JPH11335298A - Therapeutic agent for leukemia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject agent significantly improving leukemia and useful for preventing or treating the leukemia by compounding an insulin resistance-improving substance as an active ingredient. SOLUTION: This therapeutic agent for leukemia contains an insulin resistance-improving substance, preferably 5-[4-(6-hydroxy-2,5,7,8- tetramethylchroman-2-ylmethoxy)benzyl]thiazoline-2,4-dione, as an active ingredient, preferably in an amount of 1-30 wt.% based on the total amount of the medicine. The agent is preferably administer, for example, at a daily dose of 1-500 mg for an adult with one or several portions, when orally administered. When intravenously administered, the agent is preferably administer at a daily dose of 0.1-200 mg for an adult with one or several portions.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a prophylactic or therapeutic agent for leukemia containing an insulin sensitizer as an active ingredient, and a composition for preventing or treating leukemia containing an insulin sensitizer as an active ingredient. For preventing or treating leukemia by using an insulin sensitizer or a pharmacologically effective amount of an insulin sensitizer to a warm-blooded animal for the manufacture of a medicament for preventing or treating leukemia About.

[0002]

2. Description of the Related Art Leukemia is a disease based on systematic and unrestricted proliferation of blood cell-forming tissues, and is regarded as a malignant tumor of hematopoietic tissues. Clinically, abnormal blood cells that are not normally found in peripheral blood appear, causing the proliferation and infiltration of leukemic cells into the bone marrow and other systemic organs. It is characterized by various organ disorders due to The frequency of occurrence is increasing worldwide, and the major causes of leukemia are genetic factors and viral infections such as retroviruses. Currently, chemotherapy, radiation therapy, immunotherapy, and a combination thereof are used as treatments for leukemia.

Conventionally, as a therapeutic agent for leukemia, for example, in acute leukemia which accounts for about 80% of leukemia in Japan, antimetabolites cytarabine (Ara-C), 6-mercaptopurine (6-MP), methotrexate (MXM) ), Anticancer antibiotics daunorubicin (DNR), idarubicin (IDR), alkylating agent cyclophosphamide (CY), plant alkaloid vincristine (VCR), podophyllotoxin derivative etoposide (VP-16), etc. However, in chronic leukemia, which accounts for about 20%, the alkylating agent busulfan (BUS
), Nimustine (ACNU) and the like. However, these therapeutic agents have various side effects such as nausea, vomiting, myelosuppression, liver injury, mucosal injury, myocardial injury, alopecia, hemorrhagic cystitis, and peripheral neuropathy. Therefore, a prophylactic or therapeutic agent which has a main effect of anti-leukemia and has few side effects has been desired.

[0004] By the way, the insulin sensitizer has an action of improving such a condition when the action of insulin is incomplete despite the presence of endogenous insulin. As such insulin sensitizers, compounds having various structures are known. Are disclosed, for example, in U.S. Pat. No. 4,572,912 (Japanese Patent Application Laid-Open No.
No. EP139421A); US Pat. No. 4,687,777.
No. (Japanese Patent Application Laid-Open No. 61-267580;
No. 9); U.S. Pat. No. 4,703,052 (JP-A-61-2).
No. 71287, Japanese Patent Publication No. 5-86953); U.S. Pat.
260445 (JP-A-1-131169); EP0
708098A (JP-A-9-48779); WO95
/ 18125; EP0676398A (JP-A-7-33)
0728); EP0745600A; EP03323
32A (JP-A-1-272574); EP06049
83A (JP-A-6-247945); WO94 / 01
433 (JP-A-6-80667); JP-A-4-693
No. 83; WO92 / 02520 (Tokuhei 6-50053)
No. 8); WO 91/07107 (JP-A-3-17047).
No. 8, JP-B-7-8882); U.S. Pat.
No. 17 (JP-A-3-90071); U.S. Pat.
7405 (JP-A-2-292272); WO89 /
086651 (Japanese Patent Application Laid-Open No. 1-272574); U.S. Pat.
No. 91 (JP-A-64-13076); U.S. Pat.
97393, 4948900 (JP-A-64-5667).
No. 5, JP-B 5-5832); U.S. Pat.
No. 55 (JP-A-64-38090); U.S. Pat.
No. 25610 (Japanese Patent Application Laid-Open No. 61-85372,
US Pat. No. 4,461,902 (JP-A-58-118577, Japanese Patent Publication No. 2-57546); US Pat. Nos. 4,287,200, 4,340,605, and 44381.
41, 4444479 (JP-A-55-22636,
JP-B-62-42903); and the like.

[0005] At present, insulin sensitizers are used as preventive or therapeutic agents for diabetes, as well as other diabetic complications.
It is known that it can be used for prevention or treatment of various diseases. For example, Japanese Unexamined Patent Publication No. 60-51189 (U.S. Pat. No. 4,572,912, EP 139421A)
5- [4- (6-hydroxy-).
2,5,7,8-Tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione (hereinafter referred to as “troglitazone”) is a thiazolidine derivative having an activity of enhancing insulin action.
It is also known as a prophylactic and / or therapeutic agent for diabetes [Diabetes, 37, 1459 (1988); Diabetes Care, 15, 107]
5 (1992)].

On the other hand, Japanese Patent Application Laid-Open Nos.
Proc. Natl. Acad. Sci., 94, 237 (1992) as published after JP-A-124623, JP-A-9-136877 and JP-A-9-194467 and the priority date of the present application.
7), WO9740017, WO9829120 and WO
9839006 describes a thiazolidinedione compound and an oxazolidinedione compound, and also discloses that these compounds have an anticancer effect. However, leukemia is not disclosed as a specific disease, and there is no description or suggestion that an insulin sensitizer is useful for prevention or treatment of leukemia. In addition, since the sensitivity of cancer cells to a drug may vary depending on the type of cancer, for example, a therapeutic agent for breast cancer or pancreatic cancer is not always useful as a therapeutic agent for leukemia.

Also, as disclosed on or after the priority date of the present application, Chem. Pharm. Bull., 45 (11), 1805 (1997) describes retinoid compounds having a thiazolidinedione structure. Discloses that the compound has an activity to induce differentiation of leukemia cells. However, these retinoid compounds having a thiazolidinedione structure are not included in the claims of the present application, and there is no direct description that they can be used as therapeutic agents for leukemia.

Further, as published after the priority date of the present application, WO9825598 and WO9829113
Describe thiazolidinedione compounds, and also discloses that these compounds can be therapeutic agents for leukemia. However, these compounds are not compatible with PPARγ (P
It is used as an agonist or activator of eroxisome Proliferator-Activated Receptor. On the other hand, the use of the compound in the present application is not limited to use as an agonist or activator of PPARγ.

[0009]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies on the pharmacological activity of an insulin sensitizer, and as a result, the insulin sensitizer significantly improved leukemia, and showed a prophylactic or therapeutic agent for leukemia. The present invention has been completed by finding that it is useful as an agent.

[0010]

The present invention relates to a preventive or therapeutic agent for leukemia containing an insulin sensitizer as an active ingredient, and a prophylactic or therapeutic agent for leukemia containing an insulin sensitizer as an active ingredient. The use of an insulin sensitizer for producing a medicament for the prevention or treatment of leukemia or a method for preventing leukemia by administering a pharmacologically effective amount of an insulin sensitizer to a warm-blooded animal; or Regarding treatment methods.

In particular, the insulin sensitizer is preferably a thiazolidinedione compound, an iminothiazolidinone compound, a diiminothiazolidine compound, a thioxothiazolidinone compound, or an iminotriazole. Compounds, oxazolidinedione (oxazolidinedione) compounds, isoxazolidinedione (isoxazolidinedione) compounds and oxadiazolidinedione (oxadiazolidinedione) compounds, preferably thiazolidinedione compounds, oxazolidinedione compounds, isoxazolidinedione compounds and oxadiazones. Lysine dione compounds, more preferably thiazolidinedione compounds, iminothiazolidinone compounds and diiminothiazolidine compounds, particularly preferably thiazolidinedione compounds and A Zorijinjion compound, optimally about prophylactic or therapeutic agents of leukemia containing compound is a thiazolidinedione compound as an active ingredient. The thiazolidinedione compound and the like include pharmacologically acceptable salts thereof.

As such an insulin sensitizer, the following compounds can be specifically exemplified. (I) JP-A-60-51189 (JP-B-2-31)
No. 079), US Pat. No. 4,572,912 and EP
139421A includes: (1) General formula (I)

[0013]

Embedded image [Wherein, R ^1a and R ^2a are the same or different and each represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, R ^3a represents a hydrogen atom, an aliphatic acyl group having 1 to 6 carbon atoms,
Cycloalkylcarbonyl groups having 6 to 8 carbon, substituents (a) may have an ^a benzoyl or naphthoyl group (said substituent (a) ^a is an alkyl group having 1 to 4 carbon atoms An alkoxy group having 1 to 4 carbon atoms, a hydroxy group, a halogen atom, an amino group,
A monoalkylamino group having 1 to 4 carbon atoms, a dialkylamino group having 1 to 4 carbon atoms, each of which is the same or different, or a nitro group; ), A 4- to 7-membered heterocyclic acyl group containing 1 to 3 heteroatoms selected from a heteroatom group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, a phenylacetyl group, a phenylpropionyl group, and at least one A phenylacetyl or phenylpropionyl group, a cinnamoyl group, an alkoxycarbonyl group having 2 to 7 carbon atoms or a benzyloxycarbonyl group substituted with halogen, wherein R ^4a and R ^5a are the same or different and each represents a hydrogen atom, 1 to 5
Represents an alkyl group or an alkoxy group having 1 to 5 carbon having a number, or R ^4a and R ^5a together indicates alkylenedioxy group having 1 to 4 carbon atoms, Y ^a and Z ^a is identical or different and each represents an oxygen atom or an imino group, n ^a is an integer of 1 to 3. Or a pharmacologically acceptable salt thereof.

[0014] In the compound having the general formula ^{(I), R 1a, R} 2a, R 3a, R 4a, R 5a, Y a, Z a, n a
And exemplary definitions represented by substituent (a) ^a, pharmacologically acceptable type of salt, the preparation of a compound having the general formula (I), compound examples, the details of such embodiments described in the above publication acids Have been.

In the above formula, when R ^1a , R ^2a , R ^4a or R ^5a represents an alkyl group, the group is a linear or branched alkyl group having 1 to 5 carbon atoms; For example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1-
Ethylpropyl and 2-ethylpropyl. It is preferably an alkyl group having 1 to 4 carbon atoms, and most preferably a methyl group.

When R ^3a represents an aliphatic acyl group having 1 to 6 carbon atoms, the group is a linear or branched aliphatic acyl group such as formyl, acetyl, propionyl, butyryl, Isobutyryl, pivaloyl, valeryl, isovaleryl and hexanoyl.

When R ^3a represents a cycloalkylcarbonyl group, the group is a group having 6 to 8 carbon atoms (for example, the cycloalkyl moiety has 5 to 7 carbon atoms), for example, cyclopentylcarbonyl, cyclohexylcarbonyl,
Cycloheptylcarbonyl.

When R ^3a represents a heterocyclic acyl group, the group is a group in which a heterocyclic group is bonded to a carbonyl group. The heterocyclic moiety is a 4- to 7-membered ring, preferably a 5- or 6-membered ring, and has 1 to 3, preferably 1 or 2 selected from a heteroatom group consisting of a nitrogen atom, an oxygen atom and a sulfur atom. , Optimally one heteroatom. If the heterocyclic moiety has three heteroatoms, preferably all are nitrogen atoms or one or two are nitrogen atoms and accordingly two or one are oxygen and / or sulfur atoms. The heterocyclic moiety is preferably an aromatic ring. Preferably, the heterocyclic acyl group is furoyl (preferably 2-furoyl), thenoyl (preferably 3-thenoyl), 3-pyridinecarbonyl (nicotinoyl), 4-
It is a pyridinecarbonyl (isonicotinoyl) group.

When R ^3a represents an alkoxycarbonyl group, the group is a linear or branched alkoxycarbonyl group having from 1 to 6, that is, 2 to 7 carbon atoms in total. For example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl. It is preferably an alkoxycarbonyl group having 2 to 4 carbon atoms, and most preferably an ethoxycarbonyl group.

Substituent (a) When ^a represents an alkyl group,
This group is a linear or branched alkyl group having 1 to 4 carbon atoms, and is, for example, the same as the alkyl groups exemplified for R ^1a and R ^2a .

Substituent (a) When ^a represents an alkoxy group, the group is a linear or branched alkoxy group having 1 to 4 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy. , Butoxy, isobutoxy, s-butoxy and t-butoxy. Preferably it is a methoxy group.

Substituent (a) When ^a represents ^a halogen atom, the atom is fluorine, chlorine, bromine or iodine.

Substituent (a) When ^a represents a monoalkylamino group, the group is a linear or branched alkylamino group having 1 to 4 carbon atoms, for example, methylamino, ethylamino , Propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino and t-butylamino. Preferably it is a methylamino group.

Substituent (a) When ^a represents a dialkylamino group, the group is a linear or branched dialkylamino group in which each alkyl moiety has 1 to 4 carbon atoms. , Diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, di-s-butylamino, di-t-butylamino, N-methyl-N-ethylamino, N-methyl-N-propylamino, N- Methyl-N-isopropylamino, N-methyl-N-butylamino, N-methyl-N-isobutylamino, N-methyl-Ns-butylamino, N-methyl-Nt-butylamino, N-ethyl -N-propylamino, N-ethyl-N-isopropylamino, N-ethyl-N-butylamino, N-ethyl-N-isobutyl Mino, N-ethyl-N-s-butylamino, N-ethyl-N-t-butylamino, N-propyl-N-isopropylamino, N-propyl-N-butylamino, N-propyl-N-isobutylamino , N
-Propyl-Ns-butylamino, N-propyl-N
-T-butylamino, N-isopropyl-N-butylamino, N-isopropyl-N-isobutylamino, N-
Isopropyl-Ns-butylamino, N-isopropyl-N-t-butylamino, N-butyl-N-isobutylamino, N-butyl-Ns-butylamino, N-butyl-Nt-butylamino , N-isobutyl-N-s
-Butylamino, N-isobutyl-Nt-butylamino, Ns-butyl-Nt-butylamino. Preferably, it is a dimethylamino group.

When R ^4a or R ^5a represents an alkoxy group,
The group is a linear or branched alkoxy group having 1 to 5 carbon atoms, such as methoxy, ethoxy,
Propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentyloxy. It is preferably an alkoxy group having 1 to 4 carbon atoms, and most preferably a methoxy group.

When R ^4a and R ^5a together represent an alkylenedioxy group, the group is an alkylenedioxy group having 1 to 4 carbon atoms, such as methylenedioxy, ethylenedioxy, propylenedioxy. Oxy, trimethylenedioxy and tetramethylenedioxy. Preferably, they are a methylenedioxy group and an ethylenedioxy group.

Among the compounds having the general formula (I), preferred compounds are shown below. (2) The compound wherein R ^1a is an alkyl group having 1 to 4 carbon atoms. (3) The compound wherein R ^1a is a methyl group. (4) The compound wherein R ^2a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. (5) The compound wherein R ^2a is a hydrogen atom or a methyl group. (6) The compound wherein R ^3a is a hydrogen atom, an aliphatic acyl group having 1 to 4 carbon atoms, a benzoyl or naphthoyl group having no substituent, or an alkoxycarbonyl group having 2 to 4 carbon atoms. (7) The compound wherein R ^3a is a hydrogen atom, an acetyl group, a benzoyl group or an ethoxycarbonyl group. (8) The compound wherein R ^3a is a hydrogen atom, an acetyl group or an ethoxycarbonyl group. (9) The compound wherein R ^4a is an alkyl group having 1 to 4 carbon atoms. (10) The compound wherein R ^4a is a methyl group or a t-butyl group. (11) The compound wherein R ^5a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. (12) The compound wherein R ^5a is a hydrogen atom or a methyl group.

However, for R ^1a , in the order of (2) and (3), for R ^2a , the order of (4) and (5), and for R ^3a , the order of (6)-(8), In R ^4a (9),
In order (10), in R ^5a is (11), in the order of (12), good specific ranking is increased.

Also, (2)-(3), (4)-(5),
(6)-(8), (9)-(10) and (11)-(1
It is also preferable to select 2 to 5 from 2) and arbitrarily combine them.
For example, it is shown below. (13) R ^1a is an alkyl group having 1 to 4 carbon atoms, R ^2a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ^3a is a hydrogen atom, 1 carbon atom An aliphatic acyl group having 1 to 4 carbon atoms, a benzoyl or naphthoyl group having no substituent or an alkoxycarbonyl group having 2 to 4 carbon atoms, and R ^4a is an alkyl group having 1 to 4 carbon atoms. Wherein R ^5a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. (14) R ^1a is an alkyl group having 1 to 4 carbon atoms, R ^2a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ^3a is a hydrogen atom, an acetyl group,
A benzoyl group or an ethoxycarbonyl group;
^4a is an alkyl group having 1 to 4 carbon atoms;
^The compound wherein ^5a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. (15) R ^1a is a methyl group, R ^2a is a hydrogen atom or a methyl group, R ^3a is a hydrogen atom, an acetyl group or an ethoxycarbonyl group, and R ^4a is a methyl group or t
A compound wherein R ^5a is a hydrogen atom or a methyl group.

Further preferred compounds are shown below. (16) 5- [4- (6-hydroxy-2,5,7,8
-Tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione (hereinafter referred to as troglitazone), 5- [4- (6-hydroxy-2-methyl-7-t-butylchroman-2-ylmethoxy) ) Benzyl] thiazolidine-2,4-dione (hereinafter referred to as compound C), 5- [4- (6-hydroxy-2-ethyl-5,7,8-trimethylchroman-2-ylmethoxy) benzyl] thiazolidine- 2,4-dione, 5-
[4- (6-hydroxy-2-isobutyl-5,7,8
-Trimethylchroman-2-ylmethoxy) benzyl]
Thiazolidine-2,4-dione, 5- [4- (6-acetoxy-2,5,7,8-tetramethylchroman-2-
Ylmethoxy) benzyl] thiazolidine-2,4-dione and 5- [4- (6-ethoxycarbonyloxy-
2,5,7,8-Tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione (hereinafter referred to as compound D). (II) JP-A-61-267580 (JP-B 5-66)
No. 956) and US Pat. No. 4,687,777.
(1) General formula (II)

[0031]

Embedded image Or a pharmacologically acceptable salt thereof.

The above-mentioned publications contain details of pharmacologically acceptable salts of the compound having the above general formula (II), methods for preparing the compound having the above general formula (II), examples of compounds and examples. Are listed.

Among the compounds having the general formula (II), preferred compounds are shown below. (2) 5- {4- [2- (3-ethyl-2-pyridyl)
Ethoxy] benzyl} -2,4-thiazolidinedione,
5- {4- [2- (4-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione, 5-
{4- [2- (5-ethyl-2-pyridyl) ethoxy]
Benzyl} -2,4-thiazolidinedione (hereinafter referred to as “pioglitazone”) and 5- {4- [2- (6-
Ethyl-2-pyridyl) ethoxy] benzyl {-2,4
-Thiazolidinedione. (III) JP-A-61-271287 (JP-B-5-8)
No. 6953) and U.S. Pat. No. 4,703,052: (1) General formula (III)

[0034]

Embedded image Wherein the dashed line represents a single bond or a non-bond, n ^c is 0,
^Xc is an oxygen atom, a sulfur atom, a sulfinyl group (S = O), a sulfonyl group (S (= O) (=
O)), wherein R ^c is a hydrogen atom, a methyl group or an ethyl group, and R ^1c is a hydrogen atom, a cycloalkyl group having 5 to 7 carbon atoms, a methyl-substituted cycloalkyl having 6 to 8 carbon atoms. Group, pyridyl group, thienyl group, furyl group, naphthyl group, p-biphenylyl group, tetrahydrofuranyl group, tetrahydrothienyl group, tetrahydropyranyl group, C ₆ H ₄ W ^2c group [W ^2c is a hydrogen atom, hydroxy group, fluorine Atom, chlorine atom, bromine atom, carbon number 1-4
An alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or an alkylthio group having 1 to 4 carbon atoms. Or an alk-W ^1c group [alk is an alkylene group having 1 to 6 carbon atoms, an ethylidene group or an isopropylidene group, W ^1c is a hydrogen atom, a hydroxy group, an alkoxy group having 1 to 4 carbon atoms, 1 to 4 carbon atoms
Alkylthio group, pyridyl group, furyl group, thienyl group, tetrahydrofuryl group, tetrahydrothienyl group, naphthyl group, cycloalkyl group having 5 to 7 carbon atoms, or C ₆ H ₄ W ^2c group. R ^2c is a hydrogen atom or a methyl group, R ^3c is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a C ₆ H ₄ W ^2c group or a benzyl group, and R ^4c is a hydrogen atom , and the when R ^1c and R ^2c are taken together, they form an alkylene group having 4 to 6 carbon atoms, R ^3c and R ^4c are each a hydrogen atom, R ^3c and R ^{When 4c} are taken together, they form an alkylene group having 4 to 6 carbon atoms, R ^1c and R ^2c are each a hydrogen atom, and R ^2c and R ^3c are taken together. In some cases, they form an alkylene group having 3 or 4 carbon atoms, and R ^1c and R ^4c
Is a hydrogen atom. Or a pharmacologically acceptable salt thereof.

