JP2843281B2 - Oxime derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to hyperlipidemia, hyperglycemia, obesity, impaired glucose tolerance (impaired glucose toleranc).
e: IGT status, insulin resistant non-glucose intolerance (insul)
in resistant non-IGT (NGT) status, insulin resistance, cachexia, psoriasis, diabetic complications, arteriosclerosis, hypertension, osteoporosis, and polycystic ovary syndrome (polycystic)
The present invention relates to an oxime derivative or a salt thereof, which improves ovary syndrome (PCOS), fatty liver, gestational diabetes mellitus (GDM), etc., and further has an aldose reductase inhibitory activity, a method for producing the same, and a use thereof.

[0002]

2. Description of the Related Art Conventionally, as an agent for treating diabetes and hyperglycemia,
Insulin and tributamide, sulfonylurea compounds such as glipizide have been used.Recently, thiazolidinedione derivatives (e.g., Y.
l., 30, pp. 3580-3600 (1982); JP-A-55-22
No. 636 (JP-B-62-42903);
No. 51189 (Japanese Patent Publication No. 2-31079);
JP-A-85372; JP-A-61-286376; JP-A-1-131169; JP-A-2-83384;
-213913; EP-A-0444160
No. 5; WO92 / 07839A (= Tokuhyo Hei 6-502)
146)], oxazolidine-2,4-dione derivatives (for example, JP-A-3-170478, WO92 / 025)
20A), N-hydroxyureido group or 3,5-
Compounds having a dioxooxadiazolidine-2-yl group [for example, WO92 / 03425A (= Japanese Unexamined Patent Publication No.
No. 508054)] is known.

[0003] The relationship between these thiazolidine compounds and various diseases is described, for example, in the following literature. Effects of thiazolidine compounds on hyperglycemia
Diabetes., 32 (9) , 804-810 (1983); Diabete
s., 37 (11) , 1549-1558 (1988); Prog. Clin. Biol.
Res., 265 , 177-192 (1988); Metabolism., 37 (3) ,
276-280 (1988); Arzneimittelforschung., 40 (1) ,
37-42 (1990); Arzneimittelforschung., 40 (2,
Pt 1) , 156-162 (1990); Arzneimittelforschun
g., 40 (3) , 263-267 (1990);

The effect of thiazolidine compounds on hyperlipidemia is described in Diabetes., 40 (12) , 1669-1674 (1991);
Am. J. Physiol., 267 (1, Pt 1) , E95-E101 (1994);
Diabetes., 43 (10) , 1203-1210 (1994);

[0005] Insufficient glucose tolerance and insulin resistance
Arzneimittelforschu
ng.,40 (2, Pt 1), 156-162 (1990); Metabolis
m.,40 (10)Diabetes., 1025-1030 (1991);43
(2), 204-211 (1994); N. Engl. J. Med.,331 (18), 1
226-1227 (1994);

The effects of thiazolidine compounds on hypertension are reported in Metabolism., 42 (1) , 75-80 (1993);
mJPhysiol., 265 (4, Pt 2) , R726-R732 (1993); D
iabetes. 43 (2) , 204-211 (1994);

The effect of thiazolidine compounds on cachexia is described in Endocrinology., 135 (5) , 2279-2282 (1994);
Endocrinology., 136 (4) , 1474-1481 (1995);

The effect on nephropathy is “diabetes”, 38
Volume Extra Issue, (1995) (The 38th Annual Meeting of the Diabetes Society of Japan Program / Abstract Collection: The 38th Annual Meeting of the Diabetes Association, 1995).

The effects of thiazolidine compounds on coronary artery disease are described in Am. J. Physiol., 265 (4, Pt 2) , R726-R73.
2 (1993); Hypertension., 24 (2) , 170-175 (1994);
And so on.

The effect of thiazolidine compounds on arteriosclerosis is described in Am. J. Physyol., 265 (4, Pt 2) , R726-R73.
2 (1993);

Furthermore, in recent years, a normal person having insulin resistance without glucose intolerance has a high risk of developing diabetes [insulin resistant non-glucose intolerance (insulin registrant).
antnon-IGT: NGT). ] N.Engl.J.Me
d., 331 (18) , 1226-1227 (1994); It is suggested that a drug that improves insulin resistance is useful as a preventive drug for the onset of diabetes in normal individuals as described above.

[0012]

DISCLOSURE OF THE INVENTION The present inventors have found that hyperlipidemia, hyperglycemia, obesity,
Glucose intolerance, insulin resistant non-glucose intolerance,
An oxime derivative or the like that improves insulin resistance, cachexia, psoriasis, diabetic complications, arteriosclerosis, hypertension, osteoporosis, polycystic ovary syndrome, fatty liver, gestational diabetes, etc., and further has an aldose reductase inhibitory action or a oxime derivative thereof. The present inventors have made intensive studies on salt and completed the present invention.

That is, the present invention relates to hyperlipidemia, hyperglycemia, obesity, impaired glucose tolerance, impaired insulin resistance, impaired glucose tolerance, insulin resistance, cachexia, psoriasis, diabetic complications (eg, retinopathy). , Nephropathy, neuropathy, cataract, coronary artery disease, etc.), arteriosclerosis, hypertension, osteoporosis, polycystic ovary syndrome, fatty liver, gestational diabetes, etc. I do.

[0014]

The present invention provides a compound represented by the general formula (I):

[0015]

Embedded image

An oxime derivative having the formula:

In the above formula, R ¹ is a hydrogen atom or a group having 1 carbon atom.
And represents a linear or branched alkyl group having from 6 to 6.

R ² represents a linear or branched alkylene group having 2 to 6 carbon atoms.

R ³ is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 4 carbon atoms, 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 monoalkylamino group having 1 to 4 carbon atoms, The same or different, each alkyl is a linear or branched dialkylamino group having 1 to 4 carbon atoms, an aryl group having 6 to 10 carbon atoms or an aralkyl group having 7 to 12 carbon atoms. Show.

X represents an aryl group having 6 to 10 carbon atoms which may have 1 to 3 substituents or a heteroaromatic ring group which may have 1 to 3 substituents. Show.

Here, the substitution component is 1) carbon number 1
A linear or branched alkyl group having 1 to 4 carbon atoms; 2) a linear or branched halogenated alkyl group having 1 to 4 carbon atoms; 3) a hydroxy group; A linear or branched acyloxy group having 1 to 4 carbon atoms, 5) a linear or branched alkoxy group having 1 to 4 carbon atoms,
6) a linear or branched alkylenedioxy group having 1 to 4 carbon atoms; 7) a 7 to 12 carbon atoms.
8) a linear or branched alkylthio group having 1 to 4 carbon atoms, 9) a linear or branched alkylsulfonyl having 1 to 4 carbon atoms Group) 10) halogen atom, 11) nitro group, 12) amino group, 13) linear or branched monoalkylamino group having 1 to 4 carbon atoms, 14) same or different alkyl groups A linear or branched dialkylamino group having 1 to 4 carbon atoms, 15) an aralkyl group having 7 to 12 carbon atoms, 16) an aryl group having 6 to 10 carbon atoms (the aryl group) Is a linear or branched alkyl having 1 to 6 carbons,
Straight or branched alkyl halide having 1 to 4 carbon atoms, straight or branched alkoxy having 1 to 4 carbon atoms, halogen or having 1 to 4 carbon atoms Linear or branched alkylenedioxy, which may be substituted) 17) aryloxy group having 6 to 10 carbon atoms (the aryl group is a straight-chain having 1 to 6 carbon atoms) Or a branched-chain alkyl, a straight-chain or branched-chain alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched-chain alkoxy having 1 to 4 carbon atoms,
Halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms, which may be substituted); 18) an arylthio group having 6 to 10 carbon atoms (the aryl group may have Linear or branched alkyl having 1 to 6 carbon atoms, 1 to 4 carbon atoms
Linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkyl having 1 to 4 carbon atoms. A substituted or unsubstituted alkylenedioxy group; 19) an arylsulfonyl group having 6 to 10 carbon atoms (the aryl group is a linear or branched chain having 1 to 6 carbon atoms) Alkyl, linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or 1 to 4 carbon atoms Or a substituted or unsubstituted linear or branched alkylenedioxy), 2
0) an arylsulfonylamino group having 6 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbon atoms, and 1 to 4 carbon atoms)
Linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkyl having 1 to 4 carbon atoms. It may be substituted with a branched alkylenedioxy. The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), 21) heteroaromatic group, 22) heteroaromatic oxy group, 23) heteroaromatic ring A thio group, 24) a heteroaromatic sulfonyl group, and 25) a heteroaromatic sulfonylamino group (the nitrogen atom may be substituted by a straight-chain or branched alkyl having 1 to 6 carbon atoms) And.

Y is an oxygen atom, a sulfur atom or a group> N-
R ⁴ is shown.

(Wherein R ⁴ 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) Z represents a group.

[0024]

Embedded image

Is shown.

Further, the present invention relates to a method for producing an oxime derivative having the above general formula (I) or a salt thereof, and its use.

Here, R ¹ , R ³ and R ⁴ have 1 carbon atoms.
When a straight-chain or branched alkyl group having from 6 to 6 is indicated, examples of the alkyl group include methyl,
Ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-
Dimethylpropyl, 1,2-dimethylpropyl, 2,2
-Dimethylpropyl, 1-ethylpropyl, hexyl,
1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2, 3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-
Ethylbutyl, 1,1,2-trimethylpropyl and 1,2,2-trimethylpropyl and the like can be mentioned. Preferably, it is a linear or branched alkyl group having 1 to 4 carbon atoms. More preferred are methyl, ethyl, propyl, isopropyl, butyl and isobutyl. Most preferably, it is methyl and ethyl.

Preferably, R ¹ is a hydrogen atom or a carbon atom
And a straight-chain or branched alkyl group having 4 to 4 carbon atoms.

When R ² represents a linear or branched alkylene group having 2 to 6 carbon atoms, examples of the alkylene group include ethylene, methylethylene, ethylethylene and 1,1-dimethylethylene. 1,1,2-dimethylethylene, trimethylene, 1-methyltrimethylene, 1-ethyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, tetramethylene,
Pentamethylene and hexamethylene can be mentioned. Preferably, it is a linear or branched alkylene group having 2 to 5 carbon atoms. Most preferably, it is a linear or branched alkylene group having 2 to 3 carbon atoms. Specific examples include ethylene, methylethylene, ethylethylene, trimethylene, 1-methyltrimethylene, 1-ethyltrimethylene and 2-methyltrimethylene.

When R ³ represents a linear or branched alkoxy group having 1 to 4 carbon atoms, examples of the alkoxy group include methoxy, ethoxy, propoxy, isopropoxy, butoxy and s-butoxy. , T-butoxy and isobutoxy.
Preferably it is methoxy.

When R ³ represents an alkylthio group having 1 to 4 carbon atoms, examples of the alkylthio group include methylthio, ethylthio, propylthio, isopropylthio, butylthio, s-butylthio, t-butylthio and isobutylthio. I can give it. Preferably it is methylthio.

When R ³ represents a halogen atom, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Preferably they are a fluorine atom, a chlorine atom and a bromine atom. Most preferably, it is a fluorine atom and a chlorine atom.

[0033] When R ³ is showing a monoalkylamino group having from 1 to 4 carbon atoms, examples of the monoalkylamino group, for example methylamino, ethylamino, propylamino, isopropylamino, butylamino, s- butylamino , T-butylamino and isobutylamino. Preferred are methylamino and ethylamino.

[0034] When the alkyl R ³ is the same or different is showing a dialkylamino group having from 1 to 4 carbon atoms, examples of the dialkylamino group, for example dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino , N-methyl-N-ethylamino and N-ethyl-N-isopropylamino. Preferred are dimethylamino and diethylamino.

When R ³ represents an aryl group having 6 to 10 carbon atoms, examples of the aryl group include phenyl and naphthyl. Most preferably, it is phenyl.
When X described below represents an aryl group, the aryl group may have 1 to 3 substituents similar to the substituents of the aryl group.

When R ³ represents an aralkyl group having 7 to 12 carbon atoms, the aralkyl group is a group in which an alkyl group having 1 to 4 carbon atoms is substituted with the above-described aryl group. Yes, for example, benzyl, phenethyl, 3-phenylpropyl, 4-phenylbutyl,
Examples thereof include 1-naphthylmethyl and 2-naphthylmethyl. Preferably they are benzyl and phenethyl. Most preferably benzyl. When X described below represents an aryl group, the aryl group may have 1 to 3 substituents similar to the substituents of the aryl group.

Preferably, R ³ is a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms,
An alkoxy group having 1 or 2 carbon atoms, 1 carbon atom
Or, it is an alkylthio group having two or a halogen atom.

When R ⁴ represents a linear or branched acyl group having 1 to 8 carbon atoms, examples of the acyl group include formyl, acetyl, propionyl, butyryl, pentanoyl, hexanoyl, heptanoyl,
Alkanoyl groups such as octanoyl, benzoyl, p
-Aroyl groups such as toluoyl can be mentioned. It is preferably an alkanoyl group, more preferably a linear or branched alkanoyl group having 2 to 5 carbon atoms, most preferably an acetyl group.

When X represents an aryl group having 6 to 10 carbon atoms, examples of the aryl group include phenyl and naphthyl. Preferably it is phenyl. The aryl group may be substituted with one to three substituents shown below.

When X represents a substituted or unsubstituted heteroaromatic ring group, the unsubstituted heteroaromatic ring group has a monocyclic or bicyclic ring system. When it comprises a two-ring system, at least one ring is at least a heterocyclic ring. In the case of a two-ring system, the ring is a condensed ring, and one ring may be a heterocyclic ring and the other ring may be a carbocyclic ring, or may be a bicyclic coheterocyclic ring. Heterocycles are 5- or 6-membered rings, which have 1 to 4 nitrogen, oxygen and / or sulfur atoms. A carbocycle is an aryl group having 6 to 10 carbon atoms. A monocyclic ring is called a heteroaromatic monocyclic group, and a bicyclic ring is called a heteroaromatic fused ring group. In the case of a ring having 4 heteroatoms, preferably 4
All are nitrogen atoms and there are no oxygen and / or sulfur atoms. In the case of a ring having three heteroatoms, preferably three, two or one is a nitrogen atom and one or two is an oxygen atom and / or a sulfur atom. In the case of a ring having two hetero atoms, preferably 2, 1, or 0 is a nitrogen atom, and 0, 1, or 2 is an oxygen atom and / or a sulfur atom. When X represents a substituted heteroaromatic ring group, it may be substituted with 1 to 3 substituents shown below. Preferably the substitution is one or two,
More preferably, there is one substitution.

Examples of the heteroaromatic monocyclic group include pyrrolyl groups such as 2-pyrrolyl and 3-pyrrolyl; furyl groups such as 2-furyl and 3-furyl; 2-thienyl and 3-furyl.
A thienyl group such as thienyl; a pyridyl group such as 2-pyridyl, 3-pyridyl and 4-pyridyl; an imidazolyl group such as 2-imidazolyl and 4-imidazolyl;
Pyrazolyl groups such as pyrazolyl and 4-pyrazolyl; 2
An oxazolyl group such as -oxazolyl, 4-oxazolyl, 5-oxazolyl; 3-isoxazolyl, 4-
Isoxazolyl groups such as isoxazolyl and 5-isoxazolyl; 2-thiazolyl, 4-thiazolyl, 5
A thiazolyl group such as thiazolyl; an isothiazolyl group such as 3-isothiazolyl, 4-isothiazolyl or 5-isothiazolyl; like 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl Triazolyl group; thiadiazolyl group such as 1,3,4-thiadiazol-2-yl; oxadiazolyl group such as 1,3,4-oxadiazol-2-yl; tetrazolyl group such as 5-tetrazolyl; -Pyridazinyl, 4
Pyridazinyl groups such as -pyridazinyl; pyrimidinyl groups such as 2-pyrimidinyl, 4-pyrimidinyl and 5-pyrimidinyl; pyrazinyl groups; 1,4-oxazine-2
Oxazinyl groups such as -yl and 1,4-oxazin-3-yl; and thiazinyl groups such as 1,4-thiazin-2-yl and 1,4-thiazin-3-yl.

The heteroaromatic fused ring group includes, for example, indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl
Indolyl groups such as yl, indol-7-yl; like indazol-2-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indazol-7-yl Indazolyl group; benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-
5-yl, benzofuran-6-yl, benzofuran-7
Benzofuranyl groups such as -yl; benzothiophene-
Benzothiophenyl groups such as 2-yl, benzothiophen-3-yl, benzothiophen-4-yl, benzothiophen-5-yl, benzothiophen-6-yl, benzothiophen-7-yl; benzimidazole-2
Benzimidazolyl groups such as -yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl, benzimidazol-7-yl; benzoxazol-2-yl, benzoxazol-4-yl, Benzoxazol-5-yl, benzoxazol-6-yl, benzoxazol-7-
Benzothiazolyl groups such as benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl, benzothiazol-6-yl and benzothiazol-7-yl;
Quinolyl groups such as 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl and 8-quinolyl; such as 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl and 8-isoquinolyl Isoquinolyl group; 1,4-benzoxazin-2-yl,
Benzoxazinyl groups such as 1,4-benzoxazin-3-yl; 1,4-benzothiazin-2-yl;
Benzothiazinyl groups such as 1,4-benzothiazin-3-yl; pyrrolo [2, such as pyrrolo [2,3-b] pyrid-2-yl, pyrrolo [2,3-b] pyrid-3-yl; 3-b! Pyridyl group; furo [2,3-b] pyridyl group such as furo [2,3-b] pyrid-2-yl, furo [2,3-b] pyrid-3-yl; thieno [ 2,3-
b] pyrid-2-yl, thieno [2,3-b] pyridi-
Thieno [2,3-b] pyridyl groups such as 3-yl;
1,8-naphthyridin-2-yl, 1,8-naphthyridin-3-yl, 1,5-naphthyridin-2-yl, 1,
Naphthyridinyl groups such as 5-naphthyridin-3-yl; imidazopyridyl groups such as imidazo [4,5-b] pyrid-2-yl and imidazo [4,5-b] pyrid-5-yl; oxazolo [4 Oxazolopyridyl groups such as, 5-b] pyrid-2-yl, oxazolo [5,4-b] pyrid-2-yl; and thiazolo [4,5-
b] thiazolopyridyl groups such as pyridi-2-yl and thiazolo [4,5-c] pyrid-2-yl;

Preferably, the heteroaromatic monocyclic group has 5 to 3 nitrogen, oxygen and / or sulfur atoms.
Or a 6-membered ring group, and the pyrrolyl group, furyl group, thienyl group, pyridyl group, imidazolyl group, pyrazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, triazolyl group, thiadiazolyl group, oxadiazolyl group, pyridazinyl group , A pyrimidinyl group and a pyrazinyl group. Preferably, the heteroaromatic fused ring group is
A condensed ring group of a benzene ring and a 5- or 6-membered heteroaromatic monocyclic ring having 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms. Group, benzoimidazolyl group, benzoxazolyl group, benzothiazolyl group, quinolyl group, and isoquinolyl group.

Most preferably, the heteroaromatic monocyclic groups are imidazolyl, oxazolyl and pyridyl, and the heteroaromatic fused ring groups are indolyl, quinolyl and isoquinolyl.

When X represents an aryl group or a heteroaromatic ring group, the aryl group and the heteroaromatic ring group may have 1 to 3 substituents as described above. 1) a linear or branched alkyl group having 1 to 6 carbon atoms; 2) a linear or branched halogenated alkyl group having 1 to 4 carbon atoms; ) Hydroxy group, 4) carbon number 1
A straight-chain or branched acyloxy group having 1 to 4 carbon atoms; 5) a straight-chain or branched alkoxy group having 1 to 4 carbon atoms;
Linear or branched alkylenedioxy group having 7 carbon atoms; 7) an aralkyloxy group having 7 to 12 carbon atoms; 8) a linear or branched alkylene dioxy group having 1 to 4 carbon atoms. An alkylthio group, 9) a linear or branched alkylsulfonyl group having 1 to 4 carbon atoms, 10) a halogen atom, 11) a nitro group,
12) an amino group; 13) a linear or branched monoalkylamino group having 1 to 4 carbon atoms;
14) straight or branched dialkylamino groups having the same or different alkyls each having 1 to 4 carbon atoms; 15) aralkyl groups having 7 to 12 carbon atoms; 16) 6 to 10 carbon atoms. Aryl groups having 1 to 6 carbon atoms, such as straight-chain or branched alkyl groups, straight-chain or branched alkyl halide groups having 1 to 4 carbon atoms,
Straight-chain or branched alkoxy having 1 to 4 carbon atoms, which may be substituted by halogen or straight-chain or branched alkylenedioxy having 1 to 4 carbon atoms), 17) an aryloxy group having 6 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl having 1 to 4 carbons) A branched alkyl halide, a linear or branched alkoxy having 1 to 4 carbons, a halogen or a linear or branched alkylenedioxy having 1 to 4 carbons 18) an arylthio group having 6 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbon atoms, 1 to a straight-chain or branched alkyl halide having 4, 1 -C 4
Linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkylenedioxy having 1 to 4 carbon atoms), 19) 6 carbon atoms An arylsulfonyl group having 1 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbons, a linear or branched halogen having 1 to 4 carbons) Alkyl, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or 1 to 4 carbon atoms
20) an arylsulfonylamino group having 6 to 10 carbon atoms (the aryl group may have 1 to 6 carbon atoms) A straight-chain or branched alkyl having 1 to 4 carbon atoms, a straight-chain or branched alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched alkyl having 1 to 4 carbon atoms The nitrogen atom may be substituted by alkoxy, halogen, or linear or branched alkylenedioxy having 1 to 4 carbon atoms, wherein the nitrogen atom is linear or branched having 1 to 6 carbon atoms. May be substituted with alkyl in the form of
21) heteroaromatic ring group, 22) heteroaromatic oxy group, 2
3) a heteroaromatic thio group; 24) a heteroaromatic sulfonyl group; and 25) a heteroaromatic sulfonylamino group (where the nitrogen atom is substituted by a straight-chain or branched alkyl having 1 to 6 carbon atoms). ).

The substituent is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, 1 to 4 carbon atoms.
Linear or branched alkoxy group having 1 to 4 carbon atoms, linear or branched alkylthio group having 1 to 4 carbon atoms, halogen atom, linear chain having 1 to 4 carbon atoms or A branched monoalkylamino group,
When each alkyl is the same or different and represents a straight-chain or branched dialkylamino group having 1 to 4 carbon atoms or an aralkyl group having 7 to 12 carbon atoms, for example, the above-mentioned R ³ may be used. Similar groups can be mentioned. When the substituent represents a linear or branched halogenated alkyl group having 1 to 4 carbon atoms, examples of the halogenated alkyl group include chloromethyl, bromomethyl, fluoromethyl, iodomethyl, and difluoromethyl. , Trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,
2,2-trichloroethyl, trichloromethyl and the like can be mentioned. Preferably, fluoromethyl, difluoromethyl and trifluoromethyl can be mentioned.

When the substituent represents a linear or branched acyloxy group having 1 to 4 carbon atoms, it is preferably an alkanoyl group or an alkenoyl group,
More preferably, it is an alkanoyl group. Examples of the acyloxy group include formyloxy, acetoxy, propionyloxy, and butyryloxy. Preferably, acetoxy can be used.

When the substituent represents a straight-chain or branched alkylenedioxy group having 1 to 4 carbon atoms, examples of the alkylenedioxy group include methylenedioxy, ethylenedioxy and trialkylenedioxy. Methylenedioxy,
Examples include tetramethylenedioxy, propylenedioxy and the like. Preferable examples include methylenedioxy and ethylenedioxy.

When the substituent represents an aralkyloxy group having 7 to 12 carbon atoms, examples of the aralkyloxy group include aralkyloxy groups in which aralkyl is the same aralkyl as described for R ^3. . Examples of such aralkyloxy groups include benzyloxy, phenethyloxy, 3-phenylpropoxy, 4-phenylbutoxy, 1-naphthylmethoxy,
2-naphthylmethoxy and the like can be mentioned. Preferable examples include benzyloxy, phenethyloxy, 1-naphthylmethoxy and 2-naphthylmethoxy.

When the substituent represents a linear or branched alkylsulfonyl group having 1 to 4 carbon atoms, examples of the alkylsulfonyl group include methylsulfonyl, ethylsulfonyl, propylsulfonyl, and isopropylsulfonyl. Butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, t-butylsulfonyl and the like. Preferable examples include methylsulfonyl, ethylsulfonyl and isopropylsulfonyl groups.

The substituted group is an aryl group having 6 to 10 carbon atoms (the aryl group is a straight-chain or branched alkyl having 1 to 6 carbons, a straight-chained alkyl having 1 to 4 carbons). Linear or branched alkyl halides, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkyl having 1 to 4 carbon atoms Alkyl (which may be substituted with alkylenedioxy), the alkyl, halogenated alkyl, alkoxy, halogen and alkylenedioxy have the same meanings as described above for the substitution of R ³ and X.

As the aryl group, for example, phenyl,
1-naphthyl, 2-naphthyl, 4-methylphenyl, 4
-Trifluoromethylphenyl, 4-methoxyphenyl, 3-ethoxyphenyl, 4-fluorophenyl,
-Chlorophenyl, 3-bromophenyl, 3,4-methylenedioxyphenyl and the like. Preferred are phenyl, 4-methoxyphenyl and 3,4-methylenedioxyphenyl.

An aryloxy group having 6 to 10 carbon atoms as the substituent (the aryl group is a linear or branched alkyl having 1 to 6 carbon atoms,
Straight-chain or branched alkyl halide having 1 to 4 carbon atoms, straight-chain or branched alkoxy having 1 to 4 carbon atoms, halogen or straight-chain alkyl having 1 to 4 carbon atoms Alternatively, the alkyl, halogenated alkyl, alkoxy, halogen and alkylenedioxy have the same meanings as described above.

Examples of the aryloxy group include phenoxy, 1-naphthoxy, 2-naphthoxy, 4-methylphenoxy, 4-trifluoromethylphenoxy,
Methoxyphenoxy, 3-ethoxyphenoxy, 4-chlorophenoxy, 3-bromophenoxy, 3,4-methylenedioxyphenoxy and the like can be mentioned.
Preferably it is phenoxy.

The substituted group is an arylthio group having 6 to 10 carbon atoms (the aryl group is a straight-chain or branched alkyl having 1 to 6 carbons, a straight-chained alkyl having 1 to 4 carbons). Linear or branched alkyl halides, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkyl having 1 to 4 carbon atoms Alkyl (which may be substituted with alkylenedioxy), the alkyl, halogenated alkyl, alkoxy, halogen and alkylenedioxy have the same meanings as described above.

Examples of the arylthio group include phenylthio, 4-methylphenylthio, 4-trifluoromethylphenylthio, 4-methoxyphenylthio, 3-ethoxyphenylthio, 4-chlorophenylthio, 3-bromophenylthio, , 4-methylenedioxyphenylthio, 1-naphthylthio, 2-naphthylthio and the like. Preferably it is phenylthio.

An arylsulfonyl group having 6 to 10 carbon atoms (the aryl group is a linear or branched alkyl group having 1 to 6 carbon atoms, and having 1 to 4 carbon atoms); Linear or branched alkyl halide, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or 1 carbon atom
Or 4 substituted or unsubstituted linear or branched alkylenedioxy), alkyl, halogenated alkyl, alkoxy, halogen,
Alkylenedioxy has the same meaning as described above.

Examples of the arylsulfonyl group include phenylsulfonyl, 4-methylphenylsulfonyl,
4-trifluoromethylphenylsulfonyl, 4-methoxyphenylsulfonyl, 3-ethoxyphenylsulfonyl, 4-chlorophenylsulfonyl, 3-bromophenylsulfonyl, 3,4-methylenedioxyphenylsulfonyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl And so on. Preferably it is phenylsulfonyl.

An arylsulfonylamino group in which the substituent has 6 to 10 carbon atoms (the aryl group has 1 to 5 carbon atoms);
Linear or branched alkyl having 1 to 4 carbon atoms, linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkyl having 1 to 4 carbon atoms, It may be substituted by a branched alkoxy, a halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms. The nitrogen atom may be substituted by a straight-chain or branched-chain alkyl having 1 to 6 carbons).
Alkylenedioxy has the same meaning as described above.

The arylsulfonylamino group includes
For example, phenylsulfonylamino, 4-methylphenylsulfonylamino, 4-trifluoromethylphenylsulfonylamino, 4-methoxyphenylsulfonylamino, 3-ethoxyphenylsulfonylamino, 4-chlorophenylsulfonylamino, 3-bromophenylsulfonylamino, 3, 4-methylenedioxyphenylsulfonylamino, N-methylphenylsulfonylamino,
Examples thereof include 1-naphthylsulfonylamino, 2-naphthylsulfonylamino, and N-methylnaphthylsulfonylamino. Preferably, they are phenylsulfonylamino and N-methylphenylsulfonylamino.

When the substituent represents a heteroaromatic group, examples of the group include furyl, thienyl, oxazolyl,
Mention may be made of isoxazolyl, thiazolyl, imidazolyl, quinolyl, isoquinolyl, indolyl and pyridyl. Preferably imidazolyl, quinolyl,
Pyridyl can be given.

When the substituent represents a heteroaromatic oxy group, examples of the oxy group include furyloxy, thienyloxy, oxazolyloxy, isoxazolyloxy, thiazolyloxy, imidazolyloxy, quinolyloxy and isoquinolyl. Oxy, indolyloxy, pyridyloxy and the like can be mentioned. Preferably, they are isoxazolyloxy and pyridyloxy.

When the substituent represents a heteroaromatic thio group, examples of the thio group include furylthio, thienylthio, oxazolylthio, isoxazolylthio, thiazolylthio, imidazolylthio, quinolylthio, isoquinolylthio, indolylthio, and pyridylthio. be able to. Preferably, they are isoxazolylthio and pyridylthio.

When the substituent represents a heteroaromatic ring sulfonyl group, examples of the sulfonyl group include furylsulfonyl, thienylsulfonyl, oxazolylsulfonyl,
Isoxazolylsulfonyl, thiazolylsulfonyl,
Imidazolylsulfonyl, quinolylsulfonyl, isoquinolylsulfonyl, indolylsulfonyl, pyridylsulfonyl and the like. Preferred are imidazolylsulfonyl, isoxazolylsulfonyl and pyridylsulfonyl.

In the case where the substituent represents a heteroaromatic sulfonylamino group (the nitrogen atom may be substituted by a linear or branched alkyl having 1 to 6 carbon atoms), Is, for example, furylsulfonylamino, thienylsulfonylamino, oxazolylsulfonylamino, isoxazolylsulfonylamino, thiazolylsulfonylamino, imidazolylsulfonylamino, N-methylimidazolylsulfonylamino, quinolylsulfonylamino, isoquinolylsulfonyl amino,
Indolylsulfonylamino, pyridylsulfonylamino, N-methylpyridylsulfonylamino and the like can be mentioned. Preferred are imidazolylsulfonylamino, N-methylimidazolylsulfonylamino, pyridylsulfonylamino, N-methylpyridylsulfonylamino.

