Plasminogen Activator Inhibitor-1 Inhibitor

FIELD OF INVENTION

The present invention relates to 5-membered heterocyclic derivatives which are useful as plasminogen activator inhibitor-1 (hereinafter referred to as PAI-1) inhibitors.

BACKGROUND ART

Blood coagulation system consists of a cascade reaction which comprises numbers of combinations of various kinds of proteases and precursors (substrates) thereof, and is regulated mainly depending upon blood endothelial cells. When the blood endothelial cells are disordered to collapse cascade regulation of the blood coagulation, a thrombotic tendency is increased to lead to stenosis or occlusion of blood vessels. The thrombus is a blood component which is coagulated intravascularly, and examples of the component thereof include fibrin, platelet, erythrocyte, leukocyte and the like.

Fibrinolytic system is a rather simple system as compared with the blood coagulation system. However, factors related to the fibrinolytic system are deeply related not only to an intravascular dissolution of thrombus but also to various reactions, which occur in tissues, such as movement or migration of cell; ovulation; cell proliferation; angiogenesis; reconstruction (remodeling) of tissue; inflammatory response and the like. The fibrinolytic system is driven by serine proteases. The plasminogen is converted into plasmin by a plasminogen activator (hereinafter referred to as PA); a tissue-type plasminogen activator (hereinafter referred to as tPA); or a urokinase-type plasminogen activator (hereinafter referred to as uPA), and the resulting plasmin degrades a fibrin thrombus and tissue protein. The fibrinolytic reaction is regulated and modulated by a plasminogen activator inhibitor-1 (PAI-1), a specific inhibitory protein against plasminogen activator existing in vivo. PAI-1 forms a complex with PA in a ratio of one to one to inhibit actions thereof. PAI-1 released from an activated platelet binds to fibrin to exist around the fibrin in a concentrated form, especially at the site of thrombogenesis, and inhibits an activity of tPA effectively. Furthermore, PAI-1 prompts hyperplasia of vascular wall to promote progress of cardiovascular lesion caused by inhibiting degradation of extracellular matrix by a protease. An activity of the fibrinolytic system is regulated by a balance between PA and PAI-1. Therefore, an increase or a decrease of production of PAI-1 in cells or a variation of an activity of PAI-1 molecule is reflected immediately in the activity of the fibrinolytic system in blood. Accordingly, a therapeutic effect for thrombotic diseases is expected by inhibiting PAI-1 activity followed by promoting the activation of PA.

PAI-1 binds to vitronectin which is a cell adhesion molecule to inhibit adhesion of cells to the extracellular matrix. Therefore, a therapeutic effect for diseases caused by movement or migration of cell is also expected. Furthermore, plasmin which is indirectly activated by an inhibition of PAI-1 relates to an activation of transforming growth factor which is a cell proliferation inhibitory cytokine or to an activation of collagenase. Therefore, a therapeutic effect for diseases caused by cell proliferation, angiogenesis, and remodeling of tissue is also expected.

It has been reported that an expression of PAI-1 is increased at the lesion of arteriosclerosis to increase risks of thrombotic diseases such as myocardial infarction, deep vein thrombosis, sepsis, disseminated intravascular coagulation and the like (see, “Proceeding of the National Academy of Sciences of the United States of America,” (USA), 1992, Vol. 89, No. 15, p. 6998-7002), and a PAI-1 transgenic mouse shows a thrombogenic tendency (refer to “Nature,” (England), 1990, Vol. 346, No. 6279, p. 74-76).

It has been reported that a mouse model of obesity shows a significantly higher blood level of PAI-1, and it has further been reported that PAI-1 is synthesized not only in endothelial tissues and hepatic tissues but also in adipose tissues, and an amount of synthesized PAI-1 is rapidly increased, especially in visceral fat (see, “Molecular Medicine,” (USA), 1996, Vol. 2, No. 5, p. 568-582). Furthermore, it has been reported that a PAI-1 gene knock out mouse model of obesity shows a decrease of body weight, and a lowering of blood levels of glucose and insulin (see, “The FASEB Journal,” (USA), 2001, Vol. 15, No. 10, p. 1840-1842), therefore, these results suggest a possibility that PAI-1 aggravates various symptoms caused by an accumulation of fats. It has been reported that PAI-1 exists specifically in cancerous tissues to be involved in regulation of physiological function of cancer cells, and a PAI-1 antibody inhibits metastasis of cancer in a cancer model (refer to “General & Diagnostic Pathology,” (Germany), 1995, Vol. 141, No. 1, p. 41-48). It has also been reported that, when a transplantation of malignant keratinocytes into PAI-1 knock out mouse is carried out, invasion of cancer and angiogenesis are inhibited (refer to “Nature Medicine,” (USA), 1998, Vol. 4, No. 8, p. 923-928).

Furthermore, it has been reported that PAI-1 is secreted from mast cell (see, “The Journal of Immunology,” (USA), 2000, Vol. 165, No. 6, p. 3154-3161), and an accumulation of extracellular matrix in an airway of a mouse model of asthma is alleviated by PAI-1 knockout (see, “Biochemical and Biophysical Research Communications,” (USA), 2002, Vol. 294, No. 5, p. 1155-1160).

An arterial lesion as an acute or a chronic rejection after cardiac or renal transplantation is thought to be caused by progressions such as progression of fibrogenesis of tissue, progression of thrombogenesis, progression of proliferation and remodeling of arterial endothelial cell. In experiments of murine cardiac transplantation, when the compound of compound No. 10 described in the present specification was administered, a graft survival was significantly prolonged (control group: 7.2±0.2 days; compound administered group: 9.0±0.7 days (p<0.05)) and an incidence of vascular intimal thickening was decreased to about one third (control group: 64.5±5.8%; compound administered group: 21.7±4.9% (p<0.05)) in comparison with control group. Accordingly, the compounds that can inhibit PAI-1 are considered to have inhibitory effects against acute rejections and arterial lesions after organ transplantation such as cardiac transplantation, renal transplantation or the like.

Therefore, compounds having specific inhibitory activity against PAI-1 are expected to be agents useful for diseases caused by thrombogenesis, fibrogenesis, accumulation of visceral fat, cell proliferation, angiogenesis, deposition and remodeling of extracellular matrix, and cell movement and migration.

An anthranilic acid derivative AR-H029953XX (see, “Biochemistry,” (USA), 1998, Vol. 37, No. 5, p. 1227-1234); diketopiperazine derivatives (see, the pamphlets of International Patent Publication WO95/32190 and International Patent Publication WO95/21832, and the specification of British Patent Application No. 2372740); indoleacetic acid derivatives (see, the pamphlet of International Patent Publication WO03/000253); aryloxyacetic acid derivatives (see, the pamphlet of International Patent Publication WO03/000258); naphthyloxyacetic acid derivatives (see, the pamphlet of International Patent Publication WO03/000649); naphthylbenzofuran derivatives (see, the pamphlet of International Patent Publication WO03/000671); naphthylindole derivatives (see, the pamphlet of International Patent Publication WO03/000684) and the like are known as the compounds having inhibitory activity against PAI-1.

As the thrombolytic agents clinically used at present, plasminogen activator enzymatic preparation such as tPA, uPA, streptokinase, single-stranded uPA, mutated tPA obtained by modification of the amino acid sequence of tPA and the like are known. However, these agents have serious problems in that route of administration of these agents is either intra-coronary arterial or intravenous injection, and no orally administrable preparations has been provided, these agents have a short half life in blood, and these agents increases a risk of bleeding at the sites other than the thrombotic site, for example, in brain, by an administration thereof.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a low molecular compound which is useful for preventive and/or therapeutic treatment of diseases with stenosis or occlusion caused by thrombus.

Another object of the present invention is to provide an antithrombotic compound with few hemorrhagic diatheses by selective inhibition of PAI-1 which is highly expressed in local lesions and a following indirect activation of PA.

Further object of the present invention is to provide a medicament which is provided in the form of injections as well as in a form of preparation depending on a target disease and a purpose of application by using the low molecular compound which inhibits PAI-1.

Still further object of the present invention is to provide low molecular compounds which are useful for preventive and/or therapeutic treatment of other diseases caused by an expression of PAI-1, an enhancement of PAI-1 activity, or a lowering of plasmin activity, for example, diseases caused by fibrogenesis, accumulation of visceral fat, cell proliferation, angiogenesis, deposition or remodeling of extracellular matrix, and cell movement and migration.

The present invention provides novel 5-membered heterocyclic derivatives to solve those objects.

The inventors of the present invention conducted searches for low molecular compounds having inhibitory activity against PAI-1 by using computerized molecular design technology to solve the aforementioned objects. For a three-dimensional structure of an activated form of PAI-1 registered in PDB (Protein Data Bank), binding sites thereof and binding modes of a known PAI-1 inhibitor AR-H029953XX were estimated, and homology modeling of a tree-dimensional structure of PAI-1, which can be bound stably with AR-H029953XX, was carried out. For the obtained ligand-binding type structure of PAI-1, an automatic search program of a three-dimensional low molecular compound database, based on the three-dimensional structure of the protein, was carried out, and compounds potentially be PAI-1 inhibitors were selected by a virtual screening out of compounds registered in a database of compounds commercially available from Sigma-Aldrich, Aldrich, Maybridge, Specs, Bionet, Labotest, Lancaster, Tocros, Tokyo Kasei Kogyo, Wako Pure Chemical Industries and the like, and registered in the compounds that were synthesized originally by the inventors of the present invention. PAI-1 inhibitory activities of these compounds were confirmed by a comparison of a tPA activity in the co-presence of the test compound and PAI-1, with a tPA activity in the presence of PAI-1. As for the compounds confirmed to have PAI-1 inhibitory activity, binding mode thereof to PAI-1 and interactions were analyzed. On the basis of these results, the present invention was achieved by further carrying out syntheses of analogous compounds and tests for confirmation of activities thereof.

The present invention thus provides:

(1) a medicament having inhibitory activity against plasminogen activator inhibitor-1, which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof:

wherein R¹represents an aromatic group which may be substituted,

R²represents an aromatic group which may be substituted,

W represents a group selected from the following connecting group W-1:

[Connecting Group W-1]

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom,

X represents sulfur atom or NH,

Y represents oxygen atom or sulfur atom,

R³represents a hydrocarbon group which may be substituted, hydroxy group which may be substituted, or carboxy group which may be esterified),

Z represents a single bond or a connecting group wherein a number of atoms in a main chain is 1 to 3 (said connecting group may be substituted).

According to preferred embodiments of the present invention, provided are:

(2) the medicament according to the aforementioned (1), wherein R¹is an aromatic group which may be substituted,

R²is an aromatic group which may be substituted,

W is a group represented by the following formula:

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom,

X represents sulfur atom or NH,

Y represents oxygen atom or sulfur atom),

Z is a single bond, methylene group, ethylene group, —CH₂CO— group, or —CH₂CONH— group;

(3) the medicament according to the aforementioned (2), wherein R¹is an aromatic group which may be substituted,

R²is an aromatic group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group;

(4) the medicament according to the aforementioned (3), wherein R¹is a phenyl group which is substituted with one to three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²is an aromatic group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group;

(5) the medicament according to the aforementioned (4), wherein R¹is a phenyl group which is substituted with two or three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²is a phenyl group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group;

(6) the medicament according to the aforementioned (5), wherein the compound represented by the general formula (I) is a compound selected from the following 14 compounds:

the compound wherein R¹is 3,4,5-trihydroxyphenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 2,3-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 2,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 3,4-dihydroxyphenyl group, R²is 2,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-bromophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-(trifluoromethyl)phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-styrylphenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 3,4-dihydroxyphenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is sulfur atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-[(3-phenoxyphenyl)acetylamino]phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-(4-phenoxybenzoylamino)phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-[3,5-bis(trifluoromethyl)phenylacetylamino]phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 3-[(3-phenoxyphenyl)acetylamino]phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 3,4-dihydroxy-5-nitrophenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is sulfur atom, Z is methylene group; and

the compound wherein R¹is 3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is sulfur atom, Z is methylene group;

(7) the medicament according to the aforementioned (3), wherein R¹is a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group), or a phenyl group which is substituted with a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the heteroaryl-substituted carbamoyl group),

R²is an aromatic group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group;

(8) the medicament according to the aforementioned (7), wherein R¹is a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group in the 3-position (said aryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group) or a phenyl group which is substituted with a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the heteroaryl-substituted carbamoyl group), and a phenyl group which is substituted with hydroxy group in the 4-position (said phenyl group may be substituted in the 5-position),

R²is a phenyl group which may be substituted,

X is sulfur atom,

Y is oxygen atom,

Z is methylene group;

(9) the medicament according to the aforementioned (8), wherein the compound represented by the general formula (I) is a compound selected from the following 11 compounds:

the compound wherein R¹is 3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²is 3,5-bis(trifluoromethyl)phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²is 4-(trifluoromethyl)phenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

- the compound wherein R¹is 4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group,

R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group; and

the compound wherein R¹is 3,4-dihydroxy-5-[3-(trifluoromethyl)phenylcarbamoyl]phenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

(10) the medicament according to the aforementioned (3), wherein R¹and R²are either the following (i) or (ii),

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group:

(i) R¹is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group), R²is an aromatic group which may be substituted;

(ii) R¹is an aromatic group which may be substituted,

R²is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group);

(11) the medicament according to the aforementioned (10), wherein the compound represented by the general formula (I) is a compound selected from the following 2 compounds:

the compound wherein R¹is 3-carboxyphenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group; and

the compound wherein R¹is 3-carboxy-4-hydroxyphenyl group, R²is 4-methoxycarbonylphenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

(12) the medicament according to the aforementioned (2), wherein the compound represented by the general formula (I) is a compound selected from the group consisting of the compounds described in the present specification as Compound Nos. 1 to 93 and Compound Nos. 301 to 475.