The compound having the above general formula (III)
And R^c , R^1c, R^2c, R^3c, R ^4c, X^c , W^1c, W
^2c, N^c And definitions of alk, pharmacologically acceptable
Kinds of salts that can be formed, compounds having the above general formula (III)
Details of the production method, examples, etc. are described in the above publications.
You.

In the above formula, when R ^1c or W ^1c represents a cycloalkyl group, the group is a cyclopentyl, cyclohexyl or cycloheptyl group.

When W ^2c represents an alkyl group or an alkoxy group, and W ^1c represents an alkoxy group, these are the same as those described above for the substitution (a) ^a .

When W ^1c or W ^2c represents an alkylthio group, the group is a linear or branched alkylthio group having 1 to 4 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, Butylthio, isobutylthio, s-butylthio and t-butylthio. Preferably it is a methylthio group.

When alk represents an alkylene group having 1 to 6 carbon atoms, the group is a linear or branched alkylene group having 1 to 6 carbon atoms, for example, methylene, methylmethylene, ethylene , Ethylidene, propylene, isopropylidene, propylidene, trimethylene,
Tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, pentamethylene, hexamethylene, 1,1-dimethyltrimethylene,
2,2-dimethyltrimethylene, 1,1-dimethyltetramethylene, and 2,2-dimethyltetramethylene.
It is preferably a linear or branched alkylene group having 1 to 4 carbon atoms, and most preferably a methylene group or an ethylene group.

When R ^3c represents an alkyl group having 1 to 6 carbon atoms, the group is preferably an alkyl group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms.
A linear or branched alkyl group having, for example, methyl, ethyl, propyl, isopropyl,
Butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl,
1-ethylpropyl, hexyl, 4-methylpentyl,
3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl and 2-ethylbutyl. Preferably 1 to 4 carbon atoms
And more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and most preferably a methyl group.

R ^1c and R ^2c together or R ^3c and R ^4c
When together represent an alkylene group having 4 to 6 carbon atoms, or when R ^2c and R ^3c together represent an alkylene group having 3 to 4 carbon atoms, the group is linear Or a branched alkylene group such as tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, pentamethylene, hexamethylene, 1,1-dimethyltrimethylene,
2,2-dimethyltrimethylene, 1,1-dimethyltetramethylene, and 2,2-dimethyltetramethylene.

Among the compounds having the general formula (III), preferred compounds are shown below. (2) R ^c is a hydrogen atom, the broken line is non-bonded,
The compound according to (1), wherein n ^c is 0 or 1. (3) R ^2c , R ^3c and R ^4c are hydrogen atoms, and R ^1c is a hydrogen atom, cyclohexyl, C ₆ H ₄ W ^2c (W ^2c is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl group or A methoxy group.) Or alk-W ^1c [alk is an alkylene group having 1 to 4 carbon atoms, an ethylidene group or an isopropylidene group, and W ^1c is a hydrogen atom, a hydroxy group, a 1 to 4 carbon atoms. Alkoxy group, cyclohexyl group or C ₆ H ₄ W ^2c . ] The compound according to (2), wherein (4) X ^c is an oxygen atom, and R ^1c is a cyclohexyl group, a cyclohexylmethyl group, a benzyl group, a fluorobenzyl group, an alkyl group having 1 to 4 carbon atoms, a hydroxymethyl group, a methoxymethyl group or an ethoxyethyl group. (3) The compound according to (3), wherein (5) The compound according to (4), wherein R ^1c is a benzyl group. (6) 5-[(2-benzyl-2,3-dihydrobenzofuran-5-yl) methyl] thiazolidine-2,4-
Dione, 5-[(2-benzyl-3,4-dihydro-2
H-benzopyran-6-yl) methyl] thiazolidine-
2,4-dione (hereinafter, referred to as "englitazone")
Or the compound according to (5), which is a sodium salt thereof. (7) The compound according to (2), wherein R ^2c and R ^3c together form a — (CH ₂ ) ₄ — group, R ^1c and R ^4c are each a hydrogen atom, and X ^c is an oxygen atom. (8) (a) R ^1c and R ^2c together form a — (CH ₂ ) ₅ — group, R ^3c and R ^4c are each a hydrogen atom, and X ^c
Is an oxygen atom, or (b) R ^3c and R ^4c together form (CH ₂ ) ₅ , R ^1c and R ^2c are each a hydrogen atom, and X ^c is an oxygen atom (2) A compound as described. (9) The method according to (3), wherein n ^c is 0, R ^1c is a hydrogen atom, a methyl group or a benzyl group, and X ^c is a sulfur atom or a sulfonyl group (S (＝ O) (＝ O)). Compound. (IV) JP-A-1-131169, U.S. Pat.
002953, 5194443, 5232925 and 5260445 include: (1) General formula (IV)

[0043]

Embedded image [In the formula, A ^1d represents a substituted or unsubstituted aromatic heterocyclic group; R ^1d represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group (wherein the aryl moiety may be substituted or unsubstituted) good) or a substituted or unsubstituted aryl group; R ^2d and R ^3d are the same or different, represent a hydrogen atom, or R ^2d and R ^3d represents a bond together; a ^2d
Represents a benzene ring having up to 5 substituents in total;
And n ^d represents an integer in the range of 2 to 6. Or a pharmaceutically acceptable salt thereof.

[0044] In the compound having the general formula ^{(IV), A 1d, R} 1d, R 2d, an exemplary definition represented by R ^3d, A ^2d and n ^d, pharmaceutically acceptable type of salt, the general formula Details of the method for producing the compound having (IV), examples thereof, and suitable compounds are described in the above publications.

When A ^1d is a substituted or unsubstituted aromatic heterocyclic group, the group is a 5- to 7-membered ring containing 1 to 3 hetero atoms selected from an oxygen atom, a sulfur atom or a nitrogen atom. An aromatic monocyclic ring or a condensed ring in which at least one ring is the aromatic heterocyclic group described above and the other ring is an aromatic heterocyclic group or an aromatic hydrocarbon group. If the aromatic heterocyclic group contains 3 heteroatoms, it is preferably all nitrogen atoms or 1 or 2 nitrogen atoms and accordingly 2 or 1
This is an oxygen atom and / or a sulfur atom.

In the case of a monocyclic aromatic heterocyclic group, for example, furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,
Pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl. It is preferably a 5- to 7-membered aromatic heterocyclic group having at least one nitrogen atom and optionally another nitrogen atom, oxygen atom or sulfur atom. The group is preferably e.g. pyrrolyl, azepinyl, pyrazolyl,
Imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl. Most preferably, for example, pyridyl, imidazolyl, oxazolyl, pyrazinyl, thiazolyl.

The various aromatic heterocyclic groups described above may form a condensed ring with other ring groups, such as indolyl, benzofuryl, benzothienyl, benzoxazolyl, benzimidazolyl, isoquinolyl, quinolyl, quinoxalyl. is there.

The aromatic heterocyclic groups mentioned may be substituted by one or more substituents selected from unsubstituted or substituents below ^{(a) d (a) d} . The number of substitutions is not particularly limited, except for the number of substitutionable positions and steric hindrance. Generally, one to three substitutions are preferred.

The substitution (a) ^d is selected from:

A halogen atom, fluorine, chlorine, bromine, iodine atom; an alkyl group having 1 to 6 carbon atoms, for example, a group similar to that described for R ^3c above; a haloalkyl group having 1 to 6 carbon atoms For example, a group in which the alkyl group described for R ^3c is substituted with one or more halogen atoms, for example, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, trifluoromethyl, trichloromethyl, 2-fluoroethyl, 2-fluoroethyl Chloroethyl, 2-
Bromoethyl, 2-iodoethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, 2,2,2
-Trichloroethyl, 2,2-dichloroethyl, 2,2
-Dibromoethyl, 3-fluoropropyl, 4-chlorobutyl, 5-fluoropentyl, 6-fluorohexyl; an alkoxy group having 1 to 6 carbon atoms, which is a straight-chain or branched-chain alkoxy group. A group having 1 to 6, preferably 1 to 4, for example, methoxy,
Ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentyloxy, isopentyloxy, neopentyloxy, 2-
Methylbutoxy, 1-ethylpropoxy, hexyloxy, 4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 1-methylpentyloxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, , 1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,3-dimethylbutoxy, and 2-ethylbutoxy. Preferably it is an alkoxy group having 1 to 4 carbon atoms, more preferably methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, most preferably a methoxy group; a fatty acid having 1 to 6 carbon atoms Group acyl groups such as those described below for R ^1d ; alkanesulfonyl groups having 1 to 6 carbon atoms such as methanesulfonyl, ethanesulfonyl, propanesulfonyl, isopropanesulfonyl, butanesulfonyl, isobutanesulfonyl, s-butanesulfonyl, t-butanesulfonyl,
Pentanesulfonyl, isopentanesulfonyl, neopentanesulfonyl, 2-methylbutanesulfonyl, 1-
Ethylpropanesulfonyl, hexanesulfonyl, 4-
Methylpentanesulfonyl, 3-methylpentanesulfonyl, 2-methylpentanesulfonyl, 1-methylpentanesulfonyl, 3,3-dimethylbutanesulfonyl,
2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl, 1,2-dimethylbutanesulfonyl, 1,3-dimethylbutanesulfonyl, 2,3-dimethylbutanesulfonyl, 2-ethylbutanesulfonyl group; carbon number 1 Haloalkanesulfonyl groups having from 2 to 6 such as fluoromethanesulfonyl, chloromethanesulfonyl, bromomethanesulfonyl, iodomethanesulfonyl, trifluoromethanesulfonyl, trichloromethanesulfonyl, 2-fluoroethanesulfonyl, 2-
Chloroethanesulfonyl, 2-bromoethanesulfonyl, 2-iodoethanesulfonyl, 2,2,2-trifluoroethanesulfonyl, 2,2-difluoroethanesulfonyl, 2,2,2-trichloroethanesulfonyl,
2,2-dichloroethanesulfonyl, 2,2-dibromoethanesulfonyl, 3-fluoropropanesulfonyl,
4-chlorobutanesulfonyl, 5-fluoropentanesulfonyl, 6-fluorohexanesulfonyl group; hydroxy group; carboxy group; alkoxycarbonyl group in which the alkoxy moiety has 1 to 6 carbon atoms, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, Isopropoxycarbonyl, butoxycarbonyl,
Isobutoxycarbonyl, s-butoxycarbonyl, t
-Butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, 2-methylbutoxycarbonyl, 1-ethylpropoxycarbonyl, hexyloxycarbonyl, 4-
Methylpentyloxycarbonyl, 3-methylpentyloxycarbonyl, 2-methylpentyloxycarbonyl, 1-methylpentyloxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl,
1,2-dimethylbutoxycarbonyl; 1,3-dimethylbutoxycarbonyl; 2,3-dimethylbutoxycarbonyl; and 2-ethylbutoxycarbonyl. It is preferably an alkoxycarbonyl group having 2 to 5 carbon atoms, more preferably methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and most preferably methoxycarbonyl. An acylamino group having 1 to 6 carbon atoms, wherein the acyl moiety is R
An acyl group having 1 to 6 carbon atoms included in the group described in ^1d ; an alkanesulfonylamino group having 1 to 6 carbon atoms, wherein the alkanesulfonyl moiety is the group described above; A haloalkanesulfonylamino group, wherein the haloalkanesulfonyl moiety is a group as described above; an amino group; a cyano group; an alkylenedioxy group, for example, when R ^4a and R ^5a together represent an alkylenedioxy group. Groups similar to those described; alkylene groups having 1 to 8 carbon atoms (forming a cycloalkyl group condensed with an aromatic ring or a heterocyclic ring), such as the groups described in alk and hexamethylene and octamethylene; A high-class group.

When R ^1d represents an alkyl group, it is preferably a group having 1 to 6 carbon atoms, and is the same as described for R ^3c above.

When R ^1d represents an acyl group, it is an aliphatic acyl group, for example, an alkanoyl group having 1 to 25 carbon atoms, preferably 1 to 20 carbon atoms, more preferably 1 to 6 carbon atoms. And most preferably 1 to 4 carbon atoms (e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, isovaleryl, hexanoyl, heptanoyl, octanoyl, lauroyl, myristoyl, tridecanoyl, palmitoyl, stearoyl groups; Is an acetyl group); a halogenated alkanoyl group having 2 to 6 carbon atoms, particularly a halogenated acetyl group (eg, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl);
The alkoxy moiety has 1 to 5 carbon atoms (preferably 1 to 3 carbon atoms).
And the alkanoyl moiety has 2 to 6 carbon atoms (preferably an acetyl group), for example, a lower alkoxyalkanoyl group such as a methoxyacetyl group, or an unsaturated similar group of these groups, especially 3 carbon atoms. An alkenoyl or alkinoyl group (e.g. acryloyl, methacryloyl, propioloyl, crotonoyl, isocrotonoyl, (E) -2-methyl-2-butenoyl group) having from 6 to 6; an aromatic acyl group, preferably an arylcarbonyl group; The group has an aryl moiety having 6 to 14 carbon atoms.
, Preferably 6 to 10, more preferably 6 or 1
0, optimally 6, the carbocyclic group is unsubstituted or has 1 to 5, preferably 1 to 3, substituents (a) ^d as defined above. Preferably, an unsubstituted group (eg, benzoyl, α-naphthoyl, β-naphthoyl group); a halogenated arylcarbonyl group (eg, 2-bromobenzoyl, 4-chlorobenzoyl group); a lower alkyl-substituted arylcarbonyl group, The component has 1 to 5 carbon atoms, preferably 1 to 4 carbon atoms (for example, 2, 4, 6-
A lower alkoxy-substituted arylcarbonyl group, preferably having 1 to 5 carbon atoms, more preferably 1 to 4 carbon atoms (eg, 4-anisoyl group); nitro substitution Arylcarbonyl group (eg, 4-nitrobenzoyl, 2-nitrobenzoyl group); lower alkoxycarbonyl-substituted arylcarbonyl group, the alkoxycarbonyl substitution of which is preferably 2 to 6 carbon atoms [eg, 2- (methoxycarbonyl) benzoyl Group]; an aryl-substituted arylcarbonyl group, and the aryl-substituted moiety is as described above, except that the substituent is further substituted with an aryl group (for example, a 4-phenylbenzoyl group); A carbonyl group, preferably having 2 to 7 carbon atoms
And more preferably 2 to 5, unsubstituted groups (for example, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, isobutoxycarbonyl group) or halogen atoms or trisubstituted silyl groups such as tri (lower alkylsilyl) Groups (eg, 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilylethoxycarbonyl); alkenyloxycarbonyl, wherein the alkenyl moiety has 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms (eg, vinyloxy Aralkyloxycarbonyl group; the aralkyl moiety is described below, and the aryl ring is preferably substituted with one or two lower alkoxy, nitro (eg, benzyloxycarbonyl, 4-methoxybenzyloxyca Boniru, 3,4-dimethoxybenzyl oxycarbonyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl group); a.

When R ^1d represents an aralkyl group, it is preferred that at least one alkyl having 1 to 6 carbon atoms be used.
Preferably, it is a group substituted with 1 to 3 aryls (the aryls are substituted with one or more, preferably 1 to 3 selected from substituents π). Preferably the aralkyl group has 1 to 4 carbon atoms, more preferably 1 to 3 and optimally 1 or 2 alkyl, wherein the alkyl is substituted with 1 to 3 unsubstituted aryl. Group (for example, benzyl, phenethyl, 1-phenylethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl group) or Groups substituted with aryl substituted with lower alkyl, lower alkoxy, nitro, halogen, cyano, alkylenedioxy having 1 to 3 carbon atoms, preferably methylenedioxy (for example, 4-methylbenzyl, 2,4 , 6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-
Methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-
Chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzyldiphenylmethyl, bis (2
-Nitrophenyl) methyl, piperonyl group).

When R ^1d represents a substituted or unsubstituted aryl group, it has 6 to 14 carbon atoms, preferably 6 to 10 carbon atoms.
And most preferably 6 or 10 carbocyclic aryl groups. The group is one aromatic ring group or two or more fused aromatic ring groups. The group is unsubstituted or substituted with one or more substituents selected from the substituents (a) ^d . The number of substitutions is not particularly limited, except for the number of substitutionable positions and steric hindrance.
Generally, one to three substitutions are preferred. Examples of the unsubstituted aryl group include phenyl, 1-naphthyl, 2-naphthyl, indenyl, phenanthrenyl, and anthracenyl group, preferably phenyl and naphthyl, and most preferably phenyl. Examples of the substituted aryl group include 2-methoxyphenyl, 3-methoxyphenyl,
-Methoxyphenyl, 2,4-dimethoxyphenyl,
2,3-dimethoxyphenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5
-Trimethoxyphenyl, 2,4,5-trimethoxyphenyl, 2,3,4-trimethoxyphenyl, 2,3,
5-trimethoxyphenyl, 2,3,6-trimethoxyphenyl, 2,4,6-trimethoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-isopropoxyphenyl, 3-iso Propoxyphenyl, 4-isopropoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,4-dimethylphenyl, 2,3-dimethylphenyl, 2,5-dimethylphenyl, 3,4-dimethyl Phenyl, 3,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2,4,
5-trimethylphenyl, 2,3,4-trimethylphenyl, 2,3,5-trimethylphenyl, 2,3,6-
Trimethylphenyl, 2,4,6-trimethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2,3-dichlorophenyl, 2,5-dichlorophenyl, 3,4-
Dichlorophenyl, 3,5-dichlorophenyl, 2,6
-Dichlorophenyl, 3,4,5-trichlorophenyl, 2,4,5-trichlorophenyl, 2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl,
2,3,6-trichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2,3-difluorophenyl, 3,4 -Difluorophenyl, 3,5-difluorophenyl, 2,6-
Difluorophenyl, 3,4,5-trifluorophenyl, 2,4,5-trifluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2,4-bis ( Trifluoromethyl) phenyl, 2,3-bis (trifluoromethyl) phenyl, 3,4-bis (trifluoromethyl) phenyl, 3,5-bis (trifluoromethyl) phenyl, 2,6-bis (trifluoro Methyl) phenyl, 3,4,5-tris (trifluoromethyl) phenyl, 2,4,5-tris (trifluoromethyl) phenyl, 2-acetamidophenyl, 3-acetamidophenyl, 4-acetamidophenyl, 2-methoxy Carbonylphenyl, 3-methoxycarbonylphenyl,
4-methoxycarbonylphenyl group.

When A ^2d is a benzene ring having a maximum of 5 substitutions, it is preferably a group selected from the above substitutions (a) ^d .

Among the compounds having the general formula (IV), preferred compounds are shown below. (2) The method according to (1), wherein A ^1d represents a substituted or unsubstituted monocyclic or condensed-ring aromatic heterocyclic group containing up to 4 heteroatoms selected from an oxygen atom, a sulfur atom or a nitrogen atom in the ring. Compound. (3) A ^1d is the formula (a), (b) or (c)

Embedded image [Wherein, R ^4d and R ^5d are the same or different and each represent a hydrogen atom,
Represents an alkyl group or a substituted or unsubstituted aryl group, or when R ^4d and R ^5d are the same or different and are bonded to a carbon atom, R ^4d and R ^5d together with the carbon atom to which they are bonded; And each of the carbon atoms represented by R ^4d and R ^5d together may be substituted or unsubstituted; and in the moiety of formula (a), X ^d is an oxygen atom or Represents a sulfur atom. ] The compound according to (1) or (2), wherein (4) The compound according to (3), wherein R ^4d and R ^5d are the same or different and each represent a hydrogen atom, an alkyl group, or a substituted or unsubstituted phenyl group. (5) R ^4d and R ^5d together form formula (d)

Embedded image (3) The compound according to (3), wherein R ^6d and R ^7d are the same or different and each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl or alkoxy group. (6) The compound according to (5), wherein R ^6d and R ^7d both represent a hydrogen atom. (7) A ^2d is the formula (e)

Embedded image (Wherein R ^8d and R ^9d are the same or different and represent a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl or alkoxy group), and any one of (1) to (6). Compound. (8) The compound according to (7), wherein R ^8d and R ^9d are the same or different and each represent a hydrogen atom. (9) Equation (f)

Embedded image Wherein A ^1d , R ^1d , R ^2d , R ^3d and ^nd are as defined for formula (IV) of (1), and R ^8d and R ^9d are defined for formula (e) of (7) As you did. ] The compound according to (1) or a pharmacologically acceptable salt thereof. (10) n ^d represents an integer of 2 or 3 (1) to (9)
13. The compound according to any one of the above. (11) The compound according to any one of (1) to (10), wherein R ^1d represents a methyl group. (12) 5- {4- (2- [N-methyl-N- (2-benzothiazolyl) amino] ethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (2- [N-methyl- N- (2-pyrimidinyl) amino] ethoxy) benzyl {thiazolidine-2,4-dione, 5- {4- [2
-(N-methyl-N- [2- (4,5-dimethylthiazolyl)] amino) ethoxy] benzyl {thiazolidine-
2,4-dione, 5- {4- (2- [N-methyl-N-
(2-Thiazolyl) amino] ethoxy) benzyl {thiazolidine-2,4-dione, 5- {4- [2- (N-methyl-N- [2- (4-phenylthiazolyl)] amino) ethoxy] Benzyl {thiazolidine-2,4-dione, 5- {4- [2- (N-methyl-N- [2- (4-
Phenyl-5-methylthiazolyl)] amino) ethoxy] benzyl {thiazolidine-2,4-dione, 5-
{4- [2- (N-methyl-N- [2- (4-methyl-
5-phenylthiazolyl)] amino) ethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [2-
(N-methyl-N- [2- (5-phenyloxazolyl)] amino) ethoxy] benzyl {thiazolidine-
2,4-dione, 5- {4- [2- (N-methyl-N-
[2- (4,5-dimethyloxazolyl)] amino) ethoxy] benzyl {thiazolidine-2,4-dione, 5
-{4- [2- (2-pyrimidinylamino) ethoxy]
Benzyl @ thiazolidine-2,4-dione, 5- @ 4-
(2- [N-acetyl-N- (2-pyrimidinyl) amino] ethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (2- [N- (2-benzothiazolyl)]
-N-benzylamino] ethoxy) benzyl {thiazolidine-2,4-dione, 5- {4- (3- [N-methyl-N- (2-benzoxazolyl) amino] propoxy)
Benzyl @ thiazolidine-2,4-dione and 5- @ 4
-(2- [N-methyl-N- (2-pyridyl) amino]
The compound according to (1), which is selected from ethoxy) benzyldithiazolidine-2,4-dione (hereinafter, referred to as “rosiglitazone”). (13) 5- {4- (2- [N-methyl-N- (2-pyridyl) amino] ethoxy) benzyl} thiazolidine-
The compound according to (1), which is 2,4-dione (rosiglitazone).