Accordingly, when X represents a substituted or unsubstituted aryl group having 6 to 10 carbon atoms or a substituted or unsubstituted heteroaromatic ring group, preferred examples thereof include a phenyl group, 1- Naphthyl group, 2-naphthyl group, m-tolyl group, p-tolyl group, 3-ethylphenyl group, 4-ethylphenyl group, 3-isopropylphenyl group, 4-isopropylphenyl group, 3-t-butylphenyl group, 4-t-butylphenyl group, 4-chloromethylphenyl group, 4-bromomethylphenyl group, 4-fluoromethylphenyl group, 4-iodomethylphenyl group,
3-difluoromethylphenyl group, 4-trifluoromethylphenyl group, 4-pentafluoroethylphenyl group, 4-trichloromethylphenyl group, 3-hydroxyphenyl group, 4-hydroxyphenyl group, 4-hydroxy-3, 5- Dimethylphenyl group, 3-acetoxyphenyl group, 4-acetoxyphenyl group, 5-acetoxy-
2-hydroxy-3,4,6-trimethylphenyl group,
3-methoxyphenyl group, 4-methoxyphenyl group, 3
-Ethoxyphenyl group, 4-ethoxyphenyl group, 3-
Isopropoxyphenyl group, 4-isopropoxyphenyl group, 3,4-methylenedioxyphenyl group, benzyloxyphenyl group, phenethyloxyphenyl group, 1-
Naphthylmethoxyphenyl group, 3-methylthiophenyl group, 4-methylthiophenyl group, 3-ethylthiophenyl group, 4-ethylthiophenyl group, 3-isopropylthiophenyl group, 4-isopropylthiophenyl group, 3-
Methylsulfonylphenyl group, 4-methylsulfonylphenyl group, 3-ethylsulfonylphenyl group, 4-ethylsulfonylphenyl group, 3-isopropylsulfonylphenyl group, 4-isopropylsulfonylphenyl group,
3-chlorophenyl group, 4-chlorophenyl group, 3-bromophenyl group, 4-bromophenyl group, 4-nitrophenyl group, 4-aminophenyl group, 3-methylaminophenyl group, 4-ethylaminophenyl group, 3- Propylaminophenyl group, 4-butylaminophenyl group, 3-
Dimethylaminophenyl, 4-diethylaminophenyl, 3-dipropylaminophenyl, 4-dibutylaminophenyl, 3-benzylphenyl, 4-benzylphenyl, 3-phenethylphenyl, 4- (1
-Naphthylmethyl) phenyl group, 3-biphenylyl group,
4-biphenylyl group, 3- (4-methylphenyl) phenyl group, 4- (4-methylphenyl) phenyl group, 3-
(4-ethylphenyl) phenyl group, 3- (4-trifluoromethylphenyl) phenyl group, 4- (4-trifluoromethylphenyl) phenyl group, 3- (4-methoxyphenyl) phenyl group, 4- (4 -Methoxyphenyl) phenyl group, 3- (2,4-dimethoxyphenyl)
Phenyl, 4- (2,4-dimethoxyphenyl) phenyl, 3- (2,5-dimethoxyphenyl) phenyl, 4- (2,5-dimethoxyphenyl) phenyl,
4- (3-chlorophenyl) phenyl group, 4- (4-chlorophenyl) phenyl group, 4- (3-bromophenyl) phenyl group, 4- (4-bromophenyl) phenyl group, 3- (3,4-methylene) Dioxyphenyl) phenyl group, 4- (3,4-methylenedioxyphenyl) phenyl group, 3-benzylphenyl group, 4-benzylphenyl group, 3-phenoxyphenyl group, 4-phenoxyphenyl group, 3-phenylthio Phenyl group, 4-phenylthiophenyl group, 3-phenylsulfonylphenyl group, 4
-Phenylsulfonylphenyl group, 3- (phenylsulfonylamino) phenyl group, 4- (phenylsulfonylamino) phenyl group, N-methyl-3- (phenylsulfonylamino) phenyl group, N-methyl-4- (phenylsulfonylamino) ) Phenyl group, 3- (imidazol-1-yl) phenyl group, 4- (imidazol-1-yl) phenyl group, 3- (1-methylimidazole-4-)
Yl) phenyl group, 4- (1-methylimidazole-4)
-Yl) phenyl group, 3- (2-furyl) phenyl group,
4- (2-furyl) phenyl group, 3- (2-thienyl)
Phenyl group, 4- (2-thienyl) phenyl group, 3-
(3-thienyl) phenyl group, 4- (3-thienyl) phenyl group, 3- (2-pyridyl) phenyl group, 4- (2
-Pyridyl) phenyl group, 3- (3-pyridyl) phenyl group, 4- (3-pyridyl) phenyl group, 3- (4-pyridyl) phenyl group, 4- (4-pyridyl) phenyl group, 4- (imidazole -1-ylthio) phenyl group,
4- (2-furylthio) phenyl group, 4- (2-thienylthio) phenyl group, 4- (2-pyridylthio) phenyl group, 4- (4-pyridylthio) phenyl group, 3- (2
-Pyridylsulfonyl) phenyl group, 4- (2-pyridylsulfonyl) phenyl group, 3- (3-pyridylsulfonyl) phenyl group, 4- (3-pyridylsulfonyl) phenyl group, 3- (2-pyridylsulfonylamino) phenyl Group, 3- (N-methyl-2-pyridylsulfonylamino) phenyl group, 4- (2-pyridylsulfonylamino) phenyl group, 4- (N-methyl-2-pyridylsulfonylamino) phenyl group, 3- (3 -Pyridylsulfonylamino) phenyl group, 3- (N-methyl-3-pyridylsulfonylamino) phenyl group, 4- (3-pyridylsulfonylamino) phenyl group, 4- (N-methyl-
3-pyridylsulfonylamino) phenyl group, 3- (oxazol-2-yl) phenyl group, 4- (oxazol-2-yl) phenyl group, 3- (oxazole-4-
Yl) phenyl group, 4- (oxazol-4-yl) phenyl group, 3- (oxazol-5-yl) phenyl group, 4- (oxazol-5-yl) phenyl group, 3-
(Thiazol-2-yl) phenyl group, 4- (thiazol-2-yl) phenyl group, 3- (thiazol-4-yl) phenyl group, 4- (thiazol-4-yl) phenyl group, 3- (thiazole -5-yl) phenyl group, 4-
A substituted or unsubstituted aryl group having 6 to 10 carbon atoms, such as a (thiazol-5-yl) phenyl group; 1-methyl-2-pyrrolyl group, 1-phenyl-2-
Pyrrolyl group, 1-benzyl-2-pyrrolyl group, 5-methyl-2-furyl group, 5-phenyl-2-furyl group, 5-
Methyl-2-thienyl group, 5-phenyl-2-thienyl group, 5-methyl-3-thienyl group, 5-phenyl-3-
Thienyl group, 1-methyl-3-pyrazolyl group, 1-phenyl-3-pyrazolyl group, 1-methyl-2-imidazolyl group, 1-phenyl-2-imidazolyl group, 1-methyl-4-imidazolyl group, 1- Phenyl-4-imidazolyl group, 1-methyl-2-phenyl-4-imidazolyl group, 1,5-dimethyl-2-phenyl-4-imidazolyl group, 1,4-dimethyl-2-phenyl-5-imidazolyl group, 4-oxazolyl group, 5-oxazolyl group, 2
-Methyl-4-oxazolyl group, 2-phenyl-4-oxazolyl group, 2-methyl-5-oxazolyl group, 2-
Phenyl-5-oxazolyl group, 4-methyl-2-phenyl-5-oxazolyl group, 5-methyl-2-phenyl-4-oxazolyl group, 4-thiazolyl group, 5-thiazolyl group, 2-methyl-4-thiazolyl Group, 2-phenyl-4-thiazolyl group, 2-methyl-5-thiazolyl group,
2-phenyl-5-thiazolyl group, 4-methyl-2-phenyl-5-thiazolyl group, 5-methyl-2-phenyl-4-thiazolyl group, 1-methyl-3-pyrazolyl group,
1-phenyl-3-pyrazolyl group, 3-methyl-5-isoxazolyl group, 3-phenyl-5-isoxazolyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 3-methyl-5-pyridyl group , 3-ethyl-5-pyridyl group, 3-phenyl-5-pyridyl group, 2-methyl-5-pyridyl group, 2-ethyl-5-pyridyl group, 2-
Phenyl-5-pyridyl group, 2-hydroxy-5-pyridyl group, 2-methoxy-5-pyridyl group, 2-ethoxy-5-pyridyl group, 2-isopropoxy-5-pyridyl group, 2-benzyloxy-5 -Pyridyl group, 2-methylthio-5-pyridyl group, 2-ethylthio-5-pyridyl group, 2-isopropylthio-5-pyridyl group, 2-methylsulfonyl-5-pyridyl group, 2-ethylsulfonyl-5-pyridyl Group, 2-isopropylsulfonyl-5-
Pyridyl group, 2-benzyl-5-pyridyl group, 2-phenoxy-5-pyridyl group, 2-phenylthio-5-pyridyl group, 2-phenylsulfonyl-5-pyridyl group, 2
-Phenylsulfonylamino-5-pyridyl group, 2-
(N-methylphenylsulfonylamino) -5-pyridyl group, 3-methyl-6-pyridyl group, 3-phenyl-6
-Pyridyl group, 2-methyl-6-pyridyl group, 2-phenyl-6-pyridyl group, 2-methyl-4-pyrimidinyl group, 2-phenyl-4-pyrimidinyl group, 2-methoxy-4-pyrimidinyl group, 2 -Ethoxy-4-pyrimidinyl group, 2-isopropoxy-4-pyrimidinyl group, 2-
Methylthio-4-pyrimidinyl group, 2-ethylthio-4
-Pyrimidinyl group, 2-isopropylthio-4-pyrimidinyl group, 2-phenylthio-4-pyrimidinyl group, 2
-Methylsulfonyl-4-pyrimidinyl group, 2-ethylsulfonyl-4-pyrimidinyl group, 2-isopropylsulfonyl-4-pyrimidinyl group, 2-phenylsulfonyl-4-pyrimidinyl group, 2-methyl-5-pyrimidinyl group, 2- Phenyl-5-pyrimidinyl group, 2-methoxy-5-pyrimidinyl group, 2-ethoxy-5-pyrimidinyl group, 2-isopropoxy-5-pyrimidinyl group, 2
-Methylthio-5-pyrimidinyl group, 2-ethylthio-
5-pyrimidinyl group, 2-isopropylthio-5-pyrimidinyl group, 2-phenylthio-5-pyrimidinyl group,
2-methylsulfonyl-5-pyrimidinyl group, 2-ethylsulfonyl-5-pyrimidinyl group, 2-isopropylsulfonyl-5-pyrimidinyl group, 2-phenylsulfonyl-5-pyrimidinyl group, 2-indolyl group, 3-indolyl group, 1-methyl-2-indolyl group, 1-methyl-3-indolyl group, 2-benzimidazolyl group, 1
-Methyl-2-benzimidazolyl group, 2-benzoxazolyl group, 2-benzthiazolyl group, 2-quinolyl group, 3-quinolyl group, 4-quinolyl group, 1-isoquinolyl group, 3-isoquinolyl group, 4-isoquinolyl Or a substituted or unsubstituted heteroaromatic group such as an 8-isoquinolyl group;

Y is a group> NR ⁴ (wherein R ⁴ is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms (having the same meaning as described for R ³ ) ) Or a linear or branched acyl group having 1 to 8 carbon atoms (including an alkanoyl group having 1 to 8 carbon atoms and an alkenoyl group having 3 to 8 carbon atoms)) In the case of showing, the group> NR ⁴ includes, for example, imino, methylimino, ethylimino, propylimino, isopropylimino, butylimino, isobutylimino, s-butylimino, t-butylimino,
Pentyl imino, 1-methylbutyl imino, 2-methylbutyl imino, 3-methylbutyl imino, 1,1-dimethylpropyl imino, 1,2-dimethylpropyl imino, 2,2-dimethylpropyl imino, 1-ethylpropyl imino Hexylimino, 1-methylpentylimino, 2-methylpentylimino, 3-methylpentylimino, 4-methylpentylimino, 1,1-dimethylbutylimino, 1,2-dimethylbutylimino, 1,3-
Dimethylbutylimino, 2,2-dimethylbutylimino, 2,3-dimethylbutylimino, 3,3-dimethylbutylimino, 1-ethylbutylimino, 1,1,2-
Trimethylpropylimino, 1,2,2-trimethylpropylimino, acetylimino, propionylimino,
Examples include butylyl imino, pentanoyl imino, hexanoyl imino, heptanoyl imino, octanoyl imino, benzoyl imino, p-toluoyl imino, and the like. Preferable are an imino group, a linear or branched alkylimino group having 1 to 4 carbon atoms, and an acetylimino group. Most preferred are imino, methylimino, ethylimino and acetylimino.

The oxime derivative having the general formula (I) of the present invention can be converted into a salt according to a conventional method. The salt of the oxime derivative having the general formula (I) is more medically used than the oxime derivative having the general formula (I). There is no particular limitation as long as it is not. In addition, there is no limitation when used for purposes other than medicine, for example, when used as an intermediate.

The oxime derivative having the general formula (I) of the present invention can be converted into an acid addition salt according to a conventional method. Such salts include, for example, hydrofluoric acid, hydrochloric acid,
Hydrohalic acid salts such as hydrobromic acid and hydroiodic acid; inorganic acid salts such as nitrate, perchlorate, sulfate and phosphate; methanesulfonic acid, trifluoromethanesulfonic acid and ethanesulfonic acid Salts of lower alkanesulfonic acids such as benzenesulfonic acid and salts of arylsulfonic acids such as p-toluenesulfonic acid; salts of amino acids such as glutamic acid and aspartic acid; acetic acid, fumaric acid, tartaric acid, oxalic acid, and maleic acid , Malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid,
Salts of carboxylic acids such as citric acid can be mentioned. Preferably, it is a pharmacologically acceptable acid addition salt.

Further, the compound having the general formula (I) can be converted into a metal salt according to a conventional method. Examples of such salts include alkali metal salts such as lithium, sodium and potassium; alkaline earth metal salts such as calcium, barium and magnesium; aluminum salts; and the like. Preferably, it is a pharmacologically acceptable metal salt.

The compound having the general formula (I) has various isomers.

For example, when Z represents a 2,4-dioxothiazolidine-5-ylmethyl group (Zb) or a 2,4-dioxooxazolidin-5-ylmethyl group (Zc),
Position 5 of the thiazolidine ring and position 5 of the oxazolidine ring are asymmetric carbon atoms. In the general formula (I),
Stereoisomers based on these asymmetric carbon atoms and equivalent and unequal mixtures of these isomers are all represented by a single formula. Therefore, in the present invention, all of these isomers and a mixture of these isomers are also included.

Further, when Z is 2,4-dioxothiazolidine-5-ylmethyl (Zb), 2,4-dioxooxazolidine-5-ylmethyl (Zc), 2,4-dioxothiazolidine-5-yridenylmethyl (Za) ), 3,5-
Dioxooxadiazolidine-2-ylmethyl (Zd)
Indicates that various tautomers exist. For example, as shown below.

[0074]

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[0075]

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[0076]

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[0077]

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In the general formula (I), tautomers based on these and equal and unequal mixtures of these isomers are all represented by a single formula. Therefore, in the present invention, all of these isomers and a mixture of these isomers are also included.

Further, in the oxime derivative having the general formula (I), a cis isomer and a trans isomer based on geometrical isomerism may be present in the oxime group. In the general formula (I), both isomers based on these and equal and unequal mixtures thereof are all represented by a single formula. Therefore, in the present invention, all of these isomers and a mixture of these isomers are also included.

Further, in the present invention, when the oxime derivative having the general formula (1) or a salt thereof forms a solvate (for example, a hydrate), it also includes all of them.

Further, in the present invention, all compounds which are metabolized in vivo and converted into the oxime derivative having the above general formula (1) or a salt thereof, so-called prodrugs are also included.

In the oxime derivative represented by the above general formula (I) or a salt thereof, (1) preferably, R ¹ is a hydrogen atom or a group having 1 to 4 carbon atoms.
A straight-chain or branched alkyl radical having pieces; R ² is a straight-chain or branched alkylene group having 2 to 5 carbon atoms; R ³ is a hydrogen atom, the number of carbon atoms X is 1 to 3; a linear or branched alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 2 carbon atoms, an alkylthio group having 1 to 2 carbon atoms, and a halogen atom; An aryl group having 6 to 10 carbon atoms which may have a substituent, or 1
A 5- to 10-membered (single or bicyclic) heteroaromatic ring group having 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms which may have 3 to 3 substituents; These groups are represented by the following substituents: 1) straight-chain or branched alkyl having 1 to 6 carbons, 2) straight-chain or branched alkyl having 1 to 4 carbons Alkyl halide of 3) hydroxy,
4) linear or branched acyloxy having 1 to 4 carbon atoms; 5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) 1 to 4 carbon atoms. A) straight-chain or branched alkylthio having 7 to 12 carbon atoms; 8) straight-chain or branched alkylthio having 1 to 4 carbon atoms; ) Carbon number 1
Linear or branched alkylsulfonyl having from 4 to 4, 10) halogen atoms, 11) carbon atoms of 7
Aralkyl having from 12 to 12) phenyl (where phenyl is straight-chain or branched alkyl having 1 to 6 carbons, straight-chain or branched having 1 to 4 carbons) Alkyl halide, straight-chain or branched alkoxy having 1 to 4 carbon atoms, halogen or straight-chain or branched alkylenedioxy having 1 to 4 carbon atoms, 13) phenoxy (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons) Linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkylenedioxy having 1 to 4 carbon atoms May be substituted), 1
4) phenylthio (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, 1 carbon Linear or branched alkoxy having 4 to 4 carbon atoms, halogen or linear or branched alkylenedioxy having 1 to 4 carbon atoms), 15) phenyl Sulfonyl (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons,
Straight-chain or branched alkoxy having 1 to 4 carbon atoms, which may be substituted by halogen or straight-chain or branched alkylenedioxy having 1 to 4 carbon atoms), 16) phenylsulfonylamino (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, carbon It may be substituted by a linear or branched alkoxy having 1 to 4 carbon atoms, halogen, or a linear or branched alkylenedioxy having 1 to 4 carbon atoms. May be substituted by linear or branched alkyl having 1 to 6 carbons), 17) furyl, thienyl, oxazolyl, isoxazolyl, thi Zolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (the nitrogen atom may be substituted by straight-chain or branched alkyl having 1 to 6 carbon atoms), and / or 19 ) Pyridylsulfonylamino (where the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms); Y is an oxygen atom, a sulfur atom or Group>
NR ⁴ (R ⁴ is a hydrogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms or a linear or branched alkanoyl group having 2 to 5 carbon atoms) Z is a 2,4-dioxothiazolidine-5-ylmethyl group, a 2,4-dioxooxazolidine-5-ylmethyl group or a 3,5-dioxooxadiazolidine-2-ylmethyl group. An oxime derivative or a salt thereof.

(2) More preferably, R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms; R ² has 2 to 5 carbon atoms A linear or branched alkylene group; R ³
Is a hydrogen atom; X is an aryl group having 6 to 10 carbon atoms which may have 1 to 3 substituents;
Or a 5- to 10-membered (single or bicyclic) heteroaromatic ring having 1 to 3 optionally substituted nitrogen, oxygen and / or sulfur atoms having 1 to 3 substituents Represents a group, and these groups are, as the substituent,
1) linear or branched alkyl having 1 to 6 carbons; 2) linear or branched alkyl halide having 1 to 4 carbons; 3) hydroxy; 4) Linear or branched alkanoyloxy having 1 to 4 carbon atoms; 5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) 1 to 4 carbon atoms. Linear or branched alkylenedioxy, 7) aralkyloxy having 7 to 12 carbons, 8) linear or branched alkylthio having 1 to 4 carbons,
9) a linear or branched alkylsulfonyl having 1 to 4 carbon atoms; 10) a fluorine atom, a chlorine atom, a bromine atom; 11) an aralkyl having 7 to 12 carbon atoms; Phenyl has 1 carbon atom
Linear or branched alkyl having 1 to 4 carbon atoms, linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkyl having 1 to 4 carbon atoms, Which may be substituted by a branched alkoxy, a halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms), 1
3) Phenoxy (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, 1 carbon Straight or branched alkoxy having 1 to 4 carbon atoms, halogen or 1 to 4 carbon atoms
14) phenylthio (the phenyl is a linear or branched alkyl having 1 to 6 carbons, Straight or branched alkyl halide having 1 to 4 carbon atoms, straight or branched alkoxy having 1 to 4 carbon atoms, halogen or having 1 to 4 carbon atoms Linear or branched alkylenedioxy, which may be substituted) 15) phenylsulfonyl (where phenyl is a linear or branched alkyl having 1 to 6 carbons, Linear or branched alkyl halide having 1 to 4 carbon atoms, 1 to 4 carbon atoms
Linear or branched alkoxy having 1 to 4 carbon atoms, which may be substituted by halogen or linear or branched alkylenedioxy having 1 to 4 carbon atoms), 16) phenylsulfonylamino (The phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, 1 to 4 carbons. May be substituted with a linear or branched alkoxy, halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms.
The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbons), 1
7) furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (where the nitrogen atom is substituted by a linear or branched alkyl having 1 to 6 carbon atoms) And / or
Or 19) may have pyridylsulfonylamino (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms); Y is an oxygen atom Z is a 2,4-dioxothiazolidine-5-ylmethyl group or a 2,4-dioxooxazolidin-5-ylmethyl group; an oxime derivative or a salt thereof.

(3) More preferably, R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 3 carbon atoms; R ² has 2 to 3 carbon atoms A linear or branched alkylene group; R ³
Is a hydrogen atom; X is a phenyl group, naphthyl group, imidazolyl group optionally having 1 to 3 substituents,
An oxazolyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group, wherein the group is substituted with: 1) a linear or branched alkyl having 1 to 6 carbons, 2) a carbon number. A linear or branched alkyl halide having 1 to 4 carbon atoms,
3) hydroxy, 4) linear or branched alkanoyloxy having 1 to 4 carbon atoms, 5) linear or branched alkoxy having 1 to 4 carbon atoms, 6) methylene Dioxy, 7) aralkyloxy having 7 to 12 carbon atoms, 8) 1 carbon atom
A straight-chain or branched alkylthio having 1 to 4 carbon atoms, 9) a straight-chain or branched alkylsulfonyl having 1 to 4 carbon atoms, 10) a fluorine atom, a chlorine atom, a bromine atom, 11 ) 7 to 12 carbon atoms
12) phenyl, which phenyl may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy, 1
3) phenoxy, wherein the phenyl may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy; 14) phenylthio, wherein the phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy. May be substituted),
15) phenylsulfonyl (the phenyl may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy) 16) phenylsulfonylamino (the phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylene The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), 17) furyl, thienyl, oxazolyl, isoxazolyl, Thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 1
8) imidazolyl (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms) and / or 19) pyridylsulfonylamino (the nitrogen atom has 1 to 6 carbon atoms) Y may be an oxygen atom; and Z may be 2,4-dioxothiazolidine-5-ylmethyl. Or an oxime derivative or a salt thereof.

(4) More preferably, R ¹ is a hydrogen atom, a methyl group or an ethyl group; R ² is an ethylene group, a trimethylene group or a methylethylene group; R ³ is a hydrogen atom; A phenyl group, a naphthyl group, an imidazolyl group, an oxazolyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group which may have 1 to 3 substituents;
1) linear or branched alkyl having 1 to 6 carbons; 2) linear or branched alkyl halide having 1 to 4 carbons; 3) hydroxy; 4) Linear or branched alkanoyloxy having 1 to 4 carbon atoms, 5) linear or branched alkoxy having 1 to 4 carbon atoms, 6) methylenedioxy, benzyloxy, Phenethyloxy, naphthylmethoxy, 7) linear or branched alkylthio having 1 to 4 carbon atoms,
8) linear or branched alkylsulfonyl having 1 to 4 carbon atoms, 9) fluorine, chlorine, bromine, 10) benzyl, 11) phenyl (the phenyl is methyl, trifluoromethyl, 12) phenoxy, wherein the phenyl is methyl,
May be substituted with trifluoromethyl, methoxy, fluoro or methylenedioxy), 13) phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, Pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino, N-methylpyridylsulfonylamino, and / or 14) imidazolyl (where the nitrogen atom is substituted by linear or branched alkyl having 1 to 6 carbon atoms) Y is an oxygen atom; Z is a 2,4-dioxothiazolidine-5-ylmethyl group; an oxime derivative or a salt thereof.

(5) More preferably, R ¹ is a hydrogen atom, a methyl group or an ethyl group; R ² is an ethylene group, a trimethylene group or a methylethylene group; R ³ is a hydrogen atom; A phenyl group, a naphthyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group which may have 1 to 3 substituents, wherein the groups are 1) 1 to 3 carbon atoms; Linear or branched alkyl having 2) trifluoromethyl, difluoromethyl, fluoromethyl, hydroxy, formyloxy, acetoxy, 3) linear or branched having 1 to 3 carbon atoms Of alkoxy,
4) methylenedioxy, benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, 5) fluorine, chlorine, bromine, 6) benzyl, phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4- Methoxyphenyl, 4-fluorophenyl, 3,4-methylenedioxyphenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, furyl, thienyl, oxazolyl, thiazolyl,
May have imidazolyl, N-methylimidazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino and / or N-methylpyridylsulfonylamino; Y is an oxygen atom; Z is 2,4- A dioxothiazolidine-5-ylmethyl group; an oxime derivative or a salt thereof.

(6) More preferably, R ¹ is a hydrogen atom, a methyl group or an ethyl group; R ² is an ethylene group; R ³ is a hydrogen atom; and X is 1 to 3 substituents. A phenyl group, a naphthyl group, a pyridyl group, a quinolyl group or an isoquinolyl group which may have, as a substituent, methyl, ethyl, isopropyl, trifluoromethyl, hydroxy, acetoxy, methoxy, ethoxy, Isopropoxy, methylenedioxy, benzyloxy, methylthio, ethylthio, methylsulfonyl,
Ethylsulfonyl, chlorine atom, benzyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino and / or N-methylpyridylsulfonylamino Y is an oxygen atom; Z is a 2,4-dioxothiazolidin-5-ylmethyl group; an oxime derivative or a salt thereof.

(7) More preferably, R ¹ is a methyl group or an ethyl group; R ² is an ethylene group; R ³ is a hydrogen atom; and X has 1 to 3 substituents. A phenyl group which may be substituted as methyl, hydroxy, acetoxy, chlorine atom, benzyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, pyridyl, X may be pyridyloxy, pyridylthio and / or pyridylsulfonyl, or X is a pyridyl group optionally having 1 to 3 substituents, wherein the group is methoxy, ethoxy as a substituent. , Isopropoxy, benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, benzyl, Phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino and / or N-methylphenylsulfonylamino; Y is an oxygen atom; Z is 2,4-dioxothiazolidin-5-ylmethyl group Is an oxime derivative or a salt thereof.

Specific examples of the oxime derivative having the general formula (I) of the present invention include the following compounds.

[0090]

