent for a disease (eg, cardiac hypertrophy, heart failure, or sputum, muscle stagnation temple), renal rickets associated with gout or hyperuricemia (eg, diabetic nephropathy, renal failure, kidney disease, or A preventive or therapeutic agent for nephritis and the like 200916098). 【化1】

[In the formula (I), 'R1 and R2 represent a hydrogen atom at the same time or independently, a halogen eyebrow trihalomethyl group, a cyano group, a hydroxyl group, an alkyl group having a carbon number of 1 to 4 or a carbon number, or R and R2 is a combination of - 〇_CH2-0-, -〇-CH2 Ο- or R2 is a ring, the carbon number is also substituted by a stone or a plurality of alkyl groups having 1 to 4 carbon atoms; A is a single bond' a substituted or unsubstituted carbon number of 1 to 6 or a cyclic alkyl group, a substituted or unsubstituted carbon number 6 to an aryl group, or a substituted or unsubstituted one having 1 ring The aryl group having a carbon number of 4 to 1 Å selected from the group consisting of a hetero atom and a nitrogen atom and a sulfur atom. {As a substituent of A, such as a halogen atom, a hydroxyl group, a nitro group, a linear chain or a branched chain. An alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent > 2 adjacent alkane _ can form a awake bond), a linear or branched chain Alkyl group having a carbon number of 1 to 6 or a linear or branched alkyl group having 1 to 6 carbon atoms, a straight chain or a carbon number of 1 to 3, a linear or branched carbon number 1~6® base 'dihalomethyl, trihalomethoxy, phenyl' oxygen , or by i, 1~4 -ch2-butyl is 1 : chain, 1 1 i oxygen: heterozygous j, cyanide-like 4 group also: base, : chain decylamine 1 200916098 A phenoxy group which may be substituted by a halogen atom. These may also be substituted for each of the ring or the thiol group by one or more of them independently - C 〇〇 R3, . s 〇 3 R3 ' -CONHR3, - S 02NHR3 'tetradecyl, 5-oxo a base-hi oxadiazolyl or a 5-oxy-diazolyl group (R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); G represents a substituted or unsubstituted carbon number of 1 ~6 straight or branched chain extension base can also be included on the way! Or a majority of 〇, S, s〇 2, NR3. (R is the same as defined above for R3. The substituent of G is a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon number of 1 to 6 or a linear or branched chain. Alkoxy group having a carbon number of 1 to fluorene (as a substituent, two alkoxy groups of the same may form an acetal ether), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy}; Represents a single bond or _s(〇)m_, m represents an integer of 〇~2; 】 a linear, branched or cyclic alkylene group when m is 0 and A is a substituted or unsubstituted carbon number of 〜6 The base group ' represents a substituted or unsubstituted carbonic acid number of 6 6 straight, cyclic or branched fluorenyl groups, substituted or unsubstituted aryl groups having 7 to 11 carbon atoms, or substituted or unsubstituted on the ring a heterocyclic group having from 4 to 10 carbon atoms of a hetero atom selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. J when m is 〇 and eight is a substituted or unsubstituted carbon number 6~ An extended aryl group of 11 or a substituted or unsubstituted substituent having a carbon number of 4 to 1 Å selected from a hetero atom of a group selected from the group consisting of an oxygen atom and a nitrogen atom Or no, steep, r ^ _ Deuterated 5 ash number 1 to 6 linear, cyclic or branched alkyl, substituted or unsubstituted carbon number} i aryl group " 4 substitution or 200916098 unsubstituted ring with 丨More than one heteroaryl group having 4 to 10 carbon atoms selected from the group consisting of oxygen atoms, nitrogen atoms and sulfur atoms. J is 'when Μ is a single bond, m is 〇 and a is a single bond, or m is 1 or 2'' represents a substituted or unsubstituted, straight-chain, cyclic or branched, aryl group having a carbon number of from 6 to 1, substituted or unsubstituted, or substituted or unsubstituted. The ring has one or more heteroaryl groups having a carbon number of 4 to 1 Å selected from a hetero atom of a group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. {As a substituent of J, a halogen atom, a thiol group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, 2 alkoxy groups adjacent thereto) It may also form an acetal bond, a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, a linear or branched chain. a thiol, linear or branched chain having a carbon number of 1 to 6 a fluorenylamino group of 1 to 6, a substituted or unsubstituted anthranilyl group, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, a COOR3 group (R3 is the same as defined above), or a phenoxy group which may be substituted by one or more halogen atoms. These may also be substituted at each position of a ring or an alkyl group by one or a plurality of each;} X represents -CH= or a nitrogen atom; γ represents - CB = or nitrogen atom; B is represented by -B 1 - B2 - B3; B1 represents a single bond or a linear or branched alkyl group having 1 to 3 carbon atoms; B2 represents a single bond, -CO- or -NR3-. (wherein R3 is the same as defined in the above R3): B3 represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxyl group, a sulfonium-10-10, and a substituted or unsubstituted straight chain or branch. a chain-like alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted linear or branched alkoxy group having 1 to 6 carbon atoms, a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, a substitution or a heteroaryl group having one or more carbon atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, having 4 to 1 Å, a substituted or unsubstituted amino group, a substituted or a non-substituted ring a carboxy, substituted or unsubstituted linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, a substituted or unsubstituted phenylsulfonyl group, a substituted or unsubstituted linear or branched chain. Aminoalkylsulfonyl group having 1 to 6 carbon atoms, substituted or unsubstituted linear or branched carbon group having 1 to 8 carbon atoms, substituted or unsubstituted linear or branched carbon number Alkoxycarbonyl group of 1 to 6, substituted or unsubstituted phenyl fluorenyl group, linear or branched thiol group having a carbon number of 1 to 6, trihalomethyl or trihalogen methoxy {as B3 The substituent is, for example, a halogen atom, a hydroxyl group, an amine group, a carboxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 The alkoxy group (which may also form a wake-up bond as two substituents adjacent to the substituent ') may be a trihalomethyl group or a trihalomethoxy group. These may also be independently substituted at one or a plurality of positions at any position}; Z represents a carbon atom or a nitrogen atom; and Q represents a carbon atom or a nitrogen atom. ]. Further, the present invention is 4-(1-((4-methyl-1-oxobenzothiophen-3-yl)methyl)benzimidazole-2-thio)butyric acid or a salt thereof. In the present invention, UR AT 1 can be inhibited by administration of a drug, and _ 値 値 can be reduced as a urate-reducing agent. Further, the agent of the present invention can be applied to gout, hyperuricemia, gout arthritis, gout nodules, urine-11 - 200916098 road stones, kidney stones, kidney disorders, gout kidneys, cardiovascular diseases, or cerebrovascular diseases, etc. A prophylactic or therapeutic agent for uric acid-related diseases. The compound of the active ingredient of the present invention or a salt thereof further inhibits the activity of the enzyme preparation, and thus can also be applied to a preventive or therapeutic agent for heart disease or kidney disease accompanied by gout or hyperuricemia. [Embodiment] The best mode for carrying out the invention The nitrogen-containing aromatic ring derivative used as the agent of the present invention or a salt-containing nitrogen-containing aromatic ring derivative thereof is a compound represented by the formula (I).

[In the formula (I), R1 and R2 represent a hydrogen atom, a halogen atom, a trihalomethyl group, a cyano group, a hydroxyl group, a linear or branched carbon number of 丨~4 or a linear chain which are simultaneously or independently. Or a branched carbon number 4 alkoxy group, or ... and R2 is a linked-0-CH2-0-, -0-CH2-CH2-0-^-ch2-ch2-ch2-R1 and R are a linkage The carbon number may also be substituted by one or more linear or branched alkyl groups having 1 to 4 carbon atoms; a linear chain of 1 to 6 and a single bond representing a substituted or unsubstituted carbon. -12-200916098 branched or cyclic alkyl, substituted or unsubstituted aryl group having 6 to n carbon atoms, or substituted or unsubstituted, having at least one oxygen atom selected from the ring, a hetero atom having a carbon atom of 4 to 10 in a hetero atom of a group of nitrogen atoms and a sulfur atom. {As a substituent of A, such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon. An alkyl group having 1 to 6 alkyl groups, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two adjacent alkoxy groups may form a waking bond), a linear or branched chain Carbon number 1 to 6 alkylthio, linear or branched carbon number 1 An alkylsulfonyl group of 6 or a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, a trihalomethyl group, a trihalogen group An oxy group, a phenyl group, an oxy group, or a phenoxy group which may be substituted by one or more halogen atoms. These may also be independently substituted by one or more at any position of the ring or alkylene group. E represents -COOR3, -S03R3, -CONHR3, -SO2NHR3, tetrazolyl, 5-oxy-1,2,4 -oxadiazolyl or 5-oxy-1,2,4-thiadiazolyl (R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); G represents a substituted or unsubstituted The linear or branched alkyl group having a carbon number of 1 to 6 may also contain one or a plurality of ruthenium, S, S02, and NR3 in the middle. {R3 is the same as the definition of V above. As a substituent of G, for example, a halogen atom, a trans group, a nitro group, an amino group, a linear bond or a branched bond having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms a group (as a substituent, two alkoxy groups adjacent to each other may also form an acetal ether), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy}; M represents a single bond or -S(0) M-, m represents an integer of 〇~2; J represents a linear-13-200916098, cyclic or branched alkyl group when m is 0 and A is a substituted or unsubstituted carbon number of 1 to 6 Substituted or unsubstituted, linear, cyclic or branched alkyl having 3 to 6 carbon atoms, substituted or unsubstituted, aryl having 7 to 11 carbon atoms, or substituted or unsubstituted, having 1 ring on the ring The above heteroaryl group having a carbon number of 4 to 1 Å selected from the group consisting of an oxygen atom, a nitrogen atom, and a hetero atom in a group of sulfur atoms. J represents a group in which m is fluorene and a represents a substituted or unsubstituted aryl group having 6 to n carbon atoms, or a substituted or unsubstituted group having at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. When the hetero atom has a carbon number of 4 to 10, the substituted aryl group is a substituted or unsubstituted carbon number of 1 to 6 linear, cyclic or branched, substituted or unsubstituted carbon number 6 to 11 The aryl group or the substituted or unsubstituted ring has a heterocyclic group having 4 or more carbon atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. J. When Μ is a single bond, „1 is 〇 and a is a single bond, or 〇1 is 1 or 2', it represents a substituted or unsubstituted linear, cyclic or branched base of 1 to 6 carbon atoms. a substituted or unsubstituted carbon number of 6 to aryl groups, or a substituted or unsubstituted ring having one or more carbon atoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms. Heteroaryl. {Substituent for J: halogen atom, hydroxyl group, nitro group, cyano group, linear or branched alkyl group having 1 to 6 carbon atoms, linear or branched carbon number 1 Alkoxy group of ～6 (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), a linear or branched carbon number! ～6 alkylthio group, a straight bond or a branched chain Alkylsulfonyl having 1 to 6 carbon atoms, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched decylamino group having 1 to 6 carbon atoms, substituted or unsubstituted Further, an anilino group, a tridentate methyl group, a trihalomethyl-14-200916098 oxy group, a phenyl group, an oxy group, a COOR3 group (R3 is the same as defined in the above R3), or a halogen atom substituted by one or more Phenoxy group, this can also be in the ring Or any position of the alkyl group is independently substituted by one or a plurality of each;} X represents -CH = or a nitrogen atom; Y represents -CB = or a nitrogen atom; and B is represented by -B 1 -B 2 - B 3 ; B 1 represents a single bond or a straight or branched alkyl group having 1 to 3 carbon atoms; B 2 represents a single bond, -CO- or -NR 3 (wherein R 3 is the same as defined above); B 3 represents hydrogen Atom, a halogen atom, a nitro group, a cyano group, a hydroxy group, a sulfonyl group, a substituted or unsubstituted linear or branched alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted linear or branched chain. An alkoxy group having 1 to 6 carbon atoms, a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, a substituted or unsubstituted ring having at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom a heteroaryl group having 4 to 10 carbon atoms, a substituted or unsubstituted amino group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted linear or branched carbon number of 1 to 6 , substituted or unsubstituted phenylsulfonyl, substituted or unsubstituted, straight or branched, aminoalkylsulfonyl having 1 to 6 carbon atoms, substituted or unsubstituted straight or branched chain Carbon number 8 a substituted or unsubstituted linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a substituted or unsubstituted phenylcarbonyl group, a linear or branched alkylthio group having 1 to 6 carbon atoms, Dihalomethyl or trihalogen methoxy {as a substituent for B3 such as: dentate atom, hydroxyl group, amine group, carboxyl group, nitro group, cyano group, linear or branched -15- 200916098 carbon number 1 ～6 alkyl, linear or branched carbon having 1 to 6 carbon atoms (the two alkoxy groups adjacent to the substituent ' may also form an acetal bond), a trihalomethyl group, or a trihalogen Methoxy. These may also be independently substituted by i or a plurality of positions at any position}; Z represents a carbon atom or a nitrogen atom; and Q represents a carbon atom or a nitrogen atom. As a linear, branched or cyclic base of the carbon number 丨~6 of the present invention, such as methyl, ethyl, (n-, i-) propyl, 2,2-dimethyl Examples of propyl, (n-, i-, t-) butyl, 1,1-dimethylbutyl, n-pentyl, cyclohexyl and the like. The alkyl group having a carbon number of 1 to 4 means that the number of carbon atoms in the group is i to 4; specifically, for example, methyl group, ethyl group, (n-, i-) propyl group, (η-, i-, s_) , t-) butyl case. As the linear or branched alkoxy group having 1 to 6 carbon atoms of the present invention, it specifically includes, for example, a methoxy group, an ethoxy group, (η-, i-) propoxy group, (11_, i-). , s-, t-) butoxy group and the like. The alkoxy group having 1 to 4 carbon atoms is the same as the above-mentioned hospital base, and means that the number of carbon atoms in the group is 1 to 4. The linear or branched alkylene group having a carbon number of 1 to 7 of the present invention is exemplified by a vinyl group, a propenyl group, a butenyl group or a pentenyl group. Examples of the aryl group having a carbon number of 6 to 11 in the present invention include a phenyl group and a naphthyl group. The aryl group having a carbon number of 7 to 1 1 means that the number of carbon atoms in the group is 7 to Η. In the present invention, 'a heterocyclic aryl group having 4 to 10 carbon atoms which has one or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, and specifically, for example, a furyl group or a thiol group. Pyrimidinyl, benzofuranyl, benzimidazolyl, quinolyl, isoquinolinyl, quinoxalinyl, benzooxadiazolyl, -16- 200916098 benzothiadiazolyl, fluorenyl, benzene And thiazolyl, benzoisoxazolyl and the like. Examples of the halogen atom of the present invention include a fluorine atom atom and an iodine atom. The linear or branched carbon number of the present invention is, for example, a methylthio group, an ethylthio group, (η -, i -) i-, s_, t-) butylthio group, and the like. As the linear or branched carbon number 1-branched alkylsulfonyl group of the present invention, specifically, for example, a methylsulfonic acid group, an (n·,i-)propyl propyl group, (n) -, i-, s-, an example of a base. #例的取代或非分的直链或支链的醇氧carbonyl, such as: methoxycarbonyl, ethoxy i_) propoxy curtain , (n-, i-, s-, t-) butoxy ore: as a linear or branched carbon number of the present invention 1~ • ethyl, ethyl or, (η-, i- Propyl ore t-) carbonyl and the like. The linear or branched carbon number 1 to 'for example of the present invention' is specifically, for example, an acetamino group, an ethylcarbonylamino group, a ore group, and an (n-, i-, s-, t-)carbonylamino group. Etc. Specific examples of the trihalomethyl group of the present invention include dibromomethyl and trichloromethyl. Specific examples of the trihalomethoxy group of the present invention include a tribromomethoxy group and a trichloromethoxy group. Thiol group, benzo, chlorine atom, bromine 6 alkylthio group propylthio group, (n-, -6 straight or fluorenyl, ethyl sulfonate t-) butyl sulfonate ^ carbon number 1~ 6 羯 羯, (η-, _ et al. 6 醯 base such as, (η-, i-, s-, 6 tyrosylamino (η-, i-) propyl: trifluoromethyl For example, trifluoromethoxy-17-200916098 and 'as a nitrogen-containing aromatic ring derivative represented by formula (I), R1 and R2 represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently; A represents a single A linear, cyclic or branched alkyl group having 1 to 5 carbon atoms; a substituted or unsubstituted alkyl group; E represents -COOR3, -S03R3, -CONHR3, -S02NHR3, tetrazol-5-yl, 5• Oxy-H4-oxadiazol-3-yl or 5-oxy-1,2,4-thiadiazole-3-yl (wherein R3 represents a hydrogen atom or a linear or branched carbon number of 1~ 6 represents a substituted or unsubstituted carbon number of 〜3 of a straight or branched alkyl group. The substituent of the G alkyl group has a halogen atom, a hydroxyl group, a nitro group. a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a a group, the adjacent two alkoxy groups may also form an acetal bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy group; Μ represents a single bond or _S(0)m_' m is 〇 An integer of ～2; J represents a substituted or unsubstituted (heteroaryl or naphthyl group having from 4 to 10 carbon atoms having one or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom) The heteroaryl or naphthyl group of J may have a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched chain. Alkoxy groups having 1 to 6 carbon atoms (the two alkoxy groups adjacent to the substituent ' may also form an acetal bond), linear or branched alkylthio groups having 1 to 6 carbon atoms, straight or branched Alkylsulfonyl group having a carbon number of 1 to 6 in a chain form, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, and a substitution Or unsubstituted hydrazine substituted phenylamino-18- 200916098, trihalomethyl, trihalomethoxy, phenyl, oxy, C〇〇R3 group, or substituted with one or more halogen atoms Oxyl group, these substituents may also be in the ring Any position is independently substituted by 1 or a plurality; X represents -CH = or a nitrogen atom; Y represents -CB = or a nitrogen atom; B is represented by -B 1 - B2 - B3; B1 represents a single bond or a linear chain Or a branched carbon number of 1 to 3; B2 represents a single bond, -CO- or -NR3-; β3 represents a hydrogen atom, a halogen atom, a hydroxyl group, a sulfonyl alcohol group, a substituted or unsubstituted carbon number 6 alkyl, substituted or unsubstituted carbon number 6 alkoxy, substituted or unsubstituted carbon number 6~^ < aryl, substituted or unsubstituted amino group, substituted or unsubstituted residue, a substituted sulfonyl group having 1 to 6 carbon atoms, an unsubstituted or unsubstituted benzene group, a substituted or unsubstituted amino group sulfonyl group having 1 to 6 carbon atoms, What is the sulfonium I w or unsubstituted carbon number 1 to 8 fluorenyl group, substituted or unsubstituted carbon number 1 to 6 仵甙 you and + _ alkoxycarbonyl group, or substituted Ge,,,, substituted The base carbonyl group. {As β3, -», ##, <Substituents such as: halogen, butyl, aryl, aryl, hydrazine, or carboxy. These may also be in the position of tt, in which one or more of them are independent of each other. Z is a carbon atom; > 'Q is a nitrogen atom. When Q is a nitrogen atom, in the formula (I), z is a carbon atom and is represented by the following formula (I)-II. -19- 200916098 【化3】