In the above (2) to (11), R ^4d ,
The definitions of the groups represented by R ^5d , R ^6d , R ^7d , R ^8d and R ^9d are described in the above publications as R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ^8.
It is listed as ⁹ . JP-A-9-48779 and EP708080A include: (1) General formula (V)

[0058]

Embedded image [Wherein, R ^1e represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms, and R ^2e represents a linear or branched alkyl group having 2 to 6 carbon atoms. R ^3e represents a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, and a carbon atom of 1
Straight-chain or branched alkoxy group having 1 to 4 carbon atoms, straight-chain or branched alkylthio group having 1 to 4 carbon atoms, halogen atom, nitro group, amino group, 1 to 4 carbon atoms A linear or branched monoalkylamino group having 4 carbon atoms, a linear or branched dialkylamino group having the same or different alkyl groups each having 1 to 4 carbon atoms, X represents an aryl group having 10 or an aralkyl group having 7 to 12 carbon atoms, and X ^e has 6 to 10 carbon atoms which may have 1 to 3 substituents (a) ^e An aryl group or an aromatic heterocyclic group optionally having 1 to 3 substituents (a) ^e , wherein the substituent (a) ^e is (i) a straight chain having 1 to 6 carbon atoms; A chain or branched alkyl group, (ii) carbon number A linear or branched alkyl halide group having 1 to 4 groups, (iii)
A hydroxy group, (iv) a linear or branched acyloxy group having 1 to 4 carbon atoms, (v) a linear or branched alkoxy group having 1 to 4 carbon atoms, vi) a linear or branched alkylenedioxy group having 1 to 4 carbon atoms, (vii)
An aralkyloxy group having 7 to 12 carbon atoms,
(Viii) a linear or branched alkylthio group having 1 to 4 carbon atoms, (ix) 1 to 4 carbon atoms
A linear or branched alkylsulfonyl group having (x) a halogen atom, (xi) a nitro group,
(Xiii) an amino group, (xiii) a linear or branched monoalkylamino group having 1 to 4 carbon atoms, and (xiv) a straight or branched alkyl group having 1 to 4 carbon atoms, each alkyl having 1 to 4 carbon atoms. A chain or branched dialkylamino group, (xv) an aralkyl group having 7 to 12 carbon atoms, (xvi) having 6 to 10 carbon atoms which may have a substituent (b) ^e Aryl group,
(Xvii) an aryloxy group having 6 to 10 carbon atoms which may have a substituent (b) ^e , (xvii
i) a carbon number of 6 to 1 which may have a substituent (b) ^e ;
An arylthio group having 0, (xix) an arylsulfonyl group having 6 to 10 carbon atoms which may have a substituent (b) ^e , and (xx) an arylsulfonyl group having a substituent (b) ^e An arylsulfonylamino group having a good number of carbon atoms of 6 to 10 (the nitrogen atom in the amino portion has 1 carbon atom
(Xxi) an aromatic heterocyclic group, (xxii) an aromatic heterocyclic oxy group, (xxii)
i) an aromatic heterocyclic thio group, (xxiv) an aromatic heterocyclic sulfonyl group, and (xxv) an aromatic heterocyclic sulfonylamino group (the nitrogen atom of the amino moiety has 1 to 6 carbon atoms.
May be substituted with a straight-chain or branched-chain alkyl. ).

Here, the substituent (b) ^e is a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms, a straight-chain or branched-chain halogen group having 1 to 4 carbon atoms. Alkyl group, linear or branched alkoxy group having 1 to 4 carbon atoms, halogen atom or 1 carbon atom
Represents a linear or branched alkylenedioxy group having from 4 to 4, and Y ^e represents an oxygen atom, a sulfur atom or a formula
A group having> N—R ^4e , wherein R ^4e is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkyl group having 1 to 8 carbon atoms, shows a branched acyl group.) indicates, Z ^e is 2,4-dioxo-thiazolidin-5-Iridenirumechiru group, 2,4-dioxothiazolidin-5-ylmethyl group, 2,4-dioxo-oxazolidinedione It represents a -5-ylmethyl group or a 3,5-dioxooxadiazolidine-2-ylmethyl group. ] Or a pharmacologically acceptable salt thereof.

In the compound having the above general formula (V)
And R^1e, R^2e, R^3e, R^4e, (A) ^e , (B)^e , X
^e , Y^e And Z^e Illustrative definition, pharmacologically acceptable
Of compounds having the above general formula (V)
Details of methods, compound examples, examples, etc. are described in the above publications.
ing.

R ^3e , substitution (a) ^e , substitution (b) ^e is an alkoxy group having 1 to 4 carbon atoms, a halogen atom or R ^3e , substitution (a) ^e is mono- or di-alkyl When it represents an amino group, these are substituted (a) ^a
It is the same as that described above.

When the substituted component (a) ^e and the substituted component (b) ^e represent an alkylenedioxy group, this is the same as the case where R ^4a and R ^5a described above together represent an alkylenedioxy group. It is.

When R ^3e and the substituent (a) ^e represent an alkylthio group, this is the same as that described for W ^2c above.

When R ^1e , R ^3e , substitution (a) ^e , substitution (b) ^e , and R ^4e represent an alkyl group having 1 to 6 carbon atoms, these are the same as those described above for R ^3c. Is the same as

When X ^e and the substituent (a) ^e represent an aromatic heterocyclic group, this is the same as that described for A ^1d above.

When R ^3e and the substituent (a) ^e represent an aralkyl group, or R ^3e , X ^e and the substituent (a) ^e represent an aryl group, these are the same as those described above for R ^1d. .

When R ^2e represents a linear or branched alkylene group having 2 to 6 carbon atoms, this is the same as described above for alk.

When the substituted component (a) ^e and the substituted component (b) ^e represent a halogenated alkyl group, the alkyl moiety is a straight or branched alkyl group having 1 to 6, preferably 1 to 3 carbon atoms. It is a branched alkyl. The number of halogen atoms is not particularly limited, except for the number of substitutable positions and steric hindrance. Generally, one to three substitutions are preferred. These include, for example, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, 2,2,2-trichloroethyl,
2,2,2-trifluoroethyl, 2-bromoethyl,
2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 2,2-dibromoethyl, 3-bromopropyl,
3-chloropropyl, 3-fluoropropyl, 3-iodopropyl, 4-bromobutyl, 4-chlorobutyl,
-Fluorobutyl, 4-iodobutyl, 5-bromopentyl, 5-chloropentyl, 5-fluoropentyl, 5
—Iodopentyl, 6-bromohexyl, 6-chlorohexyl, 6-fluorohexyl, 6-iodohexyl, and preferably trifluoromethyl, 2-bromoethyl, 2-chloroethyl, and 2-fluoroethyl.

When the substituent (a) ^e represents an acyloxy group, the group is a linear or branched aliphatic acyloxy group having 1 to 4 carbon atoms. For example, formyloxy, acetoxy, propionyloxy, butyryloxy and isobutyryloxy groups.

Substituent (a) ^e is alkylsulfonyl, aralkyloxy, aryloxy, arylthio, arylsulfonyl, arylsulfonylamino, aromatic heterocyclic oxy, aromatic heterocyclic thio, aromatic heterocyclic sulfonyl, aromatic heterocyclic When it is a sulfonylamino group, the alkyl, aralkyl, aryl and aromatic heterocyclic moieties are the same as those described above.

When R ^4e represents an acyl group having 1 to 8 carbon atoms, it is preferably aliphatic or carbocyclic aromatic,
For example, it is as follows.

In the case of an aliphatic acyl group, it preferably has 1 carbon atom.
Alkanoyl groups having from 1 to 8, more preferably 1 to 6, and most preferably 1 to 4 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, isovaleryl, hexanoyl Acetyl group; heptanoyl, octanoyl group; most preferably acetyl group; halogenated alkanoyl group having 2 to 6 carbon atoms, especially halogenated acetyl group, for example, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl group; The alkoxy moiety has 1 to 5 carbon atoms, preferably 1 to 3 carbon atoms, and the alkanoyl moiety has 2 to 6 carbon atoms, preferably an acetyl group;
A lower alkoxyalkanoyl group having, for example, a methoxyacetyl group; or an unsaturated similar group of these groups, especially an alkenoyl having 3 to 6 carbon atoms, an alkinoyl group such as acryloyl, methacryloyl, propioloyl, crotonoyl, isocrotonyl,
(E) -2-methyl-2-butenoyl group); in the case of an aromatic acyl group, an arylcarbonyl group,
For example, benzoyl, α-naphthoyl, β-naphthoyl groups; halogenated arylcarbonyl groups such as 2-bromobenzoyl, 4-chlorobenzoyl groups; lower alkyl-substituted arylcarbonyl groups such as 4-toluoyl groups; lower alkoxy-substituted arylcarbonyl A nitro-substituted arylcarbonyl group, for example, 4-nitrobenzoyl or 2-nitrobenzoyl group; a lower alkoxycarbonyl-substituted arylcarbonyl group, for example, 2- (methoxycarbonyl)
A benzoyl group;