(13) the medicament according to the aforementioned (1), wherein R¹is an aromatic group which may be substituted,

R²is an aromatic group which may be substituted,

W is a group represented by the following formula:

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom,

R³represents a hydrocarbon group which may be substituted, hydroxy group which may be substituted, or carboxy group which may be esterified),

Z is a single bond or methylene group;

(14) the medicament according to the aforementioned (13), wherein R¹is an aromatic group which may be substituted,

R²is an aromatic group which may be substituted,

R³is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group,

Z is a single bond;

(15) the medicament according to the aforementioned (14), wherein R¹is a phenyl group which is substituted with one to three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²is an aromatic group which may be substituted,

R³is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group,

Z is a single bond;

(16) the medicament according to the aforementioned (15), wherein R¹is a phenyl group which is substituted with two or three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²is a phenyl group which may be substituted,

R³is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group,

Z is a single bond;

(17) the medicament according to the aforementioned (16), wherein the compound represented by the general formula (I) is a compound selected from the following 6 compounds:

the compound wherein R¹is 2,4,5-trihydroxyphenyl group, R²is 3,5-dichlorophenyl group, R³is phenyl group, Z is a single bond;

the compound wherein R¹is 2,4,5-trihydroxyphenyl group, R²is 3,4-dichlorophenyl group, R³is isopropyl group, Z is a single bond;

the compound wherein R¹is 2,4,5-trihydroxyphenyl group, R²is 4-nitrophenyl group, R³is ethoxy group, Z is a single bond;

the compound wherein R¹is 2,4,5-trihydroxyphenyl group, R²is 3,4-dichlorophenyl group, R³is methyl group, Z is a single bond;

the compound wherein R¹is 2,4,5-trihydroxyphenyl group, R²is 3,5-dichlorophenyl group, R³is isopropyl group, Z is a single bond; and

the compound wherein R¹is 2,4,5-trihydroxyphenyl group, R²is 3-chloro-4-fluorophenyl group, R³is isopropyl group, Z is a single bond;

(18) the medicament according to the aforementioned (14), wherein R¹is a phenyl group which is substituted with C₂-C₆alkenyl group which may be substituted (said phenyl group may further be substituted with one or more substituents other than the C₂-C₆alkenyl group),

R²is an aromatic group which may be substituted,

R³is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group,

Z is a single bond;

(19) the medicament according to the aforementioned (18), wherein the compound represented by the general formula (I) is a compound selected from the following 2 compounds:

the compound wherein R¹is 2-hydroxy-5-styrylphenyl group, R²is 4-nitrophenyl group, R³is ethoxy group, Z is a single bond; and

- the compound wherein R¹is 4-styrylphenyl group, R²is 4-carboxyphenyl group, R³is isopropyl group, Z is a single bond.
  
  (20) the medicament according to the aforementioned (14), wherein R¹, R²and R³are any one of the following (i) to (iii), Z is a single bond:
  
  (i) R¹is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group), R²is an aromatic group which may be substituted,
  
  R³is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group;
  
  (ii) R¹is an aromatic group which may be substituted,
  
  R²is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group),
  
  R³is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group;
  
  (iii) R¹is an aromatic group which may be substituted,
  
  R²is an aromatic group which may be substituted,
  
  R³is carboxy group;
  
  (21) the medicament according to the aforementioned (20), wherein the compound represented by the general formula (I) is a following compound:

the compound wherein R¹is 4-styrylphenyl group, R²is 4-carboxyphenyl group, R³is isopropyl group, Z is a single bond; and

(22) the medicament according to the aforementioned (13), wherein the compound represented by the general formula (I) is a compound selected from the group consisting of the compounds described in the present specification as Compound Nos. 101 to 224 and Compound Nos. 501 to 567.

Furthermore, according to preferred embodiments of the aforementioned invention, provided are the aforementioned medicament for therapeutic and/or preventive treatment of diseases caused by an expression of PAI-1 or an enhancement of PAI-1 activity; the aforementioned medicament for preventive and/or therapeutic treatment of diseases caused by one or more abnormal conditions selected from the group consisting of thrombogenesis, fibrogenesis, accumulation of visceral fat, cell proliferation, angiogenesis, deposition or remodeling of extracellular matrix, and cell movement or migration.

From another aspect, the present invention provides use of the substance selected from the group consisting of the compound represented by the aforementioned general formula (I) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof for manufacture of the aforementioned medicament; a PAI-1 inhibitor which comprises as an active ingredient a substance selected from the group consisting of the compound represented by the aforementioned general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof; a method for inhibiting PAI-1 in mammal including a human, which comprises the step of administering an effective amount of the substance selected from the group consisting of the compound represented by the aforementioned general formula (I) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof to a mammal including a human; a method for therapeutic and/or preventive treatment of diseases caused by an expression of PAI-1 or an enhancement of PAI-1 activity in mammal including a human, which comprises the step of administering a therapeutically and/or preventively effective amount of the substance selected from the group consisting of the compound represented by the aforementioned general formula (I) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof to a mammal including a human; and a method for preventive and/or therapeutic treatment of diseases caused by one or more abnormal conditions selected from the group consisting of thrombogenesis, fibrogenesis, accumulation of visceral fat, cell proliferation, angiogenesis, deposition or remodeling of extracellular matrix, and cell movement or migration in mammal including a human, which comprises the step of administering a therapeutically and/or preventively effective amount of the substance selected from the group consisting of the compound represented by the aforementioned general formula (I) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof to a mammal including a human.

From further another aspect, the present invention provides:

(25) a compound represented by the general formula (II) or a salt thereof, or a hydrate thereof or a solvate thereof as a novel compound:

wherein R¹⁰¹represents an aromatic group which may be substituted,

R²⁰¹represents an aromatic group which may be substituted,

W¹⁰¹represents a group selected from the following connecting group W-101-1:

[Connecting Group W-101-1]

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom,

X¹⁰¹represents sulfur atom or NH,

Y¹⁰¹represents oxygen atom or sulfur atom,

R³⁰¹represents a hydrocarbon group which may be substituted, hydroxy group which may be substituted, or carboxy group which may be esterified),

Z¹⁰¹represents a single bond or a connecting group wherein a number of atoms in a main chain is 1 to 3 (said connecting group may be substituted), provided that the following compounds are excluded:

the compound wherein R¹⁰¹is 3,5-dibromo-2-hydroxyphenyl group, R²⁰¹is phenyl group, W¹⁰¹is —X¹⁰¹—C(═Y¹⁰¹)—, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-carboxyphenyl)furan-2-yl group, R²⁰¹is 3-fluorophenyl group, W¹⁰¹is —X¹⁰¹—C(═Y¹⁰¹)—, X¹⁰¹is sulfur atom, Y¹⁰¹is sulfur atom, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 3,5-dibromo-2-hydroxyphenyl group, R²⁰¹is 4-chlorophenyl group, W¹⁰¹is —X¹⁰¹—C(═Y¹⁰¹)—, X¹⁰¹is NH, Y¹⁰¹is sulfur atom, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-carboxyphenyl)furan-2-yl group, R²⁰¹is 4-methoxyphenyl group, W¹⁰¹is —X¹⁰¹—C(═Y¹⁰¹)—, X¹⁰¹is sulfur atom, Y¹⁰¹is sulfur atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 5-chloro-2-hydroxyphenyl group, R²⁰¹is phenyl group, W¹⁰¹is —X¹⁰¹—C(═Y¹⁰¹)—, X¹⁰¹is sulfur atom, Y¹⁰¹is sulfur atom, Z¹⁰¹is a single bond;

- the compound wherein R¹⁰¹is 3,5-dibromo-2-hydroxyphenyl group, R²⁰¹is phenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is hydroxy group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-bromo-2-hydroxyphenyl group, R²⁰¹is 3,4-dichlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 3-ethoxy-4-{[(thiophen-2-yl)carbonyl]oxy}phenyl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-carboxymethoxy-3-ethoxyphenyl group, R²⁰¹is 3-(trifluoromethyl)phenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-[3-(methoxycarbonyl)phenyl]furan-2-yl group, R²⁰¹is 4-fluorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is hydroxy group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(4-carboxyphenyl)furan-2-yl group, R²⁰¹is 4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is hydroxy group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3,5-dichlorophenyl)furan-2-yl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is trifluoromethyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(5-carboxy-2-chlorophenyl)furan-2-yl group, R²⁰¹is phenyl group, W¹⁰⁰is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-bromophenyl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is trifluoromethyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(2-hydroxy-5-nitrophenyl)furan-2-yl group, R²⁰¹is 3-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is hydroxy group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-bromophenyl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰⁰is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-allyloxy-3-methoxyphenyl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-benzyloxy-3-methoxyphenyl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-chlorophenyl group, R²⁰¹is phenyl group, W¹⁰⁰is —C(R³⁰¹)═N—, R³⁰¹is carboxy group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is phenyl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 2-benzyloxy-5-bromophenyl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 4-(benzylcarbamoyl)methoxy-3-bromo-5-methoxyphenyl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is phenyl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is phenyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-chlorophenyl)furan-2-yl group, R²⁰¹is 4-sulfamoylphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-chloro-4-methylphenyl)furan-2-yl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(2-chlorophenyl)furan-2-yl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-[3-(methoxycarbonyl)phenyl]furan-2-yl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-chloro-2-methylphenyl)furan-2-yl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3,5-dichlorophenyl)furan-2-yl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-fluorophenyl)furan-2-yl group, R²⁰¹is 3-carboxy-4-chlorophenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 5-(3-nitrophenyl)furan-2-yl group, R²⁰¹is 3-carboxyphenyl group, W¹⁰⁰is —C(R³⁰¹)═N—, R³⁰¹is methyl group, Z¹⁰¹is a single bond; and

the compound wherein R¹⁰¹is 5-(5-carboxy-2-chlorophenyl)furan-2-yl group, R²⁰¹is 3-(trifluoromethyl)phenyl group, W¹⁰¹is —C(R³⁰¹)═N—, R³⁰¹is hydroxy group, Z¹⁰¹is a single bond.