Further, as a nitrogen-containing aromatic ring derivative which is not a formula (I), R1 and R2 represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently, and A is a substituted or unsubstituted linear chain having a carbon number of 1 to 5. , ring or branch-shaped extension of the base; E is -COOR3, -S03R3, -CONHR3, _S02NHR3, tetradec-5-yl, 5-oxo-1,2,4·αoxadiazole_3 · a group, or a 5-oxy-1,2,4-thiadiazol-3-yl group (wherein 'R3 represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms); G represents a substitution or An unsubstituted linear or branched alkyl group having 1 to 3 carbon atoms, and the substituent of the G may have a halogen atom, a hydroxyl group 'nitro group, a cyano group, a linear chain or a branched chain. An alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having a carbon number of 丨~6 (as a substituent, two alkoxy groups adjacent thereto may form an acetal bond), a trihalomethyl group, Trihalomethoxy, phenyl, or oxy; Μ represents a single bond or -S(0)m-, m is an integer from 0 to 2; J represents a substituted or unsubstituted (having one or more selected from the ring) Heterogeneous carbon with a carbon number of 4 to 10 in the group of oxygen atoms, nitrogen atoms and sulfur atoms The substituent of the heteroaryl group of the J is a silane atom, a benzyl group, a nitro-cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched chain. Alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear chain or A branched alkyl sulfonyl group having 1 to 6 carbon atoms, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear chain of -20-200916098 or a branched carbon number of 1 to 6 An amino group, a substituted or unsubstituted acid anilide, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, a COOR 3 group, or a phenoxy group substituted by one or more halogen atoms . These substituents may also be independently substituted at one or a plurality of positions at any position of the ring; X is -CH = or a nitrogen atom; and Y is preferably a nitrogen atom. Further, as the nitrogen-containing aromatic ring derivative represented by the formula (I), R1 and R2 represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently, and A is a substituted or unsubstituted carbon number of 3 to 5; a chain, a cyclic, or a branched alkyl group; E is -COOR3 (wherein 'R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); and G represents a methylene group; Representative: -S-; J represents a substituted or unsubstituted benzoxyl or fluorenyl-methyl fluorenyl group, and the heteroaryl group of J may have a halogen atom, a linear or branched carbon Alkyl groups of 1 to 3, tridentate methyl or oxy; hydrazine is -CH=; hydrazine is preferably a nitrogen atom. Further, the compound of the nitrogen-containing aromatic ring derivative represented by the formula (I) is preferably a compound represented by the following structural formula, and these compounds also have an activity of inhibiting the enzyme preparation. -21 - 200916098 【化4】

Among the above compounds, a compound represented by the following structural formula is preferred. -22 - 200916098

α

Vs

COOH

In the above, 4-(1-((4-methylbenzothiophen-3-yl)methyl)benzimidazole-2-thio)butyric acid or 4-(1-((4-methyl-)- Phenoxybenzoin-3-yl)methyl)benzimidazole-2_thio)butyric acid is preferred, especially 4-(1-((4-methylbenzothiophene)-3-yl) )methyl)benzimidazole_2_thio)butyric acid is most desirable. Further, in the above formula (I), 'R1 and r2 represent a hydrogen atom; A represents a linear or cyclic alkyl group having a substituted or unsubstituted carbon number of 〜5; and E represents -COOR3 (wherein , R 3 is a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms; G represents a methylene group; M represents an integer of 0 to 2; and J represents a substituted or unsubstituted benzothiazide. That is, the stupid and thiophenanyl group may have a linear or branched carbon number of 1 to 3 or a oxy group; X is -c Η γ is also a desirable nitrogen atom: The respective groups of the compounds of the formula (I) are also represented by their respective groups. That is, for example, R1 and R2 represent simultaneously or independently hydrogen atoms, methyl or halogen atoms; R1 and R2 represent a hydrogen atom, a methyl group or a chlorine atom; R1 and R2 are hydrogen atoms; 23- 200916098 Example of ideal base. The agent containing a nitrogen-containing aromatic ring derivative represented by the following formula (11) or a medically acceptable salt thereof as an active ingredient can also be expected to be suitable for use in URA Τ 1 P and to reduce the use of uric acid bismuth; a prophylactic or therapeutic agent for gout, hyperuricemia, or a uric acid-related disease (eg, gout arthritis, gout nodules, urinary calculi, kidney stones, renal disorders, gout kidney, cardiovascular disease, or cerebrovascular disease); A prophylactic or therapeutic agent for heart disease (eg, cardiotrophy, heart failure, or myocardial infarction) associated with gout or hyperuricemia; kidney disease associated with gout or hyperuricemia (eg, diabetic nephropathy, renal failure) , a preventive or therapeutic agent for kidney disease, or nephritis.

[In the formula (II), 'R1 and R2 represent a hydrogen atom, a halogen atom, a trihalomethyl group, a cyano group, a hydroxyl group, a carbon number of 1 to 4, and a carbon number of 1 to 4, respectively. The oxy group, or R1 and R2 are the linked-0-CH2-0-, _0-CH2CH2-〇_ or -Ch2ch2CH2_ (where ri and R2 are attached, the carbon atom may also be 1 or a plurality of carbon atoms 1~ Substituted by an alkyl group of 4) t A represents a substituted or unsubstituted carbon number of 1 to 7 in a straight chain, a ring, or