[Table 1] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 1-1 H (CH ₂ ) ₂ H Ph O 4-Zb 1-2 H (CH ₂ ) ₂ H 1-Np O 4-Zb 1-3 H (CH ₂ ) ₂ H 2-Np O 4-Zb 1-4 H (CH ₂ ) ₂ H 4-Me -Ph O 4-Zb 1-5 H (CH ₂ ) ₂ H 4-Et-Ph O 4-Zb 1-6 H (CH ₂ ) ₂ H 3-iPr-Ph O 4-Zb 1-7 H (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zb 1-8 H (CH ₂ ) ₂ H 3-tBu-Ph O 4-Zb 1-9 H (CH ₂ ) ₂ H 4-tBu-Ph O 4- Zb 1-10 H (CH ₂ ) ₂ H 3-Cl-Ph O 4-Zb 1-11 H (CH ₂ ) ₂ H 4-Cl-Ph O 4-Zb 1-12 H (CH ₂ ) ₂ H 3 -Br-Ph O 4-Zb 1-13 H (CH ₂ ) ₂ H 4-Br-Ph O 4-Zb 1-14 H (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zb 1-15 H (CH ₂ ) ₂ H 4-Ph-Ph O 4-Zb 1-16 H (CH ₂ ) ₂ H 3-Bz-Ph O 4-Zb 1-17 H (CH ₂ ) ₂ H 4-Bz-Ph O 4-Zb 1-18 H (CH ₂ ) ₂ H 3-PhO-Ph O 4-Zb 1-19 H (CH ₂ ) ₂ H 4-PhO-Ph O 4-Zb 1-20 H (CH ₂ ) ₂ H 3-PhS-Ph O 4-Zb 1-21 H (CH ₂ ) ₂ H 4-PhS-Ph O 4-Zb 1-22 H (CH ₂ ) ₂ H 3-PhSO ₂ -Ph O 4-Zb 1-23 H (CH ₂ ) ₂ H 4-PhSO ₂ -Ph O 4-Zb 1-24 H (CH ₂ ) ₂ H 3- (Imid-1) -Ph O 4-Zb 1-25 H (CH ₂ ) ₂ H 4- (Imid-1) -Ph O 4-Zb 1- 26 H (CH ₂ ) ₂ H 3- (Imid-4) -Ph O 4-Zb 1-27 H (CH ₂ ) ₂ H 4- (Imid-4) -Ph O 4-Zb 1-28 H (CH ₂ ) ₂ H 3- (Fur -2) -Ph O 4-Zb 1- 29 H (CH ₂ ) ₂ H 4- (Fur-2) -Ph O 4-Zb 1-30 H (CH ₂ ) ₂ H 3- (Thi-2)- Ph O 4-Zb 1- 31 H (CH ₂ ) ₂ H 4- (Thi-2) -Ph O 4-Zb 1-32 H (CH ₂ ) ₂ H 3- (Thi-3) -Ph O 4- Zb 1-33 H (CH ₂ ) ₂ H 4- (Thi-3) -Ph O 4-Zb 1-34 H (CH ₂ ) ₂ H 3- (Pyr-2) -Ph O 4-Zb 1-35 H (CH ₂ ) ₂ H 4- (Pyr-2) -Ph O 4-Zb 1-36 H (CH ₂ ) ₂ H 3- (Pyr-3) -Ph O 4-Zb 1-37 H (CH ₂ ) ₂ H 4- (Pyr-3) -Ph O 4-Zb 1- 38 H (CH ₂ ) ₂ H 3- (Pyr-4) -Ph O 4-Zb 1- 39 H (CH ₂ ) ₂ H 4 -(Pyr-4) -Ph O 4-Zb 1-40 H (CH ₂ ) ₂ H 3- (Oxa-2) -Ph O 4-Zb 1-41 H (CH ₂ ) ₂ H 4- (Oxa- 2) -Ph O 4-Zb 1-42 H (CH ₂ ) ₂ H 3- (Oxa-4) -Ph O 4-Zb 1- 43 H (CH ₂ ) ₂ H 4- (Oxa-4) -Ph O 4-Zb 1- 44 H (CH ₂ ) ₂ H 3- (Oxa-5) -Ph O 4-Zb 1- 45 H (CH ₂ ) ₂ H 4- (Oxa-5) -Ph O 4-Zb 1- 46 H (CH ₂ ) ₂ H 3- (Thiz- 2) -Ph O 4-Zb 1- 47 H (CH ₂ ) ₂ H 4- (Thiz-2) -Ph O 4-Zb 1- 48 H (CH ₂ ) ₂ H 3- (Thiz-4) -Ph O 4-Zb 1- 49 H (CH ₂ ) ₂ H 4- (Thiz-4) -Ph O 4-Zb 1-50 H (CH ₂ ) ₂ H 3- (Thiz-5) -Ph O 4-Zb 1- 51 H (CH ₂ ) ₂ H 4- (Thiz-5) -Ph O 4-Zb 1- 52 H (CH ₂ ) ₂ H 1-Me-2-Pyrr O 4-Zb 1- 53 H (CH ₂ ) ₂ H 1-Ph-2-Pyrr O 4-Zb 1- 54 H (CH ₂ ) ₂ H 1-Bz-2-Pyrr O 4-Zb 1- 55 H (CH ₂ ) ₂ H 5-Me- 2-Fur O 4-Zb 1- 56 H (CH ₂ ) ₂ H 5-Ph-2-Fur O 4-Zb 1- 57 H (CH ₂ ) ₂ H 5-Me-2-Thi O 4-Zb 1 -58 H (CH ₂ ) ₂ H 5-Ph-2-Thi O 4-Zb 1-59 H (CH ₂ ) ₂ H 5-Me-3-Thi O 4-Zb 1-60 H (CH ₂ ) ₂ H 5-Ph-3-Thi O 4-Zb 1- 61 H (CH ₂ ) ₂ H 1-Me-3-Pyza O 4-Zb 1- 62 H (CH ₂ ) ₂ H 1-Ph-3-Pyza O 4-Zb 1- 63 H (CH ₂ ) ₂ H 1-Me-2-Imid O 4-Zb 1- 64 H (CH ₂ ) ₂ H 1-Ph-2-Imid O 4-Zb 1-65 H (CH ₂ ) ₂ H 1-Me-4-Imid O 4-Zb 1- 66 H (CH ₂ ) ₂ H 1-Ph-4-Imid O 4-Zb 1- 67 H (CH ₂ ) ₂ H 4- Oxa O 4-Zb 1- 68 H (CH ₂ ) ₂ H 5-Oxa O 4-Zb 1- 69 H (CH ₂ ) ₂ H 2-Me-4-Oxa O 4-Zb 1- 70 H (CH ₂ ) ₂ H 2-Ph-4-Oxa O 4-Zb 1- 71 H (CH ₂ ) ₂ H 2-Me-5-Oxa O 4-Zb 1- 72 H (CH ₂ ) ₂ H 2-P h-5-Oxa O 4-Zb 1- 73 H (CH ₂ ) ₂ H 4-Me-2-Ph-5-Oxa O 4-Zb 1- 74 H (CH ₂ ) ₂ H 5-Me-2- Ph-4-Oxa O 4-Zb 1- 75 H (CH ₂ ) ₂ H 4-Thiz O 4-Zb 1- 76 H (CH ₂ ) ₂ H 5-Thiz O 4-Zb 1- 77 H (CH ₂ ) ₂ H 2-Me-4-Thiz O 4-Zb 1- 78 H (CH ₂ ) ₂ H 2-Ph-4-Thiz O 4-Zb 1- 79 H (CH ₂ ) ₂ H 2-Me-5 -Thiz O 4-Zb 1- 80 H (CH ₂ ) ₂ H 2-Ph-5-Thiz O 4-Zb 1- 81 H (CH ₂ ) ₂ H 4-Me-2-Ph-5-Thiz O 4 -Zb 1- 82 H (CH ₂ ) ₂ H 5-Me-2-Ph-4-Thiz O 4-Zb 1- 83 H (CH ₂ ) ₂ H 1-Me-4-Pyza O 4-Zb 1- 84 H (CH ₂ ) ₂ H 1-Ph-4-Pyza O 4-Zb 1- 85 H (CH ₂ ) ₂ H 2-Me-4-Isox O 4-Zb 1-86 H (CH ₂ ) ₂ H 2-Ph-4-Isox O 4-Zb 1-87 H (CH ₂ ) ₂ H 2-Pyr O 4-Zb 1-88 H (CH ₂ ) ₂ H 3-Pyr O 4-Zb 1-89 H ( CH ₂ ) ₂ H 4-Pyr O 4-Zb 1-90 H (CH ₂ ) ₂ H 3-Me-5-Pyr O 4-Zb 1-91 H (CH ₂ ) ₂ H 3-Et-5-Pyr O 4-Zb 1- 92 H (CH ₂ ) ₂ H 3-Ph-5-Pyr O 4-Zb 1- 93 H (CH ₂ ) ₂ H 2-Me-5-Pyr O 4-Zb 1- 94 H (CH ₂ ) ₂ H 2-Et-5-Pyr O 4-Zb 1- 95 H (CH ₂ ) ₂ H 2-Ph-5-Pyr O 4-Zb 1- 96 H (CH ₂ ) ₂ H 2- MeO-5-Pyr O 4-Zb 1-97 H (CH ₂ ) ₂ H 2-EtO-5-Pyr O 4-Zb 1-98 H (CH ₂ ) ₂ H 2-iPrO -5-Pyr O 4-Zb 1- 99 H (CH ₂ ) ₂ H 2-MeS-5-Pyr O 4-Zb 1-100 H (CH ₂ ) ₂ H 2-EtS-5-Pyr O 4-Zb 1-101 H (CH ₂ ) ₂ H 2-iPrS-5-Pyr O 4-Zb 1-102 H (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pyr O 4-Zb 1-103 H (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pyr O 4-Zb 1-104 H (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zb 1-105 H (CH ₂ ) ₂ H 2-Bz -5-Pyr O 4-Zb 1-106 H (CH ₂ ) ₂ H 2-PhO-5-Pyr O 4-Zb 1-107 H (CH ₂ ) ₂ H 2-PhS-5-Pyr O 4-Zb 1-108 H (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pyr O 4-Zb 1-109 H (CH ₂ ) ₂ H 3-Me-6-Pyr O 4-Zb 1-110 H (CH ₂ ) ₂ H 3-Ph-6-Pyr O 4-Zb 1-111 H (CH ₂ ) ₂ H 2-Me-6-Pyr O 4-Zb 1-112 H (CH ₂ ) ₂ H 2-Ph-6 -Pyr O 4-Zb 1-113 H (CH ₂ ) ₂ H 2-Me-4-Pym O 4-Zb 1-114 H (CH ₂ ) ₂ H 2-Ph-4-Pym O 4-Zb 1- 115 H (CH ₂ ) ₂ H 2-MeO-4-Pym O 4-Zb 1-116 H (CH ₂ ) ₂ H 2-EtO-4-Pym O 4-Zb 1-117 H (CH ₂ ) ₂ H 2-iPrO-4-Pym O 4-Zb 1-118 H (CH ₂ ) ₂ H 2-MeS-4-Pym O 4-Zb 1-119 H (CH ₂ ) ₂ H 2-EtS-4-Pym O 4-Zb 1-120 H (CH ₂ ) ₂ H 2-iPrS-4-Pym O 4-Zb 1-121 H (CH ₂ ) ₂ H 6-MeS-4-Pym O 4-Zb 1-122 H ( CH ₂ ) ₂ H 6-EtS-4-Pym O 4-Zb 1-123 H (CH ₂ ) ₂ H 6-iPrS-4-Pym O 4- Zb 1-124 H (CH ₂ ) ₂ H 2-PhS-4-Pym O 4-Zb 1-125 H (CH ₂ ) ₂ H 2-MeSO ₂ -4-Pym O 4-Zb 1-126 H (CH ₂ ) ₂ H 2-EtSO ₂ -4-Pym O 4-Zb 1-127 H (CH ₂ ) ₂ H 2-iPrSO ₂ -4-Pym O 4-Zb 1-128 H (CH ₂ ) ₂ H 2- PhSO ₂ -4-Pym O 4-Zb 1-129 H (CH ₂ ) ₂ H 2-Me-5-Pym O 4-Zb 1-130 H (CH ₂ ) ₂ H 2-Ph-5-Pym O 4 -Zb 1-131 H (CH ₂ ) ₂ H 2-MeO-5-Pym O 4-Zb 1-132 H (CH ₂ ) ₂ H 2-EtO-5-Pym O 4-Zb 1-133 H (CH ₂ ) ₂ H 2-iPrO-5-Pym O 4-Zb 1-134 H (CH ₂ ) ₂ H 2-MeS-5-Pym O 4-Zb 1-135 H (CH ₂ ) ₂ H 2-EtS- 5-Pym O 4-Zb 1-136 H (CH ₂ ) ₂ H 2-iPrS-5-Pym O 4-Zb 1-137 H (CH ₂ ) ₂ H 2-PhS-5-Pym O 4-Zb 1 -138 H (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pym O 4-Zb 1-139 H (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pym O 4-Zb 1-140 H (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pym O 4-Zb 1-141 H (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pym O 4-Zb 1-142 H (CH ₂ ) ₂ H 2-Ind O 4-Zb 1-143 H (CH ₂ ) ₂ H 3-Ind O 4-Zb 1-144 H (CH ₂ ) ₂ H 1-Me-2-Ind O 4-Zb 1-145 H (CH ₂ ) ₂ H 1-Me-3-Ind O 4-Zb 1-146 H (CH ₂ ) ₂ H 2-Bimid O 4-Zb 1-147 H (CH ₂ ) ₂ H 2-Boxa O 4-Zb 1-148 H (CH ₂ ) ₂ H 2-Bthiz O 4-Zb 1-149 H (CH ₂ ) ₂ H 2-Quin O 4-Zb 1-150 H (CH ₂ ) ₂ H 3-Quin O 4-Zb 1-151 H (CH ₂ ) ₂ H 4-Quin O 4-Zb 1-152 H (CH ₂ ) ₂ H 1-iQuin O 4-Zb 1-153 H (CH ₂ ) ₂ H 3-iQuin O 4-Zb 1-154 H (CH ₂ ) ₂ H 4-iQuin O 4-Zb 1-155 H (CH ₂ ) ₂ H 3-MeO-Ph O 4-Zb 1-156 H (CH ₂ ) ₂ H 4-MeO-Ph O 4-Zb 1-157 H (CH ₂ ) ₂ H 3-EtO-Ph O 4- Zb 1-158 H (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zb 1-159 H (CH ₂ ) ₂ H 3-iPrO-Ph O 4-Zb 1-160 H (CH ₂ ) ₂ H 4 -iPrO-Ph O 4-Zb 1-161 H (CH ₂ ) ₂ H 3-MeS-Ph O 4-Zb 1-162 H (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zb 1-163 H (CH ₂ ) ₂ H 3-EtS-Ph O 4-Zb 1-164 H (CH ₂ ) ₂ H 4-EtS-Ph O 4-Zb 1-165 H (CH ₂ ) ₂ H 3-iPrS-Ph O 4-Zb 1-166 H (CH ₂ ) ₂ H 4-iPrS-Ph O 4-Zb 1-167 H (CH ₂ ) ₂ H 3-MeSO ₂ -Ph O 4-Zb 1-168 H (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zb 1-169 H (CH ₂ ) ₂ H 3-EtSO ₂ -Ph O 4-Zb 1-170 H (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4 -Zb 1-171 H (CH ₂ ) ₂ H 3-iPrSO ₂ -Ph O 4-Zb 1-172 H (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Zb 1-173 H (CH ₂ ) ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zb 1-174 H (CH ₂ ) ₂ H 4- (1-Me-Imid-4) -Ph O 4-Zb 1-175 H (CH ₂ ) ₂ H 1-Me-2-Ph-4-Imid O 4-Zb 1-176 H (CH ₂ ) ₂ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 1-177 H (CH ₂ ) ₂ H 1,5-di-Me- 2-Ph-4-Imid O 4-Zb 1-178 H (CH ₂ ) ₂ H 3,4-MdO-Ph O 4-Zb 1-179 H (CH ₂ ) ₂ H 4- (4-MeO-Ph ) -Ph O 4-Zb 1-180 H (CH ₂ ) ₂ H 4- (3,4-MdO-Ph) -Ph O 4-Zb 1-181 H (CH ₂ ) ₂ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zb 1-182 H (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 1-183 H (CH ₂ ) ₂ H 4- (PhSO ₂ NH) -Ph O 4-Zb 1-184 H (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 1-185 H (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ ] -Ph O 4-Zb 1-186 H (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 1-187 H (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 1-188 H (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ NH]- Ph O 4-Zb 1-189 H (CH ₂ ) ₂ H 4- (4-Me-Ph) -Ph O 4-Zb 1-190 H (CH ₂ ) ₂ H 4- (4-F-Ph)- Ph O 4-Zb 1-191 H (CH ₂ ) ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 1-192 H (CH ₂ ) ₂ H 2- [4-Me-PhSO ₂ N (Me)]-5-Pyr O 4-Zb 1-193 H (CH ₂ ) ₂ H 2-HO-5-Pyr O 4-Zb 1-194 H (CH ₂ ) ₂ H 2-BzO-5- Pyr O 4-Zb 1-195 H (CH ₂ ) ₂ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zb 1-196 H (CH ₂ ) ₂ H 4- (2,4-di -MeO-Ph) -Ph O 4-Zb 1-197 H (CH ₂ ) ₂ H 4- (2,5-d i-MeO-Ph) -Ph O 4-Zb 1-198 H (CH ₂ ) ₂ H 3-HO-Ph O 4-Zb 1-199 H (CH ₂ ) ₂ H 4-HO-Ph O 4-Zb 1-200 H (CH ₂ ) ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 1-201 H (CH ₂ ) ₂ H 4-HO-3,5 -di-Me-Ph O 4-Zb 1-202 H (CH ₂ ) ₂ H 3-AcO-Ph O 4-Zb 1-203 H (CH ₂ ) ₂ H 4-AcO-Ph O 4-Zb ── ────────────────────────────────.

[0091]

[Table 2] Examples R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 2-1 Me (CH ₂ ) ₂ H Ph O 4-Zb 2- 2 Me (CH ₂ ) ₂ H 1-Np O 4-Zb 2-3 Me (CH ₂ ) ₂ H 2-Np O 4-Zb 2- 4 Me (CH ₂ ) ₂ H 4-Me -Ph O 4-Zb 2- 5 Me (CH ₂ ) ₂ H 4-Et-Ph O 4-Zb 2-6 Me (CH ₂ ) ₂ H 3-iPr-Ph O 4-Zb 2-7 Me (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zb 2-8 Me (CH ₂ ) ₂ H 3-tBu-Ph O 4-Zb 2-9 Me (CH ₂ ) ₂ H 4-tBu-Ph O 4- Zb 2- 10 Me (CH ₂ ) ₂ H 3-Cl-Ph O 4-Zb 2- 11 Me (CH ₂ ) ₂ H 4-Cl-Ph O 4-Zb 2- 12 Me (CH ₂ ) ₂ H 3 -Br-Ph O 4-Zb 2- 13 Me (CH ₂ ) ₂ H 4-Br-Ph O 4-Zb 2- 14 Me (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zb 2- 15 Me (CH ₂ ) ₂ H 4-Ph-Ph O 4-Zb 2-16 Me (CH ₂ ) ₂ H 3-Bz-Ph O 4-Zb 2-17 Me (CH ₂ ) ₂ H 4-Bz-Ph O 4-Zb 2- 18 Me (CH ₂ ) ₂ H 3-PhO-Ph O 4-Zb 2-19 Me (CH ₂ ) ₂ H 4-PhO-Ph O 4-Zb 2-20 Me (CH ₂ ) ₂ H 3-PhS-Ph O 4-Zb 2- 21 Me (CH ₂ ) ₂ H 4-PhS-Ph O 4-Zb 2- 22 Me (CH ₂ ) ₂ H 3-PhSO ₂ -Ph O 4-Zb 2- 23 Me (CH ₂ ) ₂ H 4-PhSO _2- Ph O 4-Zb 2- 24 Me (CH ₂ ) ₂ H 3- (Imid-1) -Ph O 4-Zb 2- 25 Me (CH ₂ ) ₂ H 4- (Imid-1) -Ph O 4- Zb 2-26 Me (CH ₂ ) ₂ H 3- (Imid-4) -Ph O 4-Zb 2-27 Me (CH ₂ ) ₂ H 4- (Imid-4) -Ph O 4-Zb 2- 28 Me (CH ₂ ) ₂ H 3- (Fur-2) -Ph O 4-Zb 2- 29 Me (CH ₂ ) ₂ H 4- (Fur-2) -Ph O 4-Zb 2- 30 Me (CH ₂ ) ₂ H 3- (Thi-2) -Ph O 4-Zb 2- 31 Me (CH ₂ ) ₂ H 4- (Thi-2) -Ph O 4-Zb 2- 32 Me (CH ₂ ) ₂ H 3 -(Thi-3) -Ph O 4-Zb 2- 33 Me (CH ₂ ) ₂ H 4- (Thi-3) -Ph O 4-Zb 2- 34 Me (CH ₂ ) ₂ H 3- (Pyr- 2) -Ph O 4-Zb 2- 35 Me (CH ₂ ) ₂ H 4- (Pyr-2) -Ph O 4-Zb 2-36 Me (CH ₂ ) ₂ H 3- (Pyr-3) -Ph O 4-Zb 2- 37 Me (CH ₂ ) ₂ H 4- (Pyr-3) -Ph O 4-Zb 2- 38 Me (CH ₂ ) ₂ H 3- (Pyr-4) -Ph O 4-Zb 2-39 Me (CH ₂ ) ₂ H 4- (Pyr-4) -Ph O 4-Zb 2-40 Me (CH ₂ ) ₂ H 3- (Oxa-2) -Ph O 4-Zb 2- 41 Me (CH ₂ ) ₂ H 4- (Oxa-2) -Ph O 4-Zb 2-42 Me (CH ₂ ) ₂ H 3- (Oxa-4) -Ph O 4-Zb 2-43 Me (CH ₂ ) ₂ H 4- (Oxa-4) -Ph O 4-Zb 2-44 Me (CH ₂ ) ₂ H 3- (Oxa-5) -Ph O 4-Zb 2-45 Me (CH ₂ ) ₂ H 4- ( Oxa-5) -Ph O 4-Zb 2-46 Me (CH ₂ ) ₂ H 3- (Thiz-2) -Ph O 4-Zb 2-47 Me (CH ₂ ) ₂ H 4- (Thiz-2) -Ph O 4-Zb 2-48 Me (CH ₂ ) ₂ H 3- (Thiz-4) -Ph O 4-Zb 2-49 Me (CH ₂ ) ₂ H 4- (Thiz-4) -Ph O 4 -Zb 2- 50 Me (CH ₂ ) ₂ H 3- (Thiz-5) -Ph O 4-Zb 2- 51 Me (CH ₂ ) ₂ H 4- (Thiz-5) -Ph O 4-Zb 2- 52 Me (CH ₂ ) ₂ H 1-Me-2-Pyrr O 4-Zb 2- 53 Me (CH ₂ ) ₂ H 1-Ph-2-Pyrr O 4-Zb 2- 54 Me (CH ₂ ) ₂ H 1-Bz-2-Pyrr O 4-Zb 2- 55 Me (CH ₂ ) ₂ H 5-Me-2-Fur O 4-Zb 2-56 Me (CH ₂ ) ₂ H 5-Ph-2-Fur O 4-Zb 2-57 Me (CH ₂ ) ₂ H 5-Me-2-Thi O 4-Zb 2-58 Me (CH ₂ ) ₂ H 5-Ph-2-Thi O 4-Zb 2-59 Me ( CH ₂ ) ₂ H 5-Me-3-Thi O 4-Zb 2- 60 Me (CH ₂ ) ₂ H 5-Ph-3-Thi O 4-Zb 2- 61 Me (CH ₂ ) ₂ H 1-Me -3-Pyza O 4-Zb 2- 62 Me (CH ₂ ) ₂ H 1-Ph-3-Pyza O 4-Zb 2- 63 Me (CH ₂ ) ₂ H 1-Me-2-Imid O 4-Zb 2- 64 Me (CH ₂ ) ₂ H 1-Ph-2-Imid O 4-Zb 2- 65 Me (CH ₂ ) ₂ H 1-Me-4-Imid O 4-Zb 2- 66 Me (CH ₂ ) ₂ H 1-Ph-4-Imid O 4-Zb 2- 67 Me (CH ₂ ) ₂ H 4-Oxa O 4-Zb 2- 68 Me (CH ₂ ) ₂ H 5-Oxa O 4-Zb 2- 69 Me (CH ₂ ) ₂ H 2-Me-4-Oxa O 4-Zb 2- 70 Me (CH ₂ ) ₂ H 2-Ph-4-Ox a O 4-Zb 2- 71 Me (CH ₂ ) ₂ H 2-Me-5-Oxa O 4-Zb 2- 72 Me (CH ₂ ) ₂ H 2-Ph-5-Oxa O 4-Zb 2- 73 Me (CH ₂ ) ₂ H 4-Me-2-Ph-5-Oxa O 4-Zb 2- 74 Me (CH ₂ ) ₂ H 5-Me-2-Ph-4-Oxa O 4-Zb 2- 75 Me (CH ₂ ) ₂ H 4-Thiz O 4-Zb 2- 76 Me (CH ₂ ) ₂ H 5-Thiz O 4-Zb 2-77 Me (CH ₂ ) ₂ H 2-Me-4-Thiz O 4 -Zb 2- 78 Me (CH ₂ ) ₂ H 2-Ph-4-Thiz O 4-Zb 2- 79 Me (CH ₂ ) ₂ H 2-Me-5-Thiz O 4-Zb 2- 80 Me (CH ₂ ) ₂ H 2-Ph-5-Thiz O 4-Zb 2- 81 Me (CH ₂ ) ₂ H 4-Me-2-Ph-5-Thiz O 4-Zb 2-82 Me (CH ₂ ) ₂ H 5-Me-2-Ph-4-Thiz O 4-Zb 2- 83 Me (CH ₂ ) ₂ H 1-Me-4-Pyza O 4-Zb 2- 84 Me (CH ₂ ) ₂ H 1-Ph- 4-Pyza O 4-Zb 2- 85 Me (CH ₂ ) ₂ H 2-Me-4-Isox O 4-Zb 2- 86 Me (CH ₂ ) ₂ H 2-Ph-4-Isox O 4-Zb 2 -87 Me (CH ₂ ) ₂ H 2-Pyr O 4-Zb 2-88 Me (CH ₂ ) ₂ H 3-Pyr O 4-Zb 2- 89 Me (CH ₂ ) ₂ H 4-Pyr O 4-Zb 2-90 Me (CH ₂ ) ₂ H 3-Me-5-Pyr O 4-Zb 2- 91 Me (CH ₂ ) ₂ H 3-Et-5-Pyr O 4-Zb 2- 92 Me (CH ₂ ) ₂ H 3-Ph-5-Pyr O 4-Zb 2- 93 Me (CH ₂ ) ₂ H 2-Me-5-Pyr O 4-Zb 2- 94 Me (CH ₂ ) ₂ H 2-Et-5- Pyr O 4-Zb 2- 95 Me (CH ₂ ) ₂ H 2-Ph-5-Pyr O 4-Zb 2- 96 Me (CH ₂ ) ₂ H 2-MeO-5-Pyr O 4-Zb 2-97 Me (CH ₂ ) ₂ H 2-EtO-5-Pyr O 4-Zb 2- 98 Me (CH ₂ ) ₂ H 2- iPrO-5-Pyr O 4-Zb 2- 99 Me (CH ₂ ) ₂ H 2-MeS-5-Pyr O 4-Zb 2-100 Me (CH ₂ ) ₂ H 2-EtS-5-Pyr O 4- Zb 2-101 Me (CH ₂ ) ₂ H 2-iPrS-5-Pyr O 4-Zb 2-102 Me (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pyr O 4-Zb 2-103 Me (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pyr O 4-Zb 2-104 Me (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zb 2-105 Me (CH ₂ ) ₂ H 2- Bz-5-Pyr O 4-Zb 2-106 Me (CH ₂ ) ₂ H 2-PhO-5-Pyr O 4-Zb 2-107 Me (CH ₂ ) ₂ H 2-PhS-5-Pyr O 4- Zb 2-108 Me (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pyr O 4-Zb 2-109 Me (CH ₂ ) ₂ H 3-Me-6-Pyr O 4-Zb 2-110 Me (CH ₂ ) ₂ H 3-Ph-6-Pyr O 4-Zb 2-111 Me (CH ₂ ) ₂ H 2-Me-6-Pyr O 4-Zb 2-112 Me (CH ₂ ) ₂ H 2-Ph- 6-Pyr O 4-Zb 2-113 Me (CH ₂ ) ₂ H 2-Me-4-Pym O 4-Zb 2-114 Me (CH ₂ ) ₂ H 2-Ph-4-Pym O 4-Zb 2 -115 Me (CH ₂ ) ₂ H 2-MeO-4-Pym O 4-Zb 2-116 Me (CH ₂ ) ₂ H 2-EtO-4-Pym O 4-Zb 2-117 Me (CH ₂ ) ₂ H 2-iPrO-4-Pym O 4-Zb 2-118 Me (CH ₂ ) ₂ H 2-MeS-4-Pym O 4-Zb 2-119 Me (CH ₂ ) ₂ H 2-EtS-4-Pym O 4-Zb 2-120 Me (CH ₂ ) ₂ H 2-iPrS-4-Pym O 4-Zb 2-121 Me (CH ₂ ) ₂ H 6-MeS-4-Pym O 4-Zb 2-122 Me (CH ₂ ) ₂ H 6-EtS-4-Pym O 4-Zb 2-123 Me ( CH ₂ ) ₂ H 6-iPrS-4-Pym O 4-Zb 2-124 Me (CH ₂ ) ₂ H 2-PhS-4-Pym O 4-Zb 2-125 Me (CH ₂ ) ₂ H 2-MeSO ₂ -4-Pym O 4-Zb 2-126 Me (CH ₂ ) ₂ H 2-EtSO ₂ -4-Pym O 4-Zb 2-127 Me (CH ₂ ) ₂ H 2-iPrSO ₂ -4-Pym O 4-Zb 2-128 Me (CH ₂ ) ₂ H 2-PhSO ₂ -4-Pym O 4-Zb 2-129 Me (CH ₂ ) ₂ H 2-Me-5-Pym O 4-Zb 2-130 Me (CH ₂ ) ₂ H 2-Ph-5-Pym O 4-Zb 2-131 Me (CH ₂ ) ₂ H 2-MeO-5-Pym O 4-Zb 2-132 Me (CH ₂ ) ₂ H 2- EtO-5-Pym O 4-Zb 2-133 Me (CH ₂ ) ₂ H 2-iPrO-5-Pym O 4-Zb 2-134 Me (CH ₂ ) ₂ H 2-MeS-5-Pym O 4- Zb 2-135 Me (CH ₂ ) ₂ H 2-EtS-5-Pym O 4-Zb 2-136 Me (CH ₂ ) ₂ H 2-iPrS-5-Pym O 4-Zb 2-137 Me (CH ₂ ) ₂ H 2-PhS-5-Pym O 4-Zb 2-138 Me (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pym O 4-Zb 2-139 Me (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pym O 4-Zb 2-140 Me (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pym O 4-Zb 2-141 Me (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pym O 4 -Zb 2-142 Me (CH ₂ ) ₂ H 2-Ind O 4-Zb 2-143 Me (CH ₂ ) ₂ H 3-Ind O 4-Zb 2-144 Me (CH ₂ ) ₂ H 1-Me- 2-Ind O 4-Zb 2-145 Me (CH ₂ ) ₂ H 1-Me-3-Ind O 4-Zb 2-146 Me (CH ₂ ) ₂ H 2-Bimid O 4-Zb 2-147 Me (CH ₂ ) ₂ H 2-Boxa O 4-Zb 2 -148 Me (CH ₂ ) ₂ H 2-Bthiz O 4-Zb 2-149 Me (CH ₂ ) ₂ H 2-Quin O 4-Zb 2-150 Me (CH ₂ ) ₂ H 3-Quin O 4-Zb 2-151 Me (CH ₂ ) ₂ H 4-Quin O 4-Zb 2-152 Me (CH ₂ ) ₂ H 1-iQuin O 4-Zb 2-153 Me (CH ₂ ) ₂ H 3-iQuin O 4- Zb 2-154 Me (CH ₂ ) ₂ H 4-iQuin O 4-Zb 2-155 Me (CH ₂ ) ₂ H 3-MeO-Ph O 4-Zb 2-156 Me (CH ₂ ) ₂ H 4-MeO -Ph O 4-Zb 2-157 Me (CH ₂ ) ₂ H 3-EtO-Ph O 4-Zb 2-158 Me (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zb 2-159 Me (CH ₂ ) ₂ H 3-iPrO-Ph O 4-Zb 2-160 Me (CH ₂ ) ₂ H 4-iPrO-Ph O 4-Zb 2-161 Me (CH ₂ ) ₂ H 3-MeS-Ph O 4- Zb 2-162 Me (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zb 2-163 Me (CH ₂ ) ₂ H 3-EtS-Ph O 4-Zb 2-164 Me (CH ₂ ) ₂ H 4 -EtS-Ph O 4-Zb 2-165 Me (CH ₂ ) ₂ H 3-iPrS-Ph O 4-Zb 2-166 Me (CH ₂ ) ₂ H 4-iPrS-Ph O 4-Zb 2-167 Me (CH ₂ ) ₂ H 3-MeSO ₂ -Ph O 4-Zb 2-168 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zb 2-169 Me (CH ₂ ) ₂ H 3-EtSO ₂ -Ph O 4-Zb 2-170 Me (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4-Zb 2-171 Me (CH ₂ ) ₂ H 3-iPrSO ₂ -Ph O 4-Zb 2-172 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Zb 2-173 Me (CH ₂ ) ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zb 2-174 Me (CH ₂ ) ₂ H 4- (1-Me-Imid-4) -Ph O 4-Zb 2-175 Me (CH ₂ ) ₂ H 1-Me-2-Ph-4-Imid O 4-Zb 2 -176 Me (CH ₂ ) ₂ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 2-177 Me (CH ₂ ) ₂ H 1,5-di-Me-2-Ph- 4-Imid O 4-Zb 2-178 Me (CH ₂ ) ₂ H 3,4-MdO-Ph O 4-Zb 2-179 Me (CH ₂ ) ₂ H 4- (4-MeO-Ph) -Ph O 4-Zb 2-180 Me (CH ₂ ) ₂ H 4- (3,4-MdO-Ph) -Ph O 4-Zb 2-181 Me (CH ₂ ) ₂ H 4- [PhSO ₂ N (Me)] -Ph O 4-Zb 2-182 Me (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 2-183 Me (CH ₂ ) ₂ H 4- ( PhSO ₂ NH) -Ph O 4-Zb 2-184 Me (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 2-185 Me (CH ₂ ) ₂ H 4- [(Pyr-2) SO ₂ ] -Ph O 4-Zb 2-186 Me (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 2-187 Me (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 2-188 Me (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4- Zb 2-189 Me (CH ₂ ) ₂ H 4- (4-Me-Ph) -Ph O 4-Zb 2-190 Me (CH ₂ ) ₂ H 4- (4-F-Ph) -Ph O 4- Zb 2-191 Me (CH ₂ ) ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 2-192 Me (CH ₂ ) ₂ H 2- [4-Me-PhSO ₂ N (Me) ] -5-Pyr O 4-Zb 2-193 Me (CH ₂ ) ₂ H 2-HO-5-Pyr O 4-Zb 2-194 Me (CH ₂ ) ₂ H 2-BzO-5-Pyr O 4-Zb 2-195 Me (CH ₂ ) ₂ H 4- [(Pyr-4) SO ₂ ] -Ph O 4-Zb 2-196 Me (CH ₂ ) ₂ H 4- (2,4-di-MeO-Ph) -Ph O 4-Zb 2-197 Me (CH ₂ ) ₂ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zb 2-198 Me (CH ₂ ) ₂ H 3-HO-Ph O 4-Zb 2-199 Me (CH ₂ ) ₂ H 4-HO-Ph O 4-Zb 2-200 Me (CH ₂ ) ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 2-201 Me (CH ₂ ) ₂ H 4-HO-3,5-di-Me-Ph O 4-Zb 2-202 Me (CH ₂ ) ₂ H 3-AcO-Ph O 4-Zb 2-203 Me (CH ₂ ) ₂ H 4-AcO-Ph O 4-Zb II.