According to preferred embodiments of the present invention, provided are:

(26) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹is a phenyl group which is substituted with one to three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²⁰¹is an aromatic group which may be substituted,

the compound wherein R¹⁰¹is 3,4,5-trihydroxyphenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 2,3-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 2,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 3,4-dihydroxyphenyl group, R²⁰¹is 2,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 4-bromophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 4-(trifluoromethyl)phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 4-styrylphenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 3,4-dihydroxyphenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is sulfur atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 4-[(3-phenoxyphenyl)acetylamino]phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 4-(4-phenoxybenzoylamino)phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 4-[3,5-bis(trifluoromethyl)phenylacetylamino]phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 2,3-dihydroxyphenyl group, R²⁰¹is 3-[(3-phenoxyphenyl)acetylamino]phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 3,4-dihydroxy-5-nitrophenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is sulfur atom, Z¹⁰¹is methylene group; and

the compound wherein R¹⁰¹is 3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is sulfur atom, Z¹⁰¹is methylene group;

(29) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹is a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group), or a phenyl group which is substituted with a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the heteroaryl-substituted carbamoyl group),

R²⁰¹is an aromatic group which may be substituted,

W¹⁰¹is a group represented by the following formula:

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom,

X¹⁰¹represents sulfur atom,

Y¹⁰¹represents oxygen atom or sulfur atom),

Z¹⁰¹is methylene group;

(30) the compound according to the aforementioned (29) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹is a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group in the 3-position (said aryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group) or a phenyl group which is substituted with a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group), and a phenyl group which is substituted with hydroxy group in the 4-position (said phenyl group may be substituted in the 5-position),

R²⁰¹is a phenyl group which may be substituted,

X¹⁰¹is sulfur atom,

Y¹⁰¹is oxygen atom,

Z¹⁰¹is methylene group;

(31) the compound according to the aforementioned (30) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein the compound represented by the general formula (II) is a compound selected from the following 11 compounds:

the compound wherein R¹⁰¹is

3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 3,5-bis(trifluoromethyl)phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 4-(trifluoromethyl)phenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

the compound wherein R¹⁰¹is 4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group; and

the compound wherein R¹⁰¹is 3,4-dihydroxy-5-[3-(trifluoromethyl)phenylcarbamoyl]phenyl group, R²⁰¹is 3,4-dichlorophenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

(32) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹and R²⁰¹are either the following (i) or (ii),

X¹⁰¹is sulfur atom,

Y¹⁰¹is oxygen atom or sulfur atom,

Z¹⁰¹is methylene group:

(i) R¹⁰¹is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group), R²⁰¹is an aromatic group which may be substituted;

(ii) R¹⁰¹is an aromatic group which may be substituted,

R²⁰¹is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group);

(33) the compound according to the aforementioned (32) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein the compound represented by the general formula (II) is a compound selected from the following 2 compounds:

the compound wherein R¹⁰¹is 3-carboxyphenyl group, R²⁰¹is 3,4-dichlorophenyl group,

X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group; and

the compound wherein R¹⁰¹is 3-carboxy-4-hydroxyphenyl group, R²⁰¹is 4-methoxycarbonylphenyl group, X¹⁰¹is sulfur atom, Y¹⁰¹is oxygen atom, Z¹⁰¹is methylene group;

(34) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein the compound represented by the general formula (II) is a compound selected from the group consisting of the compounds described in the present specification as Compound Nos. 2 to 61, Compound Nos. 66 to 93, and Compound Nos. 301 to 475;

(35) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹is a phenyl group which is substituted with one to three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²⁰¹is an aromatic group which may be substituted,

W¹⁰¹is a group represented by the following formula:

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom,

R³⁰¹represents a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group),

Z¹⁰¹is a single bond;

(36) the compound according to the aforementioned (35) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹is a phenyl group which is substituted with two or three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²⁰¹is a phenyl group which may be substituted,

R³⁰¹is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group,

Z¹⁰¹is a single bond;

(37) the compound according to the aforementioned (36) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein the compound represented by the general formula (II) is a compound selected from the following 6 compounds:

the compound wherein R¹⁰¹is 2,4,5-trihydroxyphenyl group, R²⁰¹is 3,5-dichlorophenyl group, R³⁰¹is phenyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 2,4,5-trihydroxyphenyl group, R²⁰¹is 3,4-dichlorophenyl group, R³⁰¹is isopropyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 2,4,5-trihydroxyphenyl group, R²⁰¹is 4-nitrophenyl group, R³⁰¹is ethoxy group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 2,4,5-trihydroxyphenyl group, R²⁰¹is 3,4-dichlorophenyl group, R³⁰¹is methyl group, Z¹⁰¹is a single bond;

the compound wherein R¹⁰¹is 2,4,5-trihydroxyphenyl group, R²⁰¹is 3,5-dichlorophenyl group, R³⁰¹is isopropyl group, Z¹⁰¹is a single bond; and

the compound wherein R¹⁰¹is 2,4,5-trihydroxyphenyl group, R²⁰¹is 3-chloro-4-fluorophenyl group, R³⁰¹is isopropyl group, Z¹⁰¹is a single bond;

(38) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹is a phenyl group which is substituted with C₂-C₆alkenyl group which may be substituted (said phenyl group may further be substituted with one or more substituents other than the C₂-C₆alkenyl group),

R²⁰¹is an aromatic group which may be substituted,

the compound wherein R¹⁰¹is 2-hydroxy-5-styrylphenyl group, R²⁰¹is 4-nitrophenyl group, R³⁰¹is ethoxy group, Z¹⁰¹is a single bond; and

the compound wherein R¹⁰¹is 4-styrylphenyl group, R²⁰¹is 4-carboxyphenyl group, R³⁰¹is isopropyl group, Z¹⁰¹is a single bond;

(40) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein R¹⁰¹and R²⁰¹are any one of the following (i) to (iii),

W¹⁰¹is a group represented by the following formula:

(wherein a bond at the left end binds to the carbon atom and a bond at the right end binds to the nitrogen atom),

R³⁰¹is any one of the following (i) to (iii),

Z is a single bond:

(i) R¹⁰¹is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group), R²⁰¹is an aromatic group which may be substituted,

R³⁰¹is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group;

(ii) R¹⁰¹is an aromatic group which may be substituted,

R²⁰¹is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group),

R³⁰¹is a C₁-C₆alkyl group, a C₆-C₁₀aryl group which may be substituted, a C₁-C₆halogenated alkyl group, a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group, a C₁-C₆alkoxy-substituted C₁-C₆alkyl group, hydroxy group, a C₁-C₆alkoxy group, carboxy group, or a C₂-C₇alkoxycarbonyl group;

(iii) R¹⁰¹is an aromatic group which may be substituted,

R²⁰¹is an aromatic group which may be substituted, R³⁰¹is carboxy group;

(41) the compound according to the aforementioned (40) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein the compound represented by the general formula (II) is a following compound:

the compound wherein R¹⁰¹is 4-styrylphenyl group, R²⁰¹is 4-carboxyphenyl group, R³⁰¹is isopropyl group, Z¹⁰¹is a single bond; and

(42) the compound according to the aforementioned (25) or a salt thereof, or a hydrate thereof or a solvate thereof, wherein the compound represented by the general formula (II) is a compound selected from the group consisting of the compounds described in the present specification as Compound Nos. 104 to 158, Compound Nos. 166 to 167, Compound Nos. 176 to 185, Compound Nos. 194 to 219, Compound Nos. 221 to 224, and Compound Nos. 501 to 567.

From another aspect, the present invention provides a medicament which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the aforementioned general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof, use of the substance selected from the group consisting of the compound represented by the aforementioned general formula (II) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof for manufacture of the aforementioned medicament; a medicament having inhibitory activity against plasminogen activator inhibitor-1, which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the aforementioned general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof, a PAI-1 inhibitor which comprises as an active ingredient a substance selected from the group consisting of the compound represented by the aforementioned general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof; a method for inhibiting PAI-1 in mammal including a human, which comprises the step of administering an effective amount of the substance selected from the group consisting of the compound represented by the aforementioned general formula (II) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof to a mammal including a human; a method for therapeutic and/or preventive treatment of diseases caused by an expression of PAI-1 or an enhancement of PAI-1 activity in mammal including a human, which comprises the step of administering a therapeutically and/or preventively effective amount of the substance selected from the group consisting of the compound represented by the aforementioned general formula (II) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof to a mammal including a human; and a method for preventive and/or therapeutic treatment of diseases caused by one or more abnormal conditions selected from the group consisting of thrombogenesis, fibrogenesis, accumulation of visceral fat, cell proliferation, angiogenesis, deposition or remodeling of extracellular matrix, and cell movement or migration in mammal including a human, which comprises the step of administering a therapeutically and/or preventively effective amount of the substance selected from the group consisting of the compound represented by the aforementioned general formula (II) and the pharmacologically acceptable salt thereof, and the hydrate thereof and the solvate thereof to a mammal including a human.

BEST MODE FOR CARRYING OUT THE INVENTION

The terms used in the specification have the following meanings.

In the specification, for example, the formula: —X—C(═Y)— means the following formula:

and the formula: —C(R³)═N— means the following formula.

In the specification, any of fluorine atom, chlorine atom, bromine atom, or iodine atom may be used as the “halogen atom.”

Examples of the “hydrocarbon group” include an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group and the like.

The “alkyl group” or an alkyl moiety of the substituents (whose examples include, for example, an alkoxy group, an alkylsulfanyl group, a monoalkylamino group, a dialkylamino group, a halogenated alkyl group, an aralkyl group and the like), containing the alkyl moiety may be straight chain, branched chain, cyclic, or combination of these unless otherwise specifically referred to. The cyclic alkyl group may be a polycyclic alkyl group. As the alkyl group, a C₁-C₂₀alkyl group, preferably, a C₁-C₆alkyl group may be used. More specifically, examples of the alkyl group include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, neopentyl group, isopentyl group, tert-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cyclopropylmethyl group, bornyl group, adamantyl group and the like, however, examples of the alkyl group are not limited to those exemplified above.

The “alkenyl group” or an alkenyl moiety of the substituents (whose examples include, for example, an alkenyloxy group and the like), containing the alkenyl moiety may be straight chain, branched chain, cyclic, or combination of these unless otherwise specifically referred to. The cyclic alkenyl group may be a polycyclic alkenyl group. Numbers of the double bonds existing in the alkenyl group are not particularly limited. When the alkenyl group includes two or more double bonds, they may either be conjugated or non-conjugated. As the alkenyl group, a C₂-C₂₀alkenyl group, preferably, a C₂-C₆alkenyl group may be used. More specifically, examples of the alkenyl group include, for example, vinyl group, allyl group, isopropenyl group, allenyl group and the like, however, examples of the alkenyl group are not limited to those exemplified above.

The “alkynyl group” or an alkynyl moiety of the substituents (whose examples include, for example, an alkynyloxy group and the like), containing the alkynyl moiety may be straight chain, branched chain, or combination of these unless otherwise specifically referred to. Numbers of the triple bonds existing in the alkynyl group are not particularly limited. The alkynyl group may include one or more double bonds. As the alkynyl group, a C₂-C₂₀alkynyl group, preferably, a C₂-C₆alkynyl group may be used. More specifically, examples of the alkynyl group include, for example, ethynyl group, propargyl group and the like, however, examples of the alkynyl group are not limited to those exemplified above.

As the “aryl group” or an aryl moiety of the substituents (whose examples include, for example, an aralkyl group, an aryloxy group, an arylsulfanyl group, an arylamino group and the like), containing the aryl moiety, an aromatic hydrocarbon (arene) residue, which comprises 6 to 14 carbon atoms, preferably, 6 to 10 carbon atoms may be used. The arene may either be monocyclic or fused polycyclic. More specifically, examples of the arene include, for example, benzene ring, naphthalene ring, anthracene ring, phenanthrene ring and the like. Preferred examples of the aryl group include phenyl group, 1-naphthyl group, 2-naphthyl group and the like. The aryl group can bind at any position on the ring.

As the “aralkyl group” or an aralkyl moiety of the substituents (whose examples include, for example, an aralkyloxy group and the like), containing the aralkyl moiety, a C₇-C₂₀aralkyl group, preferably, a C₇-C₁₂aralkyl group may be used. More specifically, examples of the aralkyl group include, for example, benzyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-phenethyl group, 2-phenethyl group and the like, however, examples of the aralkyl group are not limited to those exemplified above.