In the compound having the above general formula (V)
Thus, suitable compounds are shown below. (2) R^1eHas a hydrogen atom or 1 to 4 carbon atoms
(1) which represents a linear or branched alkyl group
Listed compound. (3) R^1eHas a hydrogen atom or 1 to 3 carbon atoms
(1) which represents a linear or branched alkyl group
Listed compound. (4) R^1eRepresents a hydrogen atom, a methyl group or an ethyl group
The compound according to (1). (5) R^1eRepresents a methyl group or an ethyl group (1).
Compound. (6) R^2eHas a straight-chain structure having 2 to 5 carbon atoms.
Or a branched alkylene group;
Stuff. (7) R^2eIs a straight chain having 2 to 3 carbon atoms
Or a branched alkylene group;
Stuff. (8) R^2eIs ethylene group, trimethylene group or methyl
The compound according to (1), which represents an ethylene group. (9) R^2eThe compound according to (1), wherein represents an ethylene group. (10) R^3eHas a hydrogen atom and has 1 to 4 carbon atoms
Linear or branched alkyl group, having 1 or 2 carbon atoms
Alkoxy group having 1 or 2 carbon atoms,
The compound according to (1), which represents a alkylthio group or a halogen atom
Stuff. (11) R^3eIs a compound according to (1), which represents a hydrogen atom. (12) X^e Is 1 to 3 substitutions (a)^e Have
An aryl group having 6 to 10 carbon atoms which may be present,
Is 1 to 3 substitutions (a)^e Nitrogen which may have
Having 1 to 3 atoms, oxygen atoms and / or sulfur atoms
5- to 10-membered heteroaromatic (consisting of one or two rings)
A cyclic group, in which the substituent (a)^e Is (i) carbon number 1
Linear or branched alkyl having from 6 to 6
(Ii) a linear or linear group having 1 to 4 carbon atoms
Is a branched alkyl halide group, (iii) hydride
A roxy group, (iv) a linear group having 1 to 4 carbon atoms
Or a branched acyloxy group, (v) carbon number 1
Linear or branched alkoxy having from 4 to 4
(Vi) linear or straight-chain having 1 to 4 carbon atoms
Is a branched alkylenedioxy group, (vii) carbon number
An aralkyloxy group having 7 to 12 (vii
i) linear or branched having 1 to 4 carbon atoms
(Ix) having 1 to 4 carbon atoms
Linear or branched alkylsulfonyl group,
(X) a halogen atom, (xi) 7 to 12 carbon atoms
Aralkyl group having (xii) substitution (b)^e Has
(Xiii) a substituted phenyl group (b)
^e A phenoxy group optionally having: (xiv) substitution
Minutes (b)^e A phenylthio group optionally having (x)
v) Substitution (b)^e Phenylsulfo optionally having
Nyl group, (xvi) Substitution (b)^e May have
Phenylsulfonylamino group (nitrogen atom of amino moiety
Is a straight or branched chain having 1 to 6 carbon atoms
It may be substituted with alkyl. ), (Xvii)
Furyl, thienyl, oxazolyl, isoxazo
Ryl, thiazolyl, pyridyl, pyridyloxy
Group, pyridylthio group, pyridylsulfonyl group, (xv
iii) imidazolyl group (the nitrogen atom has 1 to 6 carbon atoms)
Substituted with a linear or branched alkyl having
May be. ) And / or (xix) pyridyls
A rufonylamino group (the nitrogen atom in the amino moiety has 1 carbon atom)
Substituted with straight or branched alkyl having up to 6
It may be replaced. ), Where the substitution (b)^e 
Is a straight or branched chain having 1 to 6 carbon atoms
Alkyl group, straight-chain having 1 to 4 carbon atoms or
A branched alkyl halide group having 1 to 4 carbon atoms
Linear or branched alkoxy group, halogenated
Linear or branched having 1 to 4 carbon atoms
The compound according to (1), which represents a branched alkylenedioxy group.
Stuff. (13) X^e Is 1 to 3 substitutions (a)^e Have
An aryl group having 6 to 10 carbon atoms which may be present,
Is 1 to 3 substitutions (a)^e Nitrogen which may have
Having 1 to 3 atoms, oxygen atoms and / or sulfur atoms
5- to 10-membered heteroaromatic (consisting of one or two rings)
A cyclic group, in which the substituent (a)^e Is (i) carbon number
Linear or branched alkyl having 1 to 6
(Ii) a linear or linear group having 1 to 4 carbon atoms
Is a branched alkyl halide group, (iii) hydride
A roxy group, (iv) a linear group having 1 to 4 carbon atoms
Or a branched alkanoyloxy group, (v) carbon
Linear or branched alcohols having the number 1 to 4
An xyl group, (vi) a straight chain having 1 to 4 carbon atoms
Or a branched alkylenedioxy group, (vii) charcoal
An aralkyloxy group having a prime number of 7 to 12, (v
iii) linear or branched having 1 to 4 carbon atoms
A chain alkylthio group, (ix) having 1 to 4 carbon atoms
A linear or branched alkylsulfonyl group,
 (X) a fluorine atom, a chlorine atom, a bromine atom, (xi)
An aralkyl group having 7 to 12 carbon atoms, (xi
i) Substitution (b)^e A phenyl group which may have
(Xiii) Substitution (b)^e Pheno which may have
Xy group, (xiv) Substitution (b)^e May have
Phenylthio group, (xv) substitution (b)^e Have
An optionally substituted phenylsulfonyl group, (xvi) a substituted moiety
(B) ^e Phenylsulfonylamino optionally having
Group (the nitrogen atom in the amino moiety has 1 to 6 carbon atoms)
Even if it is substituted by linear or branched alkyl
Good. ), (Xvii) furyl, thienyl, oxo
Sazolyl, isoxazolyl, thiazolyl, pyri
Jill, pyridyloxy, pyridylthio, pyridyl
A sulfonyl group, (xviii) an imidazolyl group (nitrogen
Atom is linear or branched with 1 to 6 carbon atoms
May be substituted with alkyl in the form. ), And / or
 (Xix) pyridylsulfonylamino group (amino moiety
Is a straight-chain having 1 to 6 carbon atoms or
It may be substituted with a branched alkyl. )
And the substitution (b)^e Has 1 to 6 carbon atoms
Linear or branched alkyl group, having 1 to 4 carbon atoms
Linear or branched alkyl halides
A straight or branched chain having 1 to 4 carbon atoms
Alkoxy group, halogen atom or 1 to 4 carbon atoms
Linear or branched alkylenedioxy having
The compound according to (1), which represents a group. (14) X^e Is 1 to 3 substitutions (a)^e Have
Phenyl group, naphthyl group, imidazolyl group,
Oxazolyl group, pyridyl group, indolyl group, quinolyl
Or an isoquinolyl group, wherein the substituent (a)^e 
Is selected from the group consisting of: (i) a straight-chain having 1 to 6 carbon atoms or
A branched alkyl group, (ii) having 1 to 4 carbon atoms
Linear or branched alkyl halides
Group, (iii) hydroxy group, (iv) 1 carbon atom
Linear or branched alkanoyl having at most 4
An oxy group, (v) a straight-chain having 1 to 4 carbon atoms
Or a branched alkoxy group, (vi) methylenedioxy
(Vii) Aral having 7 to 12 carbon atoms
A killoxy group, (viii) having 1 to 4 carbon atoms
A linear or branched alkylthio group, (i
x) linear or branched having 1 to 4 carbon atoms
An alkylsulfonyl group of (x) a fluorine atom, a chlorine atom
Atom, bromine atom, (xi) having 7 to 12 carbon atoms
An aralkyl group, (xii) a phenyl group (the phenyl is
Methyl, trifluoromethyl, methoxy, fluoro or
It may be substituted by methylenedioxy. ), (X
iii) a phenoxy group (where the phenyl is methyl, trifur
Oromethyl, methoxy, fluoro or methylenedioxy
May be substituted. ), (Xiv) phenylthio
Group (the phenyl is methyl, trifluoromethyl,
Substituted with xy, fluoro or methylenedioxy
Is also good. ), (Xv) a phenylsulfonyl group (the
Nyl is methyl, trifluoromethyl, methoxy, fluoro
Or it may be substituted with methylenedioxy. ),
 (Xvi) a phenylsulfonylamino group (the phenyl
Is methyl, trifluoromethyl, methoxy, fluoro or
May be substituted with methylenedioxy. Amino part
The nitrogen atom is linear or linear having 1 to 6 carbon atoms
May be substituted with a branched alkyl. ),
(Xvii) a furyl group, a thienyl group, an oxazolyl group,
Isoxazolyl, thiazolyl, pyridyl, pyri
Jiloxy group, pyridylthio group, pyridylsulfonyl
An (xviii) imidazolyl group (the nitrogen atom is carbon
Linear or branched alkyl having from 1 to 6
May be substituted with ) And / or (xi
x) a pyridylsulfonylamino group (a nitrogen atom in the amino moiety)
Is a straight or branched chain having 1 to 6 carbon atoms
May be substituted with alkyl. (1)
Listed compound. (15) X^e Is 1 to 3 substitutions
(A)^e A phenyl group, a naphthyl group,
Imidazolyl group, oxazolyl group, pyridyl group, india
Ryl, quinolyl or isoquinolyl groups, where
Substitution (a)^e Has (i) 1 to 6 carbon atoms
A linear or branched alkyl group, (ii) carbon
A linear or branched halogen having from 1 to 4
Alkyl group, (iii) hydroxy group, (i
v) linear or branched having 1 to 4 carbon atoms
An alkanoyloxy group, (v) having 1 to 4 carbon atoms
Linear or branched alkoxy groups, (vi)
Methylenedioxy, benzyloxy, phenethyl
A xy group, a naphthylmethoxy group, (vii) 1 carbon atom
Straight-chain or branched alkylthio having at most 4
(Viii) a linear group having 1 to 4 carbon atoms
Or a branched alkylsulfonyl group, (ix)
Nitrogen atom, chlorine atom, bromine atom, (x) benzyl group,
(Xi) a phenyl group (the phenyl is methyl, trifluoro,
With methyl, methoxy, fluoro or methylenedioxy
It may be substituted. ), (Xii) phenoxy group
(The phenyl is methyl, trifluoromethyl, methoxy,
Even if substituted with si, fluoro or methylenedioxy
Good. ), (Xiii) phenylthio group, phenyls
Ruphonyl group, phenylsulfonylamino group, N-methyl
Phenylsulfonylamino group, furyl group, thienyl group,
Oxazolyl group, isoxazolyl group, thiazolyl group,
Pyridyl, pyridyloxy, pyridylthio, pyri
Jilsulfonyl group, pyridylsulfonylamino group, N-
A methylpyridylsulfonylamino group, and / or (x
iv) imidazolyl group (the nitrogen atom has 1 to 6 carbon atoms)
Substituted by a linear or branched alkyl having
May be. The compound according to (1), wherein (16) X^e Is 1 to 3 substitutions (a)^e Have
Phenyl, naphthyl, pyridyl, ind
Drill group, quinolyl group or isoquinolyl group
(A)^e Has (i) 1 to 3 carbon atoms
A linear or branched alkyl group, (ii)
Trifluoromethyl group, difluoromethyl group, fluorome
Tyl group, hydroxy group, formyloxy group, acetoxy
A group, (iii) a linear or linear group having 1 to 3 carbon atoms
Is a branched alkoxy group, (iv) methylenedioxy
Si, benzyloxy, methylthio, ethylthio
Group, methylsulfonyl group, ethylsulfonyl group,
(V) fluorine atom, chlorine atom, bromine atom, (vi)
Benzyl, phenyl, 4-methylphenyl, 4-to
Trifluoromethylphenyl group, 4-methoxyphenyl
Group, 4-fluorophenyl group, 3,4-methylenedioxy
Cyphenyl group, phenoxy group, phenylthio group, phenyl
Rusulfonyl group, phenylsulfonylamino group, N-meth
Tylphenylsulfonylamino group, furyl group, thienyl
Group, oxazolyl group, thiazolyl group, imidazolyl group,
N-methylimidazolyl group, pyridyl group, pyridyloxy
Si group, pyridylthio group, pyridylsulfonyl group, pyridi
Rusulfonylamino group and / or N-methylpyridyls
The compound according to (1), which represents a rufonylamino group. (17) X^e Is 1 to 3 substitutions (a)^e Have
Phenyl, naphthyl, pyridyl, quino
Ryl group or isoquinolyl group, wherein the substituent (a)
^e Represents a methyl group, an ethyl group, an isopropyl group,
Oromethyl group, hydroxy group, acetoxy group, methoxy
Group, ethoxy group, isopropoxy group, methylenedioxy
Group, benzyloxy group, methylthio group, ethylthio group,
Methylsulfonyl group, ethylsulfonyl group, chlorine atom,
Benzyl, phenyl, phenoxy, phenylthio
Group, phenylsulfonyl group, phenylsulfonylamino
Group, N-methylphenylsulfonylamino group, pyridyl
Group, pyridyloxy group, pyridylthio group, pyridylsul
Honyl group, pyridylsulfonylamino group and / or N-
The methylpyridylsulfonylamino group according to (1),
Compound. (18) X^e Is 1 to 3 substitutions (a)^e Have
Represents a phenyl group which may be substituted, wherein a substituted group (a)^e 
Are methyl, hydroxy, acetoxy, chlorine
Benzyl, phenyl, phenoxy, phenyl
Thio group, phenylsulfonyl group, phenylsulfonyl group
Amino group, N-methylphenylsulfonylamino group, pyri
A jyl group, a pyridyloxy group, a pyridylthio group and / or
The compound according to (1), which represents a pyridylsulfonyl group. (19) X^e Is 1 to 3 substitutions (a)^e Have
Represents an optionally substituted pyridyl group, wherein a substituted moiety (a)^e 
Represents a methoxy group, an ethoxy group, an isopropoxy group,
Ziroxy group, methylthio group, ethylthio group, methyls
Ruphonyl group, ethylsulfonyl group, benzyl group, phenyl
Group, phenoxy group, phenylthio group, phenylsulfo
A phenyl group, a phenylsulfonylamino group and / or
The compound according to (1), which represents a tylphenylsulfonylamino group
Compound. (20) Y^e Is an oxygen atom, a sulfur atom or a formula> NR
^4eA group having the formula (wherein, R ^4eIs a hydrogen atom, having 1 to 3 carbon atoms
Linear or branched alkyl group or carbon
Linear or branched alkyl having 2 to 5 primes
Represents a canoyl group. The compound according to (1), wherein (21) Y^e The compound according to (1), wherein represents an oxygen atom. (22) Z^e Is 2,4-dioxothiazolidine-5
Ylmethyl group, 2,4-dioxooxazolidine-5
Ylmethyl group or 3,5-dioxooxadiazolidine
The compound according to (1), which represents a 2-ylmethyl group. (23) Z^e Is 2,4-dioxothiazolidine-5
Ylmethyl group or 2,4-dioxooxazolidine-5
-The compound according to (1), which represents an ylmethyl group. (24) Z^e Is 2,4-dioxothiazolidine-5
The compound according to (1), which represents an ylmethyl group. (25) R^1eHas a hydrogen atom or 1 to 4 carbon atoms
A straight-chain or branched alkyl group;^2eBut
A straight or branched chain having 2 to 5 carbon atoms
R represents a alkylene group;^3eIs a hydrogen atom and has 1 to 4 carbon atoms
Linear or branched alkyl group having
An alkoxy group having 1 or 2 carbon atoms, 1 or 2 carbon atoms
X represents an alkylthio group having a halogen atom;^e Is 1
Or three substitutions (a)^e 6 carbon atoms which may have
Aryl groups having 1 to 10 or 1 to 3 substitutions
Minutes (a)^e A nitrogen atom, an oxygen atom and
5- to 10-membered ring having 1 to 3 sulfur atoms
A heteroaromatic group (consisting of one or two rings),
(A)^e Has (i) 1 to 6 carbon atoms
A linear or branched alkyl group, (ii) carbon
A linear or branched halogen having from 1 to 4
Alkyl group, (iii) hydroxy group, (i
v) linear or branched having 1 to 4 carbon atoms
(V) having 1 to 4 carbon atoms
Linear or branched alkoxy groups, (vi) charcoal
Linear or branched alkyl having 1 to 4 prime numbers
A kilendioxy group, (vii) having 7 to 12 carbon atoms
An aralkyloxy group having the formula: (viii) a carbon number of 1 to
Straight-chain or branched alkylthio having 4
(Ix) linear or straight-chain having 1 to 4 carbon atoms
Is a branched alkylsulfonyl group, (x) a halogen atom
(Xi) aralkyl having 7 to 12 carbon atoms
Group, (xii) substituted (b)^e May have
Nyl group, (xiii) Substitution (b)^e Even if you have
Good phenoxy group, (xiv) substitution (b)^e Has
(Xv) a substituted phenylthio group (b)
^e A phenylsulfonyl group optionally having: (xv
i) Substitution (b)^e Phenylsulfo optionally having
Nylamino group (the nitrogen atom in the amino portion has 1 to 6 carbon atoms)
Substituted with straight-chain or branched-chain alkyl having
It may be. ), (Xvii) furyl group, thienyl
Group, oxazolyl group, isoxazolyl group, thiazolyl group
Group, pyridyl group, pyridyloxy group, pyridylthio
Group, pyridylsulfonyl group, (xviii) imidazo
Ryl group (the nitrogen atom is also a straight chain having 1 to 6 carbon atoms)
Or a branched alkyl group.
No. And / or (xix) pyridylsulfonylua
Amino group (the nitrogen atom in the amino moiety has 1 to 6 carbon atoms)
Substituted by a linear or branched alkyl
May be substituted), and the substitution (b)^e Is carbon number 1
Linear or branched alkyl having from 6 to 6
Group, straight or branched having 1 to 4 carbon atoms
A halogenated alkyl group having 1 to 4 carbon atoms
Chain or branched alkoxy groups, halogen atoms or
Is a straight or branched chain having 1 to 4 carbon atoms
Y represents an alkylenedioxy group;^e Is an oxygen atom, a sulfur field
Child or formula> NR^4eA group having the formula (wherein, R ^4eIs hydrogen field
, Linear or branched having 1 to 3 carbon atoms
An alkyl group or a linear alkyl group having 2 to 5 carbon atoms
Or a branched alkanoyl group. ); Z^e 
Is a 2,4-dioxothiazolidine-5-ylmethyl group,
2,4-dioxooxazolidin-5-ylmethyl group or
Is 3,5-dioxooxadiazolidine-2-ylmethyl
A compound represented by the formula (1): (26) R^1eHas a hydrogen atom or 1 to 4 carbon atoms
A straight-chain or branched alkyl group;^2eBut
A straight or branched chain having 2 to 5 carbon atoms
R represents a alkylene group;^3eRepresents a hydrogen atom; X^e But one
Up to three substitutions (a)^e 6 carbon atoms which may have
Aryl groups having up to 10 or 1 to 3 substituents
(A)^e A nitrogen atom, an oxygen atom and / or
Or a 5- to 10-membered ring having 1 to 3 sulfur atoms (1
A heteroaromatic ring group consisting of two or more rings).
Replacement (a)^e Are: (i) a straight chain having 1 to 6 carbon atoms
A chain or branched alkyl group, (ii) carbon number
A linear or branched halogen having 1 to 4 carbon atoms
Alkyl group, (iii) hydroxy group, (iv)
A straight or branched chain having 1 to 4 carbon atoms
Lucanoyloxy group, (v) having 1 to 4 carbon atoms
Linear or branched alkoxy group, (vi) carbon
Linear or branched alkyl having from 1 to 4
A rangeoxy group, (vii) having 7 to 12 carbon atoms
An aralkyloxy group having the formula: (viii) a carbon number of 1 to
Straight-chain or branched alkylthio having 4
A group, (ix) a linear group having 1 to 4 carbon atoms or
A branched alkylsulfonyl group, (x) a fluorine atom
Atom, chlorine atom, bromine atom, (xi) carbon number 7 to 12
(Xii) substituted aralkyl group (b)^e 
(Xiii) a phenyl group optionally having
(B)^e A phenoxy group optionally having: (xi
v) Substitution (b)^e Phenylthio optionally having
Group, (xv) substitution (b)^e May have
Nylsulfonyl group, (xvi) substitution (b) ^e Has
Optionally a phenylsulfonylamino group (amino moiety
Is a straight-chain having 1 to 6 carbon atoms or
It may be substituted with a branched alkyl. ),
(Xvii) a furyl group, a thienyl group, an oxazolyl group,
Isoxazolyl, thiazolyl, pyridyl, pyri
Jiloxy group, pyridylthio group, pyridylsulfonyl
An (xviii) imidazolyl group (the nitrogen atom is carbon
Linear or branched alkyl having from 1 to 6
May be substituted with ) And / or (xi
x) a pyridylsulfonylamino group (a nitrogen atom in the amino moiety)
Is a straight or branched chain having 1 to 6 carbon atoms
May be substituted with alkyl. ) And here
Substitution (b)^e Is a linear group having 1 to 6 carbon atoms
Or branched alkyl groups having 1 to 4 carbon atoms
Straight or branched alkyl halide group, charcoal
Linear or branched alkyl having 1 to 4 prime numbers
Having a oxy group, a halogen atom or 1 to 4 carbon atoms
Shows a linear or branched alkylenedioxy group
Y;^e Represents an oxygen atom; Z^e Is 2,4-dioxochi
Azolidine-5-ylmethyl group or 2,4-dioxo
A xazolidin-5-ylmethyl group;
Compound. (27) R^1eHas a hydrogen atom or 1 to 3 carbon atoms
A straight-chain or branched alkyl group;^2eBut
A straight or branched chain having 2 or 3 carbon atoms;
R represents a alkylene group;^3eRepresents a hydrogen atom; X^e But one
Up to three substitutions (a)^e Phenyl optionally having
Group, naphthyl group, imidazolyl group, oxazolyl group,
Lysyl, indolyl, quinolyl or isoquinolyl
A group represented by a substituent (a)^e Is (i) carbon number 1
Linear or branched alkyl having from 6 to 6
(Ii) a linear or linear group having 1 to 4 carbon atoms
Is a branched alkyl halide group, (iii) hydride
A roxy group, (iv) a linear group having 1 to 4 carbon atoms
Or a branched alkanoyloxy group, (v) carbon
Linear or branched alcohols having the number 1 to 4
Xy group, (vi) methylenedioxy group, (vii) charcoal
An aralkyloxy group having a prime number of 7 to 12, (v
iii) linear or branched having 1 to 4 carbon atoms
A chain alkylthio group, (ix) having 1 to 4 carbon atoms
Linear or branched alkylsulfonyl having
Group, (x) fluorine atom, chlorine atom, bromine atom, (x
i) an aralkyl group having 7 to 12 carbon atoms, (x
ii) phenyl group (where phenyl is methyl, trifluoro
Substitute with methyl, methoxy, fluoro or methylenedioxy
It may be replaced. ), (Xiii) phenoxy group
(The phenyl is methyl, trifluoromethyl, methoxy,
Even if substituted with si, fluoro or methylenedioxy
Good. ), (Xiv) a phenylthio group wherein the phenyl is
Methyl, trifluoromethyl, methoxy, fluoro or
It may be substituted by methylenedioxy. ), (X
v) phenylsulfonyl group (where phenyl is methyl, tri
Fluoromethyl, methoxy, fluoro or methylenedi
It may be substituted by xy. ), (Xvi) Pheni
Rusulfonylamino group (the phenyl is methyl,
Oromethyl, methoxy, fluoro or methylenedioxy
May be substituted. The nitrogen atom in the amino moiety is carbon
Linear or branched alkyl having from 1 to 6
May be substituted with ), (Xvii) ruffle
Group, thienyl group, oxazolyl group, isoxazolyl
Group, thiazolyl group, pyridyl group, pyridyloxy group,
A lysylthio group, a pyridylsulfonyl group, (xvii
i) imidazolyl group (the nitrogen atom has 1 to 6 carbon atoms)
Substituted by a linear or branched alkyl
You may. And / or (xix) pyridyl sulfo
Nylamino group (the nitrogen atom in the amino portion has 1 to 6 carbon atoms)
Substituted with straight-chain or branched-chain alkyl having
It may be. ); Y^e Represents an oxygen atom; Z
^e Is a 2,4-dioxothiazolidine-5-ylmethyl group
The compound according to (1), (28) R^1eRepresents a hydrogen atom, a methyl group or an ethyl group
R^2eIs ethylene, trimethylene or methylethyl
Represents a len group; R^3eRepresents a hydrogen atom; X^e Is 1 to 3
Replacements (a)^e A phenyl group which may have
Futyl group, imidazolyl group, oxazolyl group, pyridyl
Group, indolyl group, quinolyl group or isoquinolyl group
And the substitution (a)^e Are: (i) 1 to 6 carbon atoms
A linear or branched alkyl group having
(Ii) linear or branched having 1 to 4 carbon atoms
A chain-like halogenated alkyl group, (iii) hydroxy
(Iv) linear or straight-chain having 1 to 4 carbon atoms
Is a branched alkanoyloxy group, and (v) 1 carbon atom
Linear or branched alkoxy having at most 4
A group, (vi) a methylenedioxy group, a benzyloxy group,
Phenethyloxy group, naphthylmethoxy group, (vi
i) linear or branched having 1 to 4 carbon atoms
An alkylthio group of (viii) having 1 to 4 carbon atoms
Linear or branched alkylsulfonyl having
(Ix) a fluorine atom, a chlorine atom, a bromine atom,
(X) a benzyl group, (xi) a phenyl group (the phenyl
Is methyl, trifluoromethyl, methoxy, fluoro or
May be substituted with methylenedioxy. ),
(Xii) a phenoxy group (the phenyl is methyl, trif
Fluoromethyl, methoxy, fluoro or methylenedioxy
May be substituted with ), (Xiii) Pheni
Luthio group, phenylsulfonyl group, phenylsulfonyl
Amino group, N-methylphenylsulfonylamino group,
Ryl, thienyl, oxazolyl, isoxazolyl
Group, thiazolyl group, pyridyl group, pyridyloxy group,
Pyridylthio, pyridylsulfonyl, pyridylsul
Phonylamino group, N-methylpyridylsulfonylamino
And / or (xiv) an imidazolyl group (nitrogen atom
Is a straight or branched chain having 1 to 6 carbon atoms
It may be substituted with alkyl. ); Y^e But acid
Represents an elementary atom; Z^e Is 2,4-dioxothiazolidine-
A 5-ylmethyl group; the compound of (1). (29) R^1eRepresents a hydrogen atom, a methyl group or an ethyl group
R^2eIs ethylene, trimethylene or methylethyl
Represents a len group; R^3eRepresents a hydrogen atom; X^e Is 1 to 3
Replacements (a)^e A phenyl group which may have
Phthyl group, pyridyl group, indolyl group, quinolyl group or
Represents an isoquinolyl group, in which the substituent (a)^e Is
(I) a linear or branched chain having 1 to 3 carbon atoms
Alkyl group, (ii) trifluoromethyl group, di
Fluoromethyl group, fluoromethyl group, hydroxy group,
Formyloxy group, acetoxy group, (iii) carbon number
Linear or branched alkoxy having 1 to 3 carbon atoms
(Iv) methylenedioxy group, benzyloxy
Group, methylthio group, ethylthio group, methylsulfonyl
Group, ethylsulfonyl group, (v) fluorine atom, chlorine atom
(Vi) benzyl group, phenyl group, 4
-Methylphenyl group, 4-trifluoromethylphenyl
Group, 4-methoxyphenyl group, 4-fluorophenyl
Group, 3,4-methylenedioxyphenyl group, phenoxy
Group, phenylthio group, phenylsulfonyl group, phenyl
Sulfonylamino group, N-methylphenylsulfonylua
Mino group, furyl group, thienyl group, oxazolyl group, thia
Zolyl group, imidazolyl group, N-methylimidazolyl
Group, pyridyl group, pyridyloxy group, pyridylthio group,
Pyridylsulfonyl group, pyridylsulfonylamino group and
And / or N-methylpyridylsulfonylamino group
Y;^e Represents an oxygen atom; Z^e Is 2,4-dioxochi
It represents an azolidine-5-ylmethyl group;
Compound. (30) R^1eRepresents a hydrogen atom, a methyl group or an ethyl group
R^2eRepresents an ethylene group; R^3eRepresents a hydrogen atom;
X^e Is 1 to 3 substitutions (a)^e May have
Phenyl group, naphthyl group, pyridyl group, quinolyl group or
Represents an isoquinolyl group, in which the substituent (a)^e Is
Group, ethyl group, isopropyl group, trifluoromethyl
Group, hydroxy group, acetoxy group, methoxy group, ethoxy
Group, isopropoxy group, methylenedioxy group, benzyl
Loxy, methylthio, ethylthio, methylsul
Honyl group, ethylsulfonyl group, chlorine atom, benzyl
Group, phenyl group, phenoxy group, phenylthio group,
Nylsulfonyl group, phenylsulfonylamino group, N-
Methylphenylsulfonylamino, pyridyl, pyri
Jiloxy group, pyridylthio group, pyridylsulfonyl
Group, pyridylsulfonylamino group and / or N-methyl
Y represents a pyridylsulfonylamino group;^e Replaces the oxygen atom
Show; Z^e Is 2,4-dioxothiazolidin-5-yl
The compound according to (1), which represents a methyl group. (31) R^1eRepresents a methyl group or an ethyl group;^2eBut
R represents an ethylene group;^3eRepresents a hydrogen atom; X^e But one
Up to three substitutions (a)^e A phenyl group optionally having
Where the substitution (a)^e Is a methyl group, hydroxy
Si, acetoxy, chlorine, benzyl, phenyl
Group, phenoxy group, phenylthio group, phenylsulfoni
Group, phenylsulfonylamino group, N-methylphenyl
Rusulfonylamino group, pyridyl group, pyridyloxy
Group, a pyridylthio group and / or a pyridylsulfonyl group
Shown; Y^e Represents an oxygen atom; Z^e Is 2,4-dioxo
A thiazolidine-5-ylmethyl group;
Compound. (32) R^1eRepresents a methyl group or an ethyl group;^2eBut
R represents an ethylene group;^3eRepresents a hydrogen atom; X^e But one
Up to three substitutions (a)^e A pyridyl group optionally having
Where the substitution (a)^e Is a methoxy group, ethoxy
Group, isopropoxy group, benzyloxy group, methylthio
O, ethylthio, methylsulfonyl, ethylsul
Honyl group, benzyl group, phenyl group, phenoxy group,
Phenylthio group, phenylsulfonyl group, phenylsulfo
Nylamino group and / or N-methylphenylsulfonyl
Represents an amino group; Y^e Represents an oxygen atom; Z^e Is 2,4
-A dioxothiazolidine-5-ylmethyl group;
The compound according to (1). (33) 5- {4- (2-[([1- (4-biphenyli)
Le) ethylidene] amino) oxy] ethoxy) benzy
Ruthiazolidine-2,4-dione, 5- {4- (2-
[([1- (4-phenylsulfonylphenyl) ethyl]
Den] amino) oxy] ethoxy) benzyl @ thiazoli
Gin-2,4-dione, 5- {4- [2-([(1-
[4- (2-pyridyl) phenyl] ethylidene) amido
[No] oxy) ethoxy] benzyl @ thiazolidine-2,
4-dione (hereinafter, referred to as “compound A”), 5- ｛4
-[2-([(1- [4- (3-pyridyl) phenyl]
Ethylidene) amino] oxy) ethoxy] benzyl
Azolidine-2,4-dione, 5- {4- [2-
([(1- [4- (4-pyridyl) phenyl] ethylide
N) amino] oxy) ethoxy] benzyl @ thiazolidy
2-, 4-dione, 5- {4- (2-[([1- (2
-Phenyl-5-pyridyl) ethylidene] amino) oki
[S] ethoxy) benzyl @ thiazolidine-2,4-di
5- (4- [2-[([1- (2-methoxy-5-
Pyridyl) ethylidene] amino) oxy] ethoxy) b
Nzil @ thiazolidine-2,4-dione, 5- @ 4-
(2-[([1- (2-ethoxy-5-pyridyl) ethyl
Ridene] amino) oxy] ethoxy) benzyl @ thiazo
Lysine-2,4-dione, 5- {4- (2-[([1-
(2-Isopropoxy-5-pyridyl) ethylidene] A
Mino) oxy] ethoxy) benzyl {thiazolidine-
2,4-dione and 5- {4- (2-[([1- (2-
Benzyl-5-pyridyl) ethylidene] amino) oki
[S] ethoxy) benzyl @ thiazolidine-2,4-di
The compound according to (1), which is selected from the group consisting of: (VI) WO
95/18125: (1) General formula (VI)

[0074]

Embedded image [Wherein, R ^f is an optionally substituted aromatic hydrocarbon group, an optionally substituted cycloaliphatic hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted fused heterocyclic group, Or the following general formula

[0075]

Embedded image [Wherein, R ^1f is an ^optionally substituted aromatic hydrocarbon group, an optionally substituted cycloaliphatic hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted fused heterocyclic group. Yes,
R ^2f and R ^3f are the same or different and are a hydrogen atom or a lower alkyl group, X ^f is a group represented by an oxygen atom, a sulfur atom or a secondary amino group, and R ^4f is a hydrogen atom or a lower alkyl group. R ^5f is lower alkyl, and P ^f and Q ^f are the same or different and are a hydrogen atom, or P ^f
And Q ^f together represent a bond. ] Or a pharmacologically acceptable salt thereof.