[0092]

[Table 3] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 3-1 Et (CH ₂ ) ₂ H Ph O 4-Zb 3- 2 Et (CH ₂ ) ₂ H 1-Np O 4-Zb 3- 3 Et (CH ₂ ) ₂ H 2-Np O 4-Zb 3-4 Et (CH ₂ ) ₂ H 4-Me -Ph O 4-Zb 3-5 Et (CH ₂ ) ₂ H 4-Et-Ph O 4-Zb 3-6 Et (CH ₂ ) ₂ H 3-iPr-Ph O 4-Zb 3-7 Et (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zb 3-8 Et (CH ₂ ) ₂ H 3-tBu-Ph O 4-Zb 3-9 Et (CH ₂ ) ₂ H 4-tBu-Ph O 4- Zb 3-10 Et (CH ₂ ) ₂ H 3-Cl-Ph O 4-Zb 3-11 Et (CH ₂ ) ₂ H 4-Cl-Ph O 4-Zb 3-12 Et (CH ₂ ) ₂ H 3 -Br-Ph O 4-Zb 3-13 Et (CH ₂ ) ₂ H 4-Br-Ph O 4-Zb 3-14 Et (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zb 3-15 Et (CH ₂ ) ₂ H 4-Ph-Ph O 4-Zb 3-16 Et (CH ₂ ) ₂ H 3-Bz-Ph O 4-Zb 3-17 Et (CH ₂ ) ₂ H 4-Bz-Ph O 4-Zb 3-18 Et (CH ₂ ) ₂ H 3-PhO-Ph O 4-Zb 3-19 Et (CH ₂ ) ₂ H 4-PhO-Ph O 4-Zb 3-20 Et (CH ₂ ) ₂ H 3-PhS-Ph O 4-Zb 3- 21 Et (CH ₂ ) ₂ H 4-PhS-Ph O 4-Zb 3-22 Et (CH ₂ ) ₂ H 3-PhSO ₂ -Ph O 4-Zb 3-23 Et (CH ₂ ) ₂ H 4-PhSO _2- Ph O 4-Zb 3- 24 Et (CH ₂ ) ₂ H 3- (Imid-1) -Ph O 4-Zb 3- 25 Et (CH ₂ ) ₂ H 4- (Imid-1) -Ph O 4- Zb 3-26 Et (CH ₂ ) ₂ H 3- (Imid-4) -Ph O 4-Zb 3-27 Et (CH ₂ ) ₂ H 4- (Imid-4) -Ph O 4-Zb 3-28 Et (CH ₂ ) ₂ H 3- (Fur-2) -Ph O 4-Zb 3-29 Et (CH ₂ ) ₂ H 4- (Fur-2) -Ph O 4-Zb 3--30 Et (CH ₂ ) ₂ H 3- (Thi-2) -Ph O 4-Zb 3- 31 Et (CH ₂ ) ₂ H 4- (Thi-2) -Ph O 4-Zb 3-32 Et (CH ₂ ) ₂ H 3 -(Thi-3) -Ph O 4-Zb 3-33 Et (CH ₂ ) ₂ H 4- (Thi-3) -Ph O 4-Zb 3- 34 Et (CH ₂ ) ₂ H 3- (Pyr- 2) -Ph O 4-Zb 3-35 Et (CH ₂ ) ₂ H 4- (Pyr-2) -Ph O 4-Zb 3-36 Et (CH ₂ ) ₂ H 3- (Pyr-3) -Ph O 4-Zb 3-37 Et (CH ₂ ) ₂ H 4- (Pyr-3) -Ph O 4-Zb 3-38 Et (CH ₂ ) ₂ H 3- (Pyr-4) -Ph O 4-Zb 3-39 Et (CH ₂ ) ₂ H 4- (Pyr-4) -Ph O 4-Zb 3-40 Et (CH ₂ ) ₂ H 3- (Oxa-2) -Ph O 4-Zb 3-41 Et (CH ₂ ) ₂ H 4- (Oxa-2) -Ph O 4-Zb 3-42 Et (CH ₂ ) ₂ H 3- (Oxa-4) -Ph O 4-Zb 3-43 Et (CH ₂ ) ₂ H 4- (Oxa-4) -Ph O 4-Zb 3-44 Et (CH ₂ ) ₂ H 3- (Oxa-5) -Ph O 4-Zb 3-45 Et (CH ₂ ) ₂ H 4- ( Oxa-5) -Ph O 4-Zb 3-46 Et (CH ₂ ) ₂ H 3- (Thiz-2) -Ph O 4-Zb 3-47 Et (CH ₂ ) ₂ H 4- (Thiz-2) -Ph O 4-Zb 3-48 Et (CH ₂ ) ₂ H 3- (Thiz-4) -Ph O 4-Zb 3-49 Et (CH ₂ ) ₂ H 4- (Thiz-4) -Ph O 4 -Zb 3- 50 Et (CH ₂ ) ₂ H 3- (Thiz-5) -Ph O 4-Zb 3- 51 Et (CH ₂ ) ₂ H 4- (Thiz-5) -Ph O 4-Zb 3- 52 Et (CH ₂ ) ₂ H 1-Me-2-Pyrr O 4-Zb 3- 53 Et (CH ₂ ) ₂ H 1-Ph-2-Pyrr O 4-Zb 3- 54 Et (CH ₂ ) ₂ H 1-Bz-2-Pyrr O 4-Zb 3-55 Et (CH ₂ ) ₂ H 5-Me-2-Fur O 4-Zb 3-56 Et (CH ₂ ) ₂ H 5-Ph-2-Fur O 4-Zb 3-57 Et (CH ₂ ) ₂ H 5-Me-2-Thi O 4-Zb 3-58 Et (CH ₂ ) ₂ H 5-Ph-2-Thi O 4-Zb 3-59 Et ( CH ₂ ) ₂ H 5-Me-3-Thi O 4-Zb 3- 60 Et (CH ₂ ) ₂ H 5-Ph-3-Thi O 4-Zb 3-61 Et (CH ₂ ) ₂ H 1-Me -3-Pyza O 4-Zb 3- 62 Et (CH ₂ ) ₂ H 1-Ph-3-Pyza O 4-Zb 3- 63 Et (CH ₂ ) ₂ H 1-Me-2-Imid O 4-Zb 3-64 Et (CH ₂ ) ₂ H 1-Ph-2-Imid O 4-Zb 3-65 Et (CH ₂ ) ₂ H 1-Me-4-Imid O 4-Zb 3-66 Et (CH ₂ ) ₂ H 1-Ph-4-Imid O 4-Zb 3-67 Et (CH ₂ ) ₂ H 4-Oxa O 4-Zb 3-68 Et (CH ₂ ) ₂ H 5-Oxa O 4-Zb 3-69 Et (CH ₂ ) ₂ H 2-Me-4-Oxa O 4-Zb 3-70 Et (CH ₂ ) ₂ H 2-Ph-4-Ox a O 4-Zb 3-71 Et (CH ₂ ) ₂ H 2-Me-5-Oxa O 4-Zb 3-72 Et (CH ₂ ) ₂ H 2-Ph-5-Oxa O 4-Zb 3- 73 Et (CH ₂ ) ₂ H 4-Me-2-Ph-5-Oxa O 4-Zb 3- 74 Et (CH ₂ ) ₂ H 5-Me-2-Ph-4-Oxa O 4-Zb 3- 75 Et (CH ₂ ) ₂ H 4-Thiz O 4-Zb 3- 76 Et (CH ₂ ) ₂ H 5-Thiz O 4-Zb 3-77 Et (CH ₂ ) ₂ H 2-Me-4-Thiz O 4 -Zb 3- 78 Et (CH ₂ ) ₂ H 2-Ph-4-Thiz O 4-Zb 3- 79 Et (CH ₂ ) ₂ H 2-Me-5-Thiz O 4-Zb 3- 80 Et (CH ₂ ) ₂ H 2-Ph-5-Thiz O 4-Zb 3-81 Et (CH ₂ ) ₂ H 4-Me-2-Ph-5-Thiz O 4-Zb 3-82 Et (CH ₂ ) ₂ H 5-Me-2-Ph-4-Thiz O 4-Zb 3-83 Et (CH ₂ ) ₂ H 1-Me-4-Pyza O 4-Zb 3- 84 Et (CH ₂ ) ₂ H 1-Ph- 4-Pyza O 4-Zb 3- 85 Et (CH ₂ ) ₂ H 2-Me-4-Isox O 4-Zb 3-86 Et (CH ₂ ) ₂ H 2-Ph-4-Isox O 4-Zb 3 -87 Et (CH ₂ ) ₂ H 2-Pyr O 4-Zb 3-88 Et (CH ₂ ) ₂ H 3-Pyr O 4-Zb 3-89 Et (CH ₂ ) ₂ H 4-Pyr O 4-Zb 3-90 Et (CH ₂ ) ₂ H 3-Me-5-Pyr O 4-Zb 3-91 Et (CH ₂ ) ₂ H 3-Et-5-Pyr O 4-Zb 3-92 Et (CH ₂ ) ₂ H 3-Ph-5-Pyr O 4-Zb 3-93 Et (CH ₂ ) ₂ H 2-Me-5-Pyr O 4-Zb 3-94 Et (CH ₂ ) ₂ H 2-Et-5- Pyr O 4-Zb 3- 95 Et (CH ₂ ) ₂ H 2-Ph-5-Pyr O 4-Zb 3-96 Et (CH ₂ ) ₂ H 2-MeO-5-Pyr O 4-Zb 3-97 Et (CH ₂ ) ₂ H 2-EtO-5-Pyr O 4-Zb 3-98 Et (CH ₂ ) ₂ H 2- iPrO-5-Pyr O 4-Zb 3- 99 Et (CH ₂ ) ₂ H 2-MeS-5-Pyr O 4-Zb 3-100 Et (CH ₂ ) ₂ H 2-EtS-5-Pyr O 4- Zb 3-101 Et (CH ₂ ) ₂ H 2-iPrS-5-Pyr O 4-Zb 3-102 Et (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pyr O 4-Zb 3-103 Et (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pyr O 4-Zb 3-104 Et (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zb 3-105 Et (CH ₂ ) ₂ H 2- Bz-5-Pyr O 4-Zb 3-106 Et (CH ₂ ) ₂ H 2-PhO-5-Pyr O 4-Zb 3-107 Et (CH ₂ ) ₂ H 2-PhS-5-Pyr O 4- Zb 3-108 Et (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pyr O 4-Zb 3-109 Et (CH ₂ ) ₂ H 3-Me-6-Pyr O 4-Zb 3-110 Et (CH ₂ ) ₂ H 3-Ph-6-Pyr O 4-Zb 3-111 Et (CH ₂ ) ₂ H 2-Me-6-Pyr O 4-Zb 3-112 Et (CH ₂ ) ₂ H 2-Ph- 6-Pyr O 4-Zb 3-113 Et (CH ₂ ) ₂ H 2-Me-4-Pym O 4-Zb 3-114 Et (CH ₂ ) ₂ H 2-Ph-4-Pym O 4-Zb 3 -115 Et (CH ₂ ) ₂ H 2-MeO-4-Pym O 4-Zb 3-116 Et (CH ₂ ) ₂ H 2-EtO-4-Pym O 4-Zb 3-117 Et (CH ₂ ) ₂ H 2-iPrO-4-Pym O 4-Zb 3-118 Et (CH ₂ ) ₂ H 2-MeS-4-Pym O 4-Zb 3-119 Et (CH ₂ ) ₂ H 2-EtS-4-Pym O 4-Zb 3-120 Et (CH ₂ ) ₂ H 2-iPrS-4-Pym O 4-Zb 3-121 Et (CH ₂ ) ₂ H 6-MeS-4-Pym O 4-Zb 3-122 Et (CH ₂ ) ₂ H 6-EtS-4-Pym O 4-Zb 3-123 Et ( CH ₂ ) ₂ H 6-iPrS-4-Pym O 4-Zb 3-124 Et (CH ₂ ) ₂ H 2-PhS-4-Pym O 4-Zb 3-125 Et (CH ₂ ) ₂ H 2-MeSO ₂ -4-Pym O 4-Zb 3-126 Et (CH ₂ ) ₂ H 2-EtSO ₂ -4-Pym O 4-Zb 3-127 Et (CH ₂ ) ₂ H 2-iPrSO ₂ -4-Pym O 4-Zb 3-128 Et (CH ₂ ) ₂ H 2-PhSO ₂ -4-Pym O 4-Zb 3-129 Et (CH ₂ ) ₂ H 2-Me-5-Pym O 4-Zb 3-130 Et (CH ₂ ) ₂ H 2-Ph-5-Pym O 4-Zb 3-131 Et (CH ₂ ) ₂ H 2-MeO-5-Pym O 4-Zb 3-132 Et (CH ₂ ) ₂ H 2- EtO-5-Pym O 4-Zb 3-133 Et (CH ₂ ) ₂ H 2-iPrO-5-Pym O 4-Zb 3-134 Et (CH ₂ ) ₂ H 2-MeS-5-Pym O 4- Zb 3-135 Et (CH ₂ ) ₂ H 2-EtS-5-Pym O 4-Zb 3-136 Et (CH ₂ ) ₂ H 2-iPrS-5-Pym O 4-Zb 3-137 Et (CH ₂ ) ₂ H 2-PhS-5-Pym O 4-Zb 3-138 Et (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pym O 4-Zb 3-139 Et (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pym O 4-Zb 3-140 Et (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pym O 4-Zb 3-141 Et (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pym O 4 -Zb 3-142 Et (CH ₂ ) ₂ H 2-Ind O 4-Zb 3-143 Et (CH ₂ ) ₂ H 3-Ind O 4-Zb 3-144 Et (CH ₂ ) ₂ H 1-Me- 2-Ind O 4-Zb 3-145 Et (CH ₂ ) ₂ H 1-Me-3-Ind O 4-Zb 3-146 Et (CH ₂ ) ₂ H 2-Bimid O 4-Zb 3-147 Et (CH ₂ ) ₂ H 2-Boxa O 4-Zb 3 -148 Et (CH ₂ ) ₂ H 2-Bthiz O 4-Zb 3-149 Et (CH ₂ ) ₂ H 2-Quin O 4-Zb 3-150 Et (CH ₂ ) ₂ H 3-Quin O 4-Zb 3-151 Et (CH ₂ ) ₂ H 4-Quin O 4-Zb 3-152 Et (CH ₂ ) ₂ H 1-iQuin O 4-Zb 3-153 Et (CH ₂ ) ₂ H 3-iQuin O 4- Zb 3-154 Et (CH ₂ ) ₂ H 4-iQuin O 4-Zb 3-155 Et (CH ₂ ) ₂ H 3-MeO-Ph O 4-Zb 3-156 Et (CH ₂ ) ₂ H 4-MeO -Ph O 4-Zb 3-157 Et (CH ₂ ) ₂ H 3-EtO-Ph O 4-Zb 3-158 Et (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zb 3-159 Et (CH ₂ ) ₂ H 3-iPrO-Ph O 4-Zb 3-160 Et (CH ₂ ) ₂ H 4-iPrO-Ph O 4-Zb 3-161 Et (CH ₂ ) ₂ H 3-MeS-Ph O 4- Zb 3-162 Et (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zb 3-163 Et (CH ₂ ) ₂ H 3-EtS-Ph O 4-Zb 3-164 Et (CH ₂ ) ₂ H 4 -EtS-Ph O 4-Zb 3-165 Et (CH ₂ ) ₂ H 3-iPrS-Ph O 4-Zb 3-166 Et (CH ₂ ) ₂ H 4-iPrS-Ph O 4-Zb 3-167 Et (CH ₂ ) ₂ H 3-MeSO ₂ -Ph O 4-Zb 3-168 Et (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zb 3-169 Et (CH ₂ ) ₂ H 3-EtSO ₂ -Ph O 4-Zb 3-170 Et (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4-Zb 3-171 Et (CH ₂ ) ₂ H 3-iPrSO ₂ -Ph O 4-Zb 3-172 Et (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Zb 3-173 Et (CH ₂ ) ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zb 3-174 Et (CH ₂ ) ₂ H 4- (1-Me-Imid-4) -Ph O 4-Zb 3-175 Et (CH ₂ ) ₂ H 1-Me-2-Ph-4-Imid O 4-Zb 3 -176 Et (CH ₂ ) ₂ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 3-177 Et (CH ₂ ) ₂ H 1,5-di-Me-2-Ph- 4-Imid O 4-Zb 3-178 Et (CH ₂ ) ₂ H 3,4-MdO-Ph O 4-Zb 3-179 Et (CH ₂ ) ₂ H 4- (4-MeO-Ph) -Ph O 4-Zb 3-180 Et (CH ₂ ) ₂ H 4- (3,4-MdO-Ph) -Ph O 4-Zb 3-181 Et (CH ₂ ) ₂ H 4- [PhSO ₂ N (Me)] -Ph O 4-Zb 3-182 Et (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 3-183 Et (CH ₂ ) ₂ H 4- ( PhSO ₂ NH) -Ph O 4-Zb 3-184 Et (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 3-185 Et (CH ₂ ) ₂ H 4- [(Pyr-2) SO ₂ ] -Ph O 4-Zb 3-186 Et (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 3-187 Et (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 3-188 Et (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4- Zb 3-189 Et (CH ₂ ) ₂ H 4- (4-Me-Ph) -Ph O 4-Zb 3-190 Et (CH ₂ ) ₂ H 4- (4-F-Ph) -Ph O 4- Zb 3-191 Et (CH ₂ ) ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 3-192 Et (CH ₂ ) ₂ H 2- [4-Me-PhSO ₂ N (Me) ] -5-Pyr O 4-Zb 3-193 Et (CH ₂ ) ₂ H 2-HO-5-Pyr O 4-Zb 3-194 Et (CH ₂ ) ₂ H 2-BzO-5-Pyr O 4-Zb 3-195 Et (CH ₂ ) ₂ H 4- [(Pyr-4) SO ₂ ] -Ph O 4-Zb 3-196 Et (CH ₂ ) ₂ H 4- (2,4-di-MeO-Ph) -Ph O 4-Zb 3-197 Et (CH ₂ ) ₂ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zb 3-198 Et (CH ₂ ) ₂ H 3-HO-Ph O 4-Zb 3-199 Et (CH ₂ ) ₂ H 4-HO-Ph O 4-Zb 3-200 Et (CH ₂ ) ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 3-201 Et (CH ₂ ) ₂ H 4-HO-3,5-di-Me-Ph O 4-Zb 3-202 Et (CH ₂ ) ₂ H 3-AcO-Ph O 4-Zb 3-203 Et (CH ₂ ) ₂ H 4-AcO-Ph O 4-Zb II.

[0093]

[Table 4] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 4- 1 iPr (CH ₂ ) ₂ H Ph O 4-Zb 4- 2 iPr (CH ₂ ) ₂ H 1-Np O 4-Zb 4- 3 iPr (CH ₂ ) ₂ H 2-Np O 4-Zb 4- 4 iPr (CH ₂ ) ₂ H 4-Me -Ph O 4-Zb 4- 5 iPr (CH ₂ ) ₂ H 4-Et-Ph O 4-Zb 4- 6 iPr (CH ₂ ) ₂ H 3-iPr-Ph O 4-Zb 4- 7 iPr (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zb 4-8 iPr (CH ₂ ) ₂ H 3-tBu-Ph O 4-Zb 4- 9 iPr (CH ₂ ) ₂ H 4-tBu-Ph O 4- Zb 4- 10 iPr (CH ₂ ) ₂ H 3-Cl-Ph O 4-Zb 4- 11 iPr (CH ₂ ) ₂ H 4-Cl-Ph O 4-Zb 4- 12 iPr (CH ₂ ) ₂ H 3 -Br-Ph O 4-Zb 4- 13 iPr (CH ₂ ) ₂ H 4-Br-Ph O 4-Zb 4- 14 iPr (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zb 4- 15 iPr (CH ₂ ) ₂ H 4-Ph-Ph O 4-Zb 4-16 iPr (CH ₂ ) ₂ H 3-Bz-Ph O 4-Zb 4-17 iPr (CH ₂ ) ₂ H 4-Bz-Ph O 4-Zb 4- 18 iPr (CH ₂ ) ₂ H 3-PhO-Ph O 4-Zb 4- 19 iPr (CH ₂ ) ₂ H 4-PhO-Ph O 4-Zb 4-20 iPr (CH ₂ ) ₂ H 3-Ph S-Ph O 4-Zb 4- 21 iPr (CH ₂ ) ₂ H 4-PhS-Ph O 4-Zb 4- 22 iPr (CH ₂ ) ₂ H 3-PhSO ₂ -Ph O 4-Zb 4--23 iPr (CH ₂ ) ₂ H 4-PhSO ₂ -Ph O 4-Zb 4- 24 iPr (CH ₂ ) ₂ H 3- (Imid-1) -Ph O 4-Zb 4- 25 iPr (CH ₂ ) ₂ H 4 -(Imid-1) -Ph O 4-Zb 4-26 iPr (CH ₂ ) ₂ H 3- (Imid-4) -Ph O 4-Zb 4-27 iPr (CH ₂ ) ₂ H 4- (Imid- 4) -Ph O 4-Zb 4-28 iPr (CH ₂ ) ₂ H 3- (Fur-2) -Ph O 4-Zb 4-29 iPr (CH ₂ ) ₂ H 4- (Fur-2) -Ph O 4-Zb 4- 30 iPr (CH ₂ ) ₂ H 3- (Thi-2) -Ph O 4-Zb 4- 31 iPr (CH ₂ ) ₂ H 4- (Thi-2) -Ph O 4-Zb 4-32 iPr (CH ₂ ) ₂ H 3- (Thi-3) -Ph O 4-Zb 4-33 iPr (CH ₂ ) ₂ H 4- (Thi-3) -Ph O 4-Zb 4-34 iPr (CH ₂ ) ₂ H 3- (Pyr-2) -Ph O 4-Zb 4-35 iPr (CH ₂ ) ₂ H 4- (Pyr-2) -Ph O 4-Zb 4-36 iPr (CH ₂ ) ₂ H 3- (Pyr-3) -Ph O 4-Zb 4-37 iPr (CH ₂ ) ₂ H 4- (Pyr-3) -Ph O 4-Zb 4-38 iPr (CH ₂ ) ₂ H 3- (Pyr-4) -Ph O 4-Zb 4-39 iPr (CH ₂ ) ₂ H 4- (Pyr-4) -Ph O 4-Zb 4- 40 iPr (CH ₂ ) ₂ H 3- (Oxa-2 ) -Ph O 4-Zb 4-41 iPr (CH ₂ ) ₂ H 4- (Oxa-2) -Ph O 4-Zb 4-42 iPr (CH ₂ ) ₂ H 3- (Oxa-4) -Ph O 4-Zb 4-43 iPr (CH ₂ ) ₂ H 4- (Oxa-4) -Ph O 4-Zb 4-44 iPr (CH ₂ ) ₂ H 3- (Oxa-5) -Ph O 4-Zb 4-45 iPr (CH ₂ ) ₂ H 4- (Oxa-5) -Ph O 4-Zb 4-46 iPr (CH ₂ ) ₂ H 3- (Thiz -2) -Ph O 4-Zb 4-47 iPr (CH ₂ ) ₂ H 4- (Thiz-2) -Ph O 4-Zb 4-48 iPr (CH ₂ ) ₂ H 3- (Thiz-4)- Ph O 4-Zb 4-49 iPr (CH ₂ ) ₂ H 4- (Thiz-4) -Ph O 4-Zb 4- 50 iPr (CH ₂ ) ₂ H 3- (Thiz-5) -Ph O 4- Zb 4-51 iPr (CH ₂ ) ₂ H 4- (Thiz-5) -Ph O 4-Zb 4-52 iPr (CH ₂ ) ₂ H 1-Me-2-Pyrr O 4-Zb 4-53 iPr ( CH ₂ ) ₂ H 1-Ph-2-Pyrr O 4-Zb 4-54 iPr (CH ₂ ) ₂ H 1-Bz-2-Pyrr O 4-Zb 4-55 iPr (CH ₂ ) ₂ H 5-Me -2-Fur O 4-Zb 4-56 iPr (CH ₂ ) ₂ H 5-Ph-2-Fur O 4-Zb 4-57 iPr (CH ₂ ) ₂ H 5-Me-2-Thi O 4-Zb 4-58 iPr (CH ₂ ) ₂ H 5-Ph-2-Thi O 4-Zb 4-59 iPr (CH ₂ ) ₂ H 5-Me-3-Thi O 4-Zb 4- 60 iPr (CH ₂ ) ₂ H 5-Ph-3-Thi O 4-Zb 4-61 iPr (CH ₂ ) ₂ H 1-Me-3-Pyza O 4-Zb 4-62 iPr (CH ₂ ) ₂ H 1-Ph-3- Pyza O 4-Zb 4-63 iPr (CH ₂ ) ₂ H 1-Me-2-Imid O 4-Zb 4-64 iPr (CH ₂ ) ₂ H 1-Ph-2-Imid O 4-Zb 4-65 iPr (CH ₂ ) ₂ H 1-Me-4-Imid O 4-Zb 4-66 iPr (CH ₂ ) ₂ H 1-Ph-4-Imid O 4-Zb 4-67 iPr (CH ₂ ) ₂ H 4 -Oxa O 4-Zb 4-68 iPr (CH ₂ ) ₂ H 5-Oxa O 4-Zb 4 -69 iPr (CH ₂ ) ₂ H 2-Me-4-Oxa O 4-Zb 4- 70 iPr (CH ₂ ) ₂ H 2-Ph-4-Oxa O 4-Zb 4- 71 iPr (CH ₂ ) ₂ H 2-Me-5-Oxa O 4-Zb 4-72 iPr (CH ₂ ) ₂ H 2-Ph-5-Oxa O 4-Zb 4- 73 iPr (CH ₂ ) ₂ H 4-Me-2-Ph -5-Oxa O 4-Zb 4- 74 iPr (CH ₂ ) ₂ H 5-Me-2-Ph-4-Oxa O 4-Zb 4-75 iPr (CH ₂ ) ₂ H 4-Thiz O 4-Zb 4-76 iPr (CH ₂ ) ₂ H 5-Thiz O 4-Zb 4-77 iPr (CH ₂ ) ₂ H 2-Me-4-Thiz O 4-Zb 4-78 iPr (CH ₂ ) ₂ H 2- Ph-4-Thiz O 4-Zb 4- 79 iPr (CH ₂ ) ₂ H 2-Me-5-Thiz O 4-Zb 4- 80 iPr (CH ₂ ) ₂ H 2-Ph-5-Thiz O 4- Zb 4-81 iPr (CH ₂ ) ₂ H 4-Me-2-Ph-5-Thiz O 4-Zb 4- 82 iPr (CH ₂ ) ₂ H 5-Me-2-Ph-4-Thiz O 4- Zb 4-83 iPr (CH ₂ ) ₂ H 1-Me-4-Pyza O 4-Zb 4- 84 iPr (CH ₂ ) ₂ H 1-Ph-4-Pyza O 4-Zb 4-85 iPr (CH ₂ ) ₂ H 2-Me-4-Isox O 4-Zb 4-86 iPr (CH ₂ ) ₂ H 2-Ph-4-Isox O 4-Zb 4-87 iPr (CH ₂ ) ₂ H 2-Pyr O 4 -Zb 4-88 iPr (CH ₂ ) ₂ H 3-Pyr O 4-Zb 4-89 iPr (CH ₂ ) ₂ H 4-Pyr O 4-Zb 4-90 iPr (CH ₂ ) ₂ H 3-Me- 5-Pyr O 4-Zb 4-91 iPr (CH ₂ ) ₂ H 3-Et-5-Pyr O 4-Zb 4-92 iPr (CH ₂ ) ₂ H 3-Ph-5-Pyr O 4-Zb 4 -93 iPr (CH ₂ ) ₂ H 2-Me-5-Pyr O 4-Zb 4-94 iPr (CH ₂ ) ₂ H 2-Et-5-Pyr O 4-Zb 4-95 iPr (CH ₂ ) ₂ H 2-Ph-5-Pyr O 4-Zb 4-96 iPr ( CH ₂ ) ₂ H 2-MeO-5-Pyr O 4-Zb 4-97 iPr (CH ₂ ) ₂ H 2-EtO-5-Pyr O 4-Zb 4-98 iPr (CH ₂ ) ₂ H 2-iPrO -5-Pyr O 4-Zb 4- 99 iPr (CH ₂ ) ₂ H 2-MeS-5-Pyr O 4-Zb 4-100 iPr (CH ₂ ) ₂ H 2-EtS-5-Pyr O 4-Zb 4-101 iPr (CH ₂ ) ₂ H 2-iPrS-5-Pyr O 4-Zb 4-102 iPr (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pyr O 4-Zb 4-103 iPr (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pyr O 4-Zb 4-104 iPr (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zb 4-105 iPr (CH ₂ ) ₂ H 2-Bz -5-Pyr O 4-Zb 4-106 iPr (CH ₂ ) ₂ H 2-PhO-5-Pyr O 4-Zb 4-107 iPr (CH ₂ ) ₂ H 2-PhS-5-Pyr O 4-Zb 4-108 iPr (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pyr O 4-Zb 4-109 iPr (CH ₂ ) ₂ H 3-Me-6-Pyr O 4-Zb 4-110 iPr (CH ₂ ) ₂ H 3-Ph-6-Pyr O 4-Zb 4-111 iPr (CH ₂ ) ₂ H 2-Me-6-Pyr O 4-Zb 4-112 iPr (CH ₂ ) ₂ H 2-Ph-6 -Pyr O 4-Zb 4-113 iPr (CH ₂ ) ₂ H 2-Me-4-Pym O 4-Zb 4-114 iPr (CH ₂ ) ₂ H 2-Ph-4-Pym O 4-Zb 4- 115 iPr (CH ₂ ) ₂ H 2-MeO-4-Pym O 4-Zb 4-116 iPr (CH ₂ ) ₂ H 2-EtO-4-Pym O 4-Zb 4-117 iPr (CH ₂ ) ₂ H 2-iPrO-4-Pym O 4-Zb 4-118 iPr (CH ₂ ) ₂ H 2-MeS-4-Pym O 4-Zb 4-119 iPr (CH ₂ ) ₂ H 2-EtS-4-Pym O 4-Zb 4-120 iPr (CH ₂ ) ₂ H 2-iPrS-4-Pym O 4-Zb 4-121 iPr (CH ₂ ) ₂ H 6-MeS-4-Pym O 4-Zb 4-122 iPr (CH ₂ ) ₂ H 6-EtS-4- Pym O 4-Zb 4-123 iPr (CH ₂ ) ₂ H 6-iPrS-4-Pym O 4-Zb 4-124 iPr (CH ₂ ) ₂ H 2-PhS-4-Pym O 4-Zb 4-125 iPr (CH ₂ ) ₂ H 2-MeSO ₂ -4-Pym O 4-Zb 4-126 iPr (CH ₂ ) ₂ H 2-EtSO ₂ -4-Pym O 4-Zb 4-127 iPr (CH ₂ ) ₂ H 2-iPrSO ₂ -4-Pym O 4-Zb 4-128 iPr (CH ₂ ) ₂ H 2-PhSO ₂ -4-Pym O 4-Zb 4-129 iPr (CH ₂ ) ₂ H 2-Me-5 -Pym O 4-Zb 4-130 iPr (CH ₂ ) ₂ H 2-Ph-5-Pym O 4-Zb 4-131 iPr (CH ₂ ) ₂ H 2-MeO-5-Pym O 4-Zb 4- 132 iPr (CH ₂ ) ₂ H 2-EtO-5-Pym O 4-Zb 4-133 iPr (CH ₂ ) ₂ H 2-iPrO-5-Pym O 4-Zb 4-134 iPr (CH ₂ ) ₂ H 2-MeS-5-Pym O 4-Zb 4-135 iPr (CH ₂ ) ₂ H 2-EtS-5-Pym O 4-Zb 4-136 iPr (CH ₂ ) ₂ H 2-iPrS-5-Pym O 4-Zb 4-137 iPr (CH ₂ ) ₂ H 2-PhS-5-Pym O 4-Zb 4-138 iPr (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pym O 4-Zb 4-139 iPr (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pym O 4-Zb 4-140 iPr (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pym O 4-Zb 4-141 iPr (CH ₂ ) ₂ H 2- PhSO ₂ -5-Pym O 4-Zb 4-142 iPr (CH ₂ ) ₂ H 2-Ind O 4-Zb 4-143 iPr (CH ₂ ) ₂ H 3-Ind O 4-Zb 4-144 iPr (CH ₂ ) ₂ H 1-Me-2-Ind O 4-Zb 4-145 iPr (CH ₂ ) ₂ H 1-Me-3-Ind O 4-Zb 4-146 iPr (CH ₂ ) ₂ H 2-Bimid O 4-Zb 4-147 iPr (CH ₂ ) ₂ H 2-Boxa O 4-Zb 4-148 iPr (CH ₂ ) ₂ H 2-Bthiz O 4-Zb 4-149 iPr (CH ₂ ) ₂ H 2-Quin O 4-Zb 4-150 iPr (CH ₂ ) ₂ H 3-Quin O 4-Zb 4-151 iPr (CH ₂ ) ₂ H 4-Quin O 4-Zb 4-152 iPr (CH ₂ ) ₂ H 1- iQuin O 4-Zb 4-153 iPr (CH ₂ ) ₂ H 3-iQuin O 4-Zb 4-154 iPr (CH ₂ ) ₂ H 4-iQuin O 4-Zb 4-155 iPr (CH ₂ ) ₂ H 3 -MeO-Ph O 4-Zb 4-156 iPr (CH ₂ ) ₂ H 4-MeO-Ph O 4-Zb 4-157 iPr (CH ₂ ) ₂ H 3-EtO-Ph O 4-Zb 4-158 iPr (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zb 4-159 iPr (CH ₂ ) ₂ H 3-iPrO-Ph O 4-Zb 4-160 iPr (CH ₂ ) ₂ H 4-iPrO-Ph O 4-Zb 4-161 iPr (CH ₂ ) ₂ H 3-MeS-Ph O 4-Zb 4-162 iPr (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zb 4-163 iPr (CH ₂ ) ₂ H 3-EtS-Ph O 4-Zb 4-164 iPr (CH ₂ ) ₂ H 4-EtS-Ph O 4-Zb 4-165 iPr (CH ₂ ) ₂ H 3-iPrS-Ph O 4-Zb 4- 166 iPr (CH ₂ ) ₂ H 4-iPrS-Ph O 4-Zb 4-167 iPr (CH ₂ ) ₂ H 3-MeSO ₂ -Ph O 4-Z b 4-168 iPr (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zb 4-169 iPr (CH ₂ ) ₂ H 3-EtSO ₂ -Ph O 4-Zb 4-170 iPr (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4-Zb 4-171 iPr (CH ₂ ) ₂ H 3-iPrSO ₂ -Ph O 4-Zb 4-172 iPr (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4- Zb 4-173 iPr (CH ₂ ) ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zb 4-174 iPr (CH ₂ ) ₂ H 4- (1-Me-Imid-4)- Ph O 4-Zb 4-175 iPr (CH ₂ ) ₂ H 1-Me-2-Ph-4-Imid O 4-Zb 4-176 iPr (CH ₂ ) ₂ H 1,4-di-Me-2- Ph-5-Imid O 4-Zb 4-177 iPr (CH ₂ ) ₂ H 1,5-di-Me-2-Ph-4-Imid O 4-Zb 4-178 iPr (CH ₂ ) ₂ H 3, 4-MdO-Ph O 4-Zb 4-179 iPr (CH ₂ ) ₂ H 4- (4-MeO-Ph) -Ph O 4-Zb 4-180 iPr (CH ₂ ) ₂ H 4- (3,4 -MdO-Ph) -Ph O 4-Zb 4-181 iPr (CH ₂ ) ₂ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zb 4-182 iPr (CH ₂ ) ₂ H 4- [ (Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 4-183 iPr (CH ₂ ) ₂ H 4- (PhSO ₂ NH) -Ph O 4-Zb 4-184 iPr (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 4-185 iPr (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ ] -Ph O 4-Zb 4-186 iPr (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 4-187 iPr (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 4-188 iPr (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4-Zb 4-189 i Pr (CH ₂ ) ₂ H 4- (4-Me-Ph) -Ph O 4-Zb 4-190 iPr (CH ₂ ) ₂ H 4- (4-F-Ph) -Ph O 4-Zb 4-191 iPr (CH ₂ ) ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 4-192 iPr (CH ₂ ) ₂ H 2- [4-Me-PhSO ₂ N (Me)]-5- Pyr O 4-Zb 4-193 iPr (CH ₂ ) ₂ H 2-HO-5-Pyr O 4-Zb 4-194 iPr (CH ₂ ) ₂ H 2-BzO-5-Pyr O 4-Zb 4-195 iPr (CH ₂ ) ₂ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zb 4-196 iPr (CH ₂ ) ₂ H 4- (2,4-di-MeO-Ph) -Ph O 4-Zb 4-197 iPr (CH ₂ ) ₂ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zb 4-198 iPr (CH ₂ ) ₂ H 3-HO-Ph O 4- Zb 4-199 iPr (CH ₂ ) ₂ H 4-HO-Ph O 4-Zb 4-200 iPr (CH ₂ ) ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 4-201 iPr (CH ₂ ) ₂ H 4-HO-3,5-di-Me-Ph O 4-Zb 4-202 iPr (CH ₂ ) ₂ H 3-AcO-Ph O 4-Zb 4 -203 iPr (CH ₂ ) ₂ H 4-AcO-Ph O 4-Zb ──────────────────────────────── ──.