As the “heterocyclic group” or a heterocyclic moiety of the substituents (whose examples include, for example, a heterocyclic alkyl group, a heterocyclic oxy group and the like) containing the heterocyclic moiety, a 3- to 14-membered heterocyclic residue which comprises one or more hetero atoms such as nitrogen atom, oxygen atom, and sulfur atom may be used unless otherwise specifically referred to. In the specification, the “hetero atom” means atom other than the carbon atom, whose examples include nitrogen atom, oxygen atom, sulfur atom and the like unless otherwise specifically referred to. When the heterocyclic group comprises two or more hetero atoms, each of them may be the same or different. The hetero ring may either be monocyclic or fused polycyclic, and may be saturated, partly saturated, or aromatic. The “heteroaryl group” means a heterocyclic group whose heterocyclic moiety is aromatic, and the “non-aromatic heterocyclic group” means a heterocyclic group whose heterocyclic moiety is saturated or partly saturated. Examples of the heterocyclic group include, for example, isochromanyl group, chromanyl group, pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, piperidyl group, piperidino group, morpholinyl group, morpholino group, thiomorpholinyl group, thiomorpholino group, piperazinyl group, indolinyl group, isoindolinyl group, quinuclidinyl group, thienyl group, thianthrenyl group, furyl group, pyranyl group, isobenzofuranyl group, chromenyl group, xanthenyl group, phenoxathiinyl group, 2H-pyrrolyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, isothiazolyl group, isoxazolyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, indolizinyl group, isoindolyl group, 3H-indolyl group, indolyl group, 1H-indazolyl group, purinyl group, quinolizinyl group, isoquinolyl group, quinolyl group, phthalazinyl group, naphthyridinyl group, quinoxalinyl group, quinazolinyl group, cinnolinyl group, pteridinyl group, 4aH-carbazolyl group, carbazolyl group, β-carbolinyl group, phenanthridinyl group, acridinyl group, perimidinyl group, phenanthrolinyl group, phenazinyl group, phenoxazinyl group, phenothiazinyl group, furazanyl group, phenoxazinyl group, hexamethyleneimino group, heptamethyleneimino group, oxazolyl group, thiazolyl group, triazolyl group, tetrazolyl group and the like, however, examples of the heterocyclic group are not limited to those exemplified above. The aryl group can bind at any position on the ring. The heterocyclic group can bind at any position on the ring. The “nitrogen-containing heterocyclic group” means a heterocyclic group which comprises at least one nitrogen atom.

Examples of the “aromatic group” include aryl group and heteroaryl group.

As the “acyl group” or an acyl moiety of the substituents (whose examples include, for example, an acyloxy group, an acylamino group and the like), containing the acyl moiety, examples include, for example, formyl group, an alkanoyl group (preferably, a C₂-C₇alkanoyl group whose examples include, for example, acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, pivaloyl group and the like), an alkenylcarbonyl group (preferably, a C₃-C₇alkenylcarbonyl group whose examples include, for example, acryloyl group, methacryloyl group, crotonoyl group, isocrotonoyl group and the like), an alkynylcarbonyl group (preferably, a C₃-C₇alkynylcarbonyl group whose examples include, for example, propioloyl group and the like), an aroyl group (preferably, a C₇-C₁₁aroyl group whose examples include, for example, benzoyl group, 1-naphthoyl group, 2-naphthoyl group, and the like), an aralkylcarbonyl group (preferably, a C₈-C₁₃aralkylcarbonyl group whose examples include, for example, benzylcarbonyl group and the like), a heterocyclic carbonyl group whose examples include, for example, piperidinocarbonyl group, morpholinocarbonyl group, furoyl group, thenoyl group, nicotinoyl group, isonicotinoyl group and the like), carboxy group, an alkoxycarbonyl group, an alkenyloxycarbonyl group (preferably, a C₃-C₇alkenyloxycarbonyl group whose examples include, for example, allyloxycarbonyl group and the like), an alkynyloxycarbonyl group (preferably, a C₃-C₇alkynyloxycarbonyl group whose examples include, for example, propargyloxycarbonyl group and the like), an aryloxycarbonyl group (preferably, a C₇-C₁₁aryloxycarbonyl group whose examples include, for example, phenoxycarbonyl group and the like), an aralkyloxycarbonyl group (preferably, a C₈-C₁₃aralkyloxycarbonyl group whose examples include, for example, benzyloxycarbonyl group and the like), a heterocyclic oxycarbonyl group whose examples include, for example, 4-piperidyloxycarbonyl group, 3-pyridyloxycarbonyl group and the like, carbamoyl group, an alkylcarbamoyl group (preferably, a C₂-C₇alkylcarbamoyl group whose examples include, for example, methylcarbamoyl group and the like), a dialkylcarbamoyl group (preferably, a C₃-C₁₃dialkylcarbamoyl group whose examples include, for example, dimethylcarbamoyl group and the like), an arylcarbamoyl group (preferably, a C₇-C₁₁arylcarbamoyl group whose examples include, for example, phenylcarbamoyl group and the like), an aralkylcarbamoyl group (preferably, a C₈-C₁₃aralkylcarbamoyl group whose examples include, for example, benzylcarbamoyl group and the like), sulfo group, an alkylsulfonyl group (preferably, a C₁-C₆alkylsulfonyl group whose examples include, for example, mesyl group, propanesulfonyl group and the like), an alkenylsulfonyl group (preferably, a C₂-C₆alkenylsulfonyl group whose examples include, for example, allylsulfonyl group and the like), an alkynylsulfonyl group (preferably, a C₂-C₆alkynylsulfonyl group whose examples include, for example, propargylsulfonyl group and the like), an arylsulfonyl group (preferably, a C₆-C₁₀arylsulfonyl group whose examples include, for example, benzenesulfonyl group, 1-naphthylsulfonyl group, 2-naphthylsulfonyl group and the like), an aralkylsulfonyl group (preferably, a C₇-C₁₂aralkylsulfonyl group whose examples include, for example, benzylsulfonyl group and the like), a heterocyclic sulfonyl group whose examples include, for example, piperidinosulfonyl group, morpholinosulfonyl group, 8-quinolylsulfonyl group and the like, sulfamoyl group, an alkylsulfamonyl group (preferably, a C₁-C₆alkylsulfamonyl group whose examples include, for example, methylsulfamoyl group and the like), a dialkylsulfamonyl group (preferably, a C₂-C₁₂dialkylsulfamonyl group whose examples include, for example, dimethylsulfamoyl group and the like), an arylsulfamonyl group (preferably, a C₆-C₁₀arylsulfamonyl group whose examples include, for example, phenylsulfamoyl group and the like), an aralkylsulfamonyl group (preferably, a C₇-C₁₂alkylsulfamonyl group whose examples include, for example, benzylsulfamoyl group and the like), sulfeno group, sulfenamoyl group, phosphono group, a dialkylphosphono group (preferably, a C₂-C₁₂dialkylphosphono group whose examples include, for example, dimethylphosphono group and the like), a diaralkylphosphono group (preferably, a C₁₄-C₂₂diaralkylphosphono group whose examples include, for example, dibenzylphosphono group and the like), hydroxyphosphonyl group, thioformyl group, dithocarboxy group, hydroxythiocarboxy group, sulfanylcarbonyl group, an alkylsulfanylthiocarbonyl group (preferably, a C₁-C₆alkylsulfanylthiocarbonyl group whose examples include, for example, methylsulfanylthiocarbonyl group and the like), thiocarbamoyl group, glyoxyloyl group, oxalo group, an alkoxycarbonylcarbonyl group (preferably, a C₁-C₆alkoxycarbonylcarbonyl group whose examples include, for example, methoxalyl group and the like), an alkylcarbonylcarbonyl group (preferably, a C₁-C₆alkylcarbonylcarbonyl group whose examples include, for example, pyruvoyl group and the like) and the like, however, examples of the acyl group are not limited to those exemplified above.

As the “alkoxy group,” a C₁-C₂₀alkoxy group, preferably, a C₁-C₆alkoxy group may be used. More specifically, examples of the alkoxy group include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentyloxy group, neopentyloxy group, isopentyloxy group, tert-pentyloxy group, n-hexyloxy group, n-heptyloxy group, n-octyloxy group, cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopropylmethoxy group and the like, however, examples of the alkoxy group are not limited to those exemplified above.

As the “alkoxycarbonyl group,” a C₂-C₂₀alkoxycarbonyl group, preferably, a C₂-C₇alkoxycarbonyl group may be used. In the definition, the “C₂alkoxycarbonyl group” means methoxycarbonyl group. More specifically, examples of the alkoxycarbonyl group include, for example, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, n-butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group, n-pentyloxycarbonyl group, neopentyloxycarbonyl group, isopentyloxycarbonyl group, tert-pentyloxycarbonyl group, n-hexyloxycarbonyl group, n-heptyloxycarbonyl group, n-octyloxycarbonyl group, cyclopropyloxycarbonyl group, cyclobutyloxycarbonyl group, cyclopentyloxycarbonyl group, cyclohexyloxycarbonyl group, cyclopropylmethoxycarbonyl group and the like, however, examples of the alkoxycarbonyl group are not limited to those exemplified above.

Examples of the “carboxy group which may be esterified” include, for example, carboxy group, an alkoxycarbonyl group, an alkenyloxycarbonyl group, an alkynyloxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, a heterocyclic oxycarbonyl group and the like, however, examples of the “carboxy group which may be esterified” are not limited to those exemplified above.

In the specification, when a certain functional group is defined as “which may be substituted,” the definition means that the functional group may have one or more substituents. Numbers, kinds, and positions of substituents are not particularly limited, and when two or more substituents exist, they may be the same or different.

Examples of the substituent include, for example, halogen atoms, oxo group, thioxo group, oxido group, nitro group, nitroso group, cyano group, isocyano group, cyanato group, thiocyanato group, isocyanato group, isothiocyanato group, hydroxy group, sulfanyl group, hydrocarbon group, heterocyclic group, acyl group, amino group, hydrazino group, hydrazono group, diazenyl group, ureido group, thioureido group, guanidino group, amidino group, azido group, imino group, hydroxyamino group, hydroxyimino group, aminooxy group, diazo group, semicarbazino group, semicarbazono group, allophanyl group, hydantoyl group, boryl group, silyl group, stannyl group, selanyl group, oxido group and the like, however, examples of the substituent are not limited to those exemplified above.

The substituents exemplified above may further be substituted with one or more other substituents. Examples of these substituent include a halogenated alkyl group (preferably, a halogenated C₁-C₆alkyl group whose examples include, for example, trifluoromethyl group and the like), a hydroxyalkyl group, (preferably, a hydroxy C₁-C₆alkyl group whose examples include, for example, hydroxymethyl group and the like), a carboxyalkyl group, (preferably, a carboxy C₁-C₆alkyl group whose examples include, for example, carboxymethyl group and the like), a halogenated alkoxy group (preferably, a halogenated C₁-C₆alkoxy group whose examples include, for example, trifluoromethoxy group and the like), a halogenated alkanoyl group (preferably, a halogenated C₂-C₇alkanoyl group whose examples include, for example, trifluoroacetyl group and the like), a halogenated alkylsulfonyl group (preferably, a halogenated C₁-C₆alkylsulfonyl group whose examples include, for example, trifluoromethanesulfonyl group and the like), an alkanoyloxy group (preferably, a C₂-C₇alkanoyloxy group whose examples include, for example, acetoxy group and the like), an aroyloxy group (preferably, a C₇-C₁₁aroyloxy group whose examples include, for example, benzoyloxy group and the like), an alkylamino group (preferably, a C₁-C₆alkylamino group whose examples include, for example, methylamino group and the like), a dialkylamino group (preferably, a C₂-C₁₂dialkylamino group whose examples include, for example, dimethylamino group and the like), an alkanoylamino group (preferably, a C₂-C₇alkanoylamino group whose examples include, for example, acetylamino group and the like), an aroylamino group (preferably, a C₇-C₁₁aroylamino group whose examples include, for example, benzoylamino group and the like), an alkoxycarbonylamino group (preferably, a C₂-C₇alkoxycarbonylamino group whose examples include, for example, methoxycarbonylamino group, tert-butoxycarbonylamino group and the like), an aralkyloxycarbonylamino group (preferably, a C₈-C₁₃aralkyloxycarbonylamino group whose examples include, for example, benzyloxycarbonylamino group and the like), an alkylsulfonylamino group (preferably, a C₁-C₆alkylsulfonylamino group whose examples include, for example, mesylamino group and the like), an arylsulfonylamino group (preferably, a C₆-C₁₀arylsulfonylamino group whose examples include, for example, benzenesulfonylamino group and the like) and the like. However, the substituents explained above are for exemplification, and examples of the substituent are not limited to those exemplified above.