In the compound having the general formula (VI), R ^f , R ^1f , R ^2f , R ^3f , R ^4f , R ^5f , P ^f and Q
Examples of the definition shown by ^f , the type of pharmacologically acceptable salt,
Details of the production method of the compound having the general formula (VI), compound examples, examples, and the like are described in the above publications.

The aromatic hydrocarbon groups represented by R ^f and R ^1f are the same as those described above for R ^1d .

When R ^f and R ^1f represent a heterocyclic group or a fused heterocyclic group, they are an aromatic heterocyclic group or an aromatic fused heterocyclic group, and are the same as those described for R ^1d . Or R
^{When f} and R ^1f represent a non-aromatic heterocyclic group, it has 5 to 7 carbon atoms, and 1 to 3 of them are hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Has at least one nitrogen atom. For example, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinyl, morpholinyl, thiomorpholinyl, oxazolidinyl, thiazolidinyl, diazolidinyl, oxolanyl, thiolanyl, perhydropyridyl group.

When R ^f and R ^1f each represent a cycloaliphatic hydrocarbon group, it is preferably a cycloalkyl group, and more preferably a group having 3 to 8 carbon atoms. For example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
Cycloheptyl and cyclooctyl groups, preferably cyclopentyl and cyclohexyl groups. Alternatively, it is a cycloalkenyl group, preferably a group having 5 to 8 carbon atoms. For example, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl groups.

The above groups represented by R ^f and R ^1f may be substituted or unsubstituted. If it has been replaced,
The groups may be substituted with groups commonly used in the art, for example as described above for the substituent (a) ^e .

When R ^2f , R ^3f , R ^4f and R ^5f represent an alkyl group, they are preferably lower alkyl groups having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. For example, it is the same as that described for R ^3c and substitution (a) ^a .

Among the compounds having the above general formula (VI), preferred compounds are shown below. (2) The compound according to (1), wherein R ^4f is a hydrogen atom and R ^5f is a lower alkyl group. (3) a 5- or 6-membered optionally substituted aromatic heterocyclic group containing 1 or 2 hetero atoms selected from phenyl group, sulfur atom, oxygen atom and nitrogen atom, wherein R ^f may be substituted; Or the compound according to (2), which is a condensed aromatic heterocyclic group which may be substituted by condensing the aromatic heterocyclic ring and a benzene ring. (4) ^Rf is a 5- to 6-membered aromatic heterocyclic group containing one or two heteroatoms selected from a phenyl group, a sulfur atom, an oxygen atom and a nitrogen atom, or the above aromatic heterocycle and a benzene ring. Is a condensed aromatic heterocyclic group obtained by condensing. (5) The compound according to (3), wherein R ^f is a phenyl group or a condensed aromatic heterocyclic group in which a benzene ring and a 5- or 6-membered heterocyclic ring containing a sulfur atom are condensed. (6) R ^f is a phenyl group, a benzothienyl group, or 1
The compound according to (2), which is -methyl-1- (2-pyridylthio) methyl group. (7) The compound according to (2), wherein R ^f is a phenyl group. (8) R ^f

Embedded image The compound according to (2), which is (9) R ^1f is a phenyl group which may be substituted, or 1 or 2 selected from a sulfur atom, an oxygen atom and a nitrogen atom
The compound according to (8), which is a 5- or 6-membered aromatic heterocyclic group which may be substituted and contains 5 hetero atoms. (10) The compound according to (8), wherein R ^1f is a 5- or 6-membered aromatic heterocyclic group containing one or two hetero atoms selected from a sulfur atom, an oxygen atom and a nitrogen atom. (11) The compound according to (8), wherein R ^1f is a 5- or 6-membered aromatic heterocyclic group containing a nitrogen atom. (12) The compound according to (8), wherein R ^1f is a pyridyl group. (13) 4- [4- [2- (2-phenyl-5-methyl-4-oxazolyl) ethoxy] benzyl] -3,5-
Isoxazolidinedione, 4- [4- [2- (2-phenyl-5-methyl-4-oxazolyl) ethoxy] benzylidene] -3,5-isoxazolidinedione,
-[4- [2- (2-benzothienyl-5-methyl-4
-Oxazolyl) ethoxy] benzyl] -3,5-isoxazolidinedione and 4- [4- [2- [5-methyl- [2- (2-pyridylthio) ethyl-4-oxazolyl) ethoxy] benzyl] -3, The compound according to (1), which is 5-isoxazolidinedione. (VII) JP-A-7-330728 and EP67
6398A includes: (1) General formula (VII)

[0083]

Embedded image[Where X^g Is indole ring group, indoline ring group, aza
Indole ring group, azaindoline ring group, imidazopyridi
A ring group or an imidazopyrimidine ring group.
Represents one to three substitution components (a) described below.^g Even if you have
Well, Y^g Represents an oxygen atom or a sulfur atom;^g Is 2,
4-dioxothiazolidine-5-yridenylmethyl group,
2,4-dioxothiazolidine-5-ylmethyl group,
2,4-dioxooxazolidin-5-ylmethyl group,
3,5-dioxooxadiazolidine-2-ylmethyl
R or a N-hydroxyureidomethyl group;^g Is
Hydrogen atom, linear or branched having 1 to 4 carbon atoms
Branched alkyl group, straight chain having 1 to 4 carbon atoms
Or a branched alkoxy group, a halogen atom, a hydride
Roxy group, nitro group, substitution (b)^g May have
Amino group (substitution (b)^g Has 1 to 8 carbon atoms
Linear or branched alkyl group having 7 carbon atoms
Linear or branched aralkyl having at most 11
Group, aryl group having 6 to 10 carbon atoms, 1 carbon atom
Linear or branched aliphatic aliphatic group having from 11 to 11
Silyl group, araliphatic acyl having 8 to 12 carbon atoms
A group or an aromatic acyl group having 7 to 11 carbon atoms
You. ) Or a straight chain having 7 to 11 carbon atoms or
Represents a branched aralkyl group;^g Is an integer from 1 to 5
Where the substitution (a)^g Represents 1 to 4 carbon atoms
Linear or branched alkyl group having 1 carbon atom
Linear or branched alkoxy having from 4 to 4
Group, benzyloxy group, halogen atom, hydroxy group,
Acetoxy group, phenylthio group, 1 to 4 carbon atoms
Linear or branched alkylthio groups, trif
Fluoromethyl group, nitro group, substitution (b)^g Have
An amino group (the substitution (b)^g Represents 1 to 8 carbon atoms
Straight or branched alkyl group having one or more carbon atoms
Linear or branched ara having the number 7 to 11
Alkyl group, aryl group having 6 to 10 carbon atoms, charcoal
Linear or branched fat having 1 to 11 primes
Aliphatic acyl group, araliphatic having 8 to 12 carbon atoms
Acyl group or aromatic acyl having 7 to 11 carbon atoms
Represents a group. ), Substitution (c) ^g Carbon which may have
Aryl group having the number of 6 to 10 (the substitution (c) ^g 
Is a straight or branched chain having 1 to 4 carbon atoms
Alkyl group, straight-chain having 1 to 4 carbon atoms or
Branched alkoxy, halogen, hydroxy
Group, nitro group, phenyl group, trifluoromethyl group,
Replacement (b)^g An amino group optionally having) or substituted
Minutes (c)^g Having 7 to 11 carbon atoms which may have
Linear or branched aralkyl groups. ]
Or a pharmacologically acceptable salt thereof.
It is listed.

In the compound having the general formula (VII), R ^g , X ^g , Y ^g , Z ^g , substitution (a) ^g , substitution (b) ^g , substitution (c) ^g and ^mg Examples of the definitions shown, types of pharmacologically acceptable salts, and the above general formula (VI
Details of the production method of the compound having I), compound examples, examples, and the like are described in the above publications.

For example, when R ^g , substitution (a) ^g , and substitution (c) ^g represent an alkyl group or an alkoxy group having 1 to 4 carbon atoms, they are the same as those described above for the substitution (a) ^a . Same as the one.

When R ^g , substitution (a) ^g , and substitution (c) ^{g each} represent a halogen atom, it is the same as the above substitution (a) ^a
It is the same as that described above.

When R ^g and the substituent (a) ^g represent an aralkyl group, it is the same as that described for R ^1d above.

When the substituent (a) ^g represents an alkylthio group, it is the same as described above for W ^2c .

When the substituted moiety (a) ^g and the substituted moiety (b) ^g represent an aryl group, they are the same as those described for R ^1d above.

The substituted (b) ^g is a straight-chain or branched aliphatic acyl group having 1 to 11 carbon atoms, an araliphatic acyl group having 8 to 12 carbon atoms, or 7-carbon atoms.
When referring to an aromatic acyl group having from 1 to 11, it is the same as described for R ^1d above.

When the substituent (b) ^g represents an alkyl group having 1 to 8 carbon atoms, the group is a linear or branched alkyl group, for example, methyl, ethyl, propyl, isopropyl, butyl , Isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3, 3-dimethylbutyl,
2,2-dimethylbutyl, 1,1-dimethylbutyl,
1,2-dimethylbutyl, 1,3-dimethylbutyl,
2,3-dimethylbutyl, 2-ethylbutyl, heptyl and octyl groups. It is preferably an alkyl group having 1 to 4 carbon atoms, more preferably methyl, ethyl,
Propyl, isopropyl, butyl, isobutyl,
Most preferably, it is a methyl group.

Compounds having the above general formula (VII)
Preferred compounds are shown below. (2) X^g Is indole ring group, indoline ring group, aza
Indole ring group, imidazopyridine ring group or imidazopi
Limidine ring group, these rings are one to three
(A)^g May be substituted here.
(A)^g Is a straight-chain having 1 to 4 carbon atoms or
Branched alkyl group, straight chain having 1 to 4 carbon atoms
Or branched alkoxy groups, benzyloxy
Group, halogen atom, hydroxy group, acetoxy group,
A nilthio group, a linear group having 1 to 4 carbon atoms or
Branched alkylthio, trifluoromethyl,
Toro group, substitution (b)^g An amino group optionally having
(The substitution (b)^g Is a linear group having 1 to 8 carbon atoms
Or a branched alkyl group having 7 to 11 carbon atoms.
Straight or branched aralkyl group, carbon number
Aryl group having 6 to 10 carbon atoms, 1 to 11 carbon atoms
A linear or branched aliphatic acyl group having
Araliphatic acyl group having 8 to 12 primes or carbon
An aromatic acyl group having the number of 7 to 11 is shown. ), Small
At least one substitution (c)^g Carbon which may have
Aryl group having the number of 6 to 10 (the substitution (c)^g 
Is a straight or branched chain having 1 to 4 carbon atoms
Alkyl group, straight-chain having 1 to 4 carbon atoms or
Branched alkoxy, halogen, hydroxy
Group, nitro group, phenyl group, trifluoromethyl group,
Replacement (b)^g An amino group which may have
At least one substitution (c)^g Carbon number which may have
Linear or branched arals having 7 to 11
The compound according to (1), which represents a kill group. (3) X^g Is an indole ring group, an indoline ring group,
A dazopyridine ring group or an imidazopyrimidine ring group,
These rings have one to three substituents (a) described below. ^g With
And the substitution (a)^g Is one carbon number
A linear or branched alkyl group having at most four,
A straight or branched chain having 1 to 4 carbon atoms
Lucoxy group, benzyloxy group, halogen atom, hydro
Xy, acetoxy, phenylthio, carbon number 1 to
Straight-chain or branched alkylthio having 4
Group, trifluoromethyl group, nitro group, substitution (b)^g 
An amino group which may have the substituent (b)^g Is carbon
Linear or branched alkyl having from 1 to 8
Group, straight-chain or branched having 7 to 11 carbon atoms
Aliphatic aralkyl groups having 6 to 10 carbon atoms
A linear or branched group having 1 to 11 carbon atoms
A branched aliphatic acyl group having 8 to 12 carbon atoms
Araliphatic acyl group or aromatic group having 7 to 11 carbon atoms
Shows an aromatic acyl group. ), At least one substitution
(C)^g Having 6 to 10 carbon atoms which may have
Aryl group (the substitution (c)^g Represents 1 to 4 carbon atoms
Linear or branched alkyl group having 1 carbon atom
Linear or branched alkoxy having from 4 to 4
Group, halogen atom, hydroxy group, nitro group, phenyl
Group, trifluoromethyl group, substitution (b)^g Have
Amino group), or at least one substituted moiety
(C)^g Having 7 to 11 carbon atoms which may have
A straight or branched aralkyl group (1)
A compound as described. (4) X^g Is an indole ring group, an indoline ring group or
Represents a midazopyridine ring group, these rings having from 1 to 3
Substitution (a) described later^g May be placed here.
Replacement (a)^g Is a straight-chain having 1 to 4 carbon atoms
Or branched alkyl group having 1 to 4 carbon atoms
Linear or branched alkoxy group, benzyloxy
Group, halogen atom, hydroxy group, acetoxy group,
Enylthio group, linear or straight-chain having 1 to 4 carbon atoms
Is a branched alkylthio group, a trifluoromethyl group,
Nitro group, substitution (b)^g An amino group optionally having
(The substitution (b)^g Is a linear group having 1 to 8 carbon atoms
Or a branched alkyl group having 7 to 11 carbon atoms.
Straight or branched aralkyl group, carbon number
Aryl group having 6 to 10 carbon atoms, 1 to 11 carbon atoms
A linear or branched aliphatic acyl group having
Araliphatic acyl group having 8 to 12 primes or carbon
An aromatic acyl group having the number of 7 to 11 is shown. ), 1
Or 3 substitutions (c)^g 6 carbon atoms which may have
Aryl group having from 1 to 10 (the substitution (c)^g Is charcoal
Linear or branched alkyl having 1 to 4 prime numbers
Killed group, linear or branched having 1 to 4 carbon atoms
Chain alkoxy groups, halogen atoms, hydroxy groups,
Toro, phenyl, trifluoromethyl, substituted
(B)^g An amino group optionally having), or 1 to 3
Replacements (c) ^g 7 to 1 carbon atoms which may have
A straight or branched aralkyl group having one
The compound according to (1) above. (5) X^g Is an indoline ring or an imidazopyridine ring
And these rings have 1 to 3 substituents to be described later.
(A)^g Wherein the substituted component (a)^g 
Is a straight or branched chain having 1 to 4 carbon atoms
An alkyl group having 1 to 4 carbon atoms
Is a branched alkoxy group, benzyloxy group, halogen
Having 1 to 4 carbon atoms, a phenylthio group,
Chain or branched alkylthio group, trifluoro
The compound according to (1), which represents a methyl group or a phenyl group. (6) X^g Represents an imidazopyridine ring group;
The ring has 1 to 3 substituents (a) described below.^g Have
And the substitution (a)^g Is a methyl group, ethyl
Group, isopropyl group, methoxy group, ethoxy group, propo
Xy, isopropoxy, benzyloxy, fluorine
Atom, chlorine atom, phenylthio group, methylthio group, ethi
The compound according to (1), which represents a luthio group or a phenyl group. (7) R^g Is a hydrogen atom having 1 to 4 carbon atoms
Chain or branched alkyl group, 1 to 4 carbon atoms
A linear or branched alkoxy group having
The compound according to (1), which represents a logogen atom. (8) R^g Represents a hydrogen atom, a methoxy group, an ethoxy group,
The compound according to (1), which represents a nitrogen atom or a chlorine atom. (9) R^g Represents a hydrogen atom or a methoxy group (1)
Listed compound. (10) R^g Is a compound according to (1), which represents a hydrogen atom. (11) Y^g Is a compound according to (1), which represents an oxygen atom. (12) Z^g Is 2,4-dioxothiazolidine-5
Iridenylmethyl group, 2,4-dioxothiazolidine-
5-ylmethyl group or 2,4-dioxooxazolidine
The compound according to (1), which represents a -5-ylmethyl group. (13) Z^g Is 2,4-dioxothiazolidine-5
Iridenylmethyl group or 2,4-dioxothiazolidine
The compound according to (1), which represents a -5-ylmethyl group. (14) Z^g Is 2,4-dioxothiazolidine-5
The compound according to (1), which represents an ylmethyl group. (15) X^g Is an indole ring group, an indoline ring group,
Zaindole ring group, imidazopyridine ring group or imidazo
Represents a pyrimidine ring group, these rings each having 1 to 3
(A)^g Y^g Is oxygen source
A child or a sulfur atom;^g Is 2,4-dioxothia
Zolidine-5-yridenylmethyl group, 2,4-dioxo
Thiazolidine-5-ylmethyl group, 2,4-dioxo
Oxazolidine-5-ylmethyl group, 3,5-dioxy
Soxadiazolidine-2-ylmethyl group or N-hydrido
Roxyureidomethyl group;^g Is a hydrogen atom, carbon
Linear or branched alkyl having from 1 to 4
A straight or branched chain having 1 to 4 carbon atoms
M represents an alkoxy group or a halogen atom,^g Is one
An integer from 5 to 5, where the substitution (a)^g Is carbon number 1
Linear or branched alkyl having from 4 to 4
Group, straight or branched having 1 to 4 carbon atoms
Alkoxy, benzyloxy, halogen,
Droxy group, acetoxy group, phenylthio group, carbon number 1
Linear or branched alkylthio having from 1 to 4
O group, trifluoromethyl group, nitro group, substitution (b)
^g An amino group which may have the substituent (b)^g Is charcoal
Linear or branched alkyl having 1 to 8 primes
Killed group, linear or branched having 7 to 11 carbon atoms
A branched aralkyl group having 6 to 10 carbon atoms;
Reel group, straight chain having 1 to 11 carbon atoms or
Branched aliphatic acyl group having 8 to 12 carbon atoms
Having an araliphatic acyl group or 7 to 11 carbon atoms
Shows an aromatic acyl group. ), At least one substitution
(C)^g Having 6 to 10 carbon atoms which may have
Aryl group (the substitution (c)^g Represents 1 to 4 carbon atoms
Linear or branched alkyl group having 1 carbon atom
Linear or branched alkoxy having from 4 to 4
Group, halogen atom, hydroxy group, nitro group, phenyl
Group, trifluoromethyl group, substitution (b)^g Have
Amino group), or at least one substituted moiety
(C)^g Having 7 to 11 carbon atoms which may have
A straight or branched aralkyl group (1)
A compound as described. (16) X^g Is an indole ring group, an indoline ring group,
Represents a midazopyridine ring group or an imidazopyrimidine ring group
These rings have one to three substituents (a) described below.^g 
Y^g Represents an oxygen atom;^g Is
2,4-dioxothiazolidine-5-yridenylmethyl
Group, 2,4-dioxothiazolidine-5-ylmethyl group
Or 2,4-dioxooxazolidin-5-ylmethyl
A group represented by R^g Has a hydrogen atom and has 1 to 4 carbon atoms
Linear or branched alkyl group, having 1 to 4 carbon atoms
Linear or branched alkoxy groups having
Represents a halogen atom, m^g Represents an integer of 1 to 5;
Substitution (a)^g Is a linear chain having 1 to 4 carbon atoms
Or branched alkyl groups having 1 to 4 carbon atoms
Having a linear or branched alkoxy group, benzyl
Ruoxy group, halogen atom, hydroxy group, acetoxy
Group, phenylthio group, linear having 1 to 4 carbon atoms
Or a branched alkylthio group, trifluoromethyl
Group, nitro group, substitution (b)^g A that may have
Amino group (substituted (b)^g Has 1 to 8 carbon atoms
Linear or branched alkyl group, having 7 to 1 carbon atoms
A linear or branched aralkyl group having one,
Aryl group having 6 to 10 carbon atoms, 1 to carbon atoms
Linear or branched aliphatic acyl having 11
A araliphatic acyl group having 8 to 12 carbon atoms, or
Represents an aromatic acyl group having 7 to 11 carbon atoms.
You. ), At least one substitution (c)^g Have
Aryl groups having 6 to 10 carbon atoms (the substituted
Minutes (c)^g Is a linear group having 1 to 4 carbon atoms or
Branched alkyl group, straight chain having 1 to 4 carbon atoms
Or branched alkoxy groups, halogen atoms,
Droxy, nitro, phenyl, trifluoromethyl
Group, substitution (b)^g An amino group optionally having)
Or at least one substitution (c)^g May have
Straight or branched having 7 to 11 carbon atoms
The compound according to (1), which represents an aralkyl group represented by the formula: (17) X^g Is an indole ring group, an indoline ring group or
Represents an imidazopyridine ring group having 1 to 3 rings
(A)^g Y^g Is
Represents an oxygen atom, Z^g Is 2,4-dioxothiazolide
-5-yridenylmethyl group or 2,4-dioxochi
An azolidine-5-ylmethyl group;^g Is hydrogen field
Atom, methoxy group, ethoxy group, fluorine atom or chlorine atom
And m^g Represents an integer of 1 to 5, where
(A)^g Is a straight-chain having 1 to 4 carbon atoms or
Branched alkyl group, straight chain having 1 to 4 carbon atoms
Or branched alkoxy groups, benzyloxy
Group, halogen atom, hydroxy group, acetoxy group,
A nilthio group, a linear group having 1 to 4 carbon atoms or
Branched alkylthio, trifluoromethyl,
Toro group, substitution (b)^g An amino group optionally having
(The substitution (b)^g Is a linear group having 1 to 8 carbon atoms
Or a branched alkyl group having 7 to 11 carbon atoms.
Straight or branched aralkyl group, carbon number
Aryl group having 6 to 10 carbon atoms, 1 to 11 carbon atoms
A linear or branched aliphatic acyl group having
Araliphatic acyl group having 8 to 12 primes or carbon
An aromatic acyl group having the number of 7 to 11 is shown. ), 1
Or 3 substitutions (c)^g 6 carbon atoms which may have
Aryl group having from 1 to 10 (the substitution (c)^g Is charcoal
Linear or branched alkyl having 1 to 4 prime numbers
Killed group, linear or branched having 1 to 4 carbon atoms
Chain alkoxy groups, halogen atoms, hydroxy groups,
Toro, phenyl, trifluoromethyl, substituted
(B)^g An amino group optionally having), or 1 to 3
Replacements (c)^g 7 to 1 carbon atoms which may have
A straight or branched aralkyl group having one
The compound according to (1) above. (18) X^g Is an indoline ring group or imidazopyridine
A ring group, and these rings each have 1 to 3 substituents to be described later.
(A)^g Y^g Represents an oxygen atom,
Z^g Is 2,4-dioxothiazolidine-5-ylmethyl
And R represents^g Represents a hydrogen atom or a methoxy group;
^g Represents an integer of 1 to 5, where (a)^g Is
A straight or branched chain having 1 to 4 carbon atoms
Alkyl group, linear or branched having 1 to 4 carbon atoms
Branched alkoxy, benzyloxy, halogen source
, A phenylthio group, a straight chain having 1 to 4 carbon atoms
Or a branched alkylthio group, trifluoromethyl
The compound according to (1), which represents a phenyl group or a phenyl group. (19) X^g Represents an imidazopyridine ring group;
Has 1 to 3 substituents (a) described below.^g Have
May be, Y^g Represents an oxygen atom;^g Is 2,4-di
An oxothiazolidine-5-ylmethyl group;^g Is
Represents a hydrogen atom, m^g Represents an integer of 1 to 5, where
Substitution (a)^g Represents a methyl group, an ethyl group, or isopropyl
Group, methoxy group, ethoxy group, propoxy group, isopro
Oxy group, benzyloxy group, fluorine atom, chlorine atom,
Phenylthio, methylthio, ethylthio,
The compound according to (1), which represents a nyl group. (20) 5- {4- (3-methylimidazo [4,5-
b] Pyridin-2-ylmethoxy) benzyl @ thiazoli
Gin-2,4-dione, 5- [4- (5-chloro-3-
Methylimidazo [4,5-b] pyridin-2-ylmeth
Xy) benzyl] thiazolidine-2,4-dione, 5-
[4- (5-methoxy-3-methylimidazo [4,5-
b] pyridin-2-ylmethoxy) benzyl] thiazoly
Gin-2,4-dione, 5- [4- (5-hydroxy-
3-methylimidazo [4,5-b] pyridin-2-yl
Methoxy) benzyl] thiazolidine-2,4-dione,
5- [4- (5-ethoxy-3-methylimidazo [4,
5-b] pyridin-2-ylmethoxy) benzyl] thia
Zolidine-2,4-dione, 5- [4- (5-isopro
Poxy-3-methylimidazo [4,5-b] pyridine-
2-ylmethoxy) benzyl] thiazolidine-2,4-
Dione and 5- [4- (1-methylindoline-2-i
Rumethoxy) benzyl] thiazolidine-2,4-dione
(1) The compound according to (1), which is (VIII) JP-A-9-295970 and EP7
45600A: (1) General formula (VIII)