[0094]

[Table 5] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 5- 1 H (CH ₂ ) ₂ H Ph O 4-Zc 5- 2 H (CH ₂ ) ₂ H 1-Np O 4-Zc 5- 3 H (CH ₂ ) ₂ H 2-Np O 4-Zc 5- 4 H (CH ₂ ) ₂ H 4-Me -Ph O 4-Zc 5--5 H (CH ₂ ) ₂ H 4-Et-Ph O 4-Zc 5- 6 H (CH ₂ ) ₂ H 3-iPr-Ph O 4-Zc 5- 7 H (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zc 5- 8 H (CH ₂ ) ₂ H 3-tBu-Ph O 4-Zc 5- 9 H (CH ₂ ) ₂ H 4-tBu-Ph O 4- Zc 5- 10 H (CH ₂ ) ₂ H 3-Cl-Ph O 4-Zc 5- 11 H (CH ₂ ) ₂ H 4-Cl-Ph O 4-Zc 5- 12 H (CH ₂ ) ₂ H 3 -Br-Ph O 4-Zc 5- 13 H (CH ₂ ) ₂ H 4-Br-Ph O 4-Zc 5- 14 H (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zc 5- 15 H (CH ₂ ) ₂ H 4-Ph-Ph O 4-Zc 5- 16 H (CH ₂ ) ₂ H 3-Bz-Ph O 4-Zc 5- 17 H (CH ₂ ) ₂ H 4-Bz-Ph O 4-Zc 5- 18 H (CH ₂ ) ₂ H 3-PhO-Ph O 4-Zc 5- 19 H (CH ₂ ) ₂ H 4-PhO-Ph O 4-Zc 5- 20 H (CH ₂ ) ₂ H 3-PhS-Ph O 4-Zc 5- 21 H (CH ₂ ) ₂ H 4-PhS-Ph O 4-Zc 5- 22 H (CH ₂ ) ₂ H 3-PhSO ₂ -Ph O 4-Zc 5- 23 H (CH ₂ ) ₂ H 4-PhSO ₂ -Ph O 4-Zc 5- 24 H (CH ₂ ) ₂ H 3- (Imid-1) -Ph O 4-Zc 5- 25 H (CH ₂ ) ₂ H 4- (Imid-1) -Ph O 4-Zc 5-26 H (CH ₂ ) ₂ H 3- (Imid-4) -Ph O 4-Zc 5-27 H (CH ₂ ) ₂ H 4- (Imid-4) -Ph O 4-Zc 5-28 H (CH ₂ ) ₂ H 3- (Fur -2) -Ph O 4-Zc 5-29 H (CH ₂ ) ₂ H 4- (Fur-2) -Ph O 4-Zc 5- 30 H (CH ₂ ) ₂ H 3- (Thi-2)- Ph O 4-Zc 5-31 H (CH ₂ ) ₂ H 4- (Thi-2) -Ph O 4-Zc 5-32 H (CH ₂ ) ₂ H 3- (Thi-3) -Ph O 4- Zc 5-33 H (CH ₂ ) ₂ H 4- (Thi-3) -Ph O 4-Zc 5-34 H (CH ₂ ) ₂ H 3- (Pyr-2) -Ph O 4-Zc 5-35 H (CH ₂ ) ₂ H 4- (Pyr-2) -Ph O 4-Zc 5-36 H (CH ₂ ) ₂ H 3- (Pyr-3) -Ph O 4-Zc 5-37 H (CH ₂ ) ₂ H 4- (Pyr-3) -Ph O 4-Zc 5-38 H (CH ₂ ) ₂ H 3- (Pyr-4) -Ph O 4-Zc 5-39 H (CH ₂ ) ₂ H 4 -(Pyr-4) -Ph O 4-Zc 5- 40 H (CH ₂ ) ₂ H 3- (Oxa-2) -Ph O 4-Zc 5-41 H (CH ₂ ) ₂ H 4- (Oxa- 2) -Ph O 4-Zc 5-42 H (CH ₂ ) ₂ H 3- (Oxa-4) -Ph O 4-Zc 5-43 H (CH ₂ ) ₂ H 4- (Oxa-4) -Ph O 4-Zc 5-44 H (CH ₂ ) ₂ H 3- (Oxa-5) -Ph O 4-Zc 5-45 H (CH ₂ ) ₂ H 4- (Oxa-5) -Ph O 4-Zc 5- 46 H (CH ₂ ) ₂ H 3- (Thiz- 2) -Ph O 4-Zc 5-47 H (CH ₂ ) ₂ H 4- (Thiz-2) -Ph O 4-Zc 5-48 H (CH ₂ ) ₂ H 3- (Thiz-4) -Ph O 4-Zc 5-49 H (CH ₂ ) ₂ H 4- (Thiz-4) -Ph O 4-Zc 5- 50 H (CH ₂ ) ₂ H 3- (Thiz-5) -Ph O 4-Zc 5-51 H (CH ₂ ) ₂ H 4- (Thiz-5) -Ph O 4-Zc 5-52 H (CH ₂ ) ₂ H 1-Me-2-Pyrr O 4-Zc 5-53 H (CH ₂ ) ₂ H 1-Ph-2-Pyrr O 4-Zc 5-54 H (CH ₂ ) ₂ H 1-Bz-2-Pyrr O 4-Zc 5-55 H (CH ₂ ) ₂ H 5-Me- 2-Fur O 4-Zc 5-56 H (CH ₂ ) ₂ H 5-Ph-2-Fur O 4-Zc 5-57 H (CH ₂ ) ₂ H 5-Me-2-Thi O 4-Zc 5 -58 H (CH ₂ ) ₂ H 5-Ph-2-Thi O 4-Zc 5-59 H (CH ₂ ) ₂ H 5-Me-3-Thi O 4-Zc 5- 60 H (CH ₂ ) ₂ H 5-Ph-3-Thi O 4-Zc 5-61 H (CH ₂ ) ₂ H 1-Me-3-Pyza O 4-Zc 5-62 H (CH ₂ ) ₂ H 1-Ph-3-Pyza O 4-Zc 5-63 H (CH ₂ ) ₂ H 1-Me-2-Imid O 4-Zc 5-64 H (CH ₂ ) ₂ H 1-Ph-2-Imid O 4-Zc 5-65 H (CH ₂ ) ₂ H 1-Me-4-Imid O 4-Zc 5-66 H (CH ₂ ) ₂ H 1-Ph-4-Imid O 4-Zc 5-67 H (CH ₂ ) ₂ H 4- Oxa O 4-Zc 5-68 H (CH ₂ ) ₂ H 5-Oxa O 4-Zc 5-69 H (CH ₂ ) ₂ H 2-Me-4-Oxa O 4-Zc 5-70 H (CH ₂ ) ₂ H 2-Ph-4-Oxa O 4-Zc 5-71 H (CH ₂ ) ₂ H 2-Me-5-Oxa O 4-Zc 5-72 H (CH ₂ ) ₂ H 2-P h-5-Oxa O 4-Zc 5-73 H (CH ₂ ) ₂ H 4-Me-2-Ph-5-Oxa O 4-Zc 5- 74 H (CH ₂ ) ₂ H 5-Me-2- Ph-4-Oxa O 4-Zc 5-75 H (CH ₂ ) ₂ H 4-Thiz O 4-Zc 5-76 H (CH ₂ ) ₂ H 5-Thiz O 4-Zc 5-77 H (CH ₂ ) ₂ H 2-Me-4-Thiz O 4-Zc 5-78 H (CH ₂ ) ₂ H 2-Ph-4-Thiz O 4-Zc 5-79 H (CH ₂ ) ₂ H 2-Me-5 -Thiz O 4-Zc 5-80 H (CH ₂ ) ₂ H 2-Ph-5-Thiz O 4-Zc 5-81 H (CH ₂ ) ₂ H 4-Me-2-Ph-5-Thiz O 4 -Zc 5-82 H (CH ₂ ) ₂ H 5-Me-2-Ph-4-Thiz O 4-Zc 5- 83 H (CH ₂ ) ₂ H 1-Me-4-Pyza O 4-Zc 5- 84 H (CH ₂ ) ₂ H 1-Ph-4-Pyza O 4-Zc 5-85 H (CH ₂ ) ₂ H 2-Me-4-Isox O 4-Zc 5-86 H (CH ₂ ) ₂ H 2-Ph-4-Isox O 4-Zc 5-87 H (CH ₂ ) ₂ H 2-Pyr O 4-Zc 5-88 H (CH ₂ ) ₂ H 3-Pyr O 4-Zc 5-89 H ( CH ₂ ) ₂ H 4-Pyr O 4-Zc 5-90 H (CH ₂ ) ₂ H 3-Me-5-Pyr O 4-Zc 5-91 H (CH ₂ ) ₂ H 3-Et-5-Pyr O 4-Zc 5-92 H (CH ₂ ) ₂ H 3-Ph-5-Pyr O 4-Zc 5-93 H (CH ₂ ) ₂ H 2-Me-5-Pyr O 4-Zc 5-94 H (CH ₂ ) ₂ H 2-Et-5-Pyr O 4-Zc 5-95 H (CH ₂ ) ₂ H 2-Ph-5-Pyr O 4-Zc 5-96 H (CH ₂ ) ₂ H 2- MeO-5-Pyr O 4-Zc 5-97 H (CH ₂ ) ₂ H 2-EtO-5-Pyr O 4-Zc 5-98 H (CH ₂ ) ₂ H 2-iPrO -5-Pyr O 4-Zc 5- 99 H (CH ₂ ) ₂ H 2-MeS-5-Pyr O 4-Zc 5-100 H (CH ₂ ) ₂ H 2-EtS-5-Pyr O 4-Zc 5-101 H (CH ₂ ) ₂ H 2-iPrS-5-Pyr O 4-Zc 5-102 H (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pyr O 4-Zc 5-103 H (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pyr O 4-Zc 5-104 H (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zc 5-105 H (CH ₂ ) ₂ H 2-Bz -5-Pyr O 4-Zc 5-106 H (CH ₂ ) ₂ H 2-PhO-5-Pyr O 4-Zc 5-107 H (CH ₂ ) ₂ H 2-PhS-5-Pyr O 4-Zc 5-108 H (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pyr O 4-Zc 5-109 H (CH ₂ ) ₂ H 3-Me-6-Pyr O 4-Zc 5-110 H (CH ₂ ) ₂ H 3-Ph-6-Pyr O 4-Zc 5-111 H (CH ₂ ) ₂ H 2-Me-6-Pyr O 4-Zc 5-112 H (CH ₂ ) ₂ H 2-Ph-6 -Pyr O 4-Zc 5-113 H (CH ₂ ) ₂ H 2-Me-4-Pym O 4-Zc 5-114 H (CH ₂ ) ₂ H 2-Ph-4-Pym O 4-Zc 5- 115 H (CH ₂ ) ₂ H 2-MeO-4-Pym O 4-Zc 5-116 H (CH ₂ ) ₂ H 2-EtO-4-Pym O 4-Zc 5-117 H (CH ₂ ) ₂ H 2-iPrO-4-Pym O 4-Zc 5-118 H (CH ₂ ) ₂ H 2-MeS-4-Pym O 4-Zc 5-119 H (CH ₂ ) ₂ H 2-EtS-4-Pym O 4-Zc 5-120 H (CH ₂ ) ₂ H 2-iPrS-4-Pym O 4-Zc 5-121 H (CH ₂ ) ₂ H 6-MeS-4-Pym O 4-Zc 5-122 H ( CH ₂ ) ₂ H 6-EtS-4-Pym O 4-Zc 5-123 H (CH ₂ ) ₂ H 6-iPrS-4-Pym O 4- Zc 5-124 H (CH ₂ ) ₂ H 2-PhS-4-Pym O 4-Zc 5-125 H (CH ₂ ) ₂ H 2-MeSO ₂ -4-Pym O 4-Zc 5-126 H (CH ₂ ) ₂ H 2-EtSO ₂ -4-Pym O 4-Zc 5-127 H (CH ₂ ) ₂ H 2-iPrSO ₂ -4-Pym O 4-Zc 5-128 H (CH ₂ ) ₂ H 2- PhSO ₂ -4-Pym O 4-Zc 5-129 H (CH ₂ ) ₂ H 2-Me-5-Pym O 4-Zc 5-130 H (CH ₂ ) ₂ H 2-Ph-5-Pym O 4 -Zc 5-131 H (CH ₂ ) ₂ H 2-MeO-5-Pym O 4-Zc 5-132 H (CH ₂ ) ₂ H 2-EtO-5-Pym O 4-Zc 5-133 H (CH ₂ ) ₂ H 2-iPrO-5-Pym O 4-Zc 5-134 H (CH ₂ ) ₂ H 2-MeS-5-Pym O 4-Zc 5-135 H (CH ₂ ) ₂ H 2-EtS- 5-Pym O 4-Zc 5-136 H (CH ₂ ) ₂ H 2-iPrS-5-Pym O 4-Zc 5-137 H (CH ₂ ) ₂ H 2-PhS-5-Pym O 4-Zc 5 -138 H (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pym O 4-Zc 5-139 H (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pym O 4-Zc 5-140 H (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pym O 4-Zc 5-141 H (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pym O 4-Zc 5-142 H (CH ₂ ) ₂ H 2-Ind O 4-Zc 5-143 H (CH ₂ ) ₂ H 3-Ind O 4-Zc 5-144 H (CH ₂ ) ₂ H 1-Me-2-Ind O 4-Zc 5-145 H (CH ₂ ) ₂ H 1-Me-3-Ind O 4-Zc 5-146 H (CH ₂ ) ₂ H 2-Bimid O 4-Zc 5-147 H (CH ₂ ) ₂ H 2-Boxa O 4-Zc 5-148 H (CH ₂ ) ₂ H 2-Bthiz O 4-Zc 5-149 H (CH ₂ ) ₂ H 2-Quin O 4-Zc 5-150 H (CH ₂ ) ₂ H 3-Quin O 4-Zc 5-151 H (CH ₂ ) ₂ H 4-Quin O 4-Zc 5-152 H (CH ₂ ) ₂ H 1-iQuin O 4-Zc 5-153 H (CH ₂ ) ₂ H 3-iQuin O 4-Zc 5-154 H (CH ₂ ) ₂ H 4-iQuin O 4-Zc 5-155 H (CH ₂ ) ₂ H 3-MeO-Ph O 4-Zc 5-156 H (CH ₂ ) ₂ H 4-MeO-Ph O 4-Zc 5-157 H (CH ₂ ) ₂ H 3-EtO-Ph O 4- Zc 5-158 H (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zc 5-159 H (CH ₂ ) ₂ H 3-iPrO-Ph O 4-Zc 5-160 H (CH ₂ ) ₂ H 4 -iPrO-Ph O 4-Zc 5-161 H (CH ₂ ) ₂ H 3-MeS-Ph O 4-Zc 5-162 H (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zc 5-163 H (CH ₂ ) ₂ H 3-EtS-Ph O 4-Zc 5-164 H (CH ₂ ) ₂ H 4-EtS-Ph O 4-Zc 5-165 H (CH ₂ ) ₂ H 3-iPrS-Ph O 4-Zc 5-166 H (CH ₂ ) ₂ H 4-iPrS-Ph O 4-Zc 5-167 H (CH ₂ ) ₂ H 3-MeSO ₂ -Ph O 4-Zc 5-168 H (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zc 5-169 H (CH ₂ ) ₂ H 3-EtSO ₂ -Ph O 4-Zc 5-170 H (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4 -Zc 5-171 H (CH ₂ ) ₂ H 3-iPrSO ₂ -Ph O 4-Zc 5-172 H (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Zc 5-173 H (CH ₂ ) ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zc 5-174 H (CH ₂ ) ₂ H 4- (1-Me-Imid-4) -Ph O 4-Zc 5-175 H (CH ₂ ) ₂ H 1-Me-2-Ph-4-Imid O 4-Zc 5-176 H (CH ₂ ) ₂ H 1,4-di-Me-2-Ph-5-Imid O 4-Zc 5-177 H (CH ₂ ) ₂ H 1,5-di-Me- 2-Ph-4-Imid O 4-Zc 5-178 H (CH ₂ ) ₂ H 3,4-MdO-Ph O 4-Zc 5-179 H (CH ₂ ) ₂ H 4- (4-MeO-Ph ) -Ph O 4-Zc 5-180 H (CH ₂ ) ₂ H 4- (3,4-MdO-Ph) -Ph O 4-Zc 5-181 H (CH ₂ ) ₂ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zc 5-182 H (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zc 5-183 H (CH ₂ ) ₂ H 4- (PhSO ₂ NH) -Ph O 4-Zc 5-184 H (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zc 5-185 H (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ ] -Ph O 4-Zc 5-186 H (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zc 5-187 H (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zc 5-188 H (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ NH]- Ph O 4-Zc 5-189 H (CH ₂ ) ₂ H 4- (4-Me-Ph) -Ph O 4-Zc 5-190 H (CH ₂ ) ₂ H 4- (4-F-Ph)- Ph O 4-Zc 5-191 H (CH ₂ ) ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zc 5-192 H (CH ₂ ) ₂ H 2- [4-Me-PhSO ₂ N (Me)]-5-Pyr O 4-Zc 5-193 H (CH ₂ ) ₂ H 2-HO-5-Pyr O 4-Zc 5-194 H (CH ₂ ) ₂ H 2-BzO-5- Pyr O 4-Zc 5-195 H (CH ₂ ) ₂ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zc 5-196 H (CH ₂ ) ₂ H 4- (2,4-di -MeO-Ph) -Ph O 4-Zc 5-197 H (CH ₂ ) ₂ H 4- (2,5-d i-MeO-Ph) -Ph O 4-Zc 5-198 H (CH ₂ ) ₂ H 3-HO-Ph O 4-Zc 5-199 H (CH ₂ ) ₂ H 4-HO-Ph O 4-Zc 5-200 H (CH ₂ ) ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zc 5-201 H (CH ₂ ) ₂ H 4-HO-3,5 -di-Me-Ph O 4-Zc 5-202 H (CH ₂ ) ₂ H 3-AcO-Ph O 4-Zc 5-203 H (CH ₂ ) ₂ H 4-AcO-Ph O 4-Zc ── ────────────────────────────────.

[0095]

[Table 6] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 6-1 Me (CH ₂ ) ₂ H Ph O 4-Zc 6- 2 Me (CH ₂ ) ₂ H 1-Np O 4-Zc 6- 3 Me (CH ₂ ) ₂ H 2-Np O 4-Zc 6- 4 Me (CH ₂ ) ₂ H 4-Me -Ph O 4-Zc 6- 5 Me (CH ₂ ) ₂ H 4-Et-Ph O 4-Zc 6- 6 Me (CH ₂ ) ₂ H 3-iPr-Ph O 4-Zc 6- 7 Me (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zc 6-8 Me (CH ₂ ) ₂ H 3-tBu-Ph O 4-Zc 6-9 Me (CH ₂ ) ₂ H 4-tBu-Ph O 4- Zc 6-10 Me (CH ₂ ) ₂ H 3-Cl-Ph O 4-Zc 6-11 Me (CH ₂ ) ₂ H 4-Cl-Ph O 4-Zc 6-12 Me (CH ₂ ) ₂ H 3 -Br-Ph O 4-Zc 6- 13 Me (CH ₂ ) ₂ H 4-Br-Ph O 4-Zc 6- 14 Me (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zc 6- 15 Me (CH ₂ ) ₂ H 4-Ph-Ph O 4-Zc 6-16 Me (CH ₂ ) ₂ H 3-Bz-Ph O 4-Zc 6-17 Me (CH ₂ ) ₂ H 4-Bz-Ph O 4-Zc 6-18 Me (CH ₂ ) ₂ H 3-PhO-Ph O 4-Zc 6-19 Me (CH ₂ ) ₂ H 4-PhO-Ph O 4-Zc 6-20 Me (CH ₂ ) ₂ H 3-PhS-Ph O 4-Zc 6-21 Me (CH ₂ ) ₂ H 4-PhS-Ph O 4-Zc 6-22 Me (CH ₂ ) ₂ H 3-PhSO ₂ -Ph O 4-Zc 6- 23 Me (CH ₂ ) ₂ H 4-PhSO _2- Ph O 4-Zc 6- 24 Me (CH ₂ ) ₂ H 3- (Imid-1) -Ph O 4-Zc 6- 25 Me (CH ₂ ) ₂ H 4- (Imid-1) -Ph O 4- Zc 6- 26 Me (CH ₂ ) ₂ H 3- (Imid-4) -Ph O 4-Zc 6- 27 Me (CH ₂ ) ₂ H 4- (Imid-4) -Ph O 4-Zc 6- 28 Me (CH ₂ ) ₂ H 3- (Fur-2) -Ph O 4-Zc 6- 29 Me (CH ₂ ) ₂ H 4- (Fur-2) -Ph O 4-Zc 6-30 Me (CH ₂ ) ₂ H 3- (Thi-2) -Ph O 4-Zc 6- 31 Me (CH ₂ ) ₂ H 4- (Thi-2) -Ph O 4-Zc 6- 32 Me (CH ₂ ) ₂ H 3 -(Thi-3) -Ph O 4-Zc 6- 33 Me (CH ₂ ) ₂ H 4- (Thi-3) -Ph O 4-Zc 6- 34 Me (CH ₂ ) ₂ H 3- (Pyr- 2) -Ph O 4-Zc 6- 35 Me (CH ₂ ) ₂ H 4- (Pyr-2) -Ph O 4-Zc 6- 36 Me (CH ₂ ) ₂ H 3- (Pyr-3) -Ph O 4-Zc 6- 37 Me (CH ₂ ) ₂ H 4- (Pyr-3) -Ph O 4-Zc 6- 38 Me (CH ₂ ) ₂ H 3- (Pyr-4) -Ph O 4-Zc 6- 39 Me (CH ₂ ) ₂ H 4- (Pyr-4) -Ph O 4-Zc 6-40 Me (CH ₂ ) ₂ H 3- (Oxa-2) -Ph O 4-Zc 6- 41 Me (CH ₂ ) ₂ H 4- (Oxa-2) -Ph O 4-Zc 6- 42 Me (CH ₂ ) ₂ H 3- (Oxa-4) -Ph O 4-Zc 6- 43 Me (CH ₂ ) ₂ H 4- (Oxa-4) -Ph O 4-Zc 6-44 Me (CH ₂ ) ₂ H 3- (Oxa-5) -Ph O 4-Zc 6- 45 Me (CH ₂ ) ₂ H 4- ( Oxa-5) -Ph O 4-Zc 6- 46 Me (CH ₂ ) ₂ H 3- (Thiz-2) -Ph O 4-Zc 6- 47 Me (CH ₂ ) ₂ H 4- (Thiz-2) -Ph O 4-Zc 6- 48 Me (CH ₂ ) ₂ H 3- (Thiz-4) -Ph O 4-Zc 6- 49 Me (CH ₂ ) ₂ H 4- (Thiz-4) -Ph O 4 -Zc 6-50 Me (CH ₂ ) ₂ H 3- (Thiz-5) -Ph O 4-Zc 6- 51 Me (CH ₂ ) ₂ H 4- (Thiz-5) -Ph O 4-Zc 6- 52 Me (CH ₂ ) ₂ H 1-Me-2-Pyrr O 4-Zc 6- 53 Me (CH ₂ ) ₂ H 1-Ph-2-Pyrr O 4-Zc 6- 54 Me (CH ₂ ) ₂ H 1-Bz-2-Pyrr O 4-Zc 6- 55 Me (CH ₂ ) ₂ H 5-Me-2-Fur O 4-Zc 6- 56 Me (CH ₂ ) ₂ H 5-Ph-2-Fur O 4-Zc 6- 57 Me (CH ₂ ) ₂ H 5-Me-2-Thi O 4-Zc 6- 58 Me (CH ₂ ) ₂ H 5-Ph-2-Thi O 4-Zc 6- 59 Me ( CH ₂ ) ₂ H 5-Me-3-Thi O 4-Zc 6-60 Me (CH ₂ ) ₂ H 5-Ph-3-Thi O 4-Zc 6-61 Me (CH ₂ ) ₂ H 1-Me -3-Pyza O 4-Zc 6- 62 Me (CH ₂ ) ₂ H 1-Ph-3-Pyza O 4-Zc 6- 63 Me (CH ₂ ) ₂ H 1-Me-2-Imid O 4-Zc 6- 64 Me (CH ₂ ) ₂ H 1-Ph-2-Imid O 4-Zc 6- 65 Me (CH ₂ ) ₂ H 1-Me-4-Imid O 4-Zc 6- 66 Me (CH ₂ ) ₂ H 1-Ph-4-Imid O 4-Zc 6- 67 Me (CH ₂ ) ₂ H 4-Oxa O 4-Zc 6- 68 Me (CH ₂ ) ₂ H 5-Oxa O 4-Zc 6- 69 Me (CH ₂ ) ₂ H 2-Me-4-Oxa O 4-Zc 6- 70 Me (CH ₂ ) ₂ H 2-Ph-4-Ox a O 4-Zc 6- 71 Me (CH ₂ ) ₂ H 2-Me-5-Oxa O 4-Zc 6- 72 Me (CH ₂ ) ₂ H 2-Ph-5-Oxa O 4-Zc 6- 73 Me (CH ₂ ) ₂ H 4-Me-2-Ph-5-Oxa O 4-Zc 6- 74 Me (CH ₂ ) ₂ H 5-Me-2-Ph-4-Oxa O 4-Zc 6- 75 Me (CH ₂ ) ₂ H 4-Thiz O 4-Zc 6- 76 Me (CH ₂ ) ₂ H 5-Thiz O 4-Zc 6- 77 Me (CH ₂ ) ₂ H 2-Me-4-Thiz O 4 -Zc 6- 78 Me (CH ₂ ) ₂ H 2-Ph-4-Thiz O 4-Zc 6- 79 Me (CH ₂ ) ₂ H 2-Me-5-Thiz O 4-Zc 6- 80 Me (CH ₂ ) ₂ H 2-Ph-5-Thiz O 4-Zc 6- 81 Me (CH ₂ ) ₂ H 4-Me-2-Ph-5-Thiz O 4-Zc 6- 82 Me (CH ₂ ) ₂ H 5-Me-2-Ph-4-Thiz O 4-Zc 6- 83 Me (CH ₂ ) ₂ H 1-Me-4-Pyza O 4-Zc 6- 84 Me (CH ₂ ) ₂ H 1-Ph- 4-Pyza O 4-Zc 6- 85 Me (CH ₂ ) ₂ H 2-Me-4-Isox O 4-Zc 6- 86 Me (CH ₂ ) ₂ H 2-Ph-4-Isox O 4-Zc 6 -87 Me (CH ₂ ) ₂ H 2-Pyr O 4-Zc 6- 88 Me (CH ₂ ) ₂ H 3-Pyr O 4-Zc 6- 89 Me (CH ₂ ) ₂ H 4-Pyr O 4-Zc 6- 90 Me (CH ₂ ) ₂ H 3-Me-5-Pyr O 4-Zc 6- 91 Me (CH ₂ ) ₂ H 3-Et-5-Pyr O 4-Zc 6- 92 Me (CH ₂ ) ₂ H 3-Ph-5-Pyr O 4-Zc 6- 93 Me (CH ₂ ) ₂ H 2-Me-5-Pyr O 4-Zc 6- 94 Me (CH ₂ ) ₂ H 2-Et-5- Pyr O 4-Zc 6- 95 Me (CH ₂ ) ₂ H 2-Ph-5-Pyr O 4-Zc 6- 96 Me (CH ₂ ) ₂ H 2-MeO-5-Pyr O 4-Zc 6-97 Me (CH ₂ ) ₂ H 2-EtO-5-Pyr O 4-Zc 6-98 Me (CH ₂ ) ₂ H 2- iPrO-5-Pyr O 4-Zc 6- 99 Me (CH ₂ ) ₂ H 2-MeS-5-Pyr O 4-Zc 6-100 Me (CH ₂ ) ₂ H 2-EtS-5-Pyr O 4- Zc 6-101 Me (CH ₂ ) ₂ H 2-iPrS-5-Pyr O 4-Zc 6-102 Me (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pyr O 4-Zc 6-103 Me (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pyr O 4-Zc 6-104 Me (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zc 6-105 Me (CH ₂ ) ₂ H 2- Bz-5-Pyr O 4-Zc 6-106 Me (CH ₂ ) ₂ H 2-PhO-5-Pyr O 4-Zc 6-107 Me (CH ₂ ) ₂ H 2-PhS-5-Pyr O 4- Zc 6-108 Me (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pyr O 4-Zc 6-109 Me (CH ₂ ) ₂ H 3-Me-6-Pyr O 4-Zc 6-110 Me (CH ₂ ) ₂ H 3-Ph-6-Pyr O 4-Zc 6-111 Me (CH ₂ ) ₂ H 2-Me-6-Pyr O 4-Zc 6-112 Me (CH ₂ ) ₂ H 2-Ph- 6-Pyr O 4-Zc 6-113 Me (CH ₂ ) ₂ H 2-Me-4-Pym O
4-Zc 6-114 Me (CH ₂ ) ₂ H 2-Ph-4-Pym O 4-Zc 6-115 Me (CH ₂ ) ₂ H 2-MeO-4-Pym O 4-Zc 6-116 Me ( CH ₂ ) ₂ H 2-EtO-4-Pym O 4-Zc 6-117 Me (CH ₂ ) ₂ H 2-iPrO-4-Pym O 4-Zc 6-118 Me (CH ₂ ) ₂ H 2-MeS -4-Pym O 4-Zc 6-119 Me (CH ₂ ) ₂ H 2-EtS-4-Pym O 4-Zc 6-120 Me (CH ₂ ) ₂ H 2-iPrS-4-Pym O 4-Zc 6-121 Me (CH ₂ ) ₂ H 6-MeS-4-Pym O 4-Zc 6-122 Me (CH ₂ ) ₂ H 6-EtS-4-Pym O 4-Zc 6-123 Me (CH ₂ ) ₂ H 6-iPrS-4-Pym O 4-Zc 6-124 Me (CH ₂ ) ₂ H 2-PhS-4-Pym O 4-Zc 6-125 Me (CH ₂ ) ₂ H 2-MeSO ₂ -4 -Pym O 4-Zc 6-126 Me (CH ₂ ) ₂ H 2-EtSO ₂ -4-Pym O 4-Zc 6-127 Me (CH ₂ ) ₂ H 2-iPrSO ₂ -4-Pym O 4-Zc 6-128 Me (CH ₂ ) ₂ H 2-PhSO ₂ -4-Pym O 4-Zc 6-129 Me (CH ₂ ) ₂ H 2-Me-5-Pym O 4-Zc 6-130 Me (CH ₂ ) ₂ H 2-Ph-5-Pym O 4-Zc 6-131 Me (CH ₂ ) ₂ H 2-MeO-5-Pym O 4-Zc 6-132 Me (CH ₂ ) ₂ H 2-EtO-5 -Pym O 4-Zc 6-133 Me (CH ₂ ) ₂ H 2-iPrO-5-Pym O 4-Zc 6-134 Me (CH ₂ ) ₂ H 2-MeS-5-Pym O 4-Zc 6- 135 Me (CH ₂ ) ₂ H 2-EtS-5-Pym O 4-Zc 6-136 Me (CH ₂ ) ₂ H 2-iPrS-5-Pym O 4-Zc 6-137 Me (CH ₂ ) ₂ H 2-PhS-5-Pym O 4-Zc 6-138 Me (CH ₂ ) ₂ H 2-MeSO ₂ -5-Pym O 4-Zc 6-139 Me (CH ₂ ) ₂ H 2-EtSO ₂ -5-Pym O 4-Zc 6-140 Me (CH ₂ ) ₂ H 2-iPrSO ₂ -5-Pym O 4-Zc 6-141 Me (CH ₂ ) ₂ H 2-PhSO ₂ -5-Pym O 4-Zc 6-142 Me (CH ₂ ) ₂ H 2-Ind O 4-Zc 6-143 Me (CH ₂ ) ₂ H 3-Ind O 4-Zc 6-144 Me (CH ₂ ) ₂ H 1-Me-2-Ind O 4-Zc 6-145 Me (CH ₂ ) ₂ H 1-Me-3 -Ind O 4-Zc 6-146 Me (CH ₂ ) ₂ H 2-Bimid O 4-Zc 6-147 Me (CH ₂ ) ₂ H 2-Boxa O 4-Zc 6-148 Me (CH ₂ ) ₂ H 2-Bthiz O 4-Zc 6-149 Me (CH ₂ ) ₂ H 2-Quin O 4-Zc 6-150 Me (CH ₂ ) ₂ H 3-Quin O 4-Zc 6-151 Me (CH ₂ ) ₂ H 4-Quin O 4-Zc 6-152 Me (CH ₂ ) ₂ H 1-iQuin O 4-Zc 6-153 Me (CH ₂ ) ₂ H 3-iQuin O 4-Zc 6-154 Me (CH ₂ ) ₂ H 4-iQuin O 4-Zc 6-155 Me (CH ₂ ) ₂ H 3-MeO-Ph O 4-Zc 6-156 Me (CH ₂ ) ₂ H 4-MeO-Ph O 4-Zc 6-157 Me (CH ₂ ) ₂ H 3-EtO-Ph O 4-Zc 6-158 Me (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zc 6-159 Me (CH ₂ ) ₂ H 3-iPrO-Ph O 4-Zc 6-160 Me (CH ₂ ) ₂ H 4-iPrO-Ph O 4-Zc 6-161 Me (CH ₂ ) ₂ H 3-MeS-Ph O 4-Zc 6-162 Me (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zc 6-163 Me (CH ₂ ) ₂ H 3-EtS-Ph O 4-Zc 6-164 Me (CH ₂ ) ₂ H 4-EtS-Ph O 4-Zc 6 -165 Me (CH ₂ ) ₂ H 3-iPrS-Ph O 4-Zc 6 -166 Me (CH ₂ ) ₂ H 4-iPrS-Ph O 4-Zc 6-167 Me (CH ₂ ) ₂ H 3-MeSO ₂ -Ph O 4-Zc 6-168 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zc 6-169 Me (CH ₂ ) ₂ H 3-EtSO ₂ -Ph O 4-Zc 6-170 Me (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4-Zc 6-171 Me (CH ₂ ) ₂ H 3-iPrSO ₂ -Ph O 4-Zc 6-172 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Zc 6-173 Me (CH ₂ ) ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zc 6-174 Me (CH ₂ ) ₂ H 4- (1-Me -Imid-4) -Ph O 4-Zc 6-175 Me (CH ₂ ) ₂ H 1-Me-2-Ph-4-Imid O 4-Zc 6-176 Me (CH ₂ ) ₂ H 1,4- di-Me-2-Ph-5-Imid O 4-Zc 6-177 Me (CH ₂ ) ₂ H 1,5-di-Me-2-Ph-4-Imid O 4-Zc 6-178 Me (CH ₂ ) ₂ H 3,4-MdO-Ph O 4-Zc 6-179 Me (CH ₂ ) ₂ H 4- (4-MeO-Ph) -Ph O 4-Zc 6-180 Me (CH ₂ ) ₂ H 4- (3,4-MdO-Ph) -Ph O 4-Zc 6-181 Me (CH ₂ ) ₂ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zc 6-182 Me (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zc 6-183 Me (CH ₂ ) ₂ H 4- (PhSO ₂ NH) -Ph O 4-Zc 6-184 Me (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zc 6-185 Me (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ ] -Ph O 4 -Zc 6-186 Me (CH ₂ ) ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zc 6-187 Me (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zc 6-188 Me (CH ₂ ) ₂ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4- Zc 6-189 Me (CH ₂ ) ₂ H 4- (4-Me-Ph) -Ph O 4-Zc 6-190 Me (CH ₂ ) ₂ H 4- (4-F-Ph) -Ph O 4- Zc 6-191 Me (CH ₂ ) ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zc 6-192 Me (CH ₂ ) ₂ H 2- [4-Me-PhSO ₂ N (Me) ] -5-Pyr O 4-Zc 6-193 Me (CH ₂ ) ₂ H 2-HO-5-Pyr O 4-Zc 6-194 Me (CH ₂ ) ₂ H 2-BzO-5-Pyr O 4- Zc 6-195 Me (CH ₂ ) ₂ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zc 6-196 Me (CH ₂ ) ₂ H 4- (2,4-di-MeO-Ph ) -Ph O 4-Zc 6-197 Me (CH ₂ ) ₂ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zc 6-198 Me (CH ₂ ) ₂ H 3-HO- Ph O 4-Zc 6-199 Me (CH ₂ ) ₂ H 4-HO-Ph O 4-Zc 6-200 Me (CH ₂ ) ₂ H 5-AcO-2-HO-3,4,6-tri- Me-Ph O 4-Zc 6-201 Me (CH ₂ ) ₂ H 4-HO-3,5-di-Me-Ph O 4-Zc 6-202 Me (CH ₂ ) ₂ H 3-AcO-Ph O 4-Zc 6-203 Me (CH ₂ ) ₂ H 4-AcO-Ph O 4-Zc ──────────────────────────── ──────.