Compounds represented by the general formulas (I) and (II) are explained in details below.

In the general formula (I), W represents a group selected from the following connecting group W-1.

When W is —X—C(═Y)—, X represents sulfur atom or NH, and Y represents oxygen atom or sulfur atom. Preferably, X is sulfur atom. Preferably, Y is oxygen atom.

When W is —C(R³)═N—, R³represents a hydrocarbon group which may be substituted, hydroxy group which may be substituted, or carboxy group which may be esterified.

Preferred examples of the hydrocarbon group represented by R³include a C₁-C₆alkyl group or a C₆-C₁₀aryl group. More preferred examples include methyl group, ethyl group, isopropyl group, tert-butyl group, or phenyl group.

The hydrocarbon group represented by R³may be substituted. Preferred examples of said substituent include a halogen atom; a C₁-C₆alkoxy group (more preferably, methoxy group); hydroxy group; and a C₂-C₇alkoxycarbonyl group (more preferably, ethoxycarbonyl group).

Preferred examples of the hydrocarbon group which may be substituted represented by R³include a C₁-C₆alkyl group (more preferably, methyl group, ethyl group, isopropyl group, and tert-butyl group); a C₆-C₁₀aryl group (said aryl group may be substituted, and more preferred examples include phenyl group, 3,4,5-trimethoxyphenyl group, 4-hydroxyphenyl group, and 2-hydroxy-5-bromophenyl group); a halogenated C₁-C₆alkyl group (more preferably, trifluoromethyl group); a C₂-C₇alkoxycarbonyl-substituted C₁-C₆alkyl group (more preferably, 2-(ethoxycarbonyl)ethyl group and 3-(ethoxycarbonyl)propyl group); and a C₁-C₆alkoxy-substituted C₁-C₆alkyl group (more preferably, methoxymethyl group). Further preferred examples include methyl group, isopropyl group, or phenyl group.

Preferred examples of the hydroxy group which may be substituted represented by R³include hydroxy group or a C₁-C₆alkoxy group. More preferred examples include hydroxy group or ethoxy group, and further preferred examples include ethoxy group.

Preferred examples of the carboxy group which may be esterified represented by R³include carboxy group or a C₂-C₇alkoxycarbonyl group. More preferred examples include carboxy group or ethoxycarbonyl group.

Preferably, W is —S—C(═O)— or —C(R³)═N—.

In the general formula (I), R¹represents an aromatic group which may be substituted.

When W is —X—C(═Y)—, preferred examples of the aromatic group represented by R¹include a C₆-C₁₀aryl group or a 5- to 9-membered heteroaryl group. More preferred examples include phenyl group, furyl group, pyridyl group, benzo[2,1,3]oxadiazolyl group, or indolyl group, and most preferred examples include phenyl group.

The aromatic group represented by R¹may be substituted. Preferred examples of said substituent include a halogen atom; nitro group; a C₁-C₆alkyl group (more preferably, methyl group and isopropyl group); a C₆-C₁₀aryl group (said aryl group may be substituted, and more preferred examples include 3-carboxyphenyl group, 3,5-dichlorophenyl group, phenyl group, 3,4-dimethoxyphenyl group, 3,4-dihydroxyphenyl group, 2,6-dimethoxyphenyl group, 4-methoxyphenyl group, 2,6-dihydroxyphenyl group, and 4-hydroxyphenyl group); hydroxy group; a C₁-C₆alkoxy group (said alkoxy group may be substituted, and more preferred examples include methoxy group and methoxymethoxy group); a C₂-C₇alkoxycarbonyl group (more preferably, methoxycarbonyl group and ethoxycarbonyl group); a C₁-C₃alkylenedioxy group (more preferably, methylenedioxy group); a C₂-C₇alkanoylamino group (more preferably, acetylamino group); amino group; a C₆-C₁₀aryloxy group (more preferably, phenoxy group); a C₂-C₆alkenyl group (more preferably, styryl group); a halogenated C₁-C₆alkyl group (more preferably, trifluoromethyl group); a C₂-C₇alkoxycarbonyloxy group (more preferably, ethoxycarbonyloxy group); carboxy group; a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted, and more preferred examples include 3,4-dihydroxyphenylcarbamoyl group, 3,4-dimethoxyphenylcarbamoyl group, 4-methoxyphenylcarbamoyl group, 4-hydroxyphenylcarbamoyl group, 3-methoxyphenylcarbamoyl group, 3-hydroxyphenylcarbamoyl group, 3-trifluoromethyl-4-methoxyphenylcarbamoyl group, 3-methyl-4-hydroxyphenylcarbamoyl group, 4-carboxyphenylcarbamoyl group, 2,5-bis(trifluoromethyl)phenylcarbamoyl group, 3,5-bis(trifluoromethyl)phenylcarbamoyl group, 3-methoxy-4-(methoxycarbonyl)phenylcarbamoyl group, 3-(trifluoromethoxy)phenylcarbamoyl group, 3,4-dichlorophenylcarbamoyl group, 4-(methoxycarbonyl)phenylcarbamoyl group, 3-(methoxycarbonyl)phenylcarbamoyl group, 3-carboxyphenylcarbamoyl group, 2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl group, 2-(4-hydroxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl group, 2-chloro-5-(trifluoromethyl)phenylcarbamoyl group, 3-nitrophenylcarbamoyl group, 3,4-methylenedioxyphenylcarbamoyl group, 3,4,5-trimethoxyphenylcarbamoyl group, 2,3-dimethoxyphenylcarbamoyl group, 3,4,5-trihydroxyphenylcarbamoyl group, 2,3-dihydroxyphenylcarbamoyl group, 3-hydroxy-4-(methoxycarbonyl)phenylcarbamoyl group, phenylcarbamoyl group, 2,5-dichlorophenylcarbamoyl group, 2-fluoro-5-(trifluoromethyl)phenylcarbamoyl group, 2-methyl-5-methoxyphenylcarbamoyl group, 3-methoxy-5-(trifluoromethyl)phenylcarbamoyl group, 2-methoxy-5-methylphenylcarbamoyl group, 2-methoxycarbonyl-5-chlorophenylcarbamoyl group, 2-methoxy-5-chlorophenylcarbamoyl group, 2-methoxy-5-phenylphenylcarbamoyl group, 2-methyl-5-hydroxyphenylcarbamoyl group, 2-hydroxy-5-methyl phenylcarbamoyl group, 2-carboxy-5-chlorophenylcarbamoyl group, 3-hydroxy-5-(trifluoromethyl)phenylcarbamoyl group, (2,2-difluoro-1,3-benzodioxol-4-yl)carbamoyl group, 2,5-difluorophenylcarbamoyl group, 2-nitro-5-(trifluoromethyl)phenylcarbamoyl group, 2-methoxy-6-(tert-butyl)phenylcarbamoyl group, 2-methoxy-5-(trifluoromethyl)phenylcarbamoyl group, 2,5-dimethoxyphenylcarbamoyl group, 2-bromo-4-isopropylphenylcarbamoyl group, and 2-chloro-5-nitrophenylcarbamoyl group); a C₆-C₁₀aroylamino group (said aroyl group may be substituted, and more preferred examples include 3,4-dihydroxybenzoylamino group, 4-(trifluoromethoxy)benzoylamino group, 4-methoxybenzoylamino group, 4-hydroxybenzoylamino group, and 3,4-dimethoxybenzoylamino group); a C₈-C₁₃aralkyloxycarbonyl group (said aralkyl group may be substituted, and more preferred examples include 4-methoxybenzyloxycarbonyl group and benzyloxycarbonyl group); a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and more preferred examples include (2-chloropyridin-5-yl)carbamoyl group, (2-methoxypyridin-5-yl)carbamoyl group, and (2-hydroxypyridin-5-yl)carbamoyl group); a C₇-C₁₂aralkyl group (said aralkyl group may be substituted, and more preferred examples include 3,4-dibenzyloxybenzyl group, 3,4-dihydroxybenzyl group, 4-methoxycarbonylbenzyl group); and a C₆-C₁₀aroyl group (said aroyl group may be substituted, and more preferred examples include 3,4-dimethoxybenzoyl group, 4-methoxycarbonylbenzoyl group). Further preferred examples include hydroxy group, a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted), a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted), carboxy group, nitro group, a C₁-C₆alkyl group, or a C₁-C₆alkoxy group (said alkoxy group may be substituted). It is preferable that the aromatic group represented by R¹is substituted with one to three substituents independently selected from the aforementioned substituents.