[0093]

Embedded image[Where X^h Represents a benzimidazole ring group, wherein the group is
1 to 5 replacement parts (a) described below^h May have
K, Y^h Represents an oxygen atom or a sulfur atom;^h Is 2,4
-Dioxothiazolidine-5-yridenylmethyl group,
2,4-dioxothiazolidine-5-ylmethyl group,
2,4-dioxooxazolidin-5-ylmethyl group,
3,5-dioxooxadiazolidine-2-ylmethyl
R or a N-hydroxyureidomethyl group;^h Is
Hydrogen atom, linear or branched having 1 to 4 carbon atoms
Branched alkyl group, straight chain having 1 to 4 carbon atoms
Or a branched alkoxy group, a halogen atom, a hydride
Roxy group, nitro group, substitution (b)^h May have
Amino group (substitution (b)^h Has 1 to 8 carbon atoms
Linear or branched alkyl group having 7 carbon atoms
Linear or branched aralkyl having at most 11
Group, aryl group having 6 to 10 carbon atoms, 1 carbon atom
Linear or branched aliphatic aliphatic group having from 11 to 11
Silyl group, araliphatic acyl having 8 to 12 carbon atoms
A group or an aromatic acyl group having 7 to 11 carbon atoms
You. ) Or a straight chain having 7 to 11 carbon atoms or
Represents a branched aralkyl group;^h Is an integer from 1 to 5
Where the substitution (a)^h Represents 1 to 4 carbon atoms
Linear or branched alkyl group having 1 carbon atom
Linear or branched alkoxy having from 4 to 4
Group, benzyloxy group, halogen atom, hydroxy group,
Acetoxy group, phenylthio group, 1 to 4 carbon atoms
Linear or branched alkylthio groups, trif
Fluoromethyl group, nitro group, substitution (b)^h Have
An amino group (the substitution (b)^h Represents 1 to 8 carbon atoms
Straight or branched alkyl group having one or more carbon atoms
Linear or branched ara having the number 7 to 11
Alkyl group, aryl group having 6 to 10 carbon atoms, charcoal
Linear or branched fat having 1 to 11 primes
Aliphatic acyl group, araliphatic having 8 to 12 carbon atoms
Acyl group or aromatic acyl having 7 to 11 carbon atoms
Represents a group. ), Substitution (c) ^h Carbon which may have
Aryl group having the number of 6 to 10 (the substitution (c) ^h 
Is a straight or branched chain having 1 to 4 carbon atoms
Alkyl group, straight-chain having 1 to 4 carbon atoms or
Branched alkoxy, halogen, hydroxy
Group, nitro group, phenyl group, trifluoromethyl group,
Replacement (b)^h An amino group optionally having) or substituted
Minutes (c)^h Having 7 to 11 carbon atoms which may have
Linear or branched aralkyl groups. ]
Or a pharmaceutically acceptable salt thereof
Is described.

In the compound having the general formula (VIII), R ^h , X ^h , Y ^h , Z ^h , substitution (a) ^h , substitution (b) ^h , substitution (c) ^h and m ^h Examples of the definitions shown, types of pharmacologically acceptable salts, and the above general formula (VI
Details of the production method, compound examples, examples and the like of the compound having II) are described in the above publications.

When R ^h , substitution (a) ^h , and substitution (c) ^h represent an alkyl group or an alkoxy group having 1 to 4 carbon atoms, they are the same as those described above for the substitution (a) ^a. Is the same as

When R ^h , the substituted moiety (a) ^h and the substituted moiety (b) ^h represent an aralkyl group, it is the same as described above for R ^1d .

When R ^h , substitution (a) ^h , and substitution (c) ^h represent a halogen atom, they represent the above-mentioned substitution (a) ^a
It is the same as that described above.

When the substituent (a) ^h represents an alkylthio group, it is the same as described above for W ^2c .

When the substituted (a) ^h and the substituted (b) ^h represent an aryl group, they are the same as those described for R ^1d above.

[0100] substituents (b) ^h is a linear or branched aliphatic acyl group having 1 to 11 carbon atoms, the number araliphatic acyl group or C having 8 to 12 carbon 7
When referring to an aromatic acyl group having from 1 to 11, it is the same as described for R ^1d above.

When the substituent (b) ^h represents an alkyl group having 1 to 8 carbon atoms, it is the same as described above for the substituent (b) ^g .

Among the compounds having the above general formula (VIII), preferred compounds are shown below. (2) R ^h is a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, 1 to 4 carbon atoms
The compound according to (1), which represents a linear or branched alkoxy group having one or more halogen atoms. (3) The compound according to (1), wherein Y ^h represents an oxygen atom. (4) Z ^h is 2,4-dioxo-thiazolidin-5-ylmethyl group, 2,4-dioxothiazolidin-5-Iridenirumechiru group or 2,4-dioxo oxazolidine -5
-The compound according to (1), which represents an ylmethyl group. (5) R ^h is a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, 1 to 4 carbon atoms
Represents a linear or branched alkoxy group or a halogen atom having one, Y ^h represents an oxygen atom, Z ^h is a 2,4-dioxothiazolidine-5-ylmethyl group,
The compound according to (1), which represents a 2,4-dioxothiazolidine-5-yridenylmethyl group or a 2,4-dioxooxazolidine-5-ylmethyl group. (6) The compound according to (1), wherein Z ^h represents a 2,4-dioxothiazolidine-5-ylmethyl group or a 2,4-dioxothiazolidine-5-yridenylmethyl group. (7) The compound according to (1), wherein R ^h represents a hydrogen atom, a methyl group, a methoxy group, an ethoxy group, a fluorine atom or a chlorine atom. (8) The compound according to (1), wherein m ^h represents an integer of 1 to 3. (9) Y ^h represents an oxygen atom, Z ^h is a 2,4-dioxothiazolidine-5-ylmethyl group or a 2,4-dioxothiazolidine-5-yridenylmethyl group, and R ^h is a hydrogen atom or a methyl group A methoxy group, an ethoxy group, a fluorine atom or a chlorine atom, and m ^h represents an integer of 1 to 3. (10) X ^h represents a good benzimidazole ring group which may have a five following substituents (a) ^h from 1, wherein the substituent (a) ^h has from 1 to 4 carbon atoms Linear or branched alkyl group, linear or branched alkoxy group having 1 to 4 carbon atoms, benzyloxy group, halogen atom, phenylthio group, 1 carbon atom
(1) The compound according to (1), which represents a linear or branched alkylthio group having from 4 to 4, a trifluoromethyl group, a hydroxy group, an acetoxy group, a benzyl group or a phenyl group. (11) Z ^h is 2,4-dioxo oxazolidine-5
The compound according to (1), which represents an ylmethyl group. (12) The compound according to (1), wherein R ^h represents a hydrogen atom, a methyl group or a methoxy group. (13) X ^h is a benzimidazole ring group which may have 1 to 5 substituents (a) ^h below, wherein the substituent (a) ^h has 1 to 4 carbon atoms Linear or branched alkyl group, linear or branched alkoxy group having 1 to 4 carbon atoms, benzyloxy group, halogen atom, phenylthio group, 1 carbon atom
Represents a linear or branched alkylthio group having from 4 to 4, a trifluoromethyl group, a hydroxy group, an acetoxy group, a benzyl group or a phenyl group, Y ^h represents an oxygen atom, and Z ^h represents 2,4 -Dioxooxazolidine-
(1) The compound according to (1), wherein the compound represents a 5-ylmethyl group, R ^h represents a hydrogen atom, a methyl group or a methoxy group, and m ^h represents an integer of 1 to 3. (14) X ^h represents 1 to 5 of the following substituents (a) may have a ^h benzimidazole ring group, wherein the substituents (a) ^h is a methyl group, an ethyl group, an isopropyl group , Methoxy group, ethoxy group, propoxy group, isopropoxy group, benzyloxy group, fluorine atom, chlorine atom,
The compound according to (1), which represents a phenylthio group, a methylthio group, an ethylthio group, a hydroxy group, an acetoxy group, a benzyl group or a phenyl group. (15) The compound according to (1), wherein R ^h represents a hydrogen atom. (16) The compound according to (1), wherein m ^h is 1 or 2. (17) X ^h represents 1 to 5 of the following substituents (a) may have a ^h benzimidazole ring group, wherein the substituents (a) ^h is a methyl group, an ethyl group, an isopropyl group , Methoxy group, ethoxy group, propoxy group, isopropoxy group, benzyloxy group, fluorine atom, chlorine atom,
Phenylthio group, methylthio group, ethylthio group, a hydroxy group, an acetoxy group, a benzyl group or a phenyl group, Y ^h represents an oxygen atom, Z ^h represents a 2,4-dioxothiazolidin-5-ylmethyl radical, R The compound according to (1), wherein ^h represents a hydrogen atom and m ^h represents 1 or 2. (18) X ^h represents 1 to 5 of the following substituents (a) may have a ^h benzimidazole ring group, wherein the substituents (a) ^h is a methyl group, a methoxy group, hydroxy group The compound according to (1), which represents, an acetoxy group or a benzyl group. (19) The compound according to (1), wherein m ^h represents 1. (20) X ^h represents 1 to 5 of the following substituents (a) may have a ^h benzimidazole ring group, wherein the substituents (a) ^h is a methyl group, a methoxy group, hydroxy group represents acetoxy group or a benzyl group, Y ^h represents an oxygen atom, Z ^h is 2,4-dioxo-thiazolidin-5
Represents an ylmethyl group, R ^h represents a hydrogen atom, and m ^h represents 1
The compound according to (1), which represents (21) 5- [4- (1-methylbenzimidazole-
2-ylmethoxy) benzyl] thiazolidine-2,4-
Dione, 5- [4- (6-methoxy-1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione (hereinafter, referred to as “compound B”), 5- [4- (5- Methoxy-1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (1-benzylbenzimidazol-5-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (5-hydroxy-1,4,6,7-tetramethylbenzimidazole-
2-ylmethoxy) benzyl] thiazolidine-2,4-
Dione and 5- [4- (5-acetoxy-1,4,6,
7-tetramethylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione. (IX) JP-A-1-272574 and EP332
332A includes: (1) General formula (IX)

[0103]

Embedded image [Wherein the dotted line indicates no bond or a bond, V ⁱ is -CH
= CH -, - N = CH -, - CH = an N- or a sulfur atom, W ⁱ _{is> CH 2,>CHOH,>}CO,> C = N
OR ⁱ or a -CH = CH-, X ⁱ represents a sulfur atom, an oxygen atom,> NR ^1i, a -CH = N-or -N = CH-, Y ⁱ is = CH- or a nitrogen atom, Z ⁱ represents a hydrogen atom, an alkyl group having 1 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a phenyl group, a naphthyl group, a pyridyl group, a furyl group, a thienyl group, or the same or different carbon atoms. Alkyl having 1 to 3 carbon atoms, trifluoromethyl, alkoxy having 1 to 3 carbon atoms, phenyl group mono- or di-substituted by a group that is fluorine, chlorine or bromine, and Z ¹ⁱ is a hydrogen atom or An alkyl group having 1 to 3 carbon atoms,
ⁱ and R ¹ⁱ are the same or different and each is a hydrogen atom or a methyl group, and n ⁱ is 1, 2 or 3. Or a pharmacologically acceptable salt thereof.

In the compound having the general formula (IX), V ⁱ , W ⁱ , X ⁱ , Y ⁱ , Z ⁱ , Z ¹ⁱ , R ⁱ , R ¹ⁱ
Examples of the definitions represented by n and n ⁱ , types of pharmacologically acceptable salts, methods for producing compounds having the above general formula (IX), examples of compounds and examples are described in the above publications.

For example, when Z ⁱ is an alkyl group having 1 to 7 carbon atoms or a substituted group of Z ¹ⁱ group or phenyl represented by Z ⁱ is an alkyl group having 1 to 3 carbon atoms, these are the same as above. (B) is the same as described in ^g .

When Z ⁱ represents a cycloalkyl group having 3 to 7 carbon atoms, it is a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl group.

Among the compounds having the general formula (IX), suitable compounds are shown below. (2) Dotted line indicates no bond and ^Wi is> CO or> C
The compound according to (1), which is HOH. (3) V ⁱ is -CH = CH -, - CH = an N- or a sulfur atom, n ⁱ is 2 (2) compounds according. (4) X ⁱ is an oxygen atom, and Y ⁱ is oxazole-
The compound according to (3), wherein the compound is a nitrogen atom forming a 4-yl group, Z ⁱ is a 2-thienyl group, a 2-furyl group, a phenyl group, a substituted phenyl group or a naphthyl group, and Z ¹ⁱ is a methyl group. . (5) V ⁱ is -CH = N-or a sulfur atom, Z ⁱ
Is a phenyl. (6) V ⁱ is -CH = CH-, W ⁱ is> CO, Z ⁱ is 2- (2-furyl) group, 2-phenyl group,
The compound according to (1), which is a 2- (4-methylphenyl) group or a 2- (2-naphthyl) group. (7) The compound according to (3), wherein X ⁱ is an oxygen atom or a sulfur atom, and Y ⁱ is a nitrogen atom forming an oxazol-5-yl, thiazol-4-yl or thiazol-5-yl group. (8) X ⁱ is -CH = N- and Y ⁱ is pyrido-2
-The compound according to (3), wherein the compound is a CH group forming an yl group, or X ⁱ is an oxygen atom and Y ⁱ is a CH group forming a flu-2-yl group. (9) The compound according to (1), which is 5- {4- [3- (5-methyl-2-phenyloxazol-4-yl) propionyl] benzyl} thiazolidine-2,4-dione. (X) JP-A-6-247945 and EP6049
83A includes: (1) General formula (X)

[0108]

Embedded image [In the above general formula (X),

[0109]

Embedded image And -X ^j- represents an oxygen atom or a sulfur atom;
^j- represents = N- or = ^CR5j- , and ^R1j , ^R2j ,
R ^3j , R ^4j and R ^5j are the same or different and are each a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an alkoxy group,
Alkoxyalkoxy, aryloxy, alkanoyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, carbamoyl, alkylaminocarbonyl, arylaminocarbonyl, amino, alkylamino, alkanoyl amino group, arylcarbonylamino group, ethylenedioxy methyl group, a formyl group, a cyano group, a nitro group, or a trihalomethyl group, R ^6j
Represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group, n ^j represents an integer of 0 to 3, and the dotted line indicates that the bond of the portion may be a double bond It represents that. ] Or a pharmaceutically acceptable salt thereof.

In the compound having the general formula (X), A ^j , X ^j , Y ^j , R ^1j , R ^2j , R ^3j , R ^4j ,
Examples of the definitions represented by R ^5j , R ^6j and n ^j , types of pharmacologically acceptable salts, methods for producing compounds having the above general formula (X), examples of compounds, examples and the like are described in the above publications. Are listed.

When R ^1j , R ^2j , R ^3j , R ^4j , and R ^5j represent a halogen atom, an alkyl group, an aryl group, or an alkoxy group, and when R ^6j represents an alkyl group or an aryl group, these are substituted as described above. This is the same as that described for (a) ^a , R ^3c and R ^4a .

R ^1j , R ^2j , R ^3j , R ^4j and R ^{5j each} represent an alkoxyalkoxy group, an aryloxy group, an alkanoyloxy group, an arylcarbonyloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, an alkylaminocarbonyl group, an aryl When an aminocarbonyl group, an alkanoylamino group, or an arylcarbonylamino group is shown, each part of these groups is the same as described above.

[0113] ^{R 1j, R 2j, R 3j} , R 4j, if R ^5j represents an alkylamino group, which is mono- - or di - alkylamino group, those described in the above substituent (a) ^a Is the same as

When R ^1j , R ^2j , R ^3j , R ^4j , R ^5j represent a trihalomethyl group, this is a trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl group, preferably trifluoromethyl. It is a methyl group.

Among the compounds having the general formula (X), preferred compounds are shown below. (2) R ^1j , R ^2j , R ^3j , R ^4j and R ^5j are the same or different and are a hydrogen atom, a halogen atom, an alkyl group having 1 to 8 carbon atoms, and an aryl group having 6 to 12 carbon atoms. An alkoxy group having 1 to 8 carbon atoms, an alkoxyalkoxy group having 2 to 6 carbon atoms, 6 carbon atoms
Aryloxy group having 1 to 12 carbon atoms, 2 to 9 carbon atoms
Alkanoyloxy group having 7 to 13 carbon atoms, arylcarbonyloxy group having 7 to 13 carbon atoms, carboxyl group, alkoxycarbonyl group having 2 to 9 carbon atoms, aryloxycarbonyl group having 7 to 13 carbon atoms, carbamoyl group An alkylaminocarbonyl group having 2 to 9 carbon atoms, an arylaminocarbonyl group having 7 to 13 carbon atoms, an amino group, an alkylamino group having 1 to 8 carbon atoms, and having 2 to 9 carbon atoms R ^6j represents an alkanoylamino group, an arylcarbonylamino group having 7 to 13 carbon atoms, an ethylenedioxymethyl group, a formyl group, a cyano group, a nitro group, or a trihalomethyl group; 1 to 8 carbon atoms which may have one or more substituents selected from Alkyl group, or a halogen, nitro and aryl groups having 1 or more 12 6 to carbon atoms which may have a substituent selected from cyano (1) compounds described having. (3) R ^1j , R ^2j , R ^3j , R ^4j and R ^5j are the same or different and are a hydrogen atom, a halogen atom, an alkyl group having 1 to 8 carbon atoms, and an alkoxy group having 1 to 8 carbon atoms. An alkoxyalkoxy group having 2 to 6 carbon atoms, an alkanoyloxy group having 2 to 9 carbon atoms,
Arylcarbonyloxy group having 7 to 13 carbon atoms, carboxyl group, alkoxycarbonyl group having 2 to 9 carbon atoms, carbamoyl group, alkylaminocarbonyl group having 2 to 9 carbon atoms, 7 to 1 carbon atoms
An arylaminocarbonyl group having three, an amino group,
An alkylamino group having 1 to 8 carbon atoms, 2 carbon atoms
An alkanoylamino group having from 9 to 9, an arylcarbonylamino group having from 7 to 13 carbon atoms, an ethylenedioxymethyl group, a formyl group, a cyano group, a nitro group,
Or a trihalomethyl group, wherein R ^6j represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aryl group having 6 to 12 carbon atoms which may be substituted with halogen. Compound. (4) -X ^j- represents an oxygen atom, and Y ^j is = CR ^5j-
Wherein R ^1j , R ^2j , R ^3j , R ^4j and R ^5j are the same or different and are a hydrogen atom, a halogen atom, an alkyl group having 1 to 5 carbon atoms, and an alkoxy group having 1 to 5 carbon atoms An alkoxyalkoxy group having 2 to 6 carbon atoms, an alkanoyloxy group having 2 to 6 carbon atoms,
A carboxyl group, an alkoxycarbonyl group having 2 to 6 carbon atoms, an arylaminocarbonyl group having 7 to 13 carbon atoms, an amino group, an alkanoylamino group having 2 to 6 carbon atoms, an ethylenedioxymethyl group,
A formyl group, a cyano group, a nitro group or a trihalomethyl group, wherein R ^6j is a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or an aryl having 6 to 12 carbon atoms which may be substituted by halogen; The compound according to (1), which represents a group. (5)

Embedded image , -X ^j- represents an oxygen atom, and Y ^j represents = CR ^5j-
R ^1j , R ^2j , R ^3j and R ^4j are the same or different and each represent a hydrogen atom or a halogen atom, R ^5j represents a hydrogen atom, R ^6j represents a hydrogen atom, and n ^j represents 1. The compound according to (1), wherein the bond at the site indicated by the dotted line is a single bond. (6) 5- [6- (2-fluorobenzyloxy)-
2-naphthylmethyl] thiazolidine-2,4-dione.