[0096]

[Table 7] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 7-1 H (CH ₂ ) ₃ H Ph O 4-Zb 7- 2 H (CH ₂ ) ₃ H 1-Np O 4-Zb 7- 3 H (CH ₂ ) ₃ H 2-Np O 4-Zb 7- 4 H (CH ₂ ) ₃ H 4-Me -Ph O 4-Zb 7-5 H (CH ₂ ) ₃ H 4-Et-Ph O 4-Zb 7-6 H (CH ₂ ) ₃ H 3-iPr-Ph O 4-Zb 7- 7 H (CH ₂ ) ₃ H 4-iPr-Ph O 4-Zb 7-8 H (CH ₂ ) ₃ H 3-tBu-Ph O 4-Zb 7-9 H (CH ₂ ) ₃ H 4-tBu-Ph O 4- Zb 7-10 H (CH ₂ ) ₃ H 3-Cl-Ph O 4-Zb 7-11 H (CH ₂ ) ₃ H 4-Cl-Ph O 4-Zb 7-12 H (CH ₂ ) ₃ H 3 -Br-Ph O 4-Zb 7-13 H (CH ₂ ) ₃ H 4-Br-Ph O 4-Zb 7-14 H (CH ₂ ) ₃ H 3-Ph-Ph O 4-Zb 7-15 H (CH ₂ ) ₃ H 4-Ph-Ph O 4-Zb 7-16 H (CH ₂ ) ₃ H 3-Bz-Ph O 4-Zb 7-17 H (CH ₂ ) ₃ H 4-Bz-Ph O 4-Zb 7-18 H (CH ₂ ) ₃ H 3-PhO-Ph O 4-Zb 7-19 H (CH ₂ ) ₃ H 4-PhO-Ph O 4-Zb 7-20 H (CH ₂ ) ₃ H 3-PhS-Ph O 4-Zb 7-21 H (CH ₂ ) ₃ H 4-PhS-Ph O 4-Zb 7- 22 H (CH ₂ ) ₃ H 3-PhSO ₂ -Ph O 4-Zb 7- 23 H (CH ₂ ) ₃ H 4-PhSO ₂ -Ph O 4-Zb 7- 24 H (CH ₂ ) ₃ H 3- (Imid-1) -Ph O 4-Zb 7-25 H (CH ₂ ) ₃ H 4- (Imid-1) -Ph O 4-Zb 7- 26 H (CH ₂ ) ₃ H 3- (Imid-4) -Ph O 4-Zb 7- 27 H (CH ₂ ) ₃ H 4- (Imid-4) -Ph O 4-Zb 7- 28 H (CH ₂ ) ₃ H 3- (Fur -2) -Ph O 4-Zb 7- 29 H (CH ₂ ) ₃ H 4- (Fur-2) -Ph O 4-Zb 7-30 H (CH ₂ ) ₃ H 3- (Thi-2)- Ph O 4-Zb 7- 31 H (CH ₂ ) ₃ H 4- (Thi-2) -Ph O 4-Zb 7- 32 H (CH ₂ ) ₃ H 3- (Thi-3) -Ph O 4- Zb 7- 33 H (CH ₂ ) ₃ H 4- (Thi-3) -Ph O 4-Zb 7- 34 H (CH ₂ ) ₃ H 3- (Pyr-2) -Ph O 4-Zb 7- 35 H (CH ₂ ) ₃ H 4- (Pyr-2) -Ph O 4-Zb 7- 36 H (CH ₂ ) ₃ H 3- (Pyr-3) -Ph O 4-Zb 7- 37 H (CH ₂ ) ₃ H 4- (Pyr-3) -Ph O 4-Zb 7- 38 H (CH ₂ ) ₃ H 3- (Pyr-4) -Ph O 4-Zb 7- 39 H (CH ₂ ) ₃ H 4 -(Pyr-4) -Ph O 4-Zb 7-40 H (CH ₂ ) ₃ H 3- (Oxa-2) -Ph O 4-Zb 7- 41 H (CH ₂ ) ₃ H 4- (Oxa- 2) -Ph O 4-Zb 7- 42 H (CH ₂ ) ₃ H 3- (Oxa-4) -Ph O 4-Zb 7- 43 H (CH ₂ ) ₃ H 4- (Oxa-4) -Ph O 4-Zb 7- 44 H (CH ₂ ) ₃ H 3- (Oxa-5) -Ph O 4-Zb 7- 45 H (CH ₂ ) ₃ H 4- (Oxa-5) -Ph O 4-Zb 7- 46 H (CH ₂ ) ₃ H 3- (Thiz- 2) -Ph O 4-Zb 7- 47 H (CH ₂ ) ₃ H 4- (Thiz-2) -Ph O 4-Zb 7- 48 H (CH ₂ ) ₃ H 3- (Thiz-4) -Ph O 4-Zb 7- 49 H (CH ₂ ) ₃ H 4- (Thiz-4) -Ph O 4-Zb 7-50 H (CH ₂ ) ₃ H 3- (Thiz-5) -Ph O 4-Zb 7- 51 H (CH ₂ ) ₃ H 4- (Thiz-5) -Ph O 4-Zb 7- 52 H (CH ₂ ) ₃ H 1-Me-2-Pyrr O 4-Zb 7- 53 H (CH ₂ ) ₃ H 1-Ph-2-Pyrr O 4-Zb 7- 54 H (CH ₂ ) ₃ H 1-Bz-2-Pyrr O 4-Zb 7- 55 H (CH ₂ ) ₃ H 5-Me- 2-Fur O 4-Zb 7- 56 H (CH ₂ ) ₃ H 5-Ph-2-Fur O 4-Zb 7- 57 H (CH ₂ ) ₃ H 5-Me-2-Thi O 4-Zb 7 -58 H (CH ₂ ) ₃ H 5-Ph-2-Thi O 4-Zb 7-59 H (CH ₂ ) ₃ H 5-Me-3-Thi O 4-Zb 7-60 H (CH ₂ ) ₃ H 5-Ph-3-Thi O 4-Zb 7- 61 H (CH ₂ ) ₃ H 1-Me-3-Pyza O 4-Zb 7- 62 H (CH ₂ ) ₃ H 1-Ph-3-Pyza O 4-Zb 7- 63 H (CH ₂ ) ₃ H 1-Me-2-Imid O 4-Zb 7- 64 H (CH ₂ ) ₃ H 1-Ph-2-Imid O 4-Zb 7- 65 H (CH ₂ ) ₃ H 1-Me-4-Imid O 4-Zb 7- 66 H (CH ₂ ) ₃ H 1-Ph-4-Imid O 4-Zb 7- 67 H (CH ₂ ) ₃ H 4- Oxa O 4-Zb 7- 68 H (CH ₂ ) ₃ H 5-Oxa O 4-Zb 7- 69 H (CH ₂ ) ₃ H 2-Me-4-Oxa O 4-Zb 7- 70 H (CH ₂ ) ₃ H 2-Ph-4-Oxa O 4-Zb 7- 71 H (CH ₂ ) ₃ H 2-Me-5-Oxa O 4-Zb 7- 72 H (CH ₂ ) ₃ H 2-P h-5-Oxa O 4-Zb 7- 73 H (CH ₂ ) ₃ H 4-Me-2-Ph-5-Oxa O 4-Zb 7- 74 H (CH ₂ ) ₃ H 5-Me-2- Ph-4-Oxa O 4-Zb 7- 75 H (CH ₂ ) ₃ H 4-Thiz O 4-Zb 7- 76 H (CH ₂ ) ₃ H 5-Thiz O 4-Zb 7- 77 H (CH ₂ ) ₃ H 2-Me-4-Thiz O 4-Zb 7- 78 H (CH ₂ ) ₃ H 2-Ph-4-Thiz O 4-Zb 7- 79 H (CH ₂ ) ₃ H 2-Me-5 -Thiz O 4-Zb 7- 80 H (CH ₂ ) ₃ H 2-Ph-5-Thiz O 4-Zb 7- 81 H (CH ₂ ) ₃ H 4-Me-2-Ph-5-Thiz O 4 -Zb 7- 82 H (CH ₂ ) ₃ H 5-Me-2-Ph-4-Thiz O 4-Zb 7- 83 H (CH ₂ ) ₃ H 1-Me-4-Pyza O 4-Zb 7- 84 H (CH ₂ ) ₃ H 1-Ph-4-Pyza O 4-Zb 7- 85 H (CH ₂ ) ₃ H 2-Me-4-Isox O 4-Zb 7-86 H (CH ₂ ) ₃ H 2-Ph-4-Isox O 4-Zb 7-87 H (CH ₂ ) ₃ H 2-Pyr O 4-Zb 7-88 H (CH ₂ ) ₃ H 3-Pyr O 4-Zb 7-89 H ( CH ₂ ) ₃ H 4-Pyr O 4-Zb 7- 90 H (CH ₂ ) ₃ H 3-Me-5-Pyr O 4-Zb 7- 91 H (CH ₂ ) ₃ H 3-Et-5-Pyr O 4-Zb 7- 92 H (CH ₂ ) ₃ H 3-Ph-5-Pyr O 4-Zb 7- 93 H (CH ₂ ) ₃ H 2-Me-5-Pyr O 4-Zb 7- 94 H (CH ₂ ) ₃ H 2-Et-5-Pyr O 4-Zb 7- 95 H (CH ₂ ) ₃ H 2-Ph-5-Pyr O 4-Zb 7- 96 H (CH ₂ ) ₃ H 2- MeO-5-Pyr O 4-Zb 7- 97 H (CH ₂ ) ₃ H 2-EtO-5-Pyr O 4-Zb 7-98 H (CH ₂ ) ₃ H 2-iPrO -5-Pyr O 4-Zb 7- 99 H (CH ₂ ) ₃ H 2-MeS-5-Pyr O 4-Zb 7-100 H (CH ₂ ) ₃ H 2-EtS-5-Pyr O 4-Zb 7-101 H (CH ₂ ) ₃ H 2-iPrS-5-Pyr O 4-Zb 7-102 H (CH ₂ ) ₃ H 2-MeSO ₂ -5-Pyr O 4-Zb 7-103 H (CH ₂ ) ₃ H 2-EtSO ₂ -5-Pyr O 4-Zb 7-104 H (CH ₂ ) ₃ H 2-iPrSO ₂ -5-Pyr O 4-Zb 7-105 H (CH ₂ ) ₃ H 2-Bz -5-Pyr O 4-Zb 7-106 H (CH ₂ ) ₃ H 2-PhO-5-Pyr O 4-Zb 7-107 H (CH ₂ ) ₃ H 2-PhS-5-Pyr O 4-Zb 7-108 H (CH ₂ ) ₃ H 2-PhSO ₂ -5-Pyr O 4-Zb 7-109 H (CH ₂ ) ₃ H 3-Me-6-Pyr O 4-Zb 7-110 H (CH ₂ ) ₃ H 3-Ph-6-Pyr O 4-Zb 7-111 H (CH ₂ ) ₃ H 2-Me-6-Pyr O 4-Zb 7-112 H (CH ₂ ) ₃ H 2-Ph-6 -Pyr O 4-Zb 7-113 H (CH ₂ ) ₃ H 2-Me-4-Pym O 4-Zb 7-114 H (CH ₂ ) ₃ H 2-Ph-4-Pym O 4-Zb 7- 115 H (CH ₂ ) ₃ H 2-MeO-4-Pym O 4-Zb 7-116 H (CH ₂ ) ₃ H 2-EtO-4-Pym O 4-Zb 7-117 H (CH ₂ ) ₃ H 2-iPrO-4-Pym O 4-Zb 7-118 H (CH ₂ ) ₃ H 2-MeS-4-Pym O 4-Zb 7-119 H (CH ₂ ) ₃ H 2-EtS-4-Pym O 4-Zb 7-120 H (CH ₂ ) ₃ H 2-iPrS-4-Pym O 4-Zb 7-121 H (CH ₂ ) ₃ H 6-MeS-4-Pym O 4-Zb 7-122 H ( CH ₂ ) ₃ H 6-EtS-4-Pym O 4-Zb 7-123 H (CH ₂ ) ₃ H 6-iPrS-4-Pym O 4- Zb 7-124 H (CH ₂ ) ₃ H 2-PhS-4-Pym O 4-Zb 7-125 H (CH ₂ ) ₃ H 2-MeSO ₂ -4-Pym O 4-Zb 7-126 H (CH ₂ ) ₃ H 2-EtSO ₂ -4-Pym O 4-Zb 7-127 H (CH ₂ ) ₃ H 2-iPrSO ₂ -4-Pym O 4-Zb 7-128 H (CH ₂ ) ₃ H 2- PhSO ₂ -4-Pym O 4-Zb 7-129 H (CH ₂ ) ₃ H 2-Me-5-Pym O 4-Zb 7-130 H (CH ₂ ) ₃ H 2-Ph-5-Pym O 4 -Zb 7-131 H (CH ₂ ) ₃ H 2-MeO-5-Pym O 4-Zb 7-132 H (CH ₂ ) ₃ H 2-EtO-5-Pym O 4-Zb 7-133 H (CH ₂ ) ₃ H 2-iPrO-5-Pym O 4-Zb 7-134 H (CH ₂ ) ₃ H 2-MeS-5-Pym O 4-Zb 7-135 H (CH ₂ ) ₃ H 2-EtS- 5-Pym O 4-Zb 7-136 H (CH ₂ ) ₃ H 2-iPrS-5-Pym O 4-Zb 7-137 H (CH ₂ ) ₃ H 2-PhS-5-Pym O 4-Zb 7 -138 H (CH ₂ ) ₃ H 2-MeSO ₂ -5-Pym O 4-Zb 7 -139 H (CH ₂ ) ₃ H 2-EtSO ₂ -5-Pym O 4-Zb 7-140 H (CH ₂ ) ₃ H 2-iPrSO ₂ -5-Pym O 4-Zb 7-141 H (CH ₂ ) ₃ H 2-PhSO ₂ -5-Pym O 4-Zb 7-142 H (CH ₂ ) ₃ H 2-Ind O 4-Zb 7-143 H (CH ₂ ) ₃ H 3-Ind O 4-Zb 7-144 H (CH ₂ ) ₃ H 1-Me-2-Ind O 4-Zb 7-145 H (CH ₂ ) ₃ H 1-Me-3-Ind O 4-Zb 7-146 H (CH ₂ ) ₃ H 2-Bimid O 4-Zb 7-147 H (CH ₂ ) ₃ H 2-Boxa O 4-Zb 7-148 H (CH ₂ ) ₃ H 2-Bthiz O 4-Zb 7-149 H (CH ₂ ) ₃ H 2-Quin O 4-Zb 7-150 H (CH ₂ ) ₃ H 3-Quin O 4-Zb 7-151 H (CH ₂ ) ₃ H 4-Quin O 4-Zb 7-152 H (CH ₂ ) ₃ H 1-iQuin O 4-Zb 7-153 H (CH ₂ ) ₃ H 3-iQuin O 4-Zb 7-154 H (CH ₂ ) ₃ H 4-iQuin O 4-Zb 7-155 H (CH ₂ ) ₃ H 3-MeO-Ph O 4-Zb 7-156 H (CH ₂ ) ₃ H 4-MeO-Ph O 4-Zb 7-157 H (CH ₂ ) ₃ H 3-EtO-Ph O 4- Zb 7-158 H (CH ₂ ) ₃ H 4-EtO-Ph O 4-Zb 7-159 H (CH ₂ ) ₃ H 3-iPrO-Ph O 4-Zb 7-160 H (CH ₂ ) ₃ H 4 -iPrO-Ph O 4-Zb 7-161 H (CH ₂ ) ₃ H 3-MeS-Ph O 4-Zb 7-162 H (CH ₂ ) ₃ H 4-MeS-Ph O 4-Zb 7-163 H (CH ₂ ) ₃ H 3-EtS-Ph O 4-Zb 7-164 H (CH ₂ ) ₃ H 4-EtS-Ph O 4-Zb 7-165 H (CH ₂ ) ₃ H 3-iPrS-Ph O 4-Zb 7-166 H (CH ₂ ) ₃ H 4-iPrS-Ph O 4-Zb 7-167 H (CH ₂ ) ₃ H 3-MeSO ₂ -Ph O 4-Zb 7-168 H (CH ₂ ) ₃ H 4-MeSO ₂ -Ph O 4-Zb 7-169 H (CH ₂ ) ₃ H 3-EtSO ₂ -Ph O 4-Zb 7-170 H (CH ₂ ) ₃ H 4-EtSO ₂ -Ph O 4 -Zb 7-171 H (CH ₂ ) ₃ H 3-iPrSO ₂ -Ph O 4-Zb 7-172 H (CH ₂ ) ₃ H 4-iPrSO ₂ -Ph O 4-Zb 7-173 H (CH ₂ ) ₃ H 3- (1-Me-Imid-4) -Ph O 4-Zb 7-174 H (CH ₂ ) ₃ H 4- (1-Me-Imid-4) -Ph O 4-Zb 7-175 H (CH ₂ ) ₃ H 1-Me-2-Ph-4-Imid O 4-Zb 7-176 H (CH ₂ ) ₃ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 7-177 H (CH ₂ ) ₃ H 1,5-di-Me- 2-Ph-4-Imid O 4-Zb 7-178 H (CH ₂ ) ₃ H 3,4-MdO-Ph O 4-Zb 7-179 H (CH ₂ ) ₃ H 4- (4-MeO-Ph ) -Ph O 4-Zb 7-180 H (CH ₂ ) ₃ H 4- (3,4-MdO-Ph) -Ph O 4-Zb 7-181 H (CH ₂ ) ₃ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zb 7-182 H (CH ₂ ) ₃ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 7-183 H (CH ₂ ) ₃ H 4- (PhSO ₂ NH) -Ph O 4-Zb 7-184 H (CH ₂ ) ₃ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 7-185 H (CH ₂ ) ₃ H 4-[(Pyr-2) SO ₂ ] -Ph O 4-Zb 7-186 H (CH ₂ ) ₃ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 7-187 H (CH ₂ ) ₃ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 7-188 H (CH ₂ ) ₃ H 4-[(Pyr-2) SO ₂ NH]- Ph O 4-Zb 7-189 H (CH ₂ ) ₃ H 4- (4-Me-Ph) -Ph O 4-Zb 7-190 H (CH ₂ ) ₃ H 4- (4-F-Ph)- Ph O 4-Zb 7-191 H (CH ₂ ) ₃ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 7-192 H (CH ₂ ) ₃ H 2- [4-Me-PhSO ₂ N (Me)]-5-Pyr O 4-Zb 7-193 H (CH ₂ ) ₃ H 2-HO-5-Pyr O 4-Zb 7-194 H (CH ₂ ) ₃ H 2-BzO-5- Pyr O 4-Zb 7-195 H (CH ₂ ) ₃ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zb 7-196 H (CH ₂ ) ₃ H 4- (2,4-di -MeO-Ph) -Ph O 4-Zb 7-197 H (CH ₂ ) ₃ H 4- (2,5-d i-MeO-Ph) -Ph O 4-Zb 7-198 H (CH ₂ ) ₃ H 3-HO-Ph O 4-Zb 7-199 H (CH ₂ ) ₃ H 4-HO-Ph O 4-Zb 7-200 H (CH ₂ ) ₃ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 7-201 H (CH ₂ ) ₃ H 4-HO-3,5 -di-Me-Ph O 4-Zb 7-202 H (CH ₂ ) ₃ H 3-AcO-Ph O 4-Zb 7-203 H (CH ₂ ) ₃ H 4-AcO-Ph O 4-Zb ── ────────────────────────────────.

[0097]