Examples of the aromatic group which may be substituted represented by R¹include, for example, a group selected from the following substituent group R-1a-1. [Substituent Group R-1a-1] 3,5-dibromo-2-hydroxyphenyl group, 2,3-dihydroxyphenyl group, 3,4-dihydroxyphenyl group, 2,4,5-trimethoxyphenyl group, 2-hydroxy-3-methylphenyl group, 3-hydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 3-ethoxycarbonyl-4-hydroxyphenyl group, 2,3,4-trihydroxyphenyl group, 3,4-dihydroxy-5-methoxyphenyl group, 5-hydroxy-2-nitrophenyl group, 3,5-dihydroxyphenyl group, 2,4-dihydroxyphenyl group, 2-hydroxy-5-nitrophenyl group, 5-(3-carboxyphenyl)furan-2-yl group, 5-chloro-2-hydroxyphenyl group, 5-(3,5-dichlorophenyl)furan-2-yl group, 3,4-methylenedioxyphenyl group, 4-bromophenyl group, benzo[2,1,3]oxadiazol-5-yl group, 4-pyridyl group, 3,4-dichlorophenyl group, 4-acetamidophenyl group, 4-aminophenyl group, 4-hydroxy-3-nitrophenyl group, 3-amino-4-hydroxyphenyl group, 3-hydroxy-4-nitrophenyl group, 4-amino-3-hydroxyphenyl group, 4-phenoxyphenyl group, 3-phenoxyphenyl group, 2-hydroxy-5-styrylphenyl group, 3-hydroxy-4-methoxyphenyl group, 3-hydroxy-4,5-methylenedioxyphenyl group, 2-fluoro-3-hydroxyphenyl group, 3-hydroxy-4-fluorophenyl group, 3-methoxy-4-chlorophenyl group, 3-hydroxy-4-chlorophenyl group, 2-methoxy-3-hydroxyphenyl group, 3-isopropyl-4-methoxyphenyl group, 3-fluoro-4-methoxyphenyl group, 3-fluoro-4-hydroxyphenyl group, 3-trifluoromethyl-4-methoxyphenyl group, 3,4-bis(ethoxycarbonyloxy)phenyl group, 3,4,5-tris(ethoxycarbonyloxy)phenyl group, 3,4-dihydroxy-5-(methoxycarbonyl)phenyl group, 3,5-dihydroxy-4-(methoxycarbonyl)phenyl group, 3-methoxy-4-hydroxy-5-(methoxycarbonyl)phenyl group, 3-methoxy-4-hydroxy-5-carboxyphenyl group, 3-methoxy-4-hydroxy-5-nitrophenyl group, 3,4-dihydroxy-5-nitrophenyl group, 3,4,5-trimethoxyphenyl group, 3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 3-carboxyphenyl group, 4-hydroxy-3-(3,4-dimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(4-methoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(4-hydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3-methoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3-hydroxyphenylcarbamoyl)phenyl group, 3-(3,4-dimethoxyphenylcarbamoyl)phenyl group, 3-carboxy-4-hydroxyphenyl group, 4-methoxy-3-(3,4-dihydroxybenzoylamino)phenyl group, 3-methoxy-4-hydroxy-5-(3-trifluoromethyl-4-methoxyphenylcarbamoyl)phenyl group, 3-methoxy-4-hydroxy-5-(3-methyl-4-hydroxyphenylcarbamoyl)phenyl group, 3-(4-methoxybenzyloxycarbonyl)-4-hydroxyphenyl group, 3-benzyloxycarbonyl-4-hydroxyphenyl group, 4-methoxy-3-[4-(trifluoromethoxy)benzoylamino]phenyl group, 4-hydroxy-3-[4-(trifluoromethoxy)benzoylamino]phenyl group, 3-[4-(trifluoromethoxy)benzoylamino]phenyl group, 3-(4-methoxybenzoylamino)phenyl group, 3-(4-hydroxybenzoylamino)phenyl group, 3-(3,4-dimethoxybenzoylamino)phenyl group, 3-(3,4-dihydroxybenzoylamino)phenyl group, 4-methoxy-3-(3,4-dimethoxybenzoylamino)phenyl group, 4-hydroxy-3-(3,4-dihydroxybenzoylamino)phenyl group, 4-methoxy-3-(4-methoxybenzoylamino)phenyl group, 4-hydroxy-3-(4-hydroxybenzoylamino)phenyl group, 3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 3-(4-carboxyphenylcarbamoyl)phenyl group, 3-methyl-4-hydroxy-5-carboxyphenyl group, 4-hydroxy-3-[(2-chloropyridin-5-yl)carbamoyl]phenyl group, 3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[2,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[3-methoxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[(2-methoxypyridin-5-yl)carbamoyl]phenyl group, 4-hydroxy-3-[(2-hydroxypyridin-5-yl)carbamoyl]phenyl group, indol-3-yl group, 1-(3,4-dibenzyloxybenzyl)indol-3-yl group, 1-(3,4-dimethoxybenzoyl)indol-3-yl group, 1-(3,4-dihydroxybenzyl)indol-3-yl group, 4-hydroxy-3-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(3,4-dichlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[4-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(4-carboxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3-carboxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-(4-hydroxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(3-nitrophenylcarbamoyl)phenyl group, 1-(4-methoxycarbonylbenzyl)indol-3-yl group, 3-phenyl-4-hydroxy-5-(benzyloxycarbonyl)phenyl group, 1-(4-methoxycarbonylbenzoyl)indol-3-yl group, 4-hydroxy-3-(3,4-methylenedioxyphenylcarbamoyl)phenyl group, 3-methoxy-4-hydroxy-5-(methoxycarbonyl)phenyl group, 3-phenyl-4-hydroxy-5-carboxyphenyl group, 3,5-bis(methoxymethoxy)-4-(methoxycarbonyl)phenyl group, 4-hydroxy-3-(3,4,5-trimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2,3-dimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[3-hydroxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 3-methoxy-4-hydroxy-5-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group, 3-methoxy-4-hydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3-methoxy-4-hydroxy-5-(phenylcarbamoyl)phenyl group, 4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[2-fluoro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-methoxy-3-(3,4-dimethoxyphenyl)phenyl group, 4-methoxy-3-(3,4-dihydroxyphenyl)phenyl group, 4-hydroxy-3-(3,4-dihydroxyphenyl)phenyl group, 3,5-dihydroxy-4-carboxyphenyl group, 4-methoxy-3-(2,6-dimethoxyphenyl)phenyl group, 4-methoxy-3-(4-methoxyphenyl)phenyl group, 4-hydroxy-3-(2,6-dihydroxyphenyl)phenyl group, 4-hydroxy-3-(2-methyl-5-methoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[3-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(2-methoxy-5-methylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methoxycarbonyl-5-chlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methoxy-5-chlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methoxy-5-phenylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methyl-5-hydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-hydroxy-5-methylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-carboxy-5-chlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[3-hydroxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[(2,2-difluoro-1,3-benzodioxol-4-yl)carbamoyl]phenyl group, 4-methoxy-3-(4-hydroxyphenyl)phenyl group, 4-hydroxy-3-(4-hydroxyphenyl)phenyl group, 3,4-dihydroxy-5-(benzyloxycarbonyl)phenyl group, 3,4-dihydroxy-5-carboxyphenyl group, 4-hydroxy-3-(2,5-difluorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[2-nitro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-methoxy-5-(tert-butyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3,4-dihydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3,4-dihydroxy-5-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(2,5-dimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-bromo-4-isopropylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group, 3,4-dihydroxy-5-(3,4-methylenedioxyphenylcarbamoyl)phenyl group, 3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group.

Preferred examples of the aromatic group which may be substituted represented by R¹include a phenyl group which is substituted with one to three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group), and specific examples include a group selected from the following substituent group R-1a-2. More preferred examples include a phenyl group which is substituted with two or three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group), and specific examples include a group selected from the following substituent group R-1a-3. Further preferred examples include 2,3-dihydroxyphenyl group, 3,4-dihydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 3,4-dihydroxy-5-nitrophenyl group, or 3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group. [Substituent Group R-1a-2] 3,5-dibromo-2-hydroxyphenyl group, 2,3-dihydroxyphenyl group, 3,4-dihydroxyphenyl group, 2-hydroxy-3-methylphenyl group, 3-hydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 3-ethoxycarbonyl-4-hydroxyphenyl group, 2,3,4-trihydroxyphenyl group, 3,4-dihydroxy-5-methoxyphenyl group, 5-hydroxy-2-nitrophenyl group, 3,5-dihydroxyphenyl group, 2,4-dihydroxyphenyl group, 2-hydroxy-5-nitrophenyl group, 5-chloro-2-hydroxyphenyl group, 4-hydroxy-3-nitrophenyl group, 3-amino-4-hydroxyphenyl group, 3-hydroxy-4-nitrophenyl group, 4-amino-3-hydroxyphenyl group, 2-hydroxy-5-styrylphenyl group, 3-hydroxy-4-methoxyphenyl group, 3-hydroxy-4,5-methylenedioxyphenyl group, 2-fluoro-3-hydroxyphenyl group, 3-hydroxy-4-fluorophenyl group, 3-hydroxy-4-chlorophenyl group, 2-methoxy-3-hydroxyphenyl group, 3-fluoro-4-hydroxyphenyl group, 3,4-dihydroxy-5-(methoxycarbonyl)phenyl group, 3,5-dihydroxy-4-(methoxycarbonyl)phenyl group, 3-methoxy-4-hydroxy-5-(methoxycarbonyl)phenyl group, 3-methoxy-4-hydroxy-5-carboxyphenyl group, 3-methoxy-4-hydroxy-5-nitrophenyl group, 3,4-dihydroxy-5-nitrophenyl group, 3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3,4-dimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(4-methoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(4-hydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3-methoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3-hydroxyphenylcarbamoyl)phenyl group, 3-carboxy-4-hydroxyphenyl group, 3-methoxy-4-hydroxy-5-(3-trifluoromethyl-4-methoxyphenylcarbamoyl)phenyl group, 3-methoxy-4-hydroxy-5-(3-methyl-4-hydroxyphenylcarbamoyl)phenyl group, 3-(4-methoxybenzyloxycarbonyl)-4-hydroxyphenyl group, 3-benzyloxycarbonyl-4-hydroxyphenyl group, 4-hydroxy-3-[4-(trifluoromethoxy)benzoylamino]phenyl group, 4-hydroxy-3-(3,4-dihydroxybenzoylamino)phenyl group, 4-hydroxy-3-(4-hydroxybenzoylamino)phenyl group, 3-methyl-4-hydroxy-5-carboxyphenyl group, 4-hydroxy-3-[(2-chloropyridin-5-yl)carbamoyl]phenyl group, 3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[2,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[3-methoxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[(2-methoxypyridin-5-yl)carbamoyl]phenyl group, 4-hydroxy-3-[(2-hydroxypyridin-5-yl)carbamoyl]phenyl group, 4-hydroxy-3-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(3,4-dichlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[4-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(4-carboxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3-carboxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-(4-hydroxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(3-nitrophenylcarbamoyl)phenyl group, 3-phenyl-4-hydroxy-5-(benzyloxycarbonyl)phenyl group, 4-hydroxy-3-(3,4-methylenedioxyphenylcarbamoyl)phenyl group, 3-methoxy-4-hydroxy-5-(methoxycarbonyl)phenyl group, 3-phenyl-4-hydroxy-5-carboxyphenyl group, 4-hydroxy-3-(3,4,5-trimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2,3-dimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[3-hydroxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 3-methoxy-4-hydroxy-5-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group, 3-methoxy-4-hydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3-methoxy-4-hydroxy-5-(phenylcarbamoyl)phenyl group, 4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[2-fluoro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(3,4-dihydroxyphenyl)phenyl group, 3,5-dihydroxy-4-carboxyphenyl group, 4-hydroxy-3-(2,6-dihydroxyphenyl)phenyl group, 4-hydroxy-3-(2-methyl-5-methoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[3-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(2-methoxy-5-methylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methoxycarbonyl-5-chlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methoxy-5-chlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methoxy-5-phenylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-methyl-5-hydroxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-hydroxy-5-methylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-carboxy-5-chlorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[3-hydroxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[(2,2-difluoro-1,3-benzodioxol-4-yl)carbamoyl]phenyl group, 4-hydroxy-3-(4-hydroxyphenyl)phenyl group, 3,4-dihydroxy-5-(benzyloxycarbonyl)phenyl group, 3,4-dihydroxy-5-carboxyphenyl group, 4-hydroxy-3-(2,5-difluorophenylcarbamoyl)phenyl group, 4-hydroxy-3-[2-nitro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-methoxy-5-(tert-butyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-[2-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3,4-dihydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3,4-dihydroxy-5-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 4-hydroxy-3-(2,5-dimethoxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-bromo-4-isopropylphenylcarbamoyl)phenyl group, 4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group, 3,4-dihydroxy-5-(3,4-methylenedioxyphenylcarbamoyl)phenyl group, 3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group. [Substituent Group R-1a-3] 2,3-dihydroxyphenyl group, 3,4-dihydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 2,3,4-trihydroxyphenyl group, 3,4-dihydroxy-5-methoxyphenyl group, 3,5-dihydroxyphenyl group, 2,4-dihydroxyphenyl group, 3,4-dihydroxy-5-(methoxycarbonyl)phenyl group, 3,5-dihydroxy-4-(methoxycarbonyl)phenyl group, 3,4-dihydroxy-5-nitrophenyl group, 3,5-dihydroxy-4-carboxyphenyl group, 3,4-dihydroxy-5-(benzyloxycarbonyl)phenyl group, 3,4-dihydroxy-5-carboxyphenyl group, 3,4-dihydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group, 3,4-dihydroxy-5-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group, 3,4-dihydroxy-5-(3,4-methylenedioxyphenylcarbamoyl)phenyl group, 3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group.

Furthermore, preferred examples of the aromatic group which may be substituted represented by R¹include a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group), or a phenyl group which is substituted with a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the heteroaryl-substituted carbamoyl group), and specific examples include a group selected from the following substituent group R-1a-4. More preferred examples include a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted) or a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted) in the 3-position, and substituted with hydroxy group in the 4-position (said phenyl group may be substituted in the 5-position), and specific examples include a group selected from the following substituent group R-1a-5. Further preferred examples include

3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group,
3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group, or
3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group.

[Substituent Group R-1a-4]
3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-dimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(4-methoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(4-hydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3-methoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3-hydroxyphenylcarbamoyl)phenyl group,
3-(3,4-dimethoxyphenylcarbamoyl)phenyl group,
3-methoxy-4-hydroxy-5-(3-trifluoromethyl-4-methoxyphenylcarbamoyl)phenyl group,
3-methoxy-4-hydroxy-5-(3-methyl-4-hydroxyphenylcarbamoyl)phenyl group,
3-(3,4-dihydroxyphenylcarbamoyl)phenyl group, 3-(4-carboxyphenylcarbamoyl)phenyl group, 4-hydroxy-3-[(2-chloropyridin-5-yl)carbamoyl]phenyl group,
3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[2,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[3-methoxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[(2-methoxypyridin-5-yl)carbamoyl]phenyl group,
4-hydroxy-3-[(2-hydroxypyridin-5-yl)carbamoyl]phenyl group,
4-hydroxy-3-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(3,4-dichlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[4-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(4-carboxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3-carboxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-(4-hydroxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(3-nitrophenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-methylenedioxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4,5-trimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,3-dimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[3-hydroxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
3-methoxy-4-hydroxy-5-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group,
3-methoxy-4-hydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
3-methoxy-4-hydroxy-5-(phenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-fluoro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2-methyl-5-methoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[3-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2-methoxy-5-methylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methoxycarbonyl-5-chlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methoxy-5-chlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methoxy-5-phenylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methyl-5-hydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-hydroxy-5-methylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-carboxy-5-chlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[3-hydroxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[(2,2-difluoro-1,3-benzodioxol-4-yl)carbamoyl]phenyl group,
4-hydroxy-3-(2,5-difluorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-nitro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-methoxy-5-(tert-butyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
3,4-dihydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
3,4-dihydroxy-5-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2,5-dimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-bromo-4-isopropylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group,
3,4-dihydroxy-5-(3,4-methylenedioxyphenylcarbamoyl)phenyl group,
3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group.