Branched alkyl or alkenyl group, may also contain one or more -〇-, -S-, -SO '-NR3- (wherein R3 represents a hydrogen atom or a straight chain or -24- 200916098 Branched carbon having 1 to 6 carbon atoms). The substituent of A is a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon number of 丨~6, a linear or branched alkoxy group having 1 to 6 carbon atoms (including When two adjacent acetal bonds are formed, a linear or branched carbon number of 1 to 6 is a thiol group, a linear or branched carbon number of 1 to 6 is a sulfonyl group, and a linear chain is used. Or a branched carbon group having 1 to 6 carbon atoms, a linear or branched carbon number of 醯~6, a mercaptoamine group, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, or A phenoxy group which may be substituted by more than one halogen atom. These substituents may also be independently substituted in one or a plurality of positions at any position of an alkyl group or an alkenyl group. E represents -COOR3 ' -S03R3, -CONHR3, -S02NHR3, tetrazolyl-5-yl, 5-oxy-1,2,4-oxadiazol-3-yl, or 5-oxy-1,2 , 4-thiadiazol-3-yl (wherein R3 represents the same as the above R3); G represents a substituted or unsubstituted, straight or branched alkyl group having 1 to 6 carbon atoms, which may also contain hydrazine Or a plurality of -〇-, -S_, _S〇2_, -NR3- (wherein R3 is the same as defined in the above r3, and when such atoms or groups are contained, these are not directly bonded to the nitrogen-containing aromatic ring) . The alkylene group may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched carbon number of 1 to 6 Alkoxy (including, when two adjacent to form an acetal bond), trihalomethyl, trihalomethoxy 'phenyl, or oxy; M represents a single bond or -S(0)m-,m An integer of 0 to 2; J represents a substituted or unsubstituted (heteroaryl group having 1 or more carbon atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a hetero atom in a group of sulfur atoms) . -25- 200916098 The heteroaryl group of j may have a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon. Alkoxy groups of 1 to 6 (including when two adjacent ones form an acetal bond), linear or branched alkylthio groups having 1 to 6 carbon atoms, linear or branched carbon number 1 Alkylsulfonyl group of ~6, linear or branched carbon group of 1 to 6 ketone group, linear or branched decylamino group having 1 to 6 carbon atoms, substituted or unsubstituted An anilino group, a di-methyl group, a dihalomethoxy group, a phenyl group, an oxy group, a COOR3 group, or a phenoxy group which may be substituted by one or more halogen atoms. These substituents may also be independently substituted at one or a plurality of positions at any position of the ring; X represents -CH = or a nitrogen atom. By the administration of the compound of the formula (I) of the present invention, the uric acid bismuth is lowered, so that the agent of the present invention can be suitably used for the use of a urate-reducing agent. It is also suitable for prophylactic or therapeutic agents for uric acid-related diseases such as gout, hyperuricemia, gout arthritis, gout nodules, urinary calculi, kidney stones, kidney disorders, gout kidney, cardiovascular disease, or cerebrovascular diseases. . The nitrogen-containing aromatic ring derivative of the active ingredient of the present invention has a hindrance to the activity of the enzyme preparation in addition to lowering the action of uric acid. By this action, the agent of the present invention can be expected to have an effect of inhibiting the enzyme preparation in addition to reducing uric acid strontium. The enzyme preparation is known to have various physiological activities as described above, and one of them has a conversion action from Ang I to Ang II. The Ang II system plays an important role in maintaining the body's constant blood pressure, such as blood pressure and body fluid volume, and has a significant impact on cardiac dysfunction and cardiac dysfunction after myocardial infarction. Based on this consideration, the A C E inhibitor, the hypertensive protein receptor-containing barrier agent has been shown to have a specific therapeutic effect as a therapeutic drug for developing heart failure and inhibiting cardiac dysfunction after myocardial infarction. However, Ang II production in human heart tissue is mainly an enzyme preparation rather than ACE, and about 80% of Ang II derived from an enzyme preparation has witnessed an increase in the activity of an enzyme preparation in myocardial tissue after myocardial infarction. After comprehensive consideration of these factors, it is considered that the agent which inhibits the activity of the enzyme preparation has a therapeutic effect which is reasonably expected to be suppressed for the prevention of heart failure and cardiac dysfunction after myocardial infarction. In addition to the enzyme preparation, the activation of IL-1 yS deteriorates the inflammatory response through the cardiovascular site, the activation of the complex protease, the breakdown of fibrin, type IV collagen, the decomposition of extracellular proteins, and the promotion of TGF-/3. In the mechanism of free differentiation and proliferation of fibroblasts, it is also considered to promote cardiac tissue fibrosis/heart tissue changes. Progression of cardiac tissue changes will lead to an important factor in the deterioration of long-term life prognosis, and inhibition of cardiac tissue changes is considered an important therapeutic target. The above-mentioned agent which inhibits the activity of the enzyme preparation is considered to have a therapeutic effect which is reasonably expected for heart disease (cardiac hypertrophy, heart failure, or myocardial infarction). In addition, the fat neck cell line containing the enzyme preparation has a urinary tubule interstitial, a vascular wall outer membrane in a normal kidney, and a companion fiber in diabetic nephropathy, rapid progressive glomerulonephritis (RPGN), and IgA nephropathy. The progression of the lesion is determined to determine the integration into the lesion. Among these diseases, the degree of fibrotic lesions and the decrease in renal function are directly proportional to the increase in the number of obese cells. It is considered that the obese cells containing the enzyme preparation are involved in the pathology of various kidney diseases -27-200916098. In addition, as a major agent of the enzyme preparation, it has a conversion effect from Ang I to Ang II, and Ang II is considered to also deeply affect the pathological formation of various renal rickets. In fact, clinically, ACE inhibitors, hypertensive protein receptors have been developed as therapeutic agents for diabetic nephropathy, showing specific therapeutic effects. As one of the main effects of the above-mentioned agents, it is considered to inhibit the inhibition of TGF-/3 produced by Ang II produced by renal tissues rather than in circulating blood. However, the major A n g 11 producing enzymes in the general organization are considered to be enzyme preparations, not ACE. In addition, in the animal experiment, the concentration of Ang Η in the renal interstitial was much higher than that in the circulating blood, and the concentration of Ang 11 was also increased with the involvement of nephropathy. After considering these considerations, it is considered to be an agent that hinders the activity of the enzyme preparation, and it is expected to have a therapeutic effect for various kidney diseases. In addition, the enzyme preparation is also considered to be degraded by the activation of the I L-1 point through the inflammatory reaction of the renal vascular dysfunction, the activation of the complex protease, the decomposition of the extracellular protein of fibrin and the decomposition of type IV collagen. 'Straight S promotes renal tissue fibrosis/change in a sequence that promotes differentiation and proliferation of free fibroblasts that promote TGF-. Renal tissue fibrosis/change progression is an important factor in long-term prognosis, and inhibition of changes in kidney tissue is considered an important therapeutic target. The above-mentioned agent which inhibits the activity of the enzyme preparation is considered to have a therapeutic effect on kidney disease (diabetic nephropathy, renal failure, kidney disease, or nephritis). The compound of the formula (I) can be synthesized by the method of -28-200916098 described in Patent Document 1 or the like. For example, 3-bromomethyl-4-methylbenzoparaphene and methyl 4-(benzopyrene-2-thio)butanoate in the presence of a base such as a tertiary amine, in toluene, etc. The coupling reaction was carried out in a hydrocarbon solvent to obtain methyl 4-((4-methylbenzothiophen-3-yl)methyl)benzimidazolethio)butanoate. In the tetrahydrofuran solvent, hydrolysis is carried out with an aqueous solution of sodium hydroxide or the like, and after neutralization, 4-(1-((4-methylbenzothiophen-3-yl)methyl)benzimidazole·2-sulfurate can be obtained. Generation) butyric acid. Further, 4-(1-((4-methyl-1-oxybenzothiophen-3-yl)methyl)benzimidazole-2-thio)butanoic acid of the compound of the present invention may be an example of the present application 5 method synthesis. 4_(1-((4-methyl-1-oxybenzonaphen-3-yl)methyl)benzimidazole-2-thio)butyric acid exists in the presence of a misaligned center Structure. 4-(1-(4-methyl-1-oxobenzothiophene-3-yl)methyl)benzimidazole-2-thio)butyric acid was racemized by the method described in Example 5 The body is obtained, and if necessary, a separate optical isomer can be obtained by a method such as asymmetric reaction or optical division. The compound of the present invention has low toxicity and good stability. As the salt of the compound of the formula (I) of the present invention, a basic group exists in the molecule, and therefore, if necessary, it can be converted into a medically acceptable acid addition salt. As the acid, such as: inorganic salts of hydrochloric acid, hydrogen bromide, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, etc.; or acetic acid, citric acid, malic acid, oxalic acid, tartaric acid, lactic acid, maleic acid, fumaric acid, methanesulfonic acid Examples of organic acids and the like. Further, as the salt of the compound of the formula (I) of the present invention, an acidic group is present in the molecule, and therefore, if necessary, it can be converted into a pharmaceutically acceptable -29-200916098-. As the salt, such as: non-toxic cationic salt, specific

Metal amines such as Na+, Κ+, etc., metal ions, propylene, propylene glycol Salt case. The active ingredient of the present invention can be used in any dosage form such as a liquid preparation, a dermatological preparation, an eye drop, a suppository or a nasal preparation. It is prepared by an additive containing the active ingredient of the present invention. As such excipients for adding lactose, white sugar, glucose, zeatin, light anhydrous citric acid, synthetic strontium calcium, etc.; crystalline cellulose vegan, sodium carboxymethyl cellulose, and starch, sodium carboxymethyl cellulose Lubricants such as sodium carboxylate, sodium carboxymethyl starch, etc.; when hydroxymethylpropyl phthalate and ethyl cellulose are used, such as: base of white petrolatum, etc. Auxiliary agent, glucose, etc.

Alkaline earth metal ions of Mg2+, Ca2+, etc., or ammonia, triethylamine, ethylene diazepam, hexahydroquinone P Qin, sister D, ethanolamine, hydrazine, hydrazine-dimethylethanolamine, amine, hydrazine- Methyl dextran amine and the like, and any suitable preparations for solid preparation, semi-solid preparation, oral preparation, and parenteral preparation (injection, transdermal, and inhalation, etc.) are used for general formulation. For solid preparations, such as: starch, potato starch, crystalline aluminum silicate, magnesium silicate aluminate, and hydrogen phosphate, carboxymethyl cellulose, hydroxypropyl cellulose polyvinylpyrrolidone, etc.; methyl cellulose Calcium, cross-carboxymethylcellulose disintegrating agent; talc, and stearic acid vitamin, hydroxymethyl methylcellulose o-benzene coating agent; coloring agent; semi-solid preparation, liquid preparation, such as: ethanol A preservative such as a paraben or a buffer such as an acid, an antioxidant such as L-ascorbic acid-30 200916098, a chelating agent such as EDT A, or a suspension agent or an emulsifier such as polysorbate 80. example. The dosage of the active ingredient of the present invention is generally from 1 to 100 mg/day. The number of administrations is generally from 1 to 3 times per day. [Examples] Hereinafter, specific description of the invention will be made by way of examples. However, the invention is not limited to the embodiments. [Example 1] Lowering uric acid in blood of healthy adult males In 6 healthy adult males, 640 mg of 4-(1-((4-methylbenzothiophen-3-yl)methyl)benzene was administered per day. And imidazole-2-thio)butyric acid. Figure 1 shows the rate of uric acid decline in blood after 7 days of administration before starting the administration. The average uric acid in the blood decreased by about -6 0%. Further, when the amount of urine excretion of uric acid was calculated, the amount of uric acid excretion in the urine before the start of administration increased. Even if the daily dose is 3 20 mg, it still shows a decrease in uric acid sputum depending on the dosage. From the results, it was revealed that 4-(1-((4-methylbenzothiophen-3-yl)methyl)benzimidazole-2-thio)butyric acid is effective as a bismuth urate reducing agent. [Example 2] Using human URAT1, cells were found to be obstructed by uric acid transport

Three + Tian A found that the vehicle PCDNA3.1 was subjected to the human URAT1 (hURATl) full-length cDNA of the second Crohning, and the human URAT1 gene was copied to the human body by using the ribonucleoprotein method of lipofactamin 2000 -31 - 200916098. Kidney cells (Η EK 2 9 3 cells). At the same time, only the found vector p c D N A 3 . 1 Η Κ Κ 2 9 3 cells (hereinafter referred to as m 〇 c k cells) was also produced. HEK293 cells or mock cells in which the human URAT1 gene was found by geneticin tolerance were selected. The uric acid identified in 14C was delivered to the cells in the same manner as described below. In the indicator, the human URAT 1 gene appeared to function. HEK293 cells and mock were found in human URAT1 using a medium adjusted to pH 7_2±0.1 containing 0.8% NaCM, 0.04% KC1 '0.1% Glucose, 0.034% NaHC03, 0.02% EDTA-Na, 0.12% HEPES, 0.05% Trypsin. The cultured cell layer of the cells was released, and a cell suspension of 4×10 5 cells/mL was prepared using Dulbeccos' modified Eagledium medium (hereinafter referred to as D-MEM medium) containing 10% fetal bovine serum. A human UR ATI of 105/mL/we 11 was prepared. A suspension of HEK293 cells and a suspension of m0Ck cells were seeded in a 24-well cell culture dish, and cultured in d_mEM medium at 37 ° C for 2 days. The uric acid delivery hinders the test. After the medium was suctioned and removed by each well, the cells were replaced with Hanks' Balanced Salt Solution (HBSS), and a pre-incubator was placed at 37 ° C for about 1 minute. After the hb ss was removed by suction, 4-(1-((4-methylbenzothiophen-3-yl)methyl)benzimidazole-2_thio) was added at various concentrations pre-warmed to 37t. Acid or 4-(1-((4-methyl-1-oxybenzothiophen-3-yl)methyl)benzimidazole-2-thio)butyric acid with a radioactive ligand (identified A solution of uric acid··final concentration i 0μΜ ) -32- 200916098 (hereinafter referred to as 1 4 C-uric acid solution) was kept at a constant temperature for 5 minutes at 37 ° C. After the reaction, the μ c _ uric acid solution was removed by suction, and washed with ice-cold HBSS three times. Human URAT1 was found to have ΗΕΚ293 cells and mock cells dissolved in 〇.imol/L NaOH aqueous solution (hereinafter referred to as cell sample), which was taken by well, mixed with cell samples and emulsified scintillator, and the radiation activity was measured with a liquid scintillator counter. The uric acid delivery rate (% of control) in each concentration of the compound of the example compound was calculated by showing the radioactivity of uric acid delivery specific for UR AT 1 (the human URT1 of the compound of the example without addition (DMSO addition) was made to 100%). Uptake), the concentration of the example compound (1 <: 5 ()) which was hindered by the uric acid delivery rate of 5 % was determined. The results are shown in Table 1 [Table 1] Name Structure hURATl Ι05〇(μΜ) 4-(1-((4-Methylbenzothiophen-3-yl)methyl)benzimidazole-2-thio) Butyric acid / -COOH 6.40 plant COOH 4-( 1 -((4-methyl-1 -oxybenzothiophen-3-yl)methyl)benzimidazole-2-thio) j 43.8 butyric acid.令-33- 200916098 It was confirmed by the above example (the uric acid transport inhibition test using human URAT1 cells) that 4-(1-((4-methylbenzothiophene-3-yl)methyl)benzimidazole- 2-thio)butyric acid and 4_(丨_((4-methyl-oxybenzothiophen-3-yl)methyl)benzimidazole_2-thio)butyric acid have hindered URAT 1 activity effect. This represents * _ (丨_(( 4 _methylbenzothiophen-3-yl)methyl)benzimidazole-2-thio)butyric acid and 4-(1-( (4-methyl-1) -oxybenzothiophene-3-yl)methyl)benzimidazole_2_thio)butyric acid inhibits reuptake of uric acid. Therefore '4-(1-(4-methylbenzothiophene-3-yl)methyl)benzimidazole-2-thio)butyric acid and 4-(1-((4-methyl-1)- Oxybenzothiophen-3-yl)methyl)benzimidazole-2-thio)butyric acid inhibits URT1 reabsorption in the kidney by hindering URAT1 activity, showing uric acid excretion and lowering blood Sodium urate. [Example 3] Modification of a human body mastce 11 enzyme preparation and a preparation of a human body mast cell enzyme preparation is a report of Epuda et al. (Journal of of biogical · chemistry, vol. 26, p. 17 17 3 (1 9 9 1 year)) modulated. That is, the supernatant of the insect cell (Th5) culture medium in which the V a c u r o virus was replaced with the coated human body m a s t c e丨 enzyme preparation, c D N A was purified by heparin agarose (farmacia). Further, according to the report of Murakami (Journal of of Biogical Chemistry, Vol. 270, p. 2218 (1995)), the human mast cell enzyme preparation was activated, and purified by heparin agarose to obtain an activated human mast cell enzyme preparation. . -34- 200916098 [Example 4] The enzyme activity of the human body mast cell enzyme preparation was inhibited from measuring 50 μl of the buffer A containing the 1 to 5 ng of the active human mast cell enzyme preparation obtained in Example 3 (〇_5~ 3.0M NaCl, 5 mM mM trihydrochloric acid, pH 8.0), after adding 2 μl of the DMSO solution containing the compound of the present invention, containing the active ingredient of the present invention, 'adding a group of ammonia containing 〇 5 mM Acesulfate-phenyl phenyl hydrazine p-nitroanilide (Bakem) 50 μl buffer a, reacted at room temperature for 5 minutes. The change in absorbance at 40 nm was measured over time to adjust the inhibitory activity. As a result, it was confirmed that I c 5 〇 = 丨n Μ or more in all the tested compounds, and the strong inhibitory activity of less than 1 ΟηΜ was obtained.