[Table 8] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 8- 1 Me (CH ₂ ) ₃ H Ph O 4-Zb 8- 2 Me (CH ₂ ) ₃ H 1-Np O 4-Zb 8- 3 Me (CH ₂ ) ₃ H 2-Np O 4-Zb 8-4 Me (CH ₂ ) ₃ H 4-Me -Ph O 4-Zb 8- 5 Me (CH ₂ ) ₃ H 4-Et-Ph O 4-Zb 8- 6 Me (CH ₂ ) ₃ H 3-iPr-Ph O 4-Zb 8- 7 Me (CH ₂ ) ₃ H 4-iPr-Ph O 4-Zb 8-8 Me (CH ₂ ) ₃ H 3-tBu-Ph O 4-Zb 8--9 Me (CH ₂ ) ₃ H 4-tBu-Ph O 4- Zb 8- 10 Me (CH ₂ ) ₃ H 3-Cl-Ph O 4-Zb 8- 11 Me (CH ₂ ) ₃ H 4-Cl-Ph O 4-Zb 8- 12 Me (CH ₂ ) ₃ H 3 -Br-Ph O 4-Zb 8- 13 Me (CH ₂ ) ₃ H 4-Br-Ph O 4-Zb 8- 14 Me (CH ₂ ) ₃ H 3-Ph-Ph O 4-Zb 8- 15 Me (CH ₂ ) ₃ H 4-Ph-Ph O 4-Zb 8-16 Me (CH ₂ ) ₃ H 3-Bz-Ph O 4-Zb 8-17 Me (CH ₂ ) ₃ H 4-Bz-Ph O 4-Zb 8--18 Me (CH ₂ ) ₃ H 3-PhO-Ph O 4-Zb 8-19 Me (CH ₂ ) ₃ H 4-PhO-Ph O 4-Zb 8-20 Me (CH ₂ ) ₃ H 3-PhS-Ph O 4-Zb 8- 21 Me (CH ₂ ) ₃ H 4-PhS-Ph O 4-Zb 8-22 Me (CH ₂ ) ₃ H 3-PhSO ₂ -Ph O 4-Zb 8--23 Me (CH ₂ ) ₃ H 4-PhSO _2- Ph O 4-Zb 8- 24 Me (CH ₂ ) ₃ H 3- (Imid-1) -Ph O 4-Zb 8- 25 Me (CH ₂ ) ₃ H 4- (Imid-1) -Ph O 4- Zb 8-26 Me (CH ₂ ) ₃ H 3- (Imid-4) -Ph O 4-Zb 8-27 Me (CH ₂ ) ₃ H 4- (Imid-4) -Ph O 4-Zb 8-28 Me (CH ₂ ) ₃ H 3- (Fur-2) -Ph O 4-Zb 8- 29 Me (CH ₂ ) ₃ H 4- (Fur-2) -Ph O 4-Zb 8--30 Me (CH ₂ ) ₃ H 3- (Thi-2) -Ph O 4-Zb 8- 31 Me (CH ₂ ) ₃ H 4- (Thi-2) -Ph O 4-Zb 8-32 Me (CH ₂ ) ₃ H 3 -(Thi-3) -Ph O 4-Zb 8-33 Me (CH ₂ ) ₃ H 4- (Thi-3) -Ph O 4-Zb 8- 34 Me (CH ₂ ) ₃ H 3- (Pyr- 2) -Ph O 4-Zb 8-35 Me (CH ₂ ) ₃ H 4- (Pyr-2) -Ph O 4-Zb 8-36 Me (CH ₂ ) ₃ H 3- (Pyr-3) -Ph O 4-Zb 8-37 Me (CH ₂ ) ₃ H 4- (Pyr-3) -Ph O 4-Zb 8- 38 Me (CH ₂ ) ₃ H 3- (Pyr-4) -Ph O 4-Zb 8- 39 Me (CH ₂ ) ₃ H 4- (Pyr-4) -Ph O 4-Zb 8- 40 Me (CH ₂ ) ₃ H 3- (Oxa-2) -Ph O 4-Zb 8- 41 Me (CH ₂ ) ₃ H 4- (Oxa-2) -Ph O 4-Zb 8-42 Me (CH ₂ ) ₃ H 3- (Oxa-4) -Ph O 4-Zb 8-43 Me (CH ₂ ) ₃ H 4- (Oxa-4) -Ph O 4-Zb 8-44 Me (CH ₂ ) ₃ H 3- (Oxa-5) -Ph O 4-Zb 8-45 Me (CH ₂ ) ₃ H 4- ( Oxa-5) -Ph O 4-Zb 8-46 Me (CH ₂ ) ₃ H 3- (Thiz-2) -Ph O 4-Zb 8-47 Me (CH ₂ ) ₃ H 4- (Thiz-2) -Ph O 4-Zb 8-48 Me (CH ₂ ) ₃ H 3- (Thiz-4) -Ph O 4-Zb 8-49 Me (CH ₂ ) ₃ H 4- (Thiz-4) -Ph O 4 -Zb 8- 50 Me (CH ₂ ) ₃ H 3- (Thiz-5) -Ph O 4-Zb 8- 51 Me (CH ₂ ) ₃ H 4- (Thiz-5) -Ph O 4-Zb 8- 52 Me (CH ₂ ) ₃ H 1-Me-2-Pyrr O 4-Zb 8- 53 Me (CH ₂ ) ₃ H 1-Ph-2-Pyrr O 4-Zb 8- 54 Me (CH ₂ ) ₃ H 1-Bz-2-Pyrr O 4-Zb 8-55 Me (CH ₂ ) ₃ H 5-Me-2-Fur O 4-Zb 8-56 Me (CH ₂ ) ₃ H 5-Ph-2-Fur O 4-Zb 8-57 Me (CH ₂ ) ₃ H 5-Me-2-Thi O 4-Zb 8-58 Me (CH ₂ ) ₃ H 5-Ph-2-Thi O 4-Zb 8-59 Me ( CH ₂ ) ₃ H 5-Me-3-Thi O 4-Zb 8- 60 Me (CH ₂ ) ₃ H 5-Ph-3-Thi O 4-Zb 8-61 Me (CH ₂ ) ₃ H 1-Me -3-Pyza O 4-Zb 8-62 Me (CH ₂ ) ₃ H 1-Ph-3-Pyza O 4-Zb 8- 63 Me (CH ₂ ) ₃ H 1-Me-2-Imid O 4-Zb 8-64 Me (CH ₂ ) ₃ H 1-Ph-2-Imid O 4-Zb 8- 65 Me (CH ₂ ) ₃ H 1-Me-4-Imid O 4-Zb 8- 66 Me (CH ₂ ) ₃ H 1-Ph-4-Imid O 4-Zb 8-67 Me (CH ₂ ) ₃ H 4-Oxa O 4-Zb 8-68 Me (CH ₂ ) ₃ H 5-Oxa O 4-Zb 8-69 Me (CH ₂ ) ₃ H 2-Me-4-Oxa O 4-Zb 8-70 Me (CH ₂ ) ₃ H 2-Ph-4-Ox a O 4-Zb 8-71 Me (CH ₂ ) ₃ H 2-Me-5-Oxa O 4-Zb 8-72 Me (CH ₂ ) ₃ H 2-Ph-5-Oxa O 4-Zb 8- 73 Me (CH ₂ ) ₃ H 4-Me-2-Ph-5-Oxa O 4-Zb 8- 74 Me (CH ₂ ) ₃ H 5-Me-2-Ph-4-Oxa O 4-Zb 8-75 Me (CH ₂ ) ₃ H 4-Thiz O 4-Zb 8- 76 Me (CH ₂ ) ₃ H 5-Thiz O 4-Zb 8-77 Me (CH ₂ ) ₃ H 2-Me-4-Thiz O 4 -Zb 8-78 Me (CH ₂ ) ₃ H 2-Ph-4-Thiz O 4-Zb 8- 79 Me (CH ₂ ) ₃ H 2-Me-5-Thiz O 4-Zb 8- 80 Me (CH ₂ ) ₃ H 2-Ph-5-Thiz O 4-Zb 8-81 Me (CH ₂ ) ₃ H 4-Me-2-Ph-5-Thiz O 4-Zb 8-82 Me (CH ₂ ) ₃ H 5-Me-2-Ph-4-Thiz O 4-Zb 8-83 Me (CH ₂ ) ₃ H 1-Me-4-Pyza O 4-Zb 8-84 Me (CH ₂ ) ₃ H 1-Ph- 4-Pyza O 4-Zb 8-85 Me (CH ₂ ) ₃ H 2-Me-4-Isox O 4-Zb 8- 86 Me (CH ₂ ) ₃ H 2-Ph-4-Isox O 4-Zb 8 -87 Me (CH ₂ ) ₃ H 2-Pyr O 4-Zb 8-88 Me (CH ₂ ) ₃ H 3-Pyr O 4-Zb 8- 89 Me (CH ₂ ) ₃ H 4-Pyr O 4-Zb 8- 90 Me (CH ₂ ) ₃ H 3-Me-5-Pyr O 4-Zb 8- 91 Me (CH ₂ ) ₃ H 3-Et-5-Pyr O 4-Zb 8- 92 Me (CH ₂ ) ₃ H 3-Ph-5-Pyr O 4-Zb 8-93 Me (CH ₂ ) ₃ H 2-Me-5-Pyr O 4-Zb 8-94 Me (CH ₂ ) ₃ H 2-Et-5- Pyr O 4-Zb 8- 95 Me (CH ₂ ) ₃ H 2-Ph-5-Pyr O 4-Zb 8- 96 Me (CH ₂ ) ₃ H 2-MeO-5-Pyr O 4-Zb 8-97 Me (CH ₂ ) ₃ H 2-EtO-5-Pyr O 4-Zb 8-98 Me (CH ₂ ) ₃ H 2- iPrO-5-Pyr O 4-Zb 8- 99 Me (CH ₂ ) ₃ H 2-MeS-5-Pyr O 4-Zb 8-100 Me (CH ₂ ) ₃ H 2-EtS-5-Pyr O 4- Zb 8-101 Me (CH ₂ ) ₃ H 2-iPrS-5-Pyr O 4-Zb 8-102 Me (CH ₂ ) ₃ H 2-MeSO ₂ -5-Pyr O 4-Zb 8-103 Me (CH ₂ ) ₃ H 2-EtSO ₂ -5-Pyr O 4-Zb 8-104 Me (CH ₂ ) ₃ H 2-iPrSO ₂ -5-Pyr O 4-Zb 8-105 Me (CH ₂ ) ₃ H 2- Bz-5-Pyr O 4-Zb 8-106 Me (CH ₂ ) ₃ H 2-PhO-5-Pyr O 4-Zb 8-107 Me (CH ₂ ) ₃ H 2-PhS-5-Pyr O 4- Zb 8-108 Me (CH ₂ ) ₃ H 2-PhSO ₂ -5-Pyr O 4-Zb 8-109 Me (CH ₂ ) ₃ H 3-Me-6-Pyr O 4-Zb 8-110 Me (CH ₂ ) ₃ H 3-Ph-6-Pyr O 4-Zb 8-111 Me (CH ₂ ) ₃ H 2-Me-6-Pyr O 4-Zb 8-112 Me (CH ₂ ) ₃ H 2-Ph- 6-Pyr O 4-Zb 8-113 Me (CH ₂ ) ₃ H 2-Me-4-Pym O 4-Zb 8-114 Me (CH ₂ ) ₃ H 2-Ph-4-Pym O 4-Zb 8 -115 Me (CH ₂ ) ₃ H 2-MeO-4-Pym O 4-Zb 8-116 Me (CH ₂ ) ₃ H 2-EtO-4-Pym O 4-Zb 8-117 Me (CH ₂ ) ₃ H 2-iPrO-4-Pym O 4-Zb 8-118 Me (CH ₂ ) ₃ H 2-MeS-4-Pym O 4-Zb 8-119 Me (CH ₂ ) ₃ H 2-EtS-4-Pym O 4-Zb 8-120 Me (CH ₂ ) ₃ H 2-iPrS-4-Pym O 4-Zb 8-121 Me (CH ₂ ) ₃ H 6-MeS-4-Pym O 4-Zb 8-122 Me (CH ₂ ) ₃ H 6-EtS-4-Pym O 4-Zb 8-123 Me ( CH ₂ ) ₃ H 6-iPrS-4-Pym O 4-Zb 8-124 Me (CH ₂ ) ₃ H 2-PhS-4-Pym O 4-Zb 8-125 Me (CH ₂ ) ₃ H 2-MeSO ₂ -4-Pym O 4-Zb 8-126 Me (CH ₂ ) ₃ H 2-EtSO ₂ -4-Pym O 4-Zb 8-127 Me (CH ₂ ) ₃ H 2-iPrSO ₂ -4-Pym O 4-Zb 8-128 Me (CH ₂ ) ₃ H 2-PhSO ₂ -4-Pym O 4-Zb 8-129 Me (CH ₂ ) ₃ H 2-Me-5-Pym O 4-Zb 8-130 Me (CH ₂ ) ₃ H 2-Ph-5-Pym O 4-Zb 8-131 Me (CH ₂ ) ₃ H 2-MeO-5-Pym O 4-Zb 8-132 Me (CH ₂ ) ₃ H 2- EtO-5-Pym O 4-Zb 8-133 Me (CH ₂ ) ₃ H 2-iPrO-5-Pym O 4-Zb 8-134 Me (CH ₂ ) ₃ H 2-MeS-5-Pym O 4- Zb 8-135 Me (CH ₂ ) ₃ H 2-EtS-5-Pym O 4-Zb 8-136 Me (CH ₂ ) ₃ H 2-iPrS-5-Pym O 4-Zb 8-137 Me (CH ₂ ) ₃ H 2-PhS-5-Pym O 4-Zb 8-138 Me (CH ₂ ) ₃ H 2-MeSO ₂ -5-Pym O 4-Zb 8-139 Me (CH ₂ ) ₃ H 2-EtSO ₂ -5-Pym O 4-Zb 8-140 Me (CH ₂ ) ₃ H 2-iPrSO ₂ -5-Pym O 4-Zb 8-141 Me (CH ₂ ) ₃ H 2-PhSO ₂ -5-Pym O 4 -Zb 8-142 Me (CH ₂ ) ₃ H 2-Ind O 4-Zb 8-143 Me (CH ₂ ) ₃ H 3-Ind O 4-Zb 8-144 Me (CH ₂ ) ₃ H 1-Me- 2-Ind O 4-Zb 8-145 Me (CH ₂ ) ₃ H 1-Me-3-Ind O 4-Zb 8-146 Me (CH ₂ ) ₃ H 2-Bimid O 4-Zb 8-147 Me (CH ₂ ) ₃ H 2-Boxa O 4-Zb 8 -148 Me (CH ₂ ) ₃ H 2-Bthiz O 4-Zb 8-149 Me (CH ₂ ) ₃ H 2-Quin O 4-Zb 8-150 Me (CH ₂ ) ₃ H 3-Quin O 4-Zb 8-151 Me (CH ₂ ) ₃ H 4-Quin O 4-Zb 8-152 Me (CH ₂ ) ₃ H 1-iQuin O 4-Zb 8-153 Me (CH ₂ ) ₃ H 3-iQuin O 4- Zb 8-154 Me (CH ₂ ) ₃ H 4-iQuin O 4-Zb 8-155 Me (CH ₂ ) ₃ H 3-MeO-Ph O 4-Zb 8-156 Me (CH ₂ ) ₃ H 4-MeO -Ph O 4-Zb 8-157 Me (CH ₂ ) ₃ H 3-EtO-Ph O 4-Zb 8-158 Me (CH ₂ ) ₃ H 4-EtO-Ph O 4-Zb 8-159 Me (CH ₂ ) ₃ H 3-iPrO-Ph O 4-Zb 8-160 Me (CH ₂ ) ₃ H 4-iPrO-Ph O 4-Zb 8-161 Me (CH ₂ ) ₃ H 3-MeS-Ph O 4- Zb 8-162 Me (CH ₂ ) ₃ H 4-MeS-Ph O 4-Zb 8-163 Me (CH ₂ ) ₃ H 3-EtS-Ph O 4-Zb 8-164 Me (CH ₂ ) ₃ H 4 -EtS-Ph O 4-Zb 8-165 Me (CH ₂ ) ₃ H 3-iPrS-Ph O 4-Zb 8-166 Me (CH ₂ ) ₃ H 4-iPrS-Ph O 4-Zb 8-167 Me (CH ₂ ) ₃ H 3-MeSO ₂ -Ph O 4-Zb 8-168 Me (CH ₂ ) ₃ H 4-MeSO ₂ -Ph O 4-Zb 8-169 Me (CH ₂ ) ₃ H 3-EtSO ₂ -Ph O 4-Zb 8-170 Me (CH ₂ ) ₃ H 4-EtSO ₂ -Ph O 4-Zb 8-171 Me (CH ₂ ) ₃ H 3-iPrSO ₂ -Ph O 4-Zb 8-172 Me (CH ₂ ) ₃ H 4-iPrSO ₂ -Ph O 4-Zb 8-173 Me (CH ₂ ) ₃ H 3- (1-Me-Imid-4) -Ph O 4-Zb 8-174 Me (CH ₂ ) ₃ H 4- (1-Me-Imid-4) -Ph O 4-Zb 8-175 Me (CH ₂ ) ₃ H 1-Me-2-Ph-4-Imid O 4-Zb 8 -176 Me (CH ₂ ) ₃ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 8-177 Me (CH ₂ ) ₃ H 1,5-di-Me-2-Ph- 4-Imid O 4-Zb 8-178 Me (CH ₂ ) ₃ H 3,4-MdO-Ph O 4-Zb 8-179 Me (CH ₂ ) ₃ H 4- (4-MeO-Ph) -Ph O 4-Zb 8-180 Me (CH ₂ ) ₃ H 4- (3,4-MdO-Ph) -Ph O 4-Zb 8-181 Me (CH ₂ ) ₃ H 4- [PhSO ₂ N (Me)] -Ph O 4-Zb 8-182 Me (CH ₂ ) ₃ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 8-183 Me (CH ₂ ) ₃ H 4- ( PhSO ₂ NH) -Ph O 4-Zb 8-184 Me (CH ₂ ) ₃ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 8-185 Me (CH ₂ ) ₃ H 4- [(Pyr-2) SO ₂ ] -Ph O 4-Zb 8-186 Me (CH ₂ ) ₃ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 8-187 Me (CH ₂ ) ₃ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 8-188 Me (CH ₂ ) ₃ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4- Zb 8-189 Me (CH ₂ ) ₃ H 4- (4-Me-Ph) -Ph O 4-Zb 8-190 Me (CH ₂ ) ₃ H 4- (4-F-Ph) -Ph O 4- Zb 8-191 Me (CH ₂ ) ₃ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 8-192 Me (CH ₂ ) ₃ H 2- [4-Me-PhSO ₂ N (Me) ] -5-Pyr O 4-Zb 8-193 Me (CH ₂ ) ₃ H 2-HO-5-Pyr O 4-Zb 8-194 Me (CH ₂ ) ₃ H 2-BzO-5-Pyr O 4-Zb 8-195 Me (CH ₂ ) ₃ H 4- [(Pyr-4) SO ₂ ] -Ph O 4-Zb 8-196 Me (CH ₂ ) ₃ H 4- (2,4-di-MeO-Ph) -Ph O 4-Zb 8-197 Me (CH ₂ ) ₃ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zb 8-198 Me (CH ₂ ) ₃ H 3-HO-Ph O 4-Zb 8-199 Me (CH ₂ ) ₃ H 4-HO-Ph O 4-Zb 8-200 Me (CH ₂ ) ₃ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 8-201 Me (CH ₂ ) ₃ H 4-HO-3,5-di-Me-Ph O 4-Zb 8-202 Me (CH ₂ ) ₃ H 3-AcO-Ph O 4-Zb 8-203 Me (CH ₂ ) ₃ H 4-AcO-Ph O 4-Zb II.

[0098]

[Table 9] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 9-1 H CH (Me) CH ₂ H Ph O 4-Zb 9- 2 H CH (Me) CH ₂ H 1-Np O 4-Zb 9- 3 H CH (Me) CH ₂ H 2-Np O 4-Zb 9- 4 H CH (Me) CH ₂ H 4-Me-Ph O 4-Zb 9- 5 H CH (Me) CH ₂ H 4-Et-Ph O 4-Zb 9- 6 H CH (Me) CH ₂ H 3-iPr-Ph O 4-Zb 9- 7 H CH (Me) CH ₂ H 4-iPr-Ph O 4-Zb 9- 8 H CH (Me) CH ₂ H 3-tBu-Ph O 4-Zb 9- 9 H CH (Me) CH ₂ H 4-tBu-Ph O 4-Zb 9- 10 H CH (Me) CH ₂ H 3-Cl-Ph O 4-Zb 9- 11 H CH (Me) CH ₂ H 4-Cl-Ph O 4-Zb 9- 12 H CH (Me) CH ₂ H 3-Br-Ph O 4-Zb 9- 13 H CH (Me) CH ₂ H 4-Br-Ph O 4-Zb 9- 14 H CH (Me) CH ₂ H 3-Ph-Ph O 4-Zb 9-15 H CH (Me) CH ₂ H 4-Ph-Ph O 4-Zb 9-16 H CH (Me) CH ₂ H 3-Bz-Ph O 4-Zb 9-17 H CH (Me) CH ₂ H 4-Bz-Ph O 4-Zb 9-18 H CH (Me) CH ₂ H 3-PhO-Ph O 4-Zb 9-19 H CH (Me) CH ₂ H 4-PhO-Ph O 4-Zb 9-20 H CH (Me) CH ₂ H 3-PhS-Ph O 4-Zb 9-21 H CH (Me) CH ₂ H 4-PhS-Ph O 4-Zb 9- 22 H CH (Me) CH ₂ H 3-PhSO ₂ -Ph O 4-Zb 9- 23 H CH (Me) CH ₂ H 4- PhSO ₂ -Ph O 4-Zb 9- 24 H CH (Me) CH ₂ H 3- (Imid-1) -Ph O 4-Zb 9- 25 H CH (Me) CH ₂ H 4- (Imid-1) -Ph O 4-Zb 9- 26 H CH (Me) CH ₂ H 3- (Imid-4) -Ph O 4-Zb 9- 27 H CH (Me) CH ₂ H 4- (Imid-4) -Ph O 4-Zb 9- 28 H CH (Me) CH ₂ H 3- (Fur-2) -Ph O 4-Zb 9- 29 H CH (Me) CH ₂ H 4- (Fur-2) -Ph O 4 -Zb 9-30 H CH (Me) CH ₂ H 3- (Thi-2) -Ph O 4-Zb 9- 31 H CH (Me) CH ₂ H 4- (Thi-2) -Ph O 4-Zb 9- 32 H CH (Me) CH ₂ H 3- (Thi-3) -Ph O 4-Zb 9- 33 H CH (Me) CH ₂ H 4- (Thi-3) -Ph O 4-Zb 9- 34 H CH (Me) CH ₂ H 3- (Pyr-2) -Ph O 4-Zb 9- 35 H CH (Me) CH ₂ H 4- (Pyr-2) -Ph O 4-Zb 9- 36 H CH (Me) CH ₂ H 3- (Pyr-3) -Ph O 4-Zb 9- 37 H CH (Me) CH ₂ H 4- (Pyr-3) -Ph O 4-Zb 9- 38 H CH ( Me) CH ₂ H 3- (Pyr-4) -Ph O 4-Zb 9- 39 H CH (Me) CH ₂ H 4- (Pyr-4) -Ph O 4-Zb 9-40 H CH (Me) CH ₂ H 3- (Oxa-2) -Ph O 4-Zb 9- 41 H CH (Me) CH ₂ H 4- (Oxa-2) -Ph O 4-Zb 9- 42 H CH (Me) CH ₂ H 3- (Oxa-4) -Ph O 4-Zb 9- 43 H CH (Me) CH ₂ H 4- (Oxa-4) -Ph O 4-Zb 9- 44 H CH (Me) CH ₂ H 3 -(Oxa-5) -Ph O 4-Zb 9- 45 H CH (Me) CH ₂ H 4- ( Oxa-5) -Ph O 4-Zb 9- 46 H CH (Me) CH ₂ H 3- (Thiz-2) -Ph O 4-Zb 9- 47 H CH (Me) CH ₂ H 4- (Thiz- 2) -Ph O 4-Zb 9- 48 H CH (Me) CH ₂ H 3- (Thiz-4) -Ph O 4-Zb 9- 49 H CH (Me) CH ₂ H 4- (Thiz-4) -Ph O 4-Zb 9- 50 H CH (Me) CH ₂ H 3- (Thiz-5) -Ph O 4-Zb 9- 51 H CH (Me) CH ₂ H 4- (Thiz-5) -Ph O 4-Zb 9- 52 H CH (Me) CH ₂ H 1-Me-2-Pyrr O 4-Zb 9- 53 H CH (Me) CH ₂ H 1-Ph-2-Pyrr O 4-Zb 9- 54 H CH (Me) CH ₂ H 1-Bz-2-Pyrr O 4-Zb 9- 55 H CH (Me) CH ₂ H 5-Me-2-Fur O 4-Zb 9- 56 H CH (Me) CH ₂ H 5-Ph-2-Fur O 4-Zb 9- 57 H CH (Me) CH ₂ H 5-Me-2-Thi O 4-Zb 9- 58 H CH (Me) CH ₂ H 5-Ph -2-Thi O 4-Zb 9- 59 H CH (Me) CH ₂ H 5-Me-3-Thi O 4-Zb 9-60 H CH (Me) CH ₂ H 5-Ph-3-Thi O 4 -Zb 9- 61 H CH (Me) CH ₂ H 1-Me-3-Pyza O 4-Zb 9- 62 H CH (Me) CH ₂ H 1-Ph-3-Pyza O 4-Zb 9- 63 H CH (Me) CH ₂ H 1-Me-2-Imid O 4-Zb 9- 64 H CH (Me) CH ₂ H 1-Ph-2-Imid O 4-Zb 9- 65 H CH (Me) CH ₂ H 1-Me-4-Imid O 4-Zb 9- 66 H CH (Me) CH ₂ H 1-Ph-4-Imid O 4-Zb 9- 67 H CH (Me) CH ₂ H 4-Oxa O 4 -Zb 9- 68 H CH (Me) CH ₂ H 5-Oxa O 4-Zb 9- 69 H CH (Me) CH ₂ H 2-Me-4-Oxa O 4-Zb 9- 70 H CH (Me) CH ₂ H 2-Ph-4-Ox a O 4-Zb 9- 71 H CH (Me) CH ₂ H 2-Me-5-Oxa O 4-Zb 9- 72 H CH (Me) CH ₂ H 2-Ph-5-Oxa O 4-Zb 9 -73 H CH (Me) CH ₂ H 4-Me-2-Ph-5-Oxa O 4-Zb 9- 74 H CH (Me) CH ₂ H 5-Me-2-Ph-4-Oxa O 4- Zb 9- 75 H CH (Me) CH ₂ H 4-Thiz O 4-Zb 9- 76 H CH (Me) CH ₂ H 5-Thiz O 4-Zb 9- 77 H CH (Me) CH ₂ H 2- Me-4-Thiz O 4-Zb 9- 78 H CH (Me) CH ₂ H 2-Ph-4-Thiz O 4-Zb 9- 79 H CH (Me) CH ₂ H 2-Me-5-Thiz O 4-Zb 9- 80 H CH (Me) CH ₂ H 2-Ph-5-Thiz O 4-Zb 9- 81 H CH (Me) CH ₂ H 4-Me-2-Ph-5-Thiz O 4- Zb 9- 82 H CH (Me) CH ₂ H 5-Me-2-Ph-4-Thiz O 4-Zb 9- 83 H CH (Me) CH ₂ H 1-Me-4-Pyza O 4-Zb 9 -84 H CH (Me) CH ₂ H 1-Ph-4-Pyza O 4-Zb 9- 85 H CH (Me) CH ₂ H 2-Me-4-Isox O 4-Zb 9- 86 H CH (Me ) CH ₂ H 2-Ph-4-Isox O 4-Zb 9-87 H CH (Me) CH ₂ H 2-Pyr O 4-Zb 9-88 H CH (Me) CH ₂ H 3-Pyr O 4- Zb 9- 89 H CH (Me) CH ₂ H 4-Pyr O 4-Zb 9- 90 H CH (Me) CH ₂ H 3-Me-5-Pyr O 4-Zb 9- 91 H CH (Me) CH ₂ H 3-Et-5-Pyr O 4-Zb 9- 92 H CH (Me) CH ₂ H 3-Ph-5-Pyr O 4-Zb 9- 93 H CH (Me) CH ₂ H 2-Me- 5-Pyr O 4-Zb 9- 94 H CH (Me) CH ₂ H 2-Et-5-Pyr O 4-Zb 9- 95 H CH (Me) CH ₂ H 2-Ph-5-Pyr O 4- Zb 9- 96 HC H (Me) CH ₂ H 2-MeO-5-Pyr O 4-Zb 9-97 H CH (Me) CH ₂ H 2-EtO-5-Pyr O 4-Zb 9-98 H CH (Me) CH ₂ H 2-iPrO-5-Pyr O 4-Zb 9- 99 H CH (Me) CH ₂ H 2-MeS-5-Pyr O 4-Zb 9-100 H CH (Me) CH ₂ H 2-EtS-5 -Pyr O 4-Zb 9-101 H CH (Me) CH ₂ H 2-iPrS-5-Pyr O 4-Zb 9-102 H CH (Me) CH ₂ H 2-MeSO ₂ -5-Pyr O 4- Zb 9-103 H CH (Me) CH ₂ H 2-EtSO ₂ -5-Pyr O 4-Zb 9-104 H CH (Me) CH ₂ H 2-iPrSO ₂ -5-Pyr O 4-Zb 9-105 H CH (Me) CH ₂ H 2-Bz-5-Pyr O 4-Zb 9-106 H CH (Me) CH ₂ H 2-PhO-5-Pyr O 4-Zb 9-107 H CH (Me) CH ₂ H 2-PhS-5-Pyr O 4-Zb 9-108 H CH (Me) CH ₂ H 2-PhSO ₂ -5-Pyr O 4-Zb 9-109 H CH (Me) CH ₂ H 3-Me -6-Pyr O 4-Zb 9-110 H CH (Me) CH ₂ H 3-Ph-6-Pyr O 4-Zb 9-111 H CH (Me) CH ₂ H 2-Me-6-Pyr O 4 -Zb 9-112 H CH (Me) CH ₂ H 2-Ph-6-Pyr O 4-Zb 9-113 H CH (Me) CH ₂ H 2-Me-4-Pym O 4-Zb 9-114 H CH (Me) CH ₂ H 2-Ph-4-Pym O 4-Zb 9-115 H CH (Me) CH ₂ H 2-MeO-4-Pym O 4-Zb 9-116 H CH (Me) CH ₂ H 2-EtO-4-Pym O 4-Zb 9-117 H CH (Me) CH ₂ H 2-iPrO-4-Pym O 4-Zb 9-118 H CH (Me) CH ₂ H 2-MeS-4 -Pym O 4-Zb 9-119 H CH (Me) CH ₂ H 2-EtS-4-Pym O 4-Zb 9-120 H CH (Me) CH ₂ H 2-iPrS-4-Pym O 4-Zb 9-121 H CH (Me) CH ₂ H 6-MeS-4-Pym O 4-Zb 9-122 H CH (Me) CH ₂ H 6-EtS-4-Pym O 4-Zb 9-123 H CH (Me) CH ₂ H 6-iPrS-4-Pym O 4-Zb 9-124 H CH (Me) CH ₂ H 2-PhS-4-Pym O 4-Zb 9-125 H CH (Me) CH ₂ H 2-MeSO ₂ -4-Pym O 4-Zb 9-126 H CH (Me) CH ₂ H 2-EtSO ₂ -4-Pym O 4-Zb 9-127 H CH (Me) CH ₂ H 2- iPrSO ₂ -4-Pym O 4-Zb 9-128 H CH (Me) CH ₂ H 2-PhSO ₂ -4-Pym O 4-Zb 9-129 H CH (Me) CH ₂ H 2-Me-5- Pym O 4-Zb 9-130 H CH (Me) CH ₂ H 2-Ph-5-Pym O 4-Zb 9-131 H CH (Me) CH ₂ H 2-MeO-5-Pym O 4-Zb 9 -132 H CH (Me) CH ₂ H 2-EtO-5-Pym O 4-Zb 9-133 H CH (Me) CH ₂ H 2-iPrO-5-Pym O 4-Zb 9-134 H CH (Me ) CH ₂ H 2-MeS-5-Pym O 4-Zb 9-135 H CH (Me) CH ₂ H 2-EtS-5-Pym O 4-Zb 9-136 H CH (Me) CH ₂ H 2- iPrS-5-Pym O 4-Zb 9-137 H CH (Me) CH ₂ H 2-PhS-5-Pym O 4-Zb 9-138 H CH (Me) CH ₂ H 2-MeSO ₂ -5-Pym O 4-Zb 9-139 H CH (Me) CH ₂ H 2-EtSO ₂ -5-Pym O 4-Zb 9-140 H CH (Me) CH ₂ H 2-iPrSO ₂ -5-Pym O 4-Zb 9-141 H CH (Me) CH ₂ H 2-PhSO ₂ -5-Pym O 4-Zb 9-142 H CH (Me) CH ₂ H 2-Ind O 4-Zb 9-143 H CH (Me) CH ₂ H 3-Ind O 4-Zb 9-144 H CH (Me) CH ₂ H 1-Me-2-Ind O 4-Zb 9-145 H CH (Me ) CH ₂ H 1-Me-3-Ind O 4-Zb 9-146 H CH (Me) CH ₂ H 2-Bimid O 4-Zb 9-147 H CH (Me) CH ₂ H 2-Boxa O 4- Zb 9-148 H CH (Me) CH ₂ H 2-Bthiz O 4-Zb 9-149 H CH (Me) CH ₂ H 2-Quin O 4-Zb 9-150 H CH (Me) CH ₂ H 3- Quin O 4-Zb 9-151 H CH (Me) CH ₂ H 4-Quin O 4-Zb 9-152 H CH (Me) CH ₂ H 1-iQuin O 4-Zb 9-153 H CH (Me) CH ₂ H 3-iQuin O 4-Zb 9-154 H CH (Me) CH ₂ H 4-iQuin O 4-Zb 9-155 H CH (Me) CH ₂ H 3-MeO-Ph O 4-Zb 9-156 H CH (Me) CH ₂ H 4-MeO-Ph O 4-Zb 9-157 H CH (Me) CH ₂ H 3-EtO-Ph O 4-Zb 9-158 H CH (Me) CH ₂ H 4- EtO-Ph O 4-Zb 9-159 H CH (Me) CH ₂ H 3-iPrO-Ph O 4-Zb 9-160 H CH (Me) CH ₂ H 4-iPrO-Ph O 4-Zb 9-161 H CH (Me) CH ₂ H 3-MeS-Ph O 4-Zb 9-162 H CH (Me) CH ₂ H 4-MeS-Ph O 4-Zb 9-163 H CH (Me) CH ₂ H 3- EtS-Ph O 4-Zb 9-164 H CH (Me) CH ₂ H 4-EtS-Ph O 4-Zb 9-165 H CH (Me) CH ₂ H 3-iPrS-Ph O 4-Zb 9-166 H CH (Me) CH ₂ H 4-iPrS-Ph O 4-Zb 9-167 H CH (Me) CH ₂ H 3-MeSO ₂ -Ph O 4-Zb 9-168 H CH (Me) CH ₂ H 4 -MeSO ₂ -Ph O 4-Zb 9-169 H CH (Me) CH ₂ H 3-EtSO ₂ -Ph O 4-Zb 9-170 H CH (Me) CH ₂ H 4-EtSO ₂ -Ph O 4- Zb 9-171 H CH (Me) CH ₂ H 3-iPrSO ₂ -Ph O 4-Zb 9-172 H CH (Me) CH ₂ H 4-iPrSO ₂ -Ph O 4-Zb 9-173 H CH (Me) CH ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zb 9 -174 H CH (Me) CH ₂ H 4- (1-Me-Imid-4) -Ph O 4-Zb 9-175 H CH (Me) CH ₂ H 1-Me-2-Ph-4-Imid O 4-Zb 9-176 H CH (Me) CH ₂ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 9-177 H CH (Me) CH ₂ H 1,5-di- Me-2-Ph-4-Imid O 4-Zb 9-178 H CH (Me) CH ₂ H 3,4-MdO-Ph O 4-Zb 9-179 H CH (Me) CH ₂ H 4- (4 -MeO-Ph) -Ph O 4-Zb 9-180 H CH (Me) CH ₂ H 4- (3,4-MdO-Ph) -Ph O 4-Zb 9-181 H CH (Me) CH ₂ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zb 9-182 H CH (Me) CH ₂ H 4-[(Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 9- 183 H CH (Me) CH ₂ H 4- (PhSO ₂ NH) -Ph O 4-Zb 9-184 H CH (Me) CH ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4- Zb 9-185 H CH (Me) CH ₂ H 4-[(Pyr-2) SO ₂ ] -Ph O 4-Zb 9-186 H CH (Me) CH ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 9-187 H CH (Me) CH ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 9-188 H CH (Me) CH ₂ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4-Zb 9-189 H CH (Me) CH ₂ H 4- (4-Me-Ph) -Ph O 4-Zb 9-190 H CH ( Me) CH ₂ H 4- (4-F-Ph) -Ph O 4-Zb 9-191 H CH (Me) CH ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 9-192 H CH (Me) CH ₂ H 2- [4-Me-PhSO ₂ N (Me)]-5-Pyr O 4-Zb 9-193 H CH (Me) CH ₂ H 2-HO-5-Pyr O 4-Zb 9-194 H CH (Me) CH ₂ H 2-BzO-5-Pyr O 4-Zb 9-195 H CH (Me) CH ₂ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zb 9-196 H CH (Me) CH ₂ H 4- (2,4-di-MeO-Ph) -Ph O 4-Zb 9- 197 H CH (Me) CH ₂ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zb 9-198 H CH (Me) CH ₂ H 3-HO-Ph O 4-Zb 9- 199 H CH (Me) CH ₂ H 4-HO-Ph O 4-Zb 9-200 H CH (Me) CH ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4 -Zb 9-201 H CH (Me) CH ₂ H 4-HO-3,5-di-Me-Ph O 4-Zb 9-202 H CH (Me) CH ₂ H 3-AcO-Ph O 4-Zb 9-203 H CH (Me) CH ₂ H 4-AcO-Ph O 4-Zb ────────────────────────────── ────.