In the compounds having the general formulas (I) to (X) or the pharmaceutically acceptable salts thereof, various isomers such as stereoisomers based on asymmetric carbon atoms exist (for example, The carbon atom at the 2-position of the chroman ring and the 5-position of the thiazolidine ring and the oxazolidine ring of the compound having the general formula (I) is an asymmetric carbon atom), and these carbon atoms in the general formulas (I) to (X) are the same. Stereoisomers based on asymmetric carbon atoms and equal and unequal mixtures of these isomers are all represented by a single formula. Accordingly, both these isomers and mixtures of these isomers are included in the present invention. Such a stereoisomer may be obtained by synthesizing a compound having the general formula (I) to (X) using an optically resolved raw material or a compound having the synthesized general formula (I) to (X) if desired. Optical division can be performed using a usual optical division method or a separation method.

Further, in the compounds having the general formulas (I) to (X) or pharmacologically acceptable salts thereof, for example, 2,4-dioxothiazolidine-5-ylmethyl group, 2,4-dioxooxazolidine Various tautomers may be present in the -5-ylmethyl group and the 3,5-dioxooxadiazolidine-5-ylmethyl group. In the above general formulas (I) to (X), the tautomers and the equivalent and unequal mixtures of the isomers are all represented by a single formula. Accordingly, both these isomers and mixtures of these isomers are included in the present invention.

Further, in the present invention, when the compound having the general formulas (I) to (X) or a pharmaceutically acceptable salt thereof forms a solvate (for example, a hydrate), these are all included. It is a thing. For example, the compound having the general formula (I) to (X) or a pharmacologically acceptable salt thereof is left in the air or recrystallized,
Absorbs water, adsorbed water may adhere, or form hydrates. The present invention includes such a solvate.

The present invention also includes all compounds which are converted into the compounds having the above-mentioned general formulas (I) to (X) or pharmacologically acceptable salts by metabolism in a living body, so-called prodrugs. It is a thing.

In the compounds of the present invention having the general formulas (I) to (X), 5- [4- (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl] is preferably used.
Ylmethoxy) benzyl] thiazolidine-2,4-dione (troglitazone), 5- [4- (6-hydroxy-
2-methyl-7-t-butylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5-
[4- (6-Hydroxy-2-ethyl-5,7,8-trimethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (6-hydroxy-2-isobutyl-5) , 7,8-Trimethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4
-Dione, 5- [4- (6-acetoxy-2,5,7,
8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (6-
Ethoxycarbonyloxy-2,5,7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- {4- [2- (3-ethyl-2-pyridyl) ethoxy] benzyl ｝ -2,4-thiazolidinedione, 5- ｛4- [2- (4-ethyl-2-
Pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione, 5- {4- [2- (5-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione (pioglitazone), 5- {4 -[2- (6-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione, 5-[(2-benzyl-2,3-dihydrobenzofuran-5-yl) methyl] thiazolidine-
2,4-dione, 5-[(2-benzyl-3,4-dihydro-2H-benzopyran-6-yl) methyl] thiazolidine-2,4-dione (englitazone), 5- {4
-(2- [N-methyl-N- (2-benzothiazolyl)
Amino] ethoxy) benzyl @ thiazolidine-2,4-
Dione, 5- {4- (2- [N-methyl-N- (2-pyrimidinyl) amino] ethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- [2- (N-methyl-
N- [2- (4,5-dimethylthiazolyl)] amino)
Ethoxy] benzyl} thiazolidine-2,4-dione,
5- {4- (2- [N-methyl-N- (2-thiazolyl) amino] ethoxy) benzyl} thiazolidine-2,
4-dione, 5- {4- [2- (N-methyl-N- [2
-(4-phenylthiazolyl)] amino) ethoxy] benzyl} thiazolidine-2,4-dione, 5- {4-
[2- (N-methyl-N- [2- (4-phenyl-5-
Methylthiazolyl)] amino) ethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [2- (N-
Methyl-N- [2- (4-methyl-5-phenylthiazolyl)] amino) ethoxy] benzyl {thiazolidine-
2,4-dione, 5- {4- [2- (N-methyl-N-
[2- (5-phenyloxazolyl)] amino) ethoxy] benzyl {thiazolidine-2,4-dione, 5-
{4- [2- (N-methyl-N- [2- (4,5-dimethyloxazolyl)] amino) ethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [2- ( 2-
Pyrimidinylamino) ethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- (2- [N-acetyl-N- (2-pyrimidinyl) amino] ethoxy) benzyl} thiazolidine-2,4-dione, 5 − ｛4- (2-
[N- (2-benzothiazolyl) -N-benzylamino] ethoxy) benzyl {thiazolidine-2,4-dione, 5- {4- (3- [N-methyl-N- (2-benzoxazolyl) amino] propoxy) Benzyl {thiazolidine-2,4-dione, 5- {4- (2- [N-methyl-N- (2-pyridyl) amino] ethoxy) benzyl}
Thiazolidine-2,4-dione (rosiglitazone), 5
-{4- (2-[([1- (4-biphenylyl) ethylidene] amino) oxy] ethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (2-[([1-
(4-phenylsulfonylphenyl) ethylidene] amino) oxy] ethoxy) benzyl {thiazolidine-2,
4-dione, 5- {4- [2-([(1- [4- (2-
Pyridyl) phenyl] ethylidene) amino] oxy) ethoxy] benzyl {thiazolidine-2,4-dione (compound A), 5- {4- [2-([(1- [4- (3-pyridyl) phenyl] ethylidene) ) Amino] oxy) ethoxy] benzyl {thiazolidine-2,4-dione, 5-
{4- [2-([(1- [4- (4-pyridyl) phenyl] ethylidene) amino] oxy] ethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- (2-
[([1- (2-phenyl-5-pyridyl) ethylidene] amino) oxy] ethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (2-[([1- (2
-Methoxy-5-pyridyl) ethylidene] amino) oxy] ethoxy) benzyl {thiazolidine-2,4-dione, 5- {4- (2-[([1- (2-ethoxy-5-
Pyridyl) ethylidene] amino) oxy] ethoxy) benzyl {thiazolidine-2,4-dione, 5- {4-
(2-[([1- (2-Isopropoxy-5-pyridyl) ethylidene] amino) oxy] ethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (2-
[([1- (2-benzyl-5-pyridyl) ethylidene] amino) oxy] ethoxy) benzyl} thiazolidine-2,4-dione, 4- {4- [2- (2-phenyl-5-methyl-4) -4 -Oxazolyl) ethoxy] benzyl} -3,5-isoxazolidinedione, 4- {4-
[2- (2-phenyl-5-methyl-4-oxazolyl) ethoxy] benzylidene} -3,5-isoxazolidinedione, 4- {4- [2- (2-benzothienyl-5-methyl-4-oxazolyl) ) Ethoxy] benzyl} -3,5-isoxazolidinedione, 4- {4-
(2- [5-methyl-2- (2-pyridylthio) ethyl-4-oxazolyl] ethoxy) benzyl} -3,5-
Isoxazolidinedione, 5- [4- (3-methylimidazo [4,5-b] pyridin-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4-
(5-chloro-3-methylimidazo [4,5-b] pyridin-2-ylmethoxy) benzyl] thiazolidine-
2,4-dione, 5- [4- (5-methoxy-3-methylimidazo [4,5-b] pyridin-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5-
[4- (5-hydroxy-3-methylimidazo [4,5
-B] pyridin-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (5-ethoxy-
3-methylimidazo [4,5-b] pyridin-2-ylmethoxy) benzyl] thiazolidine-2,4-dione;
5- [4- (5-isopropoxy-3-methylimidazo [4,5-b] pyridin-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (1-
Methylindoline-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (6 -Methoxy-1-methylbenzimidazol-2-ylmethoxy)
[Benzyl] thiazolidine-2,4-dione (compound B), 5- [4- (5-methoxy-1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- ( 1-benzylbenzimidazol-5-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (5-hydroxy-
1,4,6,7-tetramethylbenzimidazole-2
-Ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (5-acetoxy-1,4,6,7-
Tetramethylbenzimidazol-2-ylmethoxy)
[Benzyl] thiazolidine-2,4-dione, 5- {4-
[3- (5-methyl-2-phenyloxazole-4-
Yl) propionyl] benzyl @ thiazolidine-2,4
-Dione and 5- [6- (2-fluorobenzyloxy) -2-naphthylmethyl] thiazolidine-2,4-dione, and pharmacologically acceptable salts thereof.

In the compounds of the present invention having the general formulas (I) to (X), more preferably, 5- [4- (6-
Hydroxy-2,5,7,8-tetramethylchroman-
2-ylmethoxy) benzyl] thiazolidine-2,4-
Dione (troglitazone), 5- [4- (6-acetoxy-2,5,7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione,
5- [4- (6-ethoxycarbonyloxy-2,5,
7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- {4-
[2- (5-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione (pioglitazone), 5-[(2-benzyl-3,4-dihydro-2H
-Benzopyran-6-yl) methyl] thiazolidine-
2,4-dione (englitazone), 5- {4- (2-
[N-methyl-N- (2-pyridyl) amino] ethoxy) benzyl {thiazolidine-2,4-dione (rosiglitazone), 5- {4- [2-([(1- [4- (2-
Pyridyl) phenyl] ethylidene) amino] oxy) ethoxy] benzyl {thiazolidine-2,4-dione (compound A), 4- {4- [2- (2-phenyl-5-methyl-4-oxazolyl) ethoxy] benzyl ｝ -3,5
-Isoxazolidinedione, 5- [4- (5-methoxy-3-methylimidazo [4,5-b] pyridine-2-
Ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (1-methylindoline-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5-
[4- (1-Methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5-
[4- (6-Methoxy-1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4
-Dione (compound B), 5- [4- (5-hydroxy-
1,4,6,7-tetramethylbenzimidazole-2
-Ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- {4- [3- (5-methyl-2-phenyloxazol-4-yl) propionyl] benzyl} thiazolidine-2,4-dione and 5- [6- (2-fluorobenzyloxy) -2-naphthylmethyl] thiazolidine-2,4-dione; and pharmacologically acceptable salts thereof.

In the compounds of the present invention having the general formulas (I) to (X), 5- [4- (6-
Hydroxy-2,5,7,8-tetramethylchroman-
2-ylmethoxy) benzyl] thiazolidine-2,4-
Dione (troglitazone), 5- {4- [2- (5-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-
Thiazolidinedione (pioglitazone), 5- ｛4-
(2- [N-methyl-N- (2-pyridyl) amino] ethoxy) benzyl} thiazolidine-2,4-dione (rosiglitazone), 5- {4- [2-([(1- [4-
(2-pyridyl) phenyl] ethylidene) amino] oxy) ethoxy] benzyl {thiazolidine-2,4-dione (compound A) and 5- [4- (6-methoxy-1-methylbenzimidazol-2-ylmethoxy) benzyl Thiazolidine-2,4-dione (compound B), and pharmacologically acceptable salts thereof.

In the compounds of the present invention having the general formulas (I) to (X), most preferably, 5- [4- (6-
Hydroxy-2,5,7,8-tetramethylchroman-
2-ylmethoxy) benzyl] thiazolidine-2,4-
Dione (troglitazone) and pharmacologically acceptable salts thereof.

[0124]

BEST MODE FOR CARRYING OUT THE INVENTION The insulin sensitizer of the present invention is administered in various forms. The administration form is not particularly limited, but various preparation forms, patient age,
It is determined according to gender and other conditions, degree of disease, and the like.
For example, oral administration by tablets, pills, powders, granules, syrups, solutions, suspensions, emulsions, granules, capsules or the like or parenteral administration by injections or suppositories can be mentioned. In the case of injections, they may be administered intravenously, alone or as a mixture with normal replenishers such as glucose and amino acids, and if necessary alone intramuscularly, intradermally,
It is administered subcutaneously or intraperitoneally. A preferred dosage form is oral administration.

These various preparations use, as the main ingredient, known auxiliaries which can be usually used in the field of known pharmaceutical preparations such as excipients, binders, disintegrants, lubricants, solubilizers, flavors, coating agents and the like. Can be formulated.

For the preparation into tablets, carriers conventionally known in the art can be widely used, such as lactose, sucrose, glucose, starch, sodium chloride, urea, calcium carbonate, kaolin, crystalline cellulose, silica gel, and the like. Excipients such as acids, water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone sugar binder, dried starch, sodium alginate, agar Powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, etc., disintegrants, sucrose, stearin, cocoa butter, hydrogenated oil, etc. Agent, first Grade ammonium bases, absorption enhancers such as sodium lauryl sulfate, glycerin, a humectant such as starch, starch, lactose, kaolin, bentonite, adsorbent such as colloidal silicic acid, purified talc, stearates,
Lubricants such as boric acid powder and polyethylene glycol can be exemplified. Further, the tablet can be a tablet coated with a usual coating, if necessary, for example, a sugar-coated tablet, a gelatin-encapsulated tablet, an enteric-coated tablet, a film-coated tablet or a double tablet or a multilayer tablet.

In the case of molding into a pill form, as the carrier, those conventionally known in the art can be widely used, for example, excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin and talc; Examples thereof include a gum arabic powder, a tragacanth powder, a binder such as gelatin and ethanol, and a disintegrant such as laminaran agar.

For shaping in the form of suppositories, those conventionally known in the art can be widely used as carriers, for example, polyethylene glycol, cocoa butter, higher alcohols, higher alcohol esters, gelatin, semisynthetic glyceride and the like. Can be mentioned.

When prepared as an injection, the liquid preparation and the suspension are preferably sterilized and isotonic with blood. When forming these liquid preparations, emulsions and suspensions, they may be diluted. As the agent, any one commonly used in this field can be used, for example, water, ethyl alcohol,
Examples include propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid esters. In this case, a sufficient amount of salt, glucose, or glycerin to prepare an isotonic solution may be included in the pharmaceutical preparation, and a normal solubilizing agent may be used.
A buffer, a soothing agent and the like may be added. Further, a coloring agent, a preservative, a flavor, a flavoring agent, a sweetening agent and the like and other pharmaceuticals may be added as necessary.

The amount of the active ingredient compound contained in the above-mentioned pharmaceutical preparation is not particularly limited and may be appropriately selected in a wide range, but is usually 1 to 70% by weight, preferably 1 to 30% by weight in the whole composition. Is appropriate.

In the present invention, the dosage of the insulin sensitizer is different depending on symptoms, age, administration method and the like. For example, in the case of oral administration, the lower limit is 0.1 mg per day per adult (preferably 0.1 mg / day). 1 mg) and, as an upper limit, 1000 mg (preferably 500 mg) in one or several divided doses.
In the case of intravenous administration, for adults, the lower limit is 0.01 mg (preferably 0.1 mg) and the upper limit is 500 mg (preferably 200 mg) once or several times a day. It is desirable to administer according to.

Next, the present invention will be described in more detail with reference to Examples, Test Examples and Formulation Examples.

[0133]

EXAMPLE 1 Human Leukemia Cell Proliferation Inhibitory Effect A culture of human leukemia cells was RPMI16 containing 10% non-immobilized fetal calf serum and 50 μg / ml kanamycin.
Forty solutions were used. That is, human leukemia cell KU812
(2 × 10 ⁵ cells / ml) was added to a final concentration of 2 μM troglitazone (compound name: 5- [4- (6-hydroxy-
2,5,7,8-Tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione) and cultured in a carbon dioxide gas incubator at 37 ° C. for 96 hours. The cell proliferation of human leukemia cells was determined every 24 hours by measuring the number of viable cells in a culture solution containing troglitazone and a culture solution without troglitazone by trypan blue staining. Human leukemia cell growth inhibitory activity (inhibition rate) by troglitazone was calculated by the following formula, and the results are shown in Table 1. In Table 1, “contact time” indicates the contact time between human leukemia cell KU812 and troglitazone. Human leukemia cell growth inhibitory activity (%) = [1-vitrotazone-added viable cell count / untreated viable cell count] × 100

[0134]

[Table 1] Human leukemia cell growth inhibitory activity Contact time (hours) 24 48 72 96 Growth inhibitory activity (%) 0 12.3 27.0 46.0 As is clear from Table 1, the compounds of the present invention exhibited an excellent growth inhibitory effect on human leukemia cells. [Test Example] Test Example 1 Acute toxicity Acute toxicity was measured according to a conventional method. That is, troglitazone was orally administered to three ddY mice (male) at a dose of 300 mg / kg and observed for 5 days, but all survived.
Similarly, the acute toxicity of Compounds C and D was measured and found to be 300 mg / kg or more for oral administration. [Preparation Example] A preparation containing the insulin sensitizer of the present invention as an active ingredient can be produced, for example, by the following method. Formulation Example 1 When mixed powders troglitazone 5g, lactose 895g and corn starch 100g in a blender, powder is obtained. Formulation Example 2. After mixing 5 g of granule troglitazone, 865 g of lactose and 100 g of low-substituted hydroxypropylcellulose, 10%
300 g of an aqueous solution of hydroxypropylcellulose is added and kneaded. This is granulated using an extrusion granulator and dried to obtain a granule. Formulation Example 3. Capsules 5 g of troglitazone, 115 g of lactose, 58 g of corn starch and 2 g of magnesium stearate are mixed using a V-type mixer, and the capsules are obtained by filling 180 mg each in No. 3 capsules. Formulation Example 4. Tablets 5 g of troglitazone, 90 g of lactose, 34 g of corn starch, 20 g of crystalline cellulose and 1 g of magnesium stearate are mixed in a blender, and the mixture is compressed with a tablet machine to give tablets. Formulation Example 5 When mixed powders pioglitazone 5g, lactose 895g and corn starch 100g in a blender, powder is obtained. Formulation Example 6. After mixing 5 g of granule rosiglitazone, 865 g of lactose and 100 g of low-substituted hydroxypropylcellulose, 10 g
A 300% aqueous solution of hydroxypropyl cellulose is added and kneaded. This is granulated using an extrusion granulator and dried to obtain a granule. Formulation Example 7. Capsule compound A 5g, lactose 115g, corn starch 5
After mixing 8 g and 2 g of magnesium stearate using a V-type mixer, a capsule is obtained by filling 180 mg each in a No. 3 capsule. Formulation Example 8. Tablet compound A 5 g, lactose 90 g, corn starch 34
g, 20 g of crystalline cellulose and 1 g of magnesium stearate in a blender, and then tableted with a tablet machine to give tablets.