[Example 5] Synthesis of 4-C 4 -methyl-1-oxybenzothiophen-3-yl)butyric acid methyl)benzimidazole_2-thio) 1) Synthesis of Compound No. 2 - 35- 200916098 【化8】 I rOH ac2o i /-〇ac TO -- 〇i

Vs Pyridine, THF, rt S 1 2 Add 1 (9 μg), THF (900 mL), Pyridine (81 mL) to a 2 L flask, and continue to add Ac20 (95.4 mL) under ice-cooling. 1 hour. The T H F was concentrated under reduced pressure, and extracted with H.sub.2 (5 OOmL). The organic layer was washed with 0.1 N HCl (500 mL), H 2 〇 (500 mL×2), and saturated brine (500 mL). After drying with M g S Ο 4, the filtrate was poured under reduced pressure. Obtain yellow oil 2 (1 2 0.6 2 g). (Yield 1 〇〇%) Ή NMR (CDC13): (5 7.70 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.24 (t, J = 8.0 Hz, 1H), 7.15 (d , J = 8.0Hz, 1H), 5.43(s, 2H), 2.73(s, 3H), 2.1 l(s, 3H) 2) Synthesis of Compound No. 3 [Chemical 9]

Add 2 ( 5 6 g ), A c Ο Η (500 m L ) to a 2 L beaker. Then add 30% H2〇2 (1 43 mL ) to the funnel for 1 hour. - 200916098 Stir at room temperature for 2 hours and at 40 °C for 1 hour. Add H20 (500mL) at room temperature, extract with CH2Cl2 (500mLx2), wash the organic layer with H20 (500mL), 20% aqueous sodium thiosulfate (800mL X 2 ), Η20 (500m) After drying, the mixture was dried over MgSO 4 , and the filtrate was evaporated under reduced pressure to give a white solid crystals of 1 0 0 · 2 g. The crude product was purified by a silica gel column chromatography (CH2C12: MeOH = 20:1) to afford 3 (3 2.02 g) (yield 53.3%) and 3 (12.0 g). !H NMR(CDC 13 ) : (5 7.7 8 (d, J = 7.6Hz, 1H), 7_39(t, J = 7.6Hz, 1H), 7.31(d, J = 7.6Hz, 1H), 7.02(t , J = 1.6 Hz, 1H), 5_26 (ddd, J = 1.6, 7.6, 15.6 Hz, 2H), 2.5 6 (s, 3 H ), 2 · 2 0 (s, 3H). 3) Compound No. 5 Synthesis [Chemical 1 Ο] 0Cj~S~^C〇2Me INNaOH 霣In a 3 L 3-neck flask, add 4 (72g), THF (720mL), IN NaOHaq. ( 404mL ) in 30 minutes. At room temperature, the disturbance was carried out for 3 hours. _-· Under ice cooling, add 1 NHC 1 aq · ( 4 0 4 m L ) 'H20 (1 400 mL) and stir for 1 full night. The precipitated crystals were collected by filtration, washed with H20 (200 mL×2), and then dried under reduced pressure at 45 ° C for 7.5 hours to obtain white crystals 5 ( 64.5 0 g ) (yield 94.9%). ]H NMR(MeOD) : 5 7.4 9 - 7.4 4 (m, 2H), 7.21-7.16 (m, 2H), -37- 200916098 3.30 (t, J = 7.2 Hz, 2H), 2.49 (t, J = 7.2 Hz, 2H), 2.02 (quin, J = 7.2 Hz, 2H). 4) Synthesis of compound Νο·6 [Chemical 1 1]

I wide OAc 03⁄4 + Ο: Bu ~

3 (30 g), Pd (PPh3) 4 C 8.15 g), and THF (3 20 mL) were added to a 1 L eggplant type flask, and the mixture was stirred at room temperature for 2 hours under a nitrogen atmosphere. After 2 hours, 5 (30 g) dissolved in τ H F (280 m L) was added and stirred at room temperature for 17.5 hours. The reaction solution was subjected to filtration of fluorite to remove the residue of P d , and the filtrate was evaporated under reduced pressure to give a crystal of crystals of 70.0 g. The crude product was dissolved in CH 2 C12 (1 80 m L) at 30 ° C, and then returned to room temperature to obtain crystals. White crystals (25 g) were obtained by filtration. The crystals obtained were dissolved in CH2C12: MeOH = 1 : 2, and the solvent was evaporated under reduced pressure to afford 6 (2 0 0 g) (yield 3 8.2 %). 1H NMR (CDC13): <5 7.7 1-7.74 (m, 2H), 7.44-7.3 60, 2H), 7.28-7.16 (m, 3H), 6.09 (s, 1H), 5.42 (s, 2H), 3.54 (quin, J = 6.4 Hz, 1H), 3.34 (quin, J = 6.4 Hz, 1H), 2.72 (s, 3H), 2.51-2.40 (m, 2H), 2.22 (sep, J-6.8Hz, 1H) ), 2.11 (sep. J = 6.8Hz, 1 H). -38 - 200916098 [Industrial Applicability] The agent of the present invention is applied to a URAT 1 inhibitor or a urate-reducing agent. Further, the pharmaceutical system of the present invention is applicable to uric acid-related diseases such as gout, hyperuricemia, gout arthritis, gout nodules, urinary calculi, kidney stones, renal disorders, gout kidneys, cardiovascular diseases, or cerebrovascular diseases. A prophylactic or therapeutic agent for reducing uric acid sputum, or a heart or kidney disease associated with gout or hyperuricemia, which is effective for treatment and prevention. [Simple description of the diagram] [Fig. 1] Fig. 1 represents 4-(1-((4-methylbenzothiophen-3-yl)methyl)benzoimin B-sodium 2-thio)butyric acid A graph of the rate of uric acid reduction in the blood after administration. -39-

Claims (1)