[0099]

[Table 10] Examples R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 10- 1 Me CH (Me) CH ₂ H Ph O 4-Zb 10- 2 Me CH (Me) CH ₂ H 1-Np O 4-Zb 10- 3 Me CH (Me) CH ₂ H 2-Np O 4-Zb 10- 4 Me CH (Me) CH ₂ H 4-Me-Ph O 4-Zb 10-5 Me CH (Me) CH ₂ H 4-Et-Ph O 4-Zb 10- 6 Me CH (Me) CH ₂ H 3-iPr-Ph O 4-Zb 10- 7 Me CH (Me) CH ₂ H 4-iPr-Ph O 4-Zb 10- 8 Me CH (Me) CH ₂ H 3-tBu-Ph O 4-Zb 10- 9 Me CH (Me) CH ₂ H 4-tBu-Ph O 4-Zb 10-10 Me CH (Me) CH ₂ H 3-Cl-Ph O 4-Zb 10- 11 Me CH (Me) CH ₂ H 4-Cl-Ph O 4-Zb 10- 12 Me CH (Me) CH ₂ H 3-Br-Ph O 4-Zb 10- 13 Me CH (Me) CH ₂ H 4-Br-Ph O 4-Zb 10- 14 Me CH (Me) CH ₂ H 3-Ph-Ph O 4-Zb 10-15 Me CH (Me) CH ₂ H 4-Ph-Ph O 4-Zb 10-16 Me CH (Me) CH ₂ H 3-Bz-Ph O 4-Zb 10-17 Me CH (Me) CH ₂ H 4-Bz-Ph O 4-Zb 10-18 Me CH (Me) CH ₂ H 3-PhO-Ph O 4-Zb 10-19 Me CH (Me) CH ₂ H 4-PhO-Ph O 4-Zb 10- 20 Me CH (Me) CH ₂ H 3-PhS-Ph O 4-Zb 10- 21 Me CH (Me) CH ₂ H 4-PhS-Ph O 4-Zb 10-22 Me CH (Me) CH ₂ H 3 -PhSO ₂ -Ph O 4-Zb 10- 23 Me CH (Me) CH ₂ H 4-PhSO ₂ -Ph O 4-Zb 10- 24 Me CH (Me) CH ₂ H 3- (Imid-1) -Ph O 4-Zb 10- 25 Me CH (Me) CH ₂ H 4- (Imid-1) -Ph O 4-Zb 10- 26 Me CH (Me) CH ₂ H 3- (Imid-4) -Ph O 4 -Zb 10- 27 Me CH (Me) CH ₂ H 4- (Imid-4) -Ph O 4-Zb 10- 28 Me CH (Me) CH ₂ H 3- (Fur-2) -Ph O 4-Zb 10- 29 Me CH (Me) CH ₂ H 4- (Fur-2) -Ph O 4-Zb 10- 30 Me CH (Me) CH ₂ H 3- (Thi-2) -Ph O 4-Zb 10- 31 Me CH (Me) CH ₂ H 4- (Thi-2) -Ph O 4-Zb 10- 32 Me CH (Me) CH ₂ H 3- (Thi-3) -Ph O 4-Zb 10- 33 Me CH (Me) CH ₂ H 4- (Thi-3) -Ph O 4-Zb 10- 34 Me CH (Me) CH ₂ H 3- (Pyr-2) -Ph O 4-Zb 10- 35 Me CH ( Me) CH ₂ H 4- (Pyr-2) -Ph O 4-Zb 10- 36 Me CH (Me) CH ₂ H 3- (Pyr-3) -Ph O 4-Zb 10- 37 Me CH (Me) CH ₂ H 4- (Pyr-3) -Ph O 4-Zb 10- 38 Me CH (Me) CH ₂ H 3- (Pyr-4) -Ph O 4-Zb 10- 39 Me CH (Me) CH ₂ H 4- (Pyr-4) -Ph O 4-Zb 10-40 Me CH (Me) CH ₂ H 3- (Oxa-2) -Ph O 4-Zb 10- 41 Me CH (Me) CH ₂ H 4 -(Oxa-2) -Ph O 4-Zb 10- 42 Me CH (Me) CH ₂ H 3- (Oxa-4) -Ph O 4-Zb 10- 43 Me CH (Me) CH ₂ H 4- (Oxa-4) -Ph O 4-Zb 10- 44 Me CH (Me) CH ₂ H 3- (Oxa-5) -Ph O 4-Zb 10- 45 Me CH (Me) CH ₂ H 4- (Oxa-5) -Ph O 4-Zb 10- 46 Me CH (Me) CH ₂ H 3- (Thiz-2) -Ph O 4-Zb 10- 47 Me CH (Me) CH ₂ H 4- (Thiz-2) -Ph O 4-Zb 10- 48 Me CH (Me) CH ₂ H 3- (Thiz-4) -Ph O 4-Zb 10- 49 Me CH (Me) CH ₂ H 4- (Thiz -4) -Ph O 4-Zb 10-50 Me CH (Me) CH ₂ H 3- (Thiz-5) -Ph O 4-Zb 10- 51 Me CH (Me) CH ₂ H 4- (Thiz-5 ) -Ph O 4-Zb 10- 52 Me CH (Me) CH ₂ H 1-Me-2-Pyrr O 4-Zb 10- 53 Me CH (Me) CH ₂ H 1-Ph-2-Pyrr O 4- Zb 10- 54 Me CH (Me) CH ₂ H 1-Bz-2-Pyrr O 4-Zb 10- 55 Me CH (Me) CH ₂ H 5-Me-2-Fur O 4-Zb 10- 56 Me CH (Me) CH ₂ H 5-Ph-2-Fur O 4-Zb 10-57 Me CH (Me) CH ₂ H 5-Me-2-Thi O 4-Zb 10-58 Me CH (Me) CH ₂ H 5-Ph-2-Thi O 4-Zb 10- 59 Me CH (Me) CH ₂ H 5-Me-3-Thi O 4-Zb 10-60 Me CH (Me) CH ₂ H 5-Ph-3- Thi O 4-Zb 10- 61 Me CH (Me) CH ₂ H 1-Me-3-Pyza O 4-Zb 10- 62 Me CH (Me) CH ₂ H 1-Ph-3-Pyza O 4-Zb 10 -63 Me CH (Me) CH ₂ H 1-Me-2-Imid O 4-Zb 10- 64 Me CH (Me) CH ₂ H 1-Ph-2-Imid O 4-Zb 10- 65 Me CH (Me ) CH ₂ H 1-Me-4-Imid O 4-Zb 10- 66 Me CH (Me) CH ₂ H 1-Ph-4-Imid O 4-Zb 10 -67 Me CH (Me) CH ₂ H 4-Oxa O 4-Zb 10- 68 Me CH (Me) CH ₂ H 5-Oxa O 4-Zb 10- 69 Me CH (Me) CH ₂ H 2-Me- 4-Oxa O 4-Zb 10- 70 Me CH (Me) CH ₂ H 2-Ph-4-Oxa O 4-Zb 10- 71 Me CH (Me) CH ₂ H 2-Me-5-Oxa O 4- Zb 10- 72 Me CH (Me) CH ₂ H 2-Ph-5-Oxa O 4-Zb 10- 73 Me CH (Me) CH ₂ H 4-Me-2-Ph-5-Oxa O 4-Zb 10 -74 Me CH (Me) CH ₂ H 5-Me-2-Ph-4-Oxa O 4-Zb 10- 75 Me CH (Me) CH ₂ H 4-Thiz O 4-Zb 10- 76 Me CH (Me ) CH ₂ H 5-Thiz O 4-Zb 10- 77 Me CH (Me) CH ₂ H 2-Me-4-Thiz O 4-Zb 10- 78 Me CH (Me) CH ₂ H 2-Ph-4- Thiz O 4-Zb 10- 79 Me CH (Me) CH ₂ H 2-Me-5-Thiz O 4-Zb 10- 80 Me CH (Me) CH ₂ H 2-Ph-5-Thiz O 4-Zb 10 -81 Me CH (Me) CH ₂ H 4-Me-2-Ph-5-Thiz O 4-Zb 10- 82 Me CH (Me) CH ₂ H 5-Me-2-Ph-4-Thiz O 4- Zb 10- 83 Me CH (Me) CH ₂ H 1-Me-4-Pyza O 4-Zb 10- 84 Me CH (Me) CH ₂ H 1-Ph-4-Pyza O 4-Zb 10- 85 Me CH (Me) CH ₂ H 2-Me-4-Isox O 4-Zb 10-86 Me CH (Me) CH ₂ H 2-Ph-4-Isox O 4-Zb 10-87 Me CH (Me) CH ₂ H 2-Pyr O 4-Zb 10- 88 Me CH (Me) CH ₂ H 3-Pyr O 4-Zb 10- 89 Me CH (Me) CH ₂ H 4-Pyr O 4-Zb 10- 90 Me CH (Me ) CH ₂ H 3-Me-5-Pyr O 4-Zb 10- 91 Me CH (Me) CH ₂ H 3-Et-5-Pyr O 4-Zb 10- 92 Me CH (Me) CH ₂ H 3-Ph-5-Pyr O 4-Zb 10- 93 Me CH (Me) CH ₂ H 2-Me-5 -Pyr O 4-Zb 10- 94 Me CH (Me) CH ₂ H 2-Et-5-Pyr O 4-Zb 10- 95 Me CH (Me) CH ₂ H 2-Ph-5-Pyr O 4-Zb 10- 96 Me CH (Me) CH ₂ H 2-MeO-5-Pyr O 4-Zb 10- 97 Me CH (Me) CH ₂ H 2-EtO-5-Pyr O 4-Zb 10- 98 Me CH ( Me) CH ₂ H 2-iPrO-5-Pyr O 4-Zb 10- 99 Me CH (Me) CH ₂ H 2-MeS-5-Pyr O 4-Zb 10-100 Me CH (Me) CH ₂ H 2 -EtS-5-Pyr O 4-Zb 10-101 Me CH (Me) CH ₂ H 2-iPrS-5-Pyr O 4-Zb 10-102 Me CH (Me) CH ₂ H 2-MeSO ₂ -5- Pyr O 4-Zb 10-103 Me CH (Me) CH ₂ H 2-EtSO ₂ -5-Pyr O 4-Zb 10-104 Me CH (Me) CH ₂ H 2-iPrSO ₂ -5-Pyr O 4- Zb 10-105 Me CH (Me) CH ₂ H 2-Bz-5-Pyr O 4-Zb 10-106 Me CH (Me) CH ₂ H 2-PhO-5-Pyr O 4-Zb 10-107 Me CH (Me) CH ₂ H 2-PhS-5-Pyr O 4-Zb 10-108 Me CH (Me) CH ₂ H 2-PhSO ₂ -5-Pyr O 4-Zb 10-109 Me CH (Me) CH ₂ H 3-Me-6-Pyr O 4-Zb 10-110 Me CH (Me) CH ₂ H 3-Ph-6-Pyr O 4-Zb 10-111 Me CH (Me) CH ₂ H 2-Me-6 -Pyr O 4-Zb 10-112 Me CH (Me) CH ₂ H 2-Ph-6-Pyr O 4-Zb 10-113 Me CH (Me) CH ₂ H 2-Me-4-Pym O 4-Zb 10-114 Me CH (Me) CH ₂ H 2-Ph-4-Pym O 4-Zb 10-115 Me CH (Me) CH ₂ H 2-MeO-4-Pym O 4-Zb 10-116 Me CH (Me) CH ₂ H 2-EtO-4-Pym O 4-Zb 10-117 Me CH (Me) CH ₂ H 2-iPrO-4-Pym O 4-Zb 10-118 Me CH (Me) CH ₂ H 2-MeS-4-Pym O 4-Zb 10-119 Me CH (Me) CH ₂ H 2-EtS- 4-Pym O 4-Zb 10-120 Me CH (Me) CH ₂ H 2-iPrS-4-Pym O 4-Zb 10-121 Me CH (Me) CH ₂ H 6-MeS-4-Pym O 4- Zb 10-122 Me CH (Me) CH ₂ H 6-EtS-4-Pym O 4-Zb 10-123 Me CH (Me) CH ₂ H 6-iPrS-4-Pym O 4-Zb 10-124 Me CH (Me) CH ₂ H 2-PhS-4-Pym O 4-Zb 10-125 Me CH (Me) CH ₂ H 2-MeSO ₂ -4-Pym O 4-Zb 10-126 Me CH (Me) CH ₂ H 2-EtSO ₂ -4-Pym O 4-Zb 10-127 Me CH (Me) CH ₂ H 2-iPrSO ₂ -4-Pym O 4-Zb 10-128 Me CH (Me) CH ₂ H 2-PhSO ₂ -4-Pym O 4-Zb 10-129 Me CH (Me) CH ₂ H 2-Me-5-Pym O 4-Zb 10-130 Me CH (Me) CH ₂ H 2-Ph-5-Pym O 4-Zb 10-131 Me CH (Me) CH ₂ H 2-MeO-5-Pym O 4-Zb 10-132 Me CH (Me) CH ₂ H 2-EtO-5-Pym O 4-Zb 10-133 Me CH (Me) CH ₂ H 2-iPrO-5-Pym O 4-Zb 10-134 Me CH (Me) CH ₂ H 2-MeS-5-Pym O 4-Zb 10-135 Me CH (Me) CH ₂ H 2-EtS-5-Pym O 4-Zb 10-136 Me CH (Me) CH ₂ H 2-iPrS-5-Pym O 4-Zb 10-137 Me CH (Me) CH ₂ H 2-PhS- 5-Pym O 4-Zb 10-138 Me CH (Me) CH ₂ H 2-MeSO ₂ -5-Pym O 4-Zb 10-139 Me CH (Me) CH ₂ H 2-EtSO ₂ -5-Pym O 4-Zb 10-140 Me CH (Me) CH ₂ H 2-iPrSO ₂ -5-Pym O 4-Zb 10-141 Me CH (Me) CH ₂ H 2-PhSO ₂ -5-Pym O 4-Zb 10-142 Me CH (Me) CH ₂ H 2-Ind O 4-Zb 10-143 Me CH (Me) CH ₂ H 3-Ind O 4-Zb 10-144 Me CH (Me) CH ₂ H 1-Me-2-Ind O 4-Zb 10-145 Me CH (Me) CH ₂ H 1-Me-3-Ind O 4-Zb 10-146 Me CH (Me) CH ₂ H 2-Bimid O 4-Zb 10-147 Me CH (Me) CH ₂ H 2-Boxa O 4-Zb 10- 148 Me CH (Me) CH ₂ H 2-Bthiz O 4-Zb 10-149 Me CH (Me) CH ₂ H 2-Quin O 4-Zb 10-150 Me CH (Me) CH ₂ H 3-Quin O 4 -Zb 10-151 Me CH (Me) CH ₂ H 4-Quin O 4-Zb 10-152 Me CH (Me) CH ₂ H 1-iQuin O 4-Zb 10-153 Me CH (Me) CH ₂ H 3 -iQuin O 4-Zb 10-154 Me CH (Me) CH ₂ H 4-iQuin O 4-Zb 10-155 Me CH (Me) CH ₂ H 3-MeO-Ph O 4-Zb 10-156 Me CH ( Me) CH ₂ H 4-MeO-Ph O 4-Zb 10-157 Me CH (Me) CH ₂ H 3-EtO-Ph O 4-Zb 10-158 Me CH (Me) CH ₂ H 4-EtO-Ph O 4-Zb 10-159 Me CH (Me) CH ₂ H 3-iPrO-Ph O 4-Zb 10-160 Me CH (Me) CH ₂ H 4-iPrO-Ph O 4-Zb 10-161 Me CH ( Me) CH ₂ H 3-MeS-Ph O 4-Zb 10-162 Me CH (Me) CH ₂ H 4-MeS-Ph O 4-Zb 10-163 Me CH (Me) CH ₂ H 3-EtS- Ph O 4-Zb 10-164 Me CH (Me) CH ₂ H 4-EtS-Ph O 4-Zb 10-165 Me CH (Me) CH ₂ H 3-iPrS-Ph O 4-Zb 10-166 Me CH (Me) CH ₂ H 4-iPrS-Ph O 4-Zb 10-167 Me CH (Me) CH ₂ H 3-MeSO ₂ -Ph O 4-Zb 10-168 Me CH (Me) CH ₂ H 4-MeSO ₂ -Ph O 4-Zb 10-169 Me CH (Me) CH ₂ H 3-EtSO ₂ -Ph O 4-Zb 10-170 Me CH (Me) CH ₂ H 4-EtSO ₂ -Ph O 4-Zb 10 -171 Me CH (Me) CH ₂ H 3-iPrSO ₂ -Ph O 4-Zb 10-172 Me CH (Me) CH ₂ H 4-iPrSO ₂ -Ph O 4-Zb 10-173 Me CH (Me) CH ₂ H 3- (1-Me-Imid-4) -Ph O 4-Zb 10-174 Me CH (Me) CH ₂ H 4- (1-Me-Imid-4) -Ph O 4-Zb 10-175 Me CH (Me) CH ₂ H 1-Me-2-Ph-4-Imid O 4-Zb 10-176 Me CH (Me) CH ₂ H 1,4-di-Me-2-Ph-5-Imid O 4-Zb 10-177 Me CH (Me) CH ₂ H 1,5-di-Me-2-Ph-4-Imid O 4-Zb 10-178 Me CH (Me) CH ₂ H 3,4-MdO- Ph O 4-Zb 10-179 Me CH (Me) CH ₂ H 4- (4-MeO-Ph) -Ph O 4-Zb 10-180 Me CH (Me) CH ₂ H 4- (3,4-MdO -Ph) -Ph O 4-Zb 10-181 Me CH (Me) CH ₂ H 4- [PhSO ₂ N (Me)]-Ph O 4-Zb 10-182 Me CH (Me) CH ₂ H 4- [ (Pyr-3) SO ₂ N (Me)]-Ph O 4-Zb 10-183 Me CH (Me) CH ₂ H 4- (PhSO ₂ NH) -Ph O 4-Zb 10-184 Me CH (Me) CH ₂ H 4-[(Pyr-3) SO ₂ NH] -Ph O 4-Zb 10-185 Me CH (Me) CH ₂ H 4-[(Pyr-2) SO ₂ ] -Ph O 4-Zb 10-186 Me CH (Me) CH ₂ H 4-[(Pyr-3) SO ₂ ] -Ph O 4-Zb 10-187 Me CH (Me) CH ₂ H 4-[(Pyr-2) SO ₂ N (Me)]-Ph O 4-Zb 10-188 Me CH (Me) CH ₂ H 4-[(Pyr-2) SO ₂ NH] -Ph O 4-Zb 10-189 Me CH (Me) CH ₂ H 4- (4-Me-Ph) -Ph O 4-Zb 10-190 Me CH (Me) CH ₂ H 4- (4-F- Ph) -Ph O 4-Zb 10-191 Me CH (Me) CH ₂ H 4- (4-CF ₃ -Ph) -Ph O 4-Zb 10-192 Me CH (Me) CH ₂ H 2- [4 -Me-PhSO ₂ N (Me)]-5-Pyr O 4-Zb 10-193 Me CH (Me) CH ₂ H 2-HO-5-Pyr O 4-Zb 10-194 Me CH (Me) CH ₂ H 2-BzO-5-Pyr O 4-Zb 10-195 Me CH (Me) CH ₂ H 4-[(Pyr-4) SO ₂ ] -Ph O 4-Zb 10-196 Me CH (Me) CH ₂ H 4- (2,4-di-MeO-Ph) -Ph O 4-Zb 10-197 Me CH (Me) CH ₂ H 4- (2,5-di-MeO-Ph) -Ph O 4-Zb 10-198 Me CH (Me) CH ₂ H 3-HO-Ph O 4-Zb 10-199 Me CH (Me) CH ₂ H 4-HO-Ph O 4-Zb 10-200 Me CH (Me) CH ₂ H 5-AcO-2-HO-3,4,6-tri-Me-Ph O 4-Zb 10-201 Me CH (Me) CH ₂ H 4-HO-3,5-di-Me-Ph O 4 -Zb 10-202 Me CH (Me) CH ₂ H 3-AcO-Ph O 4-Zb 10-203 Me CH (Me) CH ₂ H 4-AcO-Ph O 4-Zb ──────── ──────────────────────────.

[0100]

[Table 11] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 11- 1 HC (Me) ₂ CH ₂ H 4 -Et-Ph O 4-Zb 11- 2 HC (Me) ₂ CH ₂ H 4-iPr-Ph O 4-Zb 11- 3 HC (Me) ₂ CH ₂ H 3-Ph-Ph O 4-Zb 11- 4 HC (Me) ₂ CH ₂ H 4-Ph-Ph O 4-Zb 11-5 HC (Me) ₂ CH ₂ H 3-Pyr O 4-Zb 11-6 HC (Me) ₂ CH ₂ H 5-Me -3-Pyr O 4-Zb 11-7 HC (Me) ₂ CH ₂ H 5-Et-3-Pyr O 4-Zb 11-8 HC (Me) ₂ CH ₂ H 5-Ph-3-Pyr O 4 -Zb 11-9 HC (Me) ₂ CH ₂ H 6-Me-3-Pyr O 4-Zb 11-10 HC (Me) ₂ CH ₂ H 6-Et-3-Pyr O 4-Zb 11-11 HC (Me) ₂ CH ₂ H 6-Ph-3-Pyr O 4-Zb 11-12 HC (Me) ₂ CH ₂ H 6-MeO-3-Pyr O 4-Zb 11-13 HC (Me) ₂ CH ₂ H 6-EtO-3-Pyr O 4-Zb 11-14 HC (Me) ₂ CH ₂ H 6-iPrO-3-Pyr O 4-Zb 11-15 HC (Me) ₂ CH ₂ H 6-MeS-3 -Pyr O 4-Zb 11-16 HC (Me) ₂ CH ₂ H 6-EtS-3-Pyr O 4-Zb 11-17 HC (Me) ₂ CH ₂ H 6-iPrS-3-Pyr O 4-Zb 11-18 HC (Me) ₂ CH ₂ H 6-MeSO ₂ -3-Pyr O 4-Zb 11-19 HC (Me) ₂ CH ₂ H 6-EtSO ₂ -3-Pyr O 4-Zb 11-20 HC (Me) ₂ CH ₂ H 6-iPrSO ₂ -3-Pyr O 4-Zb 11- 21 HC (Me) ₂ CH ₂ H 6-Bz-3-Pyr O 4-Zb 11- 22 HC (Me) ₂ CH ₂ H 6-PhO-3-Pyr O 4-Zb 11- 23 HC (Me) ₂ CH ₂ H 6-PhS-3-Pyr O 4-Zb 11- 24 HC (Me) ₂ CH ₂ H 6-PhSO ₂ -3-Pyr O 4-Zb 11- 25 HC (Me) ₂ CH ₂ H 2-Quin O 4-Zb 11- 26 HC (Me) ₂ CH ₂ H 4-MeO-Ph O 4-Zb 11- 27 HC (Me) ₂ CH ₂ H 4-EtO-Ph O 4- Zb 11- 28 HC (Me) ₂ CH ₂ H 4-iPrO-Ph O 4-Zb 11- 29 HC (Me) ₂ CH ₂ H 4-MeS-Ph O 4-Zb 11-30 HC (Me) ₂ CH ₂ H 4-EtS-Ph O 4-Zb 11- 31 HC (Me) ₂ CH ₂ H 4-iPrS-Ph O 4-Zb 11- 32 HC (Me) ₂ CH ₂ H 4-MeSO ₂ -Ph O 4 -Zb 11- 33 HC (Me) ₂ CH ₂ H 4-EtSO ₂ -Ph O 4-Zb 11- 34 HC (Me) ₂ CH ₂ H 4-iPrSO ₂ -Ph O 4-Zb ────── ────────────────────────────.

[0101]

[Table 12] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 12- 1 Me C (Me) ₂ CH ₂ H 4-Et-Ph O 4-Zb 12- 2 Me C (Me) ₂ CH ₂ H 4-iPr-Ph O 4-Zb 12- 3 Me C (Me) ₂ CH ₂ H 3-Ph-Ph O 4- Zb 12- 4 Me C (Me) ₂ CH ₂ H 4-Ph-Ph O 4-Zb 12- 5 Me C (Me) ₂ CH ₂ H 3-Pyr O 4-Zb 12-6 Me C (Me) ₂ CH ₂ H 5-Me-3-Pyr O 4-Zb 12- 7 Me C (Me) ₂ CH ₂ H 5-Et-3-Pyr O 4-Zb 12- 8 Me C (Me) ₂ CH ₂ H 5 -Ph-3-Pyr O 4-Zb 12- 9 Me C (Me) ₂ CH ₂ H 6-Me-3-Pyr O 4-Zb 12- 10 Me C (Me) ₂ CH ₂ H 6-Et-3 -Pyr O 4-Zb 12- 11 Me C (Me) ₂ CH ₂ H 6-Ph-3-Pyr O 4-Zb 12-12 Me C (Me) ₂ CH ₂ H 6-MeO-3-Pyr O 4 -Zb 12- 13 Me C (Me) ₂ CH ₂ H 6-EtO-3-Pyr O 4-Zb 12- 14 Me C (Me) ₂ CH ₂ H 6-iPrO-3-Pyr O 4-Zb 12- 15 Me C (Me) ₂ CH ₂ H 6-MeS-3-Pyr O 4-Zb 12- 16 Me C (Me) ₂ CH ₂ H 6-EtS-3-Pyr O 4-Zb 12-17 Me C ( Me) ₂ CH ₂ H 6-iPrS-3-Pyr O 4-Z b 12-18 Me C (Me) ₂ CH ₂ H 6-MeSO ₂ -3-Pyr O 4-Zb 12-19 Me C (Me) ₂ CH ₂ H 6-EtSO ₂ -3-Pyr O 4-Zb 12 -20 Me C (Me) ₂ CH ₂ H 6-iPrSO ₂ -3-Pyr O 4-Zb 12- 21 Me C (Me) ₂ CH ₂ H 6-Bz-3-Pyr O 4-Zb 12-22 Me C (Me) ₂ CH ₂ H 6-PhO-3-Pyr O 4-Zb 12- 23 Me C (Me) ₂ CH ₂ H 6-PhS-3-Pyr O 4-Zb 12- 24 Me C (Me) ₂ CH ₂ H 6-PhSO ₂ -3-Pyr O 4-Zb 12- 25 Me C (Me) ₂ CH ₂ H 2-Quin O 4-Zb 12- 26 Me C (Me) ₂ CH ₂ H 4-MeO -Ph O 4-Zb 12- 27 Me C (Me) ₂ CH ₂ H 4-EtO-Ph O 4-Zb 12- 28 Me C (Me) ₂ CH ₂ H 4-iPrO-Ph O 4-Zb 12- 29 Me C (Me) ₂ CH ₂ H 4-MeS-Ph O 4-Zb 12- 30 Me C (Me) ₂ CH ₂ H 4-EtS-Ph O 4-Zb 12- 31 Me C (Me) ₂ CH ₂ H 4-iPrS-Ph O 4-Zb 12- 32 Me C (Me) ₂ CH ₂ H 4-MeSO ₂ -Ph O 4-Zb 12- 33 Me C (Me) ₂ CH ₂ H 4-EtSO _2- Ph O 4-Zb 12- 34 Me C (Me) ₂ CH ₂ H 4-iPrSO ₂ -Ph O 4-Zb ─────────────────────── ───────────.

[0102]

[Table 13] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 13- 1 H CH ₂ CH (Me) H 4 -Et-Ph O 4-Zb 13- 2 H CH ₂ CH (Me) H 4-iPr-Ph O 4-Zb 13- 3 H CH ₂ CH (Me) H 3-Ph-Ph O 4-Zb 13- 4 H CH ₂ CH (Me) H 4-Ph-Ph O 4-Zb 13- 5 H CH ₂ CH (Me) H 3-Pyr O 4-Zb 13-6 H CH ₂ CH (Me) H 5-Me -3-Pyr O 4-Zb 13-7 H CH ₂ CH (Me) H 5-Et-3-Pyr O 4-Zb 13-8 H CH ₂ CH (Me) H 5-Ph-3-Pyr O 4 -Zb 13-9 H CH ₂ CH (Me) H 6-Me-3-Pyr O 4-Zb 13-10 H CH ₂ CH (Me) H 6-Et-3-Pyr O 4-Zb 13-11 H CH ₂ CH (Me) H 6-Ph-3-Pyr O 4-Zb 13-12 H CH ₂ CH (Me) H 6-MeO-3-Pyr O 4-Zb 13-13 H CH ₂ CH (Me) H 6-EtO-3-Pyr O 4-Zb 13-14 H CH ₂ CH (Me) H 6-iPrO-3-Pyr O 4-Zb 13-15 H CH ₂ CH (Me) H 6-MeS-3 -Pyr O 4-Zb 13-16 H CH ₂ CH (Me) H 6-EtS-3-Pyr O 4-Zb 13-17 H CH ₂ CH (Me) H 6-iPrS-3-Pyr O 4-Zb 13- 18 H CH ₂ CH (Me) H 6-MeSO ₂ -3-Pyr O 4-Zb 13-19 H CH ₂ CH (Me) H 6-EtSO ₂ -3-Pyr O 4-Zb 13-20 H CH ₂ CH (Me) H 6-iPrSO ₂ -3-Pyr O 4-Zb 13- 21 H CH ₂ CH (Me) H 6-Bz-3-Pyr O 4-Zb 13- 22 H CH ₂ CH (Me) H 6-PhO-3-Pyr O 4-Zb 13- 23 H CH ₂ CH (Me) H 6-PhS-3-Pyr O 4-Zb 13- 24 H CH ₂ CH (Me) H 6-PhSO ₂ -3-Pyr O 4-Zb 13- 25 H CH ₂ CH (Me) H 2-Quin O 4-Zb 13- 26 H CH ₂ CH (Me) H 4-MeO-Ph O 4-Zb 13- 27 H CH ₂ CH (Me) H 4-EtO-Ph O 4- Zb 13- 28 H CH ₂ CH (Me) H 4-iPrO-Ph O 4-Zb 13- 29 H CH ₂ CH (Me) H 4-MeS-Ph O 4-Zb 13-30 H CH ₂ CH (Me ) H 4-EtS-Ph O 4-Zb 13- 31 H CH ₂ CH (Me) H 4-iPrS-Ph O 4-Zb 13- 32 H CH ₂ CH (Me) H 4-MeSO ₂ -Ph O 4 -Zb 13- 33 H CH ₂ CH (Me) H 4-EtSO ₂ -Ph O 4-Zb 13- 34 H CH ₂ CH (Me) H 4-iPrSO ₂ -Ph O 4-Zb ────── ────────────────────────────.

[0103]

[Table 14] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 14- 1 Me CH ₂ CH (Me) H 4 -Et-Ph O 4-Zb 14- 2 Me CH ₂ CH (Me) H 4-iPr-Ph O 4-Zb 14- 3 Me CH ₂ CH (Me) H 3-Ph-Ph O 4-Zb 14- 4 Me CH ₂ CH (Me) H 4-Ph-Ph O 4-Zb 14- 5 Me CH ₂ CH (Me) H 3-Pyr O 4-Zb 14- 6 Me CH ₂ CH (Me) H 5-Me -3-Pyr O 4-Zb 14-7 Me CH ₂ CH (Me) H 5-Et-3-Pyr O 4-Zb 14- 8 Me CH ₂ CH (Me) H 5-Ph-3-Pyr O 4 -Zb 14- 9 Me CH ₂ CH (Me) H 6-Me-3-Pyr O 4-Zb 14-10 Me CH ₂ CH (Me) H 6-Et-3-Pyr O 4-Zb 14- 11 Me CH ₂ CH (Me) H 6-Ph-3-Pyr O 4-Zb 14-12 Me CH ₂ CH (Me) H 6-MeO-3-Pyr O 4-Zb 14-13 Me CH ₂ CH (Me) H 6-EtO-3-Pyr O 4-Zb 14-14 Me CH ₂ CH (Me) H 6-iPrO-3-Pyr O 4-Zb 14-15 Me CH ₂ CH (Me) H 6-MeS-3 -Pyr O 4-Zb 14-16 Me CH ₂ CH (Me) H 6-EtS-3-Pyr O 4-Zb 14-17 Me CH ₂ CH (Me) H 6-iPrS-3-Pyr O 4-Zb 14-18 Me CH ₂ CH (Me) H 6-MeSO ₂ -3-Pyr O 4-Zb 14- 19 Me CH ₂ CH (Me) H 6-EtSO ₂ -3-Pyr O 4-Zb 14-20 Me CH ₂ CH (Me) H 6-iPrSO ₂ -3-Pyr O 4-Zb 14- 21 Me CH ₂ CH (Me) H 6-Bz-3-Pyr O 4-Zb 14-22 Me CH ₂ CH (Me) H 6-PhO- 3-Pyr O 4-Zb 14-23 Me CH ₂ CH (Me) H 6-PhS-3-Pyr O 4-Zb 14-24 Me CH ₂ CH (Me) H 6-PhSO ₂ -3-Pyr O 4 -Zb 14- 25 Me CH ₂ CH (Me) H 2-Quin O 4-Zb 14- 26 Me CH ₂ CH (Me) H 4-MeO-Ph O 4-Zb 14- 27 Me CH ₂ CH (Me) H 4-EtO-Ph O 4-