[Substituent Group R-1a-5]
3-methoxy-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-dimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(4-methoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(4-hydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3-methoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3-hydroxyphenylcarbamoyl)phenyl group,
3-methoxy-4-hydroxy-5-(3-trifluoromethyl-4-methoxyphenylcarbamoyl)phenyl group,
3-methoxy-4-hydroxy-5-(3-methyl-4-hydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[(2-chloropyridin-5-yl)carbamoyl]phenyl group,
3-methyl-4-hydroxy-5-(3,4-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[2,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[3-methoxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[(2-methoxypyridin-5-yl)carbamoyl]phenyl group,
4-hydroxy-3-[(2-hydroxypyridin-5-yl)carbamoyl]phenyl group,
4-hydroxy-3-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(3,4-dichlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[4-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(4-carboxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3-carboxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-(4-hydroxyphenoxy)-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(3-nitrophenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4-methylenedioxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4,5-trimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,3-dimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(3,4,5-trihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,3-dihydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[3-hydroxy-4-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
3-methoxy-4-hydroxy-5-[3,5-bis(trifluoromethyl)phenylcarbamoyl]phenyl group,
3-methoxy-4-hydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
3-methoxy-4-hydroxy-5-(phenylcarbamoyl)phenyl group,
4-hydroxy-3-(2,5-dichlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-fluoro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2-methyl-5-methoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-[3-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2-methoxy-5-methylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methoxycarbonyl-5-chlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methoxy-5-chlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methoxy-5-phenylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-methyl-5-hydroxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-hydroxy-5-methylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-carboxy-5-chlorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[3-hydroxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[(2,2-difluoro-1,3-benzodioxol-4-yl)carbamoyl]phenyl group,
4-hydroxy-3-(2,5-difluorophenylcarbamoyl)phenyl group,
4-hydroxy-3-[2-nitro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-methoxy-5-(tert-butyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-[2-methoxy-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
3,4-dihydroxy-5-[2-chloro-5-(trifluoromethyl)phenylcarbamoyl]phenyl group,
3,4-dihydroxy-5-[3-(methoxycarbonyl)phenylcarbamoyl]phenyl group,
4-hydroxy-3-(2,5-dimethoxyphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-bromo-4-isopropylphenylcarbamoyl)phenyl group,
4-hydroxy-3-(2-chloro-5-nitrophenylcarbamoyl)phenyl group,
3,4-dihydroxy-5-(3,4-methylenedioxyphenylcarbamoyl)phenyl group,
3,4-dihydroxy-5-[3-(trifluoromethoxy)phenylcarbamoyl]phenyl group.

Furthermore, preferred examples of the aromatic group which may be substituted represented by R¹include a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group). More preferred examples include a group selected from the following substituent group R-1a-6. Further preferred examples include 3-carboxyphenyl group or 3-carboxy-4-hydroxyphenyl group.

[Substituent Group R-1a-6] 3-methoxy-4-hydroxy-5-carboxyphenyl group, 3-carboxyphenyl group, 3-carboxy-4-hydroxyphenyl group, 3-methyl-4-hydroxy-5-carboxyphenyl group, 3-phenyl-4-hydroxy-5-carboxyphenyl group, 3,5-dihydroxy-4-carboxyphenyl group, 3,4-dihydroxy-5-carboxyphenyl group.

When W is —C(R³)═N—, preferred examples of the aromatic group represented by R¹include a C₆-C₁₄aryl group or a 5-membered heteroaryl group. More preferred examples include phenyl group, naphthyl group, anthryl group, furyl group, thienyl group, or imidazolyl group, and most preferred examples include phenyl group.

Examples of the aromatic group which may be substituted represented by R¹include, for example, a group selected from the following substituent group R-1b-1.

[Substituent Group R-1b-1] 3,5-dibromo-2-hydroxyphenyl group, 5-bromo-2-hydroxyphenyl group, 3-ethoxy-4-(thenoyloxy)phenyl group, 2,3-dihydroxyphenyl group, 3-carboxy-4-hydroxyphenyl group, 3,4-dihydroxyphenyl group, 2,4-dihydroxyphenyl group, 3-hydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 3,4-dihydroxy-5-methoxyphenyl group, 2,4,5-trihydroxyphenyl group, 2,3,4-trihydroxyphenyl group, 4-carboxymethoxy-3-ethoxyphenyl group, 5-(3-methoxycarbonylphenyl)furan-2-yl group, 5-(4-carboxyphenyl)furan-2-yl group, 5-(3,5-dichlorophenyl)furan-2-yl group, 5-(5-carboxy-2-chlorophenyl)furan-2-yl group, 4-bromophenyl group, 5-(2-hydroxy-5-nitrophenyl)furan-2-yl group, 4-allyloxy-3-methoxyphenyl group, 4-benzyloxy-3-methoxyphenyl group, 4-chlorophenyl group, phenyl group, 2-benzyloxy-5-bromophenyl group, 4-benzylcarbamoylmethoxy-3-bromo-5-methoxyphenyl group, 5-[3,5-bis(trifluoromethyl)phenyl]furan-2-yl group, 5-(2-dimethylaminoethylsulfanyl)thiophen-2-yl group, 5-(3,5-dichlorophenyl)thiophen-2-yl group, 5-(3-chlorophenyl)furan-2-yl group, 5-(3-chloro-4-methylphenyl)furan-2-yl group, 5-(2-chlorophenyl)furan-2-yl group, 5-(3-chloro-2-methylphenyl)furan-2-yl group, 5-(3-fluorophenyl)furan-2-yl group, 5-(3-nitrophenyl)furan-2-yl group, 5-bromofuran-2-yl group, 3,4-methylenedioxyphenyl group, 3,4-dichlorophenyl group, 3-methoxycarbonylphenyl group, 4-chloro-3-nitrophenyl group, 3-carboxyphenyl group, 3-methoxy-4-methylphenyl group, 4-methoxycarbonylphenyl group, 2,4,5-trimethoxyphenyl group, 4-hydroxyphenyl group, 2-hydroxy-5-styrylphenyl group, 2-hydroxy-5-methoxyphenyl group, 2,5-dihydroxyphenyl group, 2-hydroxyphenyl group, 4-phenoxyphenyl group, 2-hydroxy-3-methoxy-5-bromophenyl group, 2,3-dihydroxy-5-bromophenyl group, 2-methoxy-5-styrylphenyl group, 4-styrylphenyl group, 3-methoxy-4-hydroxy-5-bromophenyl group, 3,4-dihydroxy-5-bromophenyl group, 3,4-dimethoxy-6-styrylphenyl group, 2-(tert-butyldimethylsilyloxy)-5-styrylphenyl group, 2-hydroxynaphthalen-1-yl-group, 9-anthryl group, 2-hydroxy-5-(tert-butyl)phenyl group, 2-hydroxy-3-methoxy-6-bromophenyl group, 2,3-dihydroxy-6-bromophenyl group, 2,6-dihydroxyphenyl group, 2-bromo-4,5-dihydroxyphenyl group, 2-nitro-5-hydroxyphenyl group, 3-methoxy-4-hydroxy-5-carboxyphenyl group, 2-hydroxy-5-diethylaminophenyl group, 3-methoxy-4-hydroxy-5-nitrophenyl group, 2-nitro-5-(4-bromophenoxy)phenyl group, 2-nitro-5-(3,4-dimethoxyphenoxy)phenyl group, 3,4-dichlorophenyl group, 2-hydroxy-5-(4-phenoxystyryl)phenyl group, biphenyl-4-yl group (4-phenylphenyl group), imidazol-4-yl group.

[Substituent Group R-1b-2] 3,5-dibromo-2-hydroxyphenyl group, 5-bromo-2-hydroxyphenyl group, 2,3-dihydroxyphenyl group, 3-carboxy-4-hydroxyphenyl group, 3,4-dihydroxyphenyl group, 2,4-dihydroxyphenyl group, 3-hydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 3,4-dihydroxy-5-methoxyphenyl group, 2,4,5-trihydroxyphenyl group, 2,3,4-trihydroxyphenyl group, 4-hydroxyphenyl group, 2-hydroxy-5-styrylphenyl group, 2-hydroxy-5-methoxyphenyl group, 2,5-dihydroxyphenyl group, 2-hydroxyphenyl group, 2-hydroxy-3-methoxy-5-bromophenyl group, 2,3-dihydroxy-5-bromophenyl group, 3-methoxy-4-hydroxy-5-bromophenyl group, 3,4-dihydroxy-5-bromophenyl group, 2-hydroxy-5-(tert-butyl)phenyl group, 2-hydroxy-3-methoxy-6-bromophenyl group, 2,3-dihydroxy-6-bromophenyl group, 2,6-dihydroxyphenyl group, 2-bromo-4,5-dihydroxyphenyl group, 2-nitro-5-hydroxyphenyl group, 3-methoxy-4-hydroxy-5-carboxyphenyl group, 2-hydroxy-5-diethylaminophenyl group, 3-methoxy-4-hydroxy-5-nitrophenyl group, 2-hydroxy-5-(4-phenoxystyryl)phenyl group.

[Substituent Group R-1b-3] 2,3-dihydroxyphenyl group, 3,4-dihydroxyphenyl group, 2,4-dihydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 3,4-dihydroxy-5-methoxyphenyl group, 2,4,5-trihydroxyphenyl group, 2,3,4-trihydroxyphenyl group, 2,5-dihydroxyphenyl group, 2,3-dihydroxy-5-bromophenyl group, 3,4-dihydroxy-5-bromophenyl group, 2,3-dihydroxy-6-bromophenyl group, 2,6-dihydroxyphenyl group, 2-bromo-4,5-dihydroxyphenyl group.

Furthermore, preferred examples of the aromatic group which may be substituted represented by R¹include a phenyl group which is substituted with a C₂-C₆alkenyl group (said alkenyl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₂-C₆alkenyl group), and specific examples include a group selected from the following substituent group R-1b-4. Further preferred examples include 2-hydroxy-5-styrylphenyl group or 4-styrylphenyl group.

[Substituent Group R-1b-4] 2-hydroxy-5-styrylphenyl group, 2-methoxy-5-styrylphenyl group, 4-styrylphenyl group, 3,4-dimethoxy-6-styrylphenyl group, 2-hydroxy-5-(4-phenoxystyryl)phenyl group.

Furthermore, preferred examples of the aromatic group which may be substituted represented by R¹include a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group). More preferred examples include 3-carboxy-4-hydroxyphenyl group, 3-carboxyphenyl group, or 3-methoxy-4-hydroxy-5-carboxyphenyl group.

In the general formula (I), R²represents an aromatic group which may be substituted.

When W is —X—C(═Y)—, preferred examples of the aromatic group represented by R²include a C₆-C₁₀aryl group or a 6-membered heteroaryl group. More preferred examples include phenyl group or pyridyl group, and most preferred examples include phenyl group.