200916098 X. Patent application scope 1. A URAT1 inhibitor comprising a nitrogen-containing aromatic ring derivative represented by formula (I) or a salt thereof as an active ingredient. [In the formula (I), R1 and R2 represent a simultaneous or independent hydrogen atom, a dentate atom, a trihalomethyl group, a cyano group, a hydroxyl group, or a carbon number! ～4 alkyl or carbon number 1 to 4, or R1 and R2 are _〇_ch2-〇-, -O-CH2-CH2- 0- or -CH2-CH2-CH2- (R1 and When R2 is a ring, the number of carbon atoms or a plurality of alkyl groups having 1 to 4 carbon atoms may be substituted.) A represents a single bond 'substituted or unsubstituted carbon number 丨~6 linear 'branched, Or a cyclic alkyl group, a substituted or unsubstituted carbon number 6 to i 伸 aryl group, or a substituted or unsubstituted ring having at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. a hetero atom having a carbon number of 4 to 1 〇 of a heteroaryl group {as a substituent in A' such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon number of 1 to 6 a base, a straight chain or a branched chain having 1 to 6 carbon atoms (as a substituent, two adjacent alkoxy groups may form an acetal bond), and a linear or branched carbon number of 1 to 6 Alkylthio, linear or branched alkyl sulfonyl group having 1 to 6 carbon atoms, linear or branched chain -40 to 200916098 having a carbon number of 1 to 6 fluorenyl, linear or branched a mercaptoamine group having a carbon number of 1 to 6, a trihalomethyl group, a trihalogen methoxy group, a phenyl group, and an oxygen group Or a phenoxy group which may be substituted by one or more halogen atoms, which is equivalent to one or a plurality of substitutions of each of the ring or the alkyl group; E represents -COOR3, -S03R3, -CONHR3, -S02NHR3, tetrazolyl, 5-oxy-1,2,4-oxadiazolyl' or 5-oxo-1,2,4-thiadiazolyl (R3 is a hydrogen atom or a linear chain Or a branched alkyl group having 1 to 6 carbon atoms; G represents a substituted or unsubstituted linear or branched alkyl group having 1 to 6 carbon atoms and may also contain 1 or a plurality of hydrazines, s, s〇2, NR3, (R3 is the same as defined above, as a substituent in G, such as: halogen atom, hydroxyl group, nitro group, cyano group, linear or branched carbon number 1~6 a thiol group having a carbon number of 1 to 6 in the form of a straight chain or a branched chain (may also form a waking bond as two substituents adjacent to the substituent ', a trihalomethyl group, a halogen methoxy group, a benzene group) A group or an oxy}; Μ represents a single bond or -S(〇)m-' m represents an integer of 〇~2; J is a linear chain having a carbon number of 6~6 when m is 0 and A is a substituted or unsubstituted carbon, When a branched or cyclic alkyl group represents a substituted or unsubstituted carbon number of 3 to 6 a linear, is or branched alkyl group, a substituted or unsubstituted carbon number of 7 to 11 or substituted or unsubstituted, having at least one selected from the group consisting of an oxygen atom, a nitrogen atom, and sulfur A hetero atom of a group of atoms is a heteroaryl group having a carbon number of 4 to 10, and a carbon number of 6 to 1 or more is selected from an oxygen atom of 4 to 1 0. a substituted or unsubstituted aryl group, or a substituted or unsubstituted ring having a hetero atom of a nitrogen atom and a sulfur atom in the ring _ -41 - 200916098 base time, representing # -p· & Unsubstituted carbonic acid number 1 to 6 linear, cyclic or branch-shaped fenestration, auxiliaries of the carbon number 6 to 1 1 substituted or unsubstituted, or substituted or unsubstituted ring Female ^ (a child having one or more heteroatoms having a carbon number of 4 to 10 selected from a hetero atom of a group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, • 1 is a single bond, and „1 is 〇 VIII is a single bond 'or 111 when 1 or 2' represents a substituted or unsubstituted carbon number 1 to 6 linear, cyclic or branched k group, substituted or unsubstituted carbon number 6 to n Base, or substituted or unsubstituted a ring having 4 or more carbon atoms of a hetero atom selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, and a ring having a substituent of J, such as a halogen atom, a hydroxyl group, or a nitrate a chloro group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, 2 alkoxy groups adjacent thereto) An acetal bond can be formed, a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkyl sulfonyl group having 1 to 6 carbon atoms, a linear or branched chain a mercapto group having 1 to 6 carbon atoms, a linear or branched carbon group of 醯~6, a substituted or unsubstituted anthranilyl group, a trihalomethyl group, a trihalogenomethoxy group, a phenyl group An oxy group, a COOR3 group (R3 is the same as defined above), or a phenoxy group which may be substituted by one or more halogen atoms, which is independently substituted at one or a plurality of positions of the ring or the alkyl group. Can be: x represents -CH = or a nitrogen atom; γ represents -CB = or a nitrogen atom; B is represented by -B 1 - B 2 - B3; B1 represents a single bond, a straight or branched carbon number 1 ~3 of the alkyl group; - 42- 200916098 B represents a single bond, -CO - or - NR3- (wherein r3 is the same as defined above for r3); B3 represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxy 'sulfonic acid group' substituted or none Substituted straight or branched carbon number 1 to 6, substituted or unsubstituted linear or branched carbon number 1 to 6, acyl group, substituted or unsubstituted carbon number 6 to 1 1 aryl, substituted or unsubstituted, heteroaryl, substituted or unsubstituted amine having 4 to 10 carbon atoms and having 1 or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom a substituted, unsubstituted or unsubstituted carboxy, substituted or unsubstituted linear or branched carbon number of 1 to 6 phenyl sulfonyl, substituted or unsubstituted phenyl sulfonyl, substituted or unsubstituted straight A chain or branched alkylaminosulfonyl group having 1 to 6 carbon atoms, a substituted or unsubstituted linear or branched fluorenyl group having 1 to 8 carbon atoms, a substituted or unsubstituted linear chain or a branch. Alkoxycarbonyl group having 1 to 6 carbon atoms, substituted or unsubstituted phenylcarbonyl group, linear or branched alkylthio group having 1 to 6 carbon atoms, trihalomethyl group or trihalogen Base { as a substituent of B3 such as: halogen atom, hydroxyl group, amine group, carboxyl group, nitro group, cyano group, linear or branched alkyl group having 1 to 6 carbon atoms, linear or branched carbon Alkoxy groups of 1 to 6 (as a substituent, two alkoxy groups adjacent thereto may form an acetal bond), a trihalomethyl group, or a trihalomethoxy group, which is equal to any position in one or more It is also possible to substitute independently; Z represents a carbon atom or a nitrogen atom; Q represents a carbon atom or a nitrogen atom]. 2_ The URAT1 inhibitor according to claim 1, wherein R1 and R2 of the nitrogen-containing aromatic ring derivative represented by formula (I) represent simultaneously, or -43-200916098, each independently hydrogen atom, methyl group or A halogen atom; A is a single bond or a substituted or unsubstituted carbon number 丨~5 linear, cyclic, or branch-like extension; E represents _c〇〇R3, -S03R3, -CONHR3, -S02NHR3 'tetrazole·5-yl, 5-oxyl, 2,4-oxadiazole-3-yl, or 5-oxy-1,2,4-thiadiazole·3-yl (wherein r3 represents a hydrogen atom or a linear or branched carbon number of 1 to 6; G represents a substituted or unsubstituted linear or branched alkyl group having 1 to 3 carbon atoms; The substituent which may be a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms ( As a substituent, two adjacent oxime groups may form a waking bond, a trihalomethyl group, a trihalomethoxy group, a benzyl group, or an oxy group; Μ represents a single bond or _s(0)m_,m Is an integer from 0 to 2; J is substituted or unsubstituted (with one on the ring) a hetero atom or a naphthyl group having a carbon number of 4 to 4 selected from the group consisting of an oxygen atom, a nitrogen atom, and a hetero atom in which the sulfur atom is grouped. 'The heteroaryl group or the naphthyl group of the J may have a halogen atom or a hydroxyl group. a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, 2 adjacent to the courtyard oxygen) The base may also form a waking bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkyl sulfonyl group having 1 to 6 carbon atoms, a straight chain or a branched chain. a mercapto group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, a substituted or unsubstituted thioanilide group, a trihalomethyl group, a trihalogen methoxy group, a phenyl group, an oxy group, a C00R3 group, or a phenoxy group which may be substituted by one or more halogen atoms, and these substituents -44 - 200916098 may be independently substituted at one or a plurality of positions at any position of the ring. X is -CH= or a nitrogen atom; Y is -CB = or a nitrogen atom; B is represented by -B^B'B3; B1 represents a single bond or a straight or branched carbon number of 1 to 3. B2 represents a single bond, -CO- or -NR3-; B3 generation a hydrogen atom, a halogen atom, a hydroxyl group, a sulfonyl group, a substituted or unsubstituted linear or branched alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted linear or branched carbon number of 1 to 6 Alkoxy, substituted or unsubstituted aryl group having 6 to 11 carbon atoms, substituted or unsubstituted amino group, substituted or unsubstituted carboxy group substituted or unsubstituted linear or branched carbon number 1 ~6 $ & sulfonyl, substituted or unsubstituted phenyl sulfonyl, substituted or unsubstituted && straight or branched alkyl 1 to 6 aminoalkylsulfonyl, a substituted or unsubstituted linear or branched carbon group having 1 to 8 carbon atoms, substituted or unsubstituted or unsubstituted or substituted in a straight or branched chain having 1 to 6 carbon atoms; Phenylcarbonyl (as a substituent of oxime 3 is a halogen atom, a straight, or branched alkyl group having 1 to 6 carbon atoms, an amine group or a carboxyl group, and any of these positions may be independently one or more independently. The ground is replaced by}; Ζ is a carbon atom; Q is a nitrogen atom. 3. The URA Τ 1 inhibitor according to claim 2, wherein the nitrogen-containing aromatic ring derivative R1 and R2 represented by the formula (I) represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently independent; A is a substituted or unsubstituted linear, cyclic, or branched alkyl group having 1 to 5 carbon atoms; £ is _ -45- 200916098, -S〇3r, -C0NHR3, s〇2Nhr3, tetrazole _5 base, 5-oxy-1,2,4-oxadiazole-3-yl, or 5-oxy-Hithiadiazole_3_yl (where 'R3 represents a hydrogen atom or a straight or branched chain a C 1 to 6 alkyl group; G is a substituted or unsubstituted linear or branched alkyl group having a carbon number of 1 to 3 'the alkyl group of the G may have a substituent of a halogen atom' a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, 2 alkane adjacent thereto) An oxy group may also form an acetal bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy group; Μ represents a single bond or _S(〇)m_, m is an integer of 〇~2; j is Substituted or unsubstituted (having more than one ring selected from oxygen atoms, nitrogen atoms) And the hetero atom of the hetero atom of the group of sulfur atoms is 4 to 1 杂, and the heteroaryl group of the J may have a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear chain or a branched chain. An alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may form an acetal bond), a straight chain or a branch a chain-like alkylthio group having 1 to 6 carbon atoms, a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, and a linear chain Or a branched decylamino group having 1 to 6 carbon atoms, a substituted or unsubstituted anthranilyl group, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, a COOR3 group, or 1 The above phenoxy group may be substituted by a halogen atom. These substituents may be independently substituted at one or a plurality of positions at any position of the ring, X is -CH= or a nitrogen atom, and γ is a nitrogen atom. 4. The URAT1 inhibitor according to claim 3, wherein the nitrogen-containing aromatic ring derivative represented by the formula (I), wherein R1 and R2 represent a hydrogen atom or a methyl group which are simultaneously or independently of -46 to 200916098. a halogen atom; A is a substituted or unsubstituted linear, cyclic, or branched alkyl group having 3 to 5 carbon atoms; and E is _C〇〇R3 (wherein R3 represents a hydrogen atom or a straight chain or a branch; a chain of carbons having 1 to 6 carbon atoms; G represents a methylene group; Μ represents -S-; J represents a substituted or unsubstituted benzothiophene group or a fluorenyl-methyl fluorenyl group. The aryl group may have a halogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms, a trihalomethyl group or an oxy group; X is -CH=; Υ is a nitrogen atom. 5-A method for reducing uric acid bismuth, characterized by containing a nitrogen-containing aromatic ring derivative represented by formula (I) or a salt thereof as an active ingredient, [In the formula (I), R1 and R2 represent a hydrogen atom, a halogen atom, a halogenmethyl group, a fluorenyl group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms or a carbon number of 1 to 4, which are simultaneously or independently. R2 represents a linkage of -0-CH2-0-, -0-CH and R2 is a bond, the carbon may also be substituted by an alkyl group of 4), a single bond of A, a substituted or unsubstituted or cyclic alkane a substituted, unsubstituted or unsubstituted ring-substituted or unsubstituted carbon number of 1 to 6 linear, branched, substituted or unsubstituted carbon number 6 to 1 1 a heterocyclic aryl group having 4 to 10 carbon atoms having one or more hetero atoms selected from the group consisting of an oxygen atom, a -47-200916098 nitrogen atom and a sulfur atom in the ring {as a substituent of A: a halogen atom a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent adjacent to 2) The alkoxy group may also form an acetal bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, a straight chain or Branched carbon group having 1 to 6 carbon atoms, linear or branched carbon group having 1 to 6 carbon atoms, trihalomethyl group, trihalomethoxy group, phenyl group, oxy group, or One or more halogen atoms may be substituted with a phenoxy group' Etc. may also be substituted independently by one or a plurality of positions at any position of the ring or alkylene group; E represents _C〇〇R3, -S03R3 '-CONHR3 ' -S02NHR3, tetrazolyl, 5-oxy_1 , 2,4-oxadiazolyl, or 5-oxy-1,2,4-thiadiazolyl (R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); The linear or branched alkyl group representing a substituted or unsubstituted carbon number of 1 to 6 may also contain one or a plurality of 0, S, S 2 , and NR 3 {R3 in the same manner as defined above. The substituent of G is, for example, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon group having 1 to 6 carbon atoms, a linear bond or a branched alkoxy group having 1 to 6 carbon atoms ( As a substituent, two adjacent oxime groups may also form an acetal bond, a dihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy}; Μ represents a single bond or -S(〇)m- 'm is an integer of 〇~2; J is a substituted or unsubstituted group when m is 0' and A is a substituted or unsubstituted carbon number of 1 to 6 of a straight bond, a branched chain, or a cyclic thiol group. a linear, cyclic or branched alkyl group having a carbon number of 3 to 6 substituted or unsubstituted carbon number - 48- 200916098 11 square, or substituted or unsubstituted, having more than one carbon atom selected from the group consisting of an oxygen atom, a fluorene atom, and a hetero atom of a group of sulfur atoms 4 to 10 a heteroaryl group, wherein J is m and is an artificially substituted or unsubstituted carbon 6 to n aryl group or a substituted or unsubstituted ring having at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom When a heteropoly atom having 4 to 10 carbon atoms in a hetero atom of a group represents a substituted or unsubstituted carbon number 丨~6, a linear, cyclic or branched fluorenyl group, a substituted or unsubstituted carbon number An aryl group of 6 to 11 or a heteroaryl group having 4 to 10 carbon atoms which has one or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom in the ring, J in Μ Is a single