[0135]

The insulin sensitizer of the present invention comprises:
It is useful as a prophylactic or therapeutic agent for leukemia.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/44 613 A61K 31/44 613 31/505 601 31/505 601 606 606 606 31/52 31/52 // C07D 277/34 C07D 277/34 277/36 277/36 413/12 235 413/12 235 261 261 333 333 413 413/14 213 413/14 213 417/12 209 417/12 209 213 213 235 235 239 239 263 263 307 307 307 311 311 471/04 107 471/04 107Z 473/00 473/00 487/04 144 487/04 144

Claims (29)

[Claims] 1. A preventive or therapeutic agent for leukemia, comprising an insulin sensitizer as an active ingredient. 2. The method according to claim 1, wherein the insulin sensitizer is a thiazolidinedione compound, an iminothiazolidinone compound, a diiminothiazolidine compound, a thioxothiazolidinone compound, an iminotriazole compound, an oxazolidinedione compound, an isoxazolidine. An agent for preventing or treating leukemia, which is a compound selected from the group consisting of a dione compound and an oxadiazolidinedione compound. 3. The prevention of leukemia according to claim 1, wherein the insulin sensitizer is a compound selected from the group consisting of thiazolidinedione compounds, oxazolidinedione compounds, isoxazolidinedione compounds and oxadiazolidinedione compounds. Agent or therapeutic agent. 4. The preventive or therapeutic agent for leukemia according to claim 1, wherein the insulin sensitizer is a compound selected from the group consisting of thiazolidinedione compounds, iminothiazolidinone compounds and diiminothiazolidine compounds. 5. The preventive or therapeutic agent for leukemia according to claim 1, wherein the insulin sensitizer is a thiazolidinedione compound or an oxazolidinedione compound. 6. The preventive or therapeutic agent for leukemia according to claim 1, wherein the insulin sensitizer is a thiazolidinedione compound. 7. The method according to claim 1, wherein the insulin sensitizer is represented by the general formula (I): [Wherein, R ^1a and R ^2a are the same or different and each represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, R ^3a represents a hydrogen atom, an aliphatic acyl group having 1 to 6 carbon atoms, cycloalkylcarbonyl groups having 6 to 8 carbon, substituents (a) may have an ^a benzoyl or naphthoyl group (said substituent (a) ^a is 1 carbon atoms
An alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxy group, a halogen atom, an amino group, a monoalkylamino group having 1 to 4 carbon atoms,
The same or different, each alkyl is a dialkylamino group having 1 to 4 carbon atoms or a nitro group. ), A 4- to 7-membered heterocyclic acyl group containing 1 to 3 heteroatoms selected from a heteroatom group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, a phenylacetyl group, a phenylpropionyl group, and at least one A halogen-substituted phenylacetyl or phenylpropionyl group, a cinnamoyl group, an alkoxycarbonyl group having 2 to 7 carbon atoms or a benzyloxycarbonyl group, wherein R ^4a and R ^5a are the same or different and each have a hydrogen atom, 1
Or represents an alkyl group or an alkoxy group having 1 to 5 carbon having five, or R ^4a and R ^5a together indicates alkylenedioxy group having 1 to 4 carbon atoms, Y ^a and Z ^a are the same or different and each represents an oxygen atom or an imino group, n ^a is an integer of 1 to 3. And / or a pharmacologically acceptable salt thereof. 8. The preventive or therapeutic agent for leukemia according to claim 7, wherein R ^1a is an alkyl group having 1 to 4 carbon atoms. 9. The preventive or therapeutic agent for leukemia according to claim 7, wherein R ^1a is a methyl group. 10. The preventive or therapeutic agent for leukemia according to claim 7, wherein R ^2a is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. 11. The preventive or therapeutic agent for leukemia according to any one of claims 7 to 9, wherein R ^2a is a hydrogen atom or a methyl group. 12. The method according to claim 7, wherein R ^3a is a hydrogen atom, an aliphatic acyl group having 1 to 4 carbon atoms, a benzoyl or naphthoyl group having no substituent, or a carbon number. An agent for preventing or treating leukemia, which is an alkoxycarbonyl group having 2 to 4 alkoxy groups. 13. A prophylactic or therapeutic agent for leukemia according to any one of claims 7 to 11, wherein R ^3a is a hydrogen atom, an acetyl group, a benzoyl group or an ethoxycarbonyl group. 14. A preventive or therapeutic agent for leukemia according to any one of claims 7 to 11, wherein R ^3a is a hydrogen atom, an acetyl group or an ethoxycarbonyl group. 15. The preventive or therapeutic agent for leukemia according to claim 7, wherein R ^4a is an alkyl group having 1 to 4 carbon atoms. 16. The preventive or therapeutic agent for leukemia according to claim 7, wherein R ^4a is a methyl group or a t-butyl group. 17. The method according to claim 7, wherein R ^5a has a hydrogen atom or 1 to 3 carbon atoms.
An agent for preventing or treating leukemia which is an alkyl group. 18. The prophylactic or therapeutic agent for leukemia according to claim 7, wherein R ^5a is a hydrogen atom or a methyl group. 19. The method of claim 1, wherein the insulin sensitizer is represented by the general formula (II): A preventive or therapeutic agent for leukemia, which is a thiazolidine derivative or a pharmacologically acceptable salt thereof. 20. The method according to claim 1, wherein the insulin sensitizer is represented by the general formula (III): Wherein the dashed line represents a single bond or a non-binding, n ^c is 0, 1 or 2, X ^c represents an oxygen atom, a sulfur atom, a sulfinyl group (S =
O), a sulfonyl group (S (= O) (= O)), R ^c is a hydrogen atom, a methyl group or an ethyl group, R ^1c is a hydrogen atom, a cycloalkyl group having 5 to 7 carbon atoms. A methyl-substituted cycloalkyl group having 6 to 8 carbon atoms, a pyridyl group, a thienyl group, a furyl group, a naphthyl group, a p-biphenylyl group, a tetrahydrofuranyl group,
Tetrahydrothienyl group, tetrahydropyranyl group, C
₆ H ₄ W ^2c group [W ^2c is a hydrogen atom, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms or 1 carbon atom An alkylthio group having from 1 to 4 alkylthio groups. ]
Or an alk-W ^1c group [alk is an alkylene group having 1 to 6 carbon atoms, an ethylidene group or an isopropylidene group, and W ^1c is a hydrogen atom, a hydroxy group, an alkoxy group having 1 to 4 carbon atoms, An alkylthio group having a number of 1 to 4, a pyridyl group, a furyl group, a thienyl group,
A tetrahydrofuryl group, a tetrahydrothienyl group, a naphthyl group, a cycloalkyl group having 5 to 7 carbon atoms, or a C ₆ H ₄ W ^2c group. R ^2c is a hydrogen atom or a methyl group, R ^3c is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a C ₆ H ₄ W ^2c group or a benzyl group, and R ^4c is a hydrogen atom. When R ^1c and R ^2c are taken together, they form an alkylene group having 4 to 6 carbon atoms, and R ^3c and R ^2c
4c are each hydrogen atom, when R ^3c and R ^4c are taken together, they form an alkylene group having 4 to 6 carbon atoms, R ^1c and R
^2c are each hydrogen atom, when R ^2c and R ^3c are taken together, they form an alkylene group having 3 or 4 carbon, R ^1c
And R ^4c are each a hydrogen atom. Or a pharmacologically acceptable salt thereof, for preventing or treating leukemia. 21. The method according to claim 1, wherein the insulin sensitizer is represented by the general formula (IV): [In the formula, A ^1d represents a substituted or unsubstituted aromatic heterocyclic group; R ^1d represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group (wherein the aryl moiety may be substituted or unsubstituted) represents an) or a substituted or unsubstituted aryl group; R ^2d
And R ^3d are the same or different and represent a hydrogen atom, or R ^2d and R ^3d together represent a bond; A ^2d represents a benzene ring having a total of up to 5 substituents;
^d represents an integer in the range of 2 to 6. Or a pharmacologically acceptable salt thereof, for preventing or treating leukemia. 22. The method of claim 1, wherein the insulin sensitizer is represented by the general formula (V): [Wherein, R ^1e represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms, and R ^2e represents a linear or branched alkyl group having 2 to 6 carbon atoms. R ^3e is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 4 carbon atoms. An alkoxy group, a linear or branched alkylthio group having 1 to 4 carbon atoms, a halogen atom, a nitro group, an amino group, a linear or branched monoalkyl group having 1 to 4 carbon atoms. An alkylamino group, a straight or branched dialkylamino group having the same or different alkyl groups having 1 to 4 carbon atoms, an aryl group having 6 to 10 carbon atoms or 7 to 12 carbon atoms; an aralkyl group having, X ^e is 1 to 3 of substituents (a) aryl group, or 1 to 3 having 6 to 10 carbon atoms that may have a ^e
(A) ^e represents an aromatic heterocyclic group which may have a substituent (a) ^e , wherein the substituent (a) ^e is (i) a linear or branched chain having 1 to 6 carbon atoms An alkyl group, (ii)
A linear or branched alkyl halide group having 1 to 4 carbon atoms, (iii) a hydroxy group,
(Iv) a linear or branched acyloxy group having 1 to 4 carbon atoms, (v) a linear or branched alkoxy group having 1 to 4 carbon atoms, (v
i) a linear or branched alkylenedioxy group having 1 to 4 carbon atoms; (vii) a C7 to 1 carbon atom
An aralkyloxy group having two, (viii) a linear or branched alkylthio group having 1 to 4 carbon atoms, and (ix) a linear or branched alkylthio group having 1 to 4 carbon atoms. (X) halogen atom, (xi) nitro group, (xii) amino group, (xiii) linear or branched monoalkylamino group having 1 to 4 carbon atoms, (xiv) )
The same or different, each alkyl having 1 to 4 carbon atoms, a linear or branched dialkylamino group;
(Xv) an aralkyl group having 7 to 12 carbon atoms,
(Xvi) substituents (b) an aryl group having 6 to 10 carbon carbon atoms that may have a ^e, (xvii) substituents (b) good having 6 to 10 carbon atoms which may have a ^e a (Xviii) substituted aryl (b)
arylthio groups having in the 6 to 10 carbon atoms that may optionally have a ^e, (xix) substituents (b) an arylsulfonyl group having 6 to 10 carbon atoms that may have a ^e, (xx) An arylsulfonylamino group having 6 to 10 carbon atoms which may have a substituent (b) ^e (a nitrogen atom in the amino portion is a linear or branched alkyl having 1 to 6 carbon atoms) (Xxi) aromatic heterocyclic group, (xxii) aromatic heterocyclic oxy group, (xxiii) aromatic heterocyclic thio group, (xxiv) aromatic heterocyclic sulfonyl group, and xxv) represents an aromatic heterocyclic sulfonylamino group (the nitrogen atom in the amino portion may be substituted by linear or branched alkyl having 1 to 6 carbon atoms). Here, the substituent (b) ^e is a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms, or a straight-chain or branched-chain halogenated alkyl group having 1 to 4 carbon atoms. A straight-chain or branched alkoxy group having 1 to 4 carbon atoms, a halogen atom or 1 to 4 carbon atoms
Represents a linear or branched alkylenedioxy group having pieces, Y ^e represents an oxygen atom, a group (wherein having a sulfur atom or the formula> N-R ^4e, R ^4e represents a hydrogen atom, C 1 -C A linear or branched alkyl group having 1 to 6 carbon atoms or a linear or branched acyl group having 1 to 8 carbon atoms), and ^Ze is 2,4- Dioxothiazolidine-
A 5-yridenylmethyl group, a 2,4-dioxothiazolidine-5-ylmethyl group, a 2,4-dioxooxazolidine-5-ylmethyl group or a 3,5-dioxooxadiazolidine-2-ylmethyl group. Or an agent for preventing or treating leukemia, which is a pharmaceutically acceptable salt thereof. 23. The method according to claim 1, wherein the insulin sensitizer is represented by the general formula (VI): [Wherein, R ^f represents an optionally substituted aromatic hydrocarbon group, an optionally substituted cycloaliphatic hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted fused heterocyclic group, Or the following general formula: [Wherein, R ^1f represents an ^optionally substituted aromatic hydrocarbon group, an optionally substituted cycloaliphatic hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted fused heterocyclic group. R ^2f and R ^3f are the same or different and are a hydrogen atom or a lower alkyl group; X ^f is a group represented by an oxygen atom, a sulfur atom or a secondary amino group; and R ^4f is a hydrogen atom or a lower amino group. R ^5f is lower alkyl, P ^f and Q ^f are the same or different and are hydrogen atoms,
Or, P ^f and Q ^f together represent a bond. Or a pharmacologically acceptable salt thereof, which is a prophylactic or therapeutic agent for leukemia. 24. The method according to claim 1, wherein the insulin resistance is improved.
The good substance is represented by the general formula (VII):[Where X^g Is indole ring group, indoline ring group, azaindole
Ring group, azaindoline ring group, imidazopyridine ring group or
Represents an imidazopyrimidine ring group, and these rings are 1 to
3 replacements (a) to be described later^g Y^g Represents an oxygen atom or a sulfur atom;^g Is 2,4-dioxothiazolidine-5-yridenyl
Methyl group, 2,4-dioxothiazolidine-5-ylme
Tyl group, 2,4-dioxooxazolidin-5-ylmeth
Tyl group, 3,5-dioxooxadiazolidine-2-i
A methyl group or an N-hydroxyureidomethyl group
Then R^g Is a hydrogen atom, a straight chain having 1 to 4 carbon atoms
Or branched alkyl group having 1 to 4 carbon atoms
Linear or branched alkoxy group, halogen source
Child, hydroxy group, nitro group, substitution (b)^g Have
An amino group which may be present (substitution (b)^g Is from 1 carbon
Straight or branched alkyl group having 8 carbon atoms,
A straight-chain or branched chain having 7 to 11 primes;
An aralkyl group, an aryl group having 6 to 10 carbon atoms,
Linear or branched having 1 to 11 carbon atoms
Aliphatic fatty group having aliphatic acyl group and 8 to 12 carbon atoms
Acyl group or aromatic acyl group having 7 to 11 carbon atoms
Represents a hydroxyl group. ) Or linear having 7 to 11 carbon atoms
Or a branched aralkyl group;^g Represents an integer of 1 to 5, where (a)^g Is a straight chain having 1 to 4 carbon atoms
Chain or branched alkyl group, 1 to 4 carbon atoms
A linear or branched alkoxy group having
Ziroxy group, halogen atom, hydroxy group, acetoxy
Si group, phenylthio group, straight chain having 1 to 4 carbon atoms
Or branched alkylthio groups, trifluoromethyl
Tyl group, nitro group, substitution (b)^g May have
An amino group (the substitution (b)^g Has 1 to 8 carbon atoms
Linear or branched alkyl group having 7 to 7 carbon atoms
Linear or branched aralkyl having 11
Group, aryl group having 6 to 10 carbon atoms, 1 carbon atom
Linear or branched aliphatic aliphatic group having from 11 to 11
Silyl group, araliphatic acyl having 8 to 12 carbon atoms
A group or an aromatic acyl group having 7 to 11 carbon atoms
You. ), Substitution (c) ^g 6 carbon atoms which may have
An aryl group having from 10 to 10 (the substituent (c) ^g Is carbon
Linear or branched alkyl having from 1 to 4
A straight or branched chain having 1 to 4 carbon atoms
Alkoxy, halogen, hydroxy, nitro
B, phenyl, trifluoromethyl, substituted
(B)^g Or an amino group which may have
(C)^g Having 7 to 11 carbon atoms which may have
Linear or branched aralkyl groups. ]
Or a pharmacologically acceptable salt thereof.
An agent for preventing or treating leukemia. 25. The method according to claim 1, wherein the insulin resistance is improved.
The good substance is represented by the general formula (VIII):[Where X^h Represents a benzimidazole ring group, wherein the group is 1 to 5
Replacements (a)^h Y^h Represents an oxygen atom or a sulfur atom;^h Is 2,4-dioxothiazolidine-5-yridenyl
Methyl group, 2,4-dioxothiazolidine-5-ylme
Tyl group, 2,4-dioxooxazolidin-5-ylmeth
Tyl group, 3,5-dioxooxadiazolidine-2-i
A methyl group or an N-hydroxyureidomethyl group
Then R^h Is a hydrogen atom, a straight chain having 1 to 4 carbon atoms
Or branched alkyl group having 1 to 4 carbon atoms
Linear or branched alkoxy group, halogen source
Child, hydroxy group, nitro group, substitution (b)^h Have
An amino group which may be present (substitution (b)^h Is from 1 carbon
Straight or branched alkyl group having 8 carbon atoms,
A straight-chain or branched chain having 7 to 11 primes;
An aralkyl group, an aryl group having 6 to 10 carbon atoms,
Linear or branched having 1 to 11 carbon atoms
Aliphatic fatty group having aliphatic acyl group and 8 to 12 carbon atoms
Acyl group or aromatic acyl group having 7 to 11 carbon atoms
Represents a hydroxyl group. ) Or linear having 7 to 11 carbon atoms
Or a branched aralkyl group;^h Represents an integer of 1 to 5, where (a)^h Is a straight chain having 1 to 4 carbon atoms
Chain or branched alkyl group, 1 to 4 carbon atoms
A linear or branched alkoxy group having
Ziroxy group, halogen atom, hydroxy group, acetoxy
Si group, phenylthio group, straight chain having 1 to 4 carbon atoms
Or branched alkylthio groups, trifluoromethyl
Tyl group, nitro group, substitution (b)^h May have
An amino group (the substitution (b)^h Has 1 to 8 carbon atoms
Linear or branched alkyl group having 7 to 7 carbon atoms
Linear or branched aralkyl having 11
Group, aryl group having 6 to 10 carbon atoms, 1 carbon atom
Linear or branched aliphatic aliphatic group having from 11 to 11
Silyl group, araliphatic acyl having 8 to 12 carbon atoms
A group or an aromatic acyl group having 7 to 11 carbon atoms
You. ), Substitution (c) ^h 6 carbon atoms which may have
An aryl group having from 10 to 10 (the substituent (c) ^h Is carbon
Linear or branched alkyl having from 1 to 4
A straight or branched chain having 1 to 4 carbon atoms
Alkoxy, halogen, hydroxy, nitro
B, phenyl, trifluoromethyl, substituted
(B)^h Or an amino group which may have
(C)^h Having 7 to 11 carbon atoms which may have
Linear or branched aralkyl groups. ]
Having a fused heterocyclic compound or a pharmaceutically acceptable salt thereof
An agent for preventing or treating certain leukemias. 26. The method of claim 1, wherein the insulin sensitizer is of the general formula (IX). [Wherein the dotted line indicates no bond or a bond, V ⁱ is -CH = CH -, - N = CH -, - CH = an N- or a sulfur atom, W ⁱ is> CH _2,> CHOH,>CO,> C = NOR ⁱ
Or -CH = a CH-, X ⁱ represents a sulfur atom, an oxygen atom,> NR ^1i, a -CH = N-or -N = CH-, Y ⁱ is = CH- or a nitrogen atom, Z ⁱ Is a hydrogen atom, an alkyl group having 1 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a phenyl group, a naphthyl group, a pyridyl group, a furyl group, a thienyl group, or the same or different carbon atoms having 1 carbon atom. Alkyl having 3 to 3 carbon atoms, trifluoromethyl, 1 to 3 carbon atoms
Alkoxy, fluorine, chlorine or bromine and is monosubstituted or disubstituted phenyl group with a group having a number, Z ¹ⁱ is an alkyl group having 1 to 3 the number of hydrogen atoms or carbon, R ⁱ and R ¹ⁱ Are the same or different and are a hydrogen atom or a methyl group, and ⁿⁱ is 1, 2 or 3. Or a pharmacologically acceptable salt thereof, for preventing or treating leukemia. 27. The method of claim 1, wherein the insulin sensitizer is represented by the general formula (X): [In the above general formula (X), Wherein -X ^j- represents an oxygen atom or a sulfur atom, = Y ^j -represents = N- or = CR ^5j- , and R ^1j , R ^2j , R ^3j , R ^4j and R ^5j are the same Different from hydrogen atom, halogen atom, alkyl group, aryl group, alkoxy group, alkoxyalkoxy group, aryloxy group, alkanoyloxy group, arylcarbonyloxy group, carboxyl group, alkoxycarbonyl group, aryloxycarbonyl group, carbamoyl group, alkyl R ^6j represents an aminocarbonyl group, an arylaminocarbonyl group, an amino group, an alkylamino group, an alkanoylamino group, an arylcarbonylamino group, an ethylenedioxymethyl group, a formyl group, a cyano group, a nitro group, or a trihalomethyl group; A hydrogen atom, an optionally substituted alkyl group or an optionally substituted Represents an aryl group, n ^j represents an integer of 0 to 3, the dashed line represents the bond of the part may be a double bond. And / or a pharmacologically acceptable salt thereof. 28. The method according to claim 1, wherein the insulin sensitizer is 5- [4- (6-hydroxy-2,5,7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4. -Dione (troglitazone), 5- [4- (6-acetoxy-2,5,7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (6- Ethoxycarbonyloxy-2,5
7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- {4- [2- (5-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione (Pioglitazone), 5-[(2-benzyl-3,4-dihydro-2H-benzopyran-6-yl) methyl] thiazolidine-2,4-
Dione (engritazone), 5- {4- (2- [N-methyl-N- (2-pyridyl)]
Amino] ethoxy) benzyl @ thiazolidine-2,4-
Dione (rosiglitazone), 5- {4- [2-([(1- [4- (2-pyridyl) phenyl] ethylidene) amino] oxy] ethoxy] benzyl} thiazolidine-2,4-dione (compound A) 4- {4- [2- (2-phenyl-5-methyl-4-oxazolyl) ethoxy] benzyl} -3,5-isoxazolidinedione; 5- {4- (5-methoxy-3-methylimidazo [ 4,
5-b] pyridin-2-ylmethoxy) benzyl {thiazolidine-2,4-dione, 5- [4- (1-methylindoline-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- [4- (6-methoxy-1-methylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-
2,4-dione (compound B), 5- [4- (5-hydroxy-1,4,6,7-tetramethylbenzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- { 4- [3- (5-methyl-2-phenyloxazol-4-yl) propionyl] benzyl} thiazolidine-2,4-dione or 5- [6- (2-fluorobenzyloxy) -2-naphthyl [Methyl] thiazolidine-2,4-dione and a pharmacologically acceptable salt thereof for treating or preventing leukemia. 29. The method of claim 1, wherein the insulin sensitizer is 5- [4- (6-hydroxy-2,5,7,8-tetramethylchroman-2-ylmethoxy) benzyl] thiazolidine-2,4. -A dione (troglitazone) and a pharmacologically acceptable salt thereof, a therapeutic or prophylactic agent for leukemia.