The aromatic group represented by R²may be substituted. Preferred examples of said substituent include a halogen atom; nitro group; a C₁-C₆alkyl group (more preferably, methyl group and tert-butyl group); a C₂-C₈alkenyl group (said alkenyl group may be substituted, and more preferred examples include styryl group and 3,5-bis(trifluoromethyl)styryl group); a C₆-C₁₀aryl group (more preferably, phenyl group); a halogenated C₁-C₆alkyl group (more preferably, trifluoromethyl group); hydroxy group; a C₁-C₆alkoxy group (more preferably, methoxy group); a C₆-C₁₀aryloxy group (more preferably, phenoxy group); carboxy group; a C₂-C₇alkoxycarbonyl group (more preferably, methoxycarbonyl group); a carbamoyl-substituted C₁-C₆alkyl group (said carbamoyl group may be substituted, and more preferred examples include benzylcarbamoylmethyl group); a C₇-C₁₁aroylamino group (said aroyl group may be substituted, and more preferred examples include benzoylamino group, 3,4-dichlorobenzoylamino group, and 4-phenoxybenzoylamino group); amino group; a C₆-C₁₀aryl-substituted carbamoyl group (more preferably, phenylcarbamoyl group); a C₆-C₁₀arylamino group (more preferably, phenylamino group); a C₂-C₇alkanoylamino group (said alkanoyl group may be substituted, and more preferred examples include phenoxyacetylamino group); and a C₈-C₁₃aralkylcarbonylamino group (said aralkyl group may be substituted, and more preferred examples include (3-phenoxyphenyl)acetylamino group, phenylacetylamino group, 3-phenylpropionylamino group, and 3,5-bis(trifluoromethyl)phenylacetylamino group). Further preferred examples include a halogen atom, a C₂-C₈alkenyl group (said alkenyl group may be substituted), a C₇-C₁₁aroylamino group (said aroyl group may be substituted), a halogenated C₁-C₆alkyl group, a C₈-C₁₃aralkylcarbonylamino group (said aralkyl group may be substituted), a C₂-C₇alkoxycarbonyl group, or carboxy group. It is preferable that the aromatic group represented by R²is substituted with one to three substituents independently selected from the aforementioned substituents.

Examples of the aromatic group which may be substituted represented by R²include, for example, a group selected from the following substituent group R-2a-1. [Substituent Group R-2a-1] phenyl group, 3,5-bis(trifluoromethyl)phenyl group, 3,5-dimethoxyphenyl group, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 3,5-di(tert-butyl)-4-hydroxyphenyl group, 2,4,5-trimethoxyphenyl group, 3-phenoxyphenyl group, 2,3-dichlorophenyl group, biphenyl-4-yl group (4-phenylphenyl group), 2,4-dichlorophenyl group, 3,5-difluorophenyl group, 3,5-dimethylphenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 3-bromophenyl group, 4-bromophenyl group, 3-(trifluoromethyl)phenyl group, 4-(trifluoromethyl)phenyl group, 3,5-dibromophenyl group, 3-nitrophenyl group, 4-nitrophenyl group, 4-styrylphenyl group, 4-[3,5-bis(trifluoromethyl)styryl]phenyl group, 4-phenoxyphenyl group, 3-fluorophenyl group, 4-methoxyphenyl group, 4-chloro-3-methoxycarbonylphenyl group, 3-carboxy-4-chlorophenyl group, 2-hydroxyphenyl group, 2,5-dimethoxyphenyl group, 3,4-dimethoxyphenyl group, 3,4-dihydroxyphenyl group, 3,4,5-trihydroxyphenyl group, 4-benzylcarbamoylmethylphenyl group, 4-benzoylaminophenyl group, 4-aminophenyl group, 4-(3,4-dichlorobenzoylamino)phenyl group, 4-(phenylcarbamoyl)phenyl group, 4-(phenylamino)phenyl group, 5,6-dichloropyridin-3-yl group, 2,5-bis(trifluoromethyl)phenyl group, 4-(phenoxyacetylamino)phenyl group, 4-[(3-phenoxyphenyl)acetylamino]phenyl group, 4-(phenylacetylamino)phenyl group, 4-(3-phenylpropionylamino)phenyl group, 4-(4-phenoxybenzoylamino)phenyl group, 4-[3,5-bis(trifluoromethyl)phenylacetylamino]phenyl group, 3-(phenylamino)phenyl group, 3-[(3-phenoxyphenyl)acetylamino]phenyl group, 4-methoxycarbonylphenyl group, 4-carboxyphenyl group.

Preferred examples of the aromatic group which may be substituted represented by R²include a phenyl group which is substituted with a C₂-C₈alkenyl group (said alkenyl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₂-C₈alkenyl group), a phenyl group which is substituted with one or two halogen atoms (said phenyl group may further be substituted with one or more substituents other than the halogen atom), a phenyl group which is substituted with a C₇-C₁₁aroylamino group (said aroyl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₇-C₁₁aroylamino group), a phenyl group which is substituted with one or two halogenated C₁-C₆alkyl groups (said phenyl group may further be substituted with one or more substituents other than the halogenated C₁-C₆alkyl group), a phenyl group which is substituted with a C₈-C₁₃is aralkylcarbonylamino group (said aralkyl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₈-C₁₃aralkylcarbonylamino group), or a phenyl group which is substituted with a C₂-C₇alkoxycarbonyl group (said phenyl group may further be substituted with one or more substituents other than the C₂-C₇alkoxycarbonyl group), and specific examples include a group selected from the following substituent group R-2a-2. More preferred examples include 4-styrylphenyl group, 2,4-dichlorophenyl group, 3,4-dichlorophenyl group, 4-(4-phenoxybenzoylamino)phenyl group, 2,3-dichlorophenyl group, 4-bromophenyl group, 4-(trifluoromethyl)phenyl group, 4-[(3-phenoxyphenyl)acetylamino]phenyl group, 4-[3,5-bis(trifluoromethyl)phenylacetylamino]phenyl group, 3-[(3-phenoxyphenyl)acetylamino]phenyl group, 3,5-bis(trifluoromethyl)phenyl group, or 4-methoxycarbonylphenyl group.

[Substituent Group R-2a-2] 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 2,3-dichlorophenyl group, 2,4-dichlorophenyl group, 3,5-difluorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 3-bromophenyl group, 4-bromophenyl group, 3,5-dibromophenyl group, 4-styrylphenyl group, 4-[3,5-bis(trifluoromethyl)styryl]phenyl group, 3-fluorophenyl group, 4-chloro-3-methoxycarbonylphenyl group, 3-carboxy-4-chlorophenyl group, 4-benzoylaminophenyl group, 4-(3,4-dichlorobenzoylamino)phenyl group, 4-(4-phenoxybenzoylamino)phenyl group, 3,5-bis(trifluoromethyl)phenyl group, 3-(trifluoromethyl)phenyl group, 4-(trifluoromethyl)phenyl group, 2,5-bis(trifluoromethyl)phenyl group, 4-[(3-phenoxyphenyl)acetylamino]phenyl group, 4-(phenylacetylamino)phenyl group, 4-(3-phenylpropionylamino)phenyl group, 4-[3,5-bis(trifluoromethyl)phenylacetylamino]phenyl group, 3-[(3-phenoxyphenyl)acetylamino]phenyl group, 4-methoxycarbonylphenyl group.

Furthermore, preferred examples of the aromatic group which may be substituted represented by R²include a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group). More preferred examples include 3-carboxy-4-chlorophenyl group, or 4-carboxyphenyl group.

When W is —C(R³)═N—, preferred examples of the aromatic group represented by R²include a C₆-C₁₀aryl group or a 6-membered heteroaryl group. More preferred examples include phenyl group or pyridyl group, and most preferred examples include phenyl group.

The aromatic group represented by R²may be substituted. Preferred examples of said substituent include a halogen atom; nitro group; a C₁-C₆alkyl group (more preferably, methyl group); a halogenated C₁-C₆alkyl group (more preferably, trifluoromethyl group); a C₁-C₆alkoxy group (more preferably, methoxy group); carboxy group; a C₂-C₇alkoxycarbonyl group (more preferably, methoxycarbonyl group); sulfamoyl group; and a C₂-C₆alkenyl group (said alkenyl group may be substituted, and more preferred examples include 2-(pyridin-2-yl)vinyl group). Further preferred examples include a halogen atom, nitro group, or carboxy group. It is preferable that the aromatic group represented by R²is substituted with one or two substituents independently selected from the aforementioned substituents.

Examples of the aromatic group which may be substituted represented by R²include, for example, a group selected from the following substituent group R-2b-1. [Substituent Group R-2b-1] phenyl group, 3,4-dichlorophenyl group, 3-carboxyphenyl group, 3,5-dichlorophenyl group, 3-methoxycarbonylphenyl group, 3-(trifluoromethyl)phenyl group, 4-methylphenyl group, 4-nitrophenyl group, 3-chlorophenyl group, 3,5-bis(trifluoromethyl)phenyl group, 3-chloro-4-methylphenyl group, 2,3-dimethylphenyl group, 3-methylphenyl group, 3-methoxyphenyl group, 3-nitrophenyl group, 4-fluorophenyl group, 4-chlorophenyl group, 3-carboxy-4-chlorophenyl group, 3-ethoxycarbonylphenyl group, 4-sulfamoylphenyl group, 6-chloropyridin-3-yl group, 2,5-dichlorophenyl group, 4-carboxyphenyl group, 3-chloro-4-fluorophenyl group, 4-[2-(pyridin-2-yl)vinyl]phenyl group.

Preferred examples of the aromatic group which may be substituted represented by R²include a phenyl group which is substituted with nitro group (said phenyl group may further be substituted with one or more substituents other than the nitro group), or a phenyl group which is substituted with one or two halogen atoms (said phenyl group may further be substituted with one or more substituents other than the halogen atom), and specific examples include a group selected from the following substituent group R-2b-2. More preferred examples include 4-nitrophenyl group, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, or 3-chloro-4-fluorophenyl group.

[Substituent Group R-2b-2] 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 4-nitrophenyl group, 3-chlorophenyl group, 3-chloro-4-methylphenyl group, 3-nitrophenyl group, 4-fluorophenyl group, 4-chlorophenyl group, 3-carboxy-4-chlorophenyl group, 2,5-dichlorophenyl group, 3-chloro-4-fluorophenyl group.

In the general formula (I), Z represents a single bond or a connecting group wherein a number of atoms in a main chain is 1 to 3 (said connecting group may be substituted). The “connecting group wherein a number of atoms of main chain is 1 to 3” represented by Z means a connecting group wherein 1 to 3 atoms in a main chain link together between the nitrogen atom and R²constituting the 5-membered hetero ring. The number of atoms of the main chain is counted so as to minimize the number of connecting atoms existing between said nitrogen atom and R², regardless of the presence or absence of hetero atom(s). The connecting group represented by Z may be substituted.

When W is —X—C(═Y)—, preferred examples of Z include a single bond, methylene group, ethylene group, —CH₂CO— group, or —CH₂CONH— group. More preferred examples include methylene group.

When W is —C(R³)═N—, preferred examples of Z include a single bond or methylene group. More preferred examples include a single bond.

When W is —X—C(═Y)—, the compound wherein R¹is an aromatic group which may be substituted,

R²is an aromatic group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group is preferred as the compound represented by the general formula (I).

The compounds which correspond to any one of the following (A), (B) and (C) are more preferred:

(A) the compound wherein R¹is a phenyl group which is substituted with one to three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²is an aromatic group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group;

(B) the compound wherein R¹is a phenyl group which is substituted with a C₆-C₁₀aryl-substituted carbamoyl group (said aryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the C₆-C₁₀aryl-substituted carbamoyl group), or a phenyl group which is substituted with a heteroaryl-substituted carbamoyl group (said heteroaryl group may be substituted, and said phenyl group may further be substituted with one or more substituents other than the heteroaryl-substituted carbamoyl group),

R²is an aromatic group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group;

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group:

(ii) R¹is an aromatic group which may be substituted,

R²is a phenyl group which is substituted with carboxy group (said phenyl group may further be substituted with one or more substituents other than the carboxy group).

The compound wherein R¹is a phenyl group which is substituted with two or three hydroxy groups (said phenyl group may further be substituted with one or more substituents other than the hydroxy group),

R²is a phenyl group which may be substituted,

X is sulfur atom,

Y is oxygen atom or sulfur atom,

Z is methylene group is preferred as the compound which corresponds to the aforementioned (A).

The compound selected from the compounds represented by the following compound numbers described in the specification is more preferred:

Compound Nos. 3, 4, 8 to 27, 29 to 38, 40 to 54, 56 to 61, 70, 81 to 84, 89, 301 to 307, 309, 311 to 321, 334, 335, 338, 339, 341, 342, 344, 347, 432, 446, 463, 464, 469, 470, 474, and 475.

The compound selected from the following 14 compounds is further preferred:

the compound wherein R¹is 3,4,5-trihydroxyphenyl group, R²is 3,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 2,3-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 2,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;

the compound wherein R¹is 3,4-dihydroxyphenyl group, R²is 2,4-dichlorophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group; the compound wherein R¹is 2,3-dihydroxyphenyl group, R²is 4-bromophenyl group, X is sulfur atom, Y is oxygen atom, Z is methylene group;