bond, ^ is 〇 and a is a single bond, or when m is 1 or 2, 'represents a substituted or unsubstituted carbon number of 1 to 6 straight, cyclic or branched, substituted or unsubstituted An aryl group having 6 to 11 carbon atoms or a substituted or unsubstituted heteroaryl group having a carbon number of 4 to 1 Å selected from a hetero atom selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, Is a substituent of r, such as: a halogen atom, a hydroxyl group, a nitro group, a chloro group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 Alkoxy group (as a substituent, an adjacent alkoxy group may also form an acetal bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 Alkylsulfonyl group of 1-6, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched decylamino group having 1 to 6 carbon atoms, a substituted or unsubstituted hydrazine group An anilino group, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, a COOR3 group (R3 is the same as defined above), or a phenoxy group which may be substituted by one or more halogen atoms, and the like. -49- 200916098 may also be substituted independently by one or more at any position of the ring or alkyl group; X represents -CH = or a nitrogen atom; γ represents -CB = or a nitrogen atom; B is -B 1 - B 2 - B 3 · represents; B1 represents a single bond or a straight or branched alkyl group having 1 to 3 carbon atoms; B2 represents a single bond, -CO- or -NR3- (wherein R3 is the same as above Define the same); B3 represents a hydrogen atom a halogen atom, a nitro group, a cyano group, a hydroxyl group, a sulfonyl group substituted or unsubstituted linear or branched carbon group having 1 to 6 carbon atoms, a substituted or unsubstituted linear or branched carbon number 1 Alkoxy group of 1-6, substituted or unsubstituted aryl group having 6 to 11 carbon atoms, substituted or unsubstituted carbon having one or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom a heteroaryl group of 4 to 10, a substituted or unsubstituted amino group, a substituted or unsubstituted fluorenyl group, a substituted or unsubstituted linear or branched sulfonyl group having 1 to 6 carbon atoms, Substituted or unsubstituted phenylsulfonyl, substituted or unsubstituted linear or branched alkyl 1 to 6 aminoalkylsulfonyl, substituted or unsubstituted linear or branched carbon a 1 to 8 fluorenyl group, a substituted or unsubstituted linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a substituted or unsubstituted phenylcarbonyl group, a linear or branched carbon number of 1 to 6 a chain alkylthio-dihalomethyl group or a trihalomethoxy group (as a substituent of B3 such as a halogen atom, a hydroxyl group, an amine group, a carboxyl group, a nitro group, a cyano group, a linear or branched chain) Alkoxy groups having 1 to 6 alkyl groups, linear or branched carbon numbers of 丨~6 (two alkoxy groups adjacent to the substituent ' may form an acetal bond), and three-50-200916098 halogen Methyl or trihalomethoxy, these may be independently substituted at one or a plurality of positions at any position}; Z represents a carbon atom or a nitrogen atom; Q represents a carbon atom or a nitrogen atom]. 6. The agent for reducing uric acid bismuth according to item 5 of the patent application, wherein the nitrogen-containing aromatic ring derivative represented by the formula (I), wherein R1 and R2 represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently; A is a single bond or a substituted or unsubstituted linear, cyclic, or branched alkyl group having 1 to 5 carbon atoms; e is -COOR3, _S03R3, _C〇NHR3, _s〇2NHR3, tetrazole_5 , 5-ethoxy-1,2,4-oxadiazol-3yl, or 5-oxy-1,2,4-thiadiazole-3-yl (where 'R3 represents a hydrogen atom or a straight chain Or a branched carbon group having 1 to 6 carbon atoms; G represents a substituted or unsubstituted carbon number; a straight or branched chain of the group of ~3, which may have a substituent Such as: a halogen atom, a thiol group, a nitro group, a cyano group, a linear or branched carbon group having 1 to 6 carbon atoms, a linear or branched carbon number 6 alkoxy group (as a substituent, adjacent 2 of the electrophilic groups may also form an acetal bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy group; Μ represents a single bond or -S(0)m-, and m is 〇~2 An integer; J stands for substitution or no substitution (more than one choice on the ring) a hetero atom or a naphthyl group of a hetero atom or a naphthyl group in which a hetero atom or a naphthyl group of a hetero atom or a group of oxygen atoms, a nitrogen atom, and a sulfur atom may have a substituent of _ a a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon number of 〜6, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substitution -51 - 200916098 basis, adjacent The two alkoxy groups may also form an acetal bond, a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkyl sulfonyl group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, a substituted or unsubstituted phenylamino group, a trihalomethyl group, and a tris a halogen methoxy group, a phenyl group, an oxy group, a C〇〇R3 group, or a phenoxy group which may be substituted by one or more halogen atoms, and these substituent groups may be one at any position of the ring or Most of them are independently substituted; X is -CH = or a nitrogen atom; Y is -CB = or a nitrogen atom; B is represented by -B^BlB3; Β1 represents a single bond or a linear or branched carbon number of 1 ~3 is completed; B2 stands for single key -CO- or -NR3-; B3 represents a hydrogen atom, a halogen atom, a hydroxyl group, a sulfonyl group, a substituted or unsubstituted linear or branched alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted linear chain Or a branched alkoxy group having 1 to 6 carbon atoms, a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, a substituted or unsubstituted amino group, a substituted or unsubstituted carboxy group substituted or unsubstituted a straight or branched carbon number 6~6 sulfonyl group, a substituted or unsubstituted phenyl sulfonyl group, a substituted or unsubstituted linear or branched amino group having 1 to 6 carbon atoms a sulfonyl group, a substituted or unsubstituted linear or branched fluorenyl group having 1 to 8 carbon atoms, a substituted or unsubstituted linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms or II substituted or unsubstituted phenyl fluorenyl group {{As a substituent of B3 such as a halogen atom, a hydroxyl group, a lysine bond or a branched alkyl group having 1 to 6 carbon atoms, an amine group or a carboxyl group; It can also be used in any of the chapters -52-200916098 to replace one or more of them independently; z is a carbon atom; Q is a nitrogen atom. 1 The agent for reducing uric acid bismuth according to item 6 of the patent application, wherein the nitrogen-containing aromatic ring derivative represented by the formula (I), wherein R1 and R2 represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently; A is a substituted or unsubstituted linear, cyclic or branched alkyl group having 1 to 5 carbon atoms; e is -COOR3, _S03R3, _c〇NHR3, -S〇2Nhr3, tetrazole _5 group, 5-oxy-1,2,4-oxadin-3-yl, or 5-oxy-1,2,4-thiadiazol-3-yl (where 'R3 represents a hydrogen atom or a straight or branched chain a C 1 to 6 alkyl group; G represents a substituted or unsubstituted linear or branched alkyl group having 1 to 3 carbon atoms. The alkyl group of the G may have a halogen atom. a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, 2 adjacent to each other) An alkoxy group may also form an acetal bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy group; Μ represents a single bond or -S(0)m-, and m is an integer of 〇~2; J represents a substituted or unsubstituted one (having more than one ring selected from an oxygen atom and a nitrogen atom in the ring) And the hetero atom of the hetero atom of the group of sulfur atoms is 4 to 1 〇 of the heteroaryl group) 'The heteroaryl group of J may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, a straight chain or a branched chain. An alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may form an acetal bond), a linear chain or a chain-like alkylthio group having 1 to 6 carbon atoms, a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, and a straight Chain or branched carbon number 1 to 6-53- 200916098 Mercaptoamino group, substituted or unsubstituted anthranilyl group, trihalomethyl group, trihalomethoxy group, phenyl group, oxy group, COOR3 group Or a phenoxy group which may be substituted by one or more halogen atoms, and these substituents may be independently substituted at one or a plurality of positions at any position of the ring, X is -CH= or a nitrogen atom; γ is a nitrogen atom atom. 8 as claimed in claim 7, wherein the nitrogen-containing aromatic ring derivative represented by the formula (I) wherein R1 and R2 represent a simultaneous or independent hydrogen atom, a methyl group or a halogen atom; a linear, cyclic, or branched alkyl group having a carbon number of 3 to 5, which is substituted or unsubstituted; £ is -COOR3 (wherein 'R3 represents a hydrogen atom or a linear or branched carbon number! 6 alkyl); G represents a methylene group; Μ represents -S-; J is a substituted or unsubstituted benzothienyl or N-methylindenyl group, and the heteroaryl group of J may have a substituent It is a halogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms, a trihalomethyl group, or an oxy group; X is -CH=; Y is a nitrogen atom. A prophylactic or therapeutic agent for gout, hyperuricemia, or a uric acid-related disease, which comprises a nitrogen-containing aromatic ring derivative represented by the formula (I) or a salt thereof as an active ingredient, [In the formula (I), -54 - 200916098 R and R represent a hydrogen atom, a halogen atom, a trihalomethyl group, a cyano group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms or a carbon number of 1 to 4 at the same time or independently. The methoxy group, or R1 and R2 are a link 2_〇_CH2_〇·, ·O-CKHr 0- or -0112-(^2-(^2-(111 and 112 are connected, the carbon may also Substituted by one or more of the substituents having a carbon number of 1 to 4; A is a single bond, a substituted or unsubstituted, linear, branched, or cyclic alkyl group having 1 to 6 carbon atoms, substituted or An unsubstituted carbon number of 6 to 1 1 aryl, or a substituted or unsubstituted ring having 1 or more carbon atoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms Heteroaryl group { As a substituent of A, such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 a oxy group of 6 to 6 (as a substituent, two alkoxy groups adjacent thereto may also form a polyamide bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched chain Alkylsulfonyl group having 1 to 6 carbon atoms, linear or branched carbon group having 1 to 6 carbon atoms a straight or branched carbon group having a carbon number of 丨~6, a trihalomethyl group, a dihalomethoxy group, a phenyl group, an oxy group, or may be substituted by one or more halogen atoms. The phenoxy group ' can also be independently substituted in one or a plurality of positions at any position of the ring or alkylene group}; E represents -COOR3, ·3〇3Ϊ13, tonnhW, _s〇2Nhr3, tetrazolyl, 5- Oxy-1,2,4-oxadiazolyl, or 5-oxy-thiadiazolyl (R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); G represents A substituted or unsubstituted carbon number of 6~6 of a straight or branched chain may also contain one or more 〇, s, S02, NR3 {R3 is the same as defined above, as ^ The substituent represents halogen-55-200916098 Atom, a thiol, a nitro group, a cyano group, a linear or branched alkyl group having an alkyl group of i~6, a linear or branched carbon number 丨~6 Alkoxy (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), trihalomethyl, trihalomethoxy, phenyl, or oxy}; Μ represents a single bond or -S (0)m·, m is an integer of 〇~2; J is in m 〇' and a is a substituted or unsubstituted linear, branched, or cyclic alkyl group having 1 to 6 carbon atoms, and represents a substituted or unsubstituted linear or cyclic group having 3 to 6 carbon atoms. a branched alkyl group, a substituted or unsubstituted aryl group having 7 to U carbon atoms, or a substituted or unsubstituted group having one or more selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. a heteroaryl group having 4 to 10 carbon atoms in the atom, j having 0 or less, and an artificially substituted or unsubstituted aryl group having 6 to n carbon atoms, or a substituted or unsubstituted one or more selected from the ring. When a hetero atom having a carbon number of 4 to 10, which is a hetero atom of a group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, represents a linear or cyclic bond having a substituted or unsubstituted carbon number of 1 to 6. a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, or a substituted or unsubstituted carbon number of 4 or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. a heteroaryl group of ～10, J is a single bond, m is 〇 and a is a single bond, or m is 1 or 2' represents a substituted or unsubstituted carbon number of 1 to 6 straight, cyclic or Branched base a substituted or unsubstituted carbon number of 6 to 1 1 or a substituted or unsubstituted carbon number of 4 or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom in the ring. a heteroaryl group of 10, {as: [substituent such as: halogen atom, hydroxyl group, nitro group, cyanogen-56-200916098 group, linear or branched carbon number I~6 alkyl group, linear chain Or a branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), a linear or branched alkylthio group having 1 to 6 carbon atoms. a linear or branched alkyl sulfonyl group having 1 to 6 carbon atoms, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 An amino group, a substituted or unsubstituted anthranilyl group, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, a COOR3 group (R3 is the same as defined above), or may be one or more halogens The atom may be substituted with a phenoxy group, and these may be independently substituted in one or a plurality of positions at any position of the ring or the alkyl group} j X represents -CH = or a nitrogen atom; Y represents -CB = or a nitrogen atom; B to -B 1 - B 2 - B3 represents; B1 represents a single bond or a straight or branched alkyl group having 1 to 3 carbon atoms; B2 represents a single bond, -CO- or -NR3- (wherein R3 is the same as defined above) B represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxyl group, a fluorinated group, a substituted or unsubstituted linear or branched carbon group having 1 to 6 carbon atoms, a substituted or unsubstituted linear chain or a branched carbon group having 1 to 6 carbon atoms, a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, a substituted or unsubstituted ring, and one or more selected from an oxygen atom and a nitrogen atom. a hetero atom having a carbon number of 4 to 10, a substituted or unsubstituted amino group, a substituted or a hydrazone, a residue, a substituted or unsubstituted linear or branched chain. a sulfonyl group having 1 to 6 carbon atoms, a substituted or unsubstituted phenylsulfonyl group, a substituted or unsubstituted -57-200916098 instead of a linear or branched alkyl group having 1 to 6 carbon atoms A sulfonyl group, a substituted or unsubstituted linear or branched carbon group having 1 to 8 carbon atoms, a substituted or unsubstituted linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, substituted Or no replacement a carbonyl group, a linear or branched alkylthio group having 1 to 6 carbon atoms, a trihalomethyl group or a trihalomethoxy group. {As a substituent of B3, such as a halogen atom, a hydroxyl group, an amine group, a carboxyl group, or a nitrate a cyano group, a cyano group, a linear or branched alkyl group having a carbon number of 1 to fluorene, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, the adjacent two oxy groups are also An acetal bond may be formed, a tris-methyl group, or a trihalomethoxy group, and these may be independently substituted at one or a plurality of positions at any position}: Ζ represents a carbon atom or a nitrogen atom; Q represents a carbon atom Or nitrogen atom]. 1 如 如 申请 申请 申请 申请 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如Each of which is independently a hydrogen atom, a methyl group or a halogen atom; A is a single bond 'or a substituted or unsubstituted carbon number of 1 to 5 linear, cyclic or conjugated alkylene; E is -COOR3, -S 〇3R3, -CONHR5 S02NHR four I] sit _5_ base, 5-oxyl - chelate diazole u, or 5- and keto-1,2,4-thiazol-3-yl (where 'r3 stands for a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms; G represents a substituted or unsubstituted linear or branched alkyl group having 1 to 3 carbon atoms, and the extension of G甘1, a substituent may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, a straight _# straight i« or a branched alkyl group having 1 to 6 carbon atoms, a linear chain -58-200916098 or a branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy group. ; Μ represents a single key or - s(0)m-,m An integer of 0 to 2; J represents a substituted or unsubstituted (having a heteroaryl group or a naphthalene having 4 or more carbon atoms selected from a hetero atom selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom in the ring) The heteroaryl or naphthyl group of the J may have a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a straight chain or a branched chain. Alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, and a linear chain Or a branched alkyl sulfonyl group having 1 to 6 carbon atoms, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched fluorenylamino group having 1 to 6 carbon atoms a substituted or unsubstituted phenoxy, trihalomethyl, trihalomethoxy, phenyl, oxy, COOR3 group, or a phenoxy group substituted by one or more halogen atoms, such substitution The group may be independently substituted at one or a plurality of positions at any position of the ring; X is -CH= or a nitrogen atom; Y is -CB = or a nitrogen atom; B is represented by -B^BlB3; Β 1 represents Single bond or straight or branched The alkyl group having a carbon number of 1 to 3; Β2 represents a single bond, -CO- or -NR3-; Β3 represents a hydrogen atom, a halogen atom, a hydroxyl group, a sulfonyl group, a substituted or unsubstituted linear or branched chain. Alkyl group having 1 to 6 carbon atoms, substituted or unsubstituted linear or branched carbon group having 1 to 6 carbon atoms, substituted or unsubstituted -59-200916098 aryl group having 6 to 11 carbon atoms, substituted Or an unsubstituted amino group, a substituted or unsubstituted fluorenyl group, a substituted or unsubstituted linear or branched, decyl group having 1 to 6 carbon atoms, a substituted or unsubstituted phenyl sulfonyl group, Substituted or unsubstituted linear or branched Aminoalkylsulfonyl group having 1 to 6 carbon atoms, substituted or unsubstituted linear or branched acid group having 1 to 8 carbon number, substituted or not Substituted linear or branched carbon 6 alkoxycarbonyl group or substituted or unsubstituted phenylcarbonyl group {B3 substituent is a halogen atom, a hydroxyl group, a linear or branched carbon number of 1 to 6 The alkyl group, the amine group or the carboxyl group ' can also be independently substituted at one or a plurality of positions at any position}; z is a carbon atom; and Q is a ruthenium atom. 1 1. A prophylactic or therapeutic agent for gout, hyperuricemia, or uric acid-related diseases according to the first aspect of the patent application, wherein R1 and R2 of the nitrogen-containing aromatic ring derivative represented by formula (I) represent Simultaneously or independently of a hydrogen atom, a methyl group, or a halogen atom; Α is a substituted or unsubstituted linear, cyclic, or branched alkyl group having 1 to 5 carbon atoms; E is · COOR3, -S03R3 , -CONHR3, -S〇2NHR3, tetrazol-5-yl, 5-oxy-; i, 2,4-oxadiazol-3-yl, or 5-oxy-l,2,4-thiadiazole a -3-yl group (wherein R3 represents a hydrogen atom or a linear or branched carbon number of 1 to 6); and g represents a substituted or unsubstituted linear or branched chain of 1 to 3 carbon atoms; An alkyl group, which may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon group. Alkoxy groups of 1 to 6 (two alkoxy groups adjacent to the substituent ' may also form an acetal bond), trihalomethyl, trihalomethoxy, phenyl, or oxy; -60- 200916098 Μ represents a single key or -S(〇)m-, „! is 0~2 ; J represents a substituted or unsubstituted (heteroaryl group having 4 or more carbon atoms selected from a hetero atom selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom in the ring) The substituent having a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 (as a substituent, the adjacent two oxime groups may also form an acid-reducing bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms A sulfonyl, linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched decylamino group having 1 to 6 carbon atoms, a substituted or unsubstituted anthranilyl group, a trihalogen a methyl group, a trihalomethoxy group, a phenyl 'oxy group, a COOR3 group, or a phenoxy group which may be substituted by one or more halogen atoms, and these substituents may be one or more at any position of the ring. Each is independently substituted; X is -CH = or a nitrogen atom; γ is a nitrogen atom. 1 2. A prophylactic or therapeutic agent for gout, hyperuricemia, or a uric acid-related disease as claimed in claim 11 A 33⁄4 aromatic ring derivative represented by the formula (丨), wherein R1 and R2 represent a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently, and A is a substituted or unsubstituted linear ring having a carbon number of 3 to 5. Or a branched alkyl group; E is _c〇〇R3 (wherein R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); G represents a methyl group, and Μ represents -S - ; J Daishou and /4^ » , π-substituted or unsubstituted benzothiophene or oxime-methyl thiol, the heterocyclic aryl group of the j may have a substituent of halogen Mercapto, triatomic, linear or branched carbon number 1~ or oxy; X is -CH=; Υ is a nitrogen atom. Pre-requisites in any of the items 1 to 13. If the scope of application for patents is 9 to -61 - 200916098, the uric acid-related diseases are gout arthritis, gout nodules, urinary calculi, kidney stones, Kidney disorder, gout kidney, cardiovascular disease, or cerebrovascular disease. A prophylactic or therapeutic agent for heart disease accompanied by gout or hyperuricemia, which is characterized by containing a nitrogen-containing aromatic ring derivative represented by the formula (I) or a salt thereof as an active ingredient. [In the formula (I), R and R2 represent a hydrogen atom at the same or each independently, a halogen atom, a trihalomethyl 'cyano group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having a carbon number of 丨4. Or when R1 and R2 are linked to O-CHyO·, _〇_CH2_CH2-〇- or -CHvCHkCHkCR1 and R2 are bonded, the carbon atom may be substituted by one or more alkyl groups having 1 to 4 carbon atoms. A represents a single bond, a substituted or unsubstituted, straight-chain, branched or cyclic alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted carbon number 6 to 1 1 exoaryl group, or a substituted Or a heterocyclic aryl group having 4 to 10 carbon atoms which has one or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom in the ring. {As a substituent of A, such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon number i - 62 - 200916098 1-6 alkoxy group (as a substituent, adjacent The two alkoxy groups may also form an acetal bond, a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, Straight or branched carbon number 1 ~ 6 a mercapto group, a linear or branched carbon group having a carbon number of 丨~6, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, or a halogen atom may be substituted by one or more halogen atoms. a phenoxy group, which may be independently substituted in one or a plurality of positions at any position of the ring or alkylene group; E represents COOR3, S03R3, CONHR3, s〇2NHR3, tetrazolyl, 5-oxy- 1,2,4-oxadiazolyl, or 5-oxythiadiazolyl (R3 represents a hydrogen atom or a linear or branched alkyl group having a carbon number of 丨~6); G represents a substituted or unsubstituted The linear or branched chain of the carbon number 〖~6 may also contain one or a plurality of 0, S, s 〇 2, NR3 {R3 is the same as defined above, as a substitute for G Such as: a halogen atom, a thiol group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent) , the adjacent two alkoxy groups may also form an acetal bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy}; Μ represents a single bond, or _s(〇)m-,m Is an integer of 〇~2; J represents when m is 〇, and a is a substituted or unsubstituted linear, branched or cyclic alkyl group having a carbon number of 丨6, representing a substituted or unsubstituted linear, cyclic or branched alkane having 3 to 6 carbon atoms. a substituted or unsubstituted aryl group having 7 to 11 carbon atoms, or a substituted or unsubstituted carbon number of 4 or more hetero atoms in the ring which are grouped from an oxygen atom, a nitrogen atom, and a sulfur atom. ～1 杂 heteroaryl, -63 - 200916098 J represents m is 〇 and a is a substituted or unsubstituted carbon number 6 to 11 of an extended aryl group or a substituted or unsubstituted ring having at least one selected from the ring When the hetero atom of the oxygen atom, the nitrogen atom and the sulfur atom is in the group of 4 to 10, the heteroaryl group represents a linear, cyclic or branched bond having a substituted or unsubstituted carbon number of 1 to 6. a carbon number of a hetero group having one or more oxygen atoms, nitrogen atoms, and sulfur atoms in a ring having a carbon number of 6 to 6 or a substituted or unsubstituted ring a heteroaryl group of ~1〇, J is a single bond, „1 is 〇 and a is a single bond, or „^ is 丨 or 2' represents a substituted or unsubstituted straight chain or ring having a carbon number of 1 to 6. shape Or a branched or branched unsubstituted or unsubstituted aryl group having 6 to η carbon atoms, or a substituted or unsubstituted ring having one or more hetero atoms selected from the group consisting of an oxygen atom and a nitrogen atom and a sulfur atom. a heteroaryl group having a carbon number of 4 to 1 Å, {as a substituent of J, such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, and a straight a chain or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, an adjacent alkoxy group may also form an acetal bond), a linear or branched alkane sulfur having a carbon number of 1 to 6 a linear, branched or branched alkylsulfonyl group having 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 a mercaptoamino group, a substituted or unsubstituted anthranilyl group, a trihalomethyl 'trihalomethoxy group, a phenyl 'oxy group, a COOR3 group (R3 is the same as defined above for R3), or may be 1 More than one phenoxy group substituted with a phenoxy group, these may also be independently substituted at one or a plurality of positions at any position of the ring or alkyl group}; X represents -CH= or a nitrogen atom; -64-200916098 Y represents - CB = or nitrogen atom; B B1 represents a single bond or a linear or branched alkyl group having 1 to 3 carbon atoms; B2 represents a single bond, -CO- or -NR3- (wherein R3 is the same as defined above for R3) B3 represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxyl group, a sulfonyl group, a substituted or unsubstituted linear or branched alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted linear chain; Or a branched alkoxy group having 1 to 6 carbon atoms, a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, substituted or unsubstituted, having at least one selected from the group consisting of an oxygen atom and a nitrogen atom; a hetero atom of a hetero atom of a group of sulfur atoms 4 to 10, a heteroaryl group, a substituted or unsubstituted amino group, a substituted or unsubstituted residue, a substituted or unsubstituted linear or branched carbon number a sulfonyl group of 1 to 6 or a substituted or unsubstituted phenylsulfonyl group, a substituted or unsubstituted linear or branched alkylaminoalkylsulfonyl group having 1 to 6 carbon atoms, substituted or unsubstituted a substituted linear or branched decyl group having 1 to 8 carbon atoms, a substituted or unsubstituted linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a substituted or unsubstituted phenylcarbonyl group, Carbon number 1 a linear or branched alkylthio-bis-dentate methyl or trihalomethoxy group of 6 (as a substituent of B3 such as a halogen atom, a hydroxyl group, an amine group, a carboxyl group, a nitro group, a cyano group, or a straight a chain or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (the two alkoxy groups adjacent to the substituent ' may form an acetal bond) , tris-methyl or trihalomethoxy, these may be independently substituted at one or a plurality of positions at any position}; 2 represents a carbon atom or a nitrogen atom; -65- 200916098 Q represents a carbon atom or nitrogen atom]. 1 5 . A prophylactic or therapeutic agent for heart disease associated with gout or hyperuricemia according to item 4 of the scope of the patent application, wherein the nitrogen-containing aromatic 5 sing derivative represented by the formula (Z) R2 represents a hydrogen atom, a methyl group or a halogen atom which are simultaneously or independently independent; A is a single bond or a substituted or unsubstituted linear, cyclic or branch-shaped pendant group having a carbon number of 1 to 5; E is _ C〇〇r3, _s〇3r3, _c〇NHR3, -SC^NHR, tetrazole·5-yl, 5-oxy-indole, 2,4·oxadiazole-3-yl, or 5-oxy- 1,2,4-thiadiazolyl (wherein r3 represents a hydrogen atom or a linear or branched carbon number of 1 to 6); G represents a substituted or unsubstituted carbon number of 1 to 3 Or a branched chain of a pendant alkyl group which may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, and a linear chain. Or a branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two adjacent oxime groups may form an acetal bond), a trihalomethyl group, a trihalogen methoxy group, a phenyl group, or an oxygen group. Base; Μ represents a single bond or - S(0)m-, m is an integer from 0 to 2; a substituted or unsubstituted (heteroaryl or naphthyl group having 4 to 10 carbon atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a hetero atom in a group of sulfur atoms), the heteroaryl group of the j Or a naphthyl group may have a substituent of a national atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon number of ι~6, a linear or branched carbon number of 1 to 6 The alkoxy group (the two alkoxy groups adjacent to the substituent ' may also form an acetal bond), the linear or branched form of the alkylthio group having a carbon number of 1 to 6, a linear or branched carbon number! ～6的院基-66 - 200916098 Sulfhydryl, linear or branched carbon group 1 to 6 fluorenyl, linear or branched carbon number 1 to 6 decylamino group, substituted or not a substituted phenoxy group, a trihalomethyl group, a trihalomethoxy group, a phenyl group, an oxy group, a C〇〇r3 group, or a phenoxy group which may be substituted by one or more halogen atoms, and such substituents are also substituted Any one or a plurality of substituents may be independently substituted at any position of the ring; X is -CH = or a nitrogen atom; Y is -CB = or a nitrogen atom; B is represented by -B 1 - B 2 - B3; B1 Represents a single bond or a linear or branched carbon number of 1 to 3. B2 represents a single bond, -CO- or -NR3-; B3 represents a hydrogen atom, a halogen atom, a hydroxyl group, a sulfonyl group, a substitution or Unsubstituted linear or branched carbon number 1 to 6, substituted or unsubstituted linear or branched alkoxy group having 1 to 6 carbon atoms' substituted or unsubstituted carbon number 6~ An aryl group, a substituted or unsubstituted amino group, a substituted or unsubstituted carboxy group, a substituted or unsubstituted linear or branched carbon group having 1 to 6 carbon atoms, substituted or unsubstituted Phenylsulfonyl, substituted or Unsubstituted linear or branched amino group 1 to 6 aminoalkylsulfonyl, substituted or unsubstituted linear or branched carbon number i~8 fluorenyl, substituted or unsubstituted a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms or a substituted or unsubstituted phenylcarbonyl group; a substituent of B3 such as a halogen atom, a hydroxyl group, a linear or branched carbon number of 1 to 6 The alkyl group, the amine group or the carboxyl group may be independently substituted at one or a plurality of positions at any position}; Z is a carbon atom: Q is a nitrogen atom. -67- 200916098 16. A prophylactic or therapeutic agent for heart disease associated with gout or hyperuricemia according to claim 15 wherein R and R2 of the nitrogen-containing aromatic ring derivative represented by formula (I) Representing a hydrogen atom, a methyl group, or a halogen atom which are simultaneously or independently independent; A is a substituted or unsubstituted linear, cyclic, or branched alkyl group having 1 to 5 carbon atoms; E is -COOR3, - S03R3, -CONHR3, -S02NHR3, tetrazol-5-yl, 5-methoxy-oxime, methylene-3-yl, or 5-oxy-1,2,4-thiadiin-3-yl (where R3 represents a chlorine atom or a linear or branched alkyl group having 1 to 6 carbon atoms; and 0 represents a substituted or unsubstituted linear or branched alkyl group having 1 to 3 carbon atoms, and the extension of G The substituents which the substituent may have are a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, and a linear or branched carbon number of 1 to 6 a group (the two substituents adjacent to the substituent ' may also form an acid reduction bond), a trihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxy group; Μ represents a single bond or -S(0)m- m is an integer of 0 to 2; J is substituted or unsubstituted ( The ring has at least one heteroaryl group having 4 to 10 carbon atoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a hetero atom in a group of sulfur atoms, and the heteroaryl group of the J may have a substituent of a halogen atom. a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (substituent, 2 alkane adjacent thereto) The oxy group may also form an acetal bond, a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 or a linear or branched chain. A chain of 1 to 6 carbon atoms, a linear or branched carbon group having 1 to 6 carbon atoms, a substituted or unsubstituted anthranilyl group, a trihalomethyl group, a trihalomethoxy group , phenyl, oxy, (: OOR3 group ' or phenoxy-68-200916098 base which may also be substituted by one or more halogen atoms' may also be one or more at any position of the ring Each of them independently replaces 'X is _CH= or a nitrogen atom; γ is a nitrogen atom. 1 7 · A prophylactic or therapeutic agent for heart disease associated with gout or hyperuricemia according to claim 16 of the patent application, wherein (I) The nitrogen-containing aromatic ring derivative shown has R1 and R2 representing a simultaneous or independent hydrogen atom, a methyl group or a halogen atom; and A is a substituted or unsubstituted linear, cyclic or branched carbon number of 3 to 5. The alkyl group; E is -COOR3 (wherein R3 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms); G represents a methylene group; Μ represents -S-; J represents a substitution Or an unsubstituted benzothiophene group or a fluorenyl-methyl hydrazide group. The heteroaryl group of the J may have a halogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms, Trihalomethyl or oxy; X is -CH=; Υ is a nitrogen atom. 1 8 The pharmaceutical agent according to any one of claims 1 to 7 wherein the heart disease is cardiac hypertrophy, heart failure, or myocardial infarction. A preventive or therapeutic agent for kidney disease associated with gout or hyperuricemia, which comprises a nitrogen-containing aromatic ring derivative represented by formula (I) or a salt thereof as an active ingredient. [Formula (I)-69-200916098 R1 and R2 represent a hydrogen atom, a halogen atom, a trihalomethyl group, a cyano group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms or a carbon number of 1 to 4, which are simultaneously or independently. Alkoxy, or R1 and R2 are _〇_CH2_〇_, _〇_Ch2_Ch2_〇- or - CHyCHs-CHa-Cn1 and r2 are connected, the carbon atom may also be one or more carbons Substituted by the number 1~4 of the hospital base); A is a single bond, substituted or unsubstituted carbon number 1 to 6 linear, branched, or cyclic alkyl, substituted or unsubstituted carbon number 6 a heterocyclic aryl group having a carbon number of 4 to 10 which is a hetero atom having at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, which is substituted or unsubstituted on the ring. The substituent of A is: a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 (The two alkoxy groups adjacent to the substituent ' may also form a polyamide bond), a linear or branched alkylthio group having 1 to 6 carbon atoms, or a linear or branched carbon number of 1 to 6 Alkylsulfonyl, linear or branched carbon number a hexyl, linear or branched carbon group having 1 to 6 carbon atoms, a trihalomethyl group, a trihalogen methoxy group, a phenyl group, an oxy group, or a halogen atom substituted by one or more halogen atoms It may also be a phenoxy group, which may be independently substituted by one or a plurality of whites at any position of the ring or alkylene group}; E represents _C〇〇R3, -S〇3R3, -CONHR3, -§ 〇2nhR3, tetrazolyl '5-oxy d, 2 〆-oxadiazolyl or oxy·1,2,4-thiadiazolyl (R represents a hydrogen atom or a linear or branched carbon number 1 ～6的院基); G represents a substituted or unsubstituted carbon number of 1 to 6 straight or branched chain of the base of the course 'can also contain one or a plurality of 0, S, sc> 2, nr3 { R3 is the same as defined in the above R3, and as a substituent of G, such as: halogen-70-200916098, hydroxyl, nitro, cyano, linear or branched carbon number] ~6 alkyl, straight a bond or a branched carbon oxime 6 (as a substituent, two adjacent oxy groups may form a waking bond), a tridentate methyl group, a tridentate methoxy group, a phenyl group, Or oxy}; Μ represents a single bond or _S(0)m_, m is an integer of 〇~2; J When m is 〇 and A is a substituted or unsubstituted carbon number of 〜6, which is a linear, branched, or cyclic extension, it represents a substituted or unsubstituted linear or cyclic carbon number of 3 to 6. a branched or branched alkyl group, a substituted or unsubstituted carbon number of 7 to 11 or a substituted or unsubstituted ring having at least one selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. a hetero atom having a carbon number of 4 to 1 Å, J is a aryl group and m is a substituted or unsubstituted carbon number of 6 to n, or a substituted or unsubstituted one or more of the ring. a heterocyclic aryl group having a carbon number of 4 to 1 Å selected from a hetero atom of a group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, and representing a substituted or unsubstituted linear, cyclic or branched carbon number of 1 to 6. a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, or a substituted or unsubstituted carbon having more than one hetero atom selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom in the ring. a heteroaryl group of 4 to 10, which has a linear bond, a cyclic or a carbon number of 1 to 6 when m is a single bond, m is 0, and A is a single bond, or m is 1 or 2. Branched courtyard a substituted or unsubstituted carbon number of 6 to 1 1 or a substituted or unsubstituted carbon number of 4 or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom in the ring. a heteroaryl group of 10, {a substituent of J' such as: a halogen atom, a hydroxyl group, a nitro group, -71 - 200916098 a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear chain Or a branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may also form an acetal bond), a linear or branched alkylthio group having 1 to 6 carbon atoms. a linear or branched alkyl sulfonyl group having 1 to 6 carbon atoms, a linear or branched fluorenyl group having 1 to 6 carbon atoms, a linear or branched carbon number of 1 to 6 Amino, substituted or unsubstituted anthranilyl, trihalomethyl, trihalomethoxy, phenyl, oxy, COOR3 (R3 is the same as defined above for R3)' or may be 1 The above phenoxy group substituted by a halogen atom may be independently substituted in one or a plurality of positions at any position of the ring or the alkyl group}; X represents -CH= or a nitrogen atom; Y represents -CB= or a nitrogen atom. ; B series with -B 1 - B 2 - B 3 is shown; B1 represents a single bond or a linear or branched alkyl group having 1 to 3 carbon atoms; B2 represents a single bond, _C〇^_N; R3_ (wherein R3 is the same as The above definition of R3); B3 represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxyl group, a sulfonyl group, a substituted or unsubstituted linear or branched alkyl group having 1 to 6 carbon atoms, substituted or not. a substituted linear or branched alkoxy group having 1 to 6 carbon atoms, a substituted or unsubstituted aryl group having 6 to 11 carbon atoms, or a substituted or unsubstituted ring having at least one selected from the group consisting of oxygen atoms and nitrogen a hetero atom having a carbon atom number of 4 to 10, a substituted or unsubstituted amino group, a substituted or unsubstituted thiol group, a substituted or unsubstituted linear or branched chain. Carbon number 1 to 6 tk acid group, substituted or unsubstituted phenylsulfonyl group, substituted or unsubstituted -72-200916098 instead of linear or branched amino group alkyl sulfonate having 1 to 6 carbon number A linear or branched, linear or branched, decyl group having 1 to 8 carbon atoms, substituted or #substituted linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, substituted or Unsubstituted phenyl carbonyl a linear or branched alkylthio group having a carbon number of 1 to 6, a trihalomethyl group, or a trihalomethoxy group {B3 substituent such as a halogen atom, a thiol group, a fee group, a residue, a nitro group a cyano group having a carbon number of 1 to 6 and an alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may form an acetal bond), a trihalomethyl group, or a trihalogen. A methoxy group, which may be independently substituted at one or a plurality of positions at any position}; Z represents a carbon atom or a nitrogen atom; Q represents a carbon atom or a nitrogen atom]. 2. A prophylactic or therapeutic agent for kidney disease associated with gout or hyperuricemia according to claim 19, wherein the nitrogen-containing aromatic ring derivative represented by formula (I) and R2 represent simultaneous or respective a separate hydrogen atom, a methyl group or a halogen atom; a linear or cyclic chain of 1 to 5, -S03R3, -CONHR3 A is a single bond or a substituted or unsubstituted carbon number, or a branched alkyl group; _C〇〇R3, _S02NHR3, tetrazole-5_ 或, 基5_兴基·1,2,4-oxadiazole_3_yl, or 5-oxy-1,2,4-thiadiazole_ 3_ (Glycine (/, R in R represents a hydrogen atom or a linear or branched carbon number of 1 to 6). G represents a substituted or unsubstituted carbon number alkyl group, and the G extension The alkyl group may have a linear or branched substituent of 1 to 3 such as a halogen atom, a hydroxyl group, a nitro group, a cyano group, a chain or a branched carbon number, or a linear or branched carbon number of 1 to 1 6 1 to 6 alkoxy group (alkyl as a substituent, straight, adjacent 2 - 73 - 200916098 alkoxy groups may also form an acetal bond), trisocene methyl, trihalomethoxy, benzene Base, or oxy; Μ represents a single bond Or - S(0)m_; m is an integer of 0 to 2; J represents a substituted or unsubstituted carbon number of 4 or more hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom ～10 heteroaryl or naphthyl), the heteroaryl or naphthyl group of J may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, a linear or branched carbon number of 1 to 6 Alkyl, linear or branched alkoxy group having 1 to 6 carbon atoms (substituent, two alkoxy groups adjacent thereto may also form an acetal bond), linear or branched carbon number 1 to 6 Alkylthio group, linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, linear or branched carbon group having 1 to 6 carbon atoms, linear or branched carbon number 1 ～6-decylamino, substituted or unsubstituted hydrazino, trihalomethyl, trihalomethoxy, phenyl 'oxy, COOR3 group, or substituted by more than j halogen atoms a phenoxy group, these substituents may also be independently substituted at one or a plurality of positions at any position of the ring; X is -CH = or a nitrogen atom; Y is -CB = or a nitrogen atom B is - Β^Ι^- Β3 shows; the alkyl group; B1 represents a single bond A straight or branched carbon number 1 to B2 represents a single bond, -CO- or -NR3.; an aryl group having 6 to 11 carbon atoms, a substituted or unsubstituted amino group, and B3 represents a hydrogen atom, a halogen atom, or a hydroxyl group. a sulfonyl group, a substituted or unsubstituted linear or branched bond having a carbon number of 丨~6, a substituted or unsubstituted linear or branched alkoxy group having 1 to 6 carbon atoms, substituted or Unsubstituted or unsubstituted -74 - 200916098 carboxy, substituted or unsubstituted linear or branched carbyl sulfonyl, substituted or unsubstituted phenyl sulfonyl, substituted straight or branched a linear or branched carbon group having a carbon number of from 1 to 6 in the form of a straight or branched chain having a carbon number of from 1 to 6 and a linear or branched alkoxy group having a carbon number of from 1 to 6 a carbonyl group or a phenyl fluorenyl group. {As a substituent of B3, for example, a straight or branched alkyl group having 1 to 6 carbon atoms, an amine group or a carboxyl group may have one or a plurality of positions. Independently substituted}; Z is a carbon atom; Q is a nitrogen atom. 2 1. A prophylactic or therapeutic agent for kidney disease associated with gout, as claimed in claim 20, wherein the nitrogen atomic aromatic derivative has R1 and R2 representing simultaneously or each independently, a methyl group or a halogen atom. A is a substituted or unsubstituted carbon number chain, a cyclic 'or branched alkyl group; E is -COOR3, CONHR3, -S02NHR3, tetrazol-5-yl, 5-oxy-1,2〆 Or a 5-oxy-1,2,4-thiadiazol-3-yl group (wherein R3. or a linear or branched alkyl group having 1 to 6 carbon atoms); a linear or branched alkyl group of 1 to 3, which may have a substituent of a halogen atom, a hydroxyl group, a nitro group, or a cyanogen: a branched alkyl group having 1 to 6 carbon atoms, a straight chain or a branched chain a carbon-like oxy group (as a substituent, two adjacent oximes may be), a dihalomethyl group, a trihalomethoxy group, a phenyl group, or an oxygen single bond or -S(〇)m-; m An integer of 〇~2; J represents an alkane of 1 to 6 or an unsubstituted, substituted or unsubstituted or unsubstituted or unsubstituted, hydroxy, phenyl group, such as any or high uric acid) The hydrogen atom 1~5 is straight S 〇3 R3 ^ . 〖-oxadiazole _ 3 - represents a hydrogen atom table substituted or absent; G alkyl group, linear or number 1~6 forming acetal bond S; Μ represents or unsubstituted -75- 200916098 (the ring has more than one selected from oxygen a hetero atom having 4 to 10 carbon atoms in a hetero atom of a group of atoms, a nitrogen atom, and a sulfur atom, and the heteroaryl group of the j may have a substituent of a halogen atom, a hydroxyl group, a nitro group, a cyano group, or a straight a chain or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms (as a substituent, two alkoxy groups adjacent thereto may form an acetal bond) a linear or branched alkylthio group having 1 to 6 carbon atoms, a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, or a linear or branched carbon number of 1 to 6 Mercapto, linear or branched decylamino group having 1 to 6 carbon atoms, substituted or unsubstituted anthranilyl group, trihalomethyl group, trihalomethoxy group, phenyl group, oxy group, COOR3 group Or a phenoxy group which may be substituted by one or more halogen atoms. 'The substituents may also be independently substituted at one or a plurality of positions at any position of the ring, 'X is -CH= or a nitrogen atom, and γ is a nitrogen. atom. 22. The prophylactic or therapeutic agent for kidney disease associated with gout or hyperuricemia according to the second aspect of the patent application, wherein the nitrogen-containing aromatic ring derivative represented by the formula has R1 and R2 representing simultaneous or independent a hydrogen atom, a methyl group or a halogen atom; A is a substituted or unsubstituted direct bond group having a carbon number of 3 to 5, a cyclic or a bond; E is -CO〇R3 (preferably, R3 represents hydrogen) Atom or a linear or branched carbon number of 1 to 6; G represents a methylene group; Μ represents -S-: J represents a substituted or unsubstituted benzothiophene or fluorene-methyl hydrazine. The heteroaryl group of the J may have a halogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms, a trihalomethyl group, or an oxy group; X is -CH=; atom. 2 3 · The agent according to any one of the claims 9-9 to 2, wherein the kidney disease is diabetic nephropathy, renal failure, kidney disease or nephritis-76-200916098 24. A 4- (1) -((4-Methoxy-1-oxybenzothiophen-3-yl)methyl)benzimidazole-2-thio)butanoic acid or a salt thereof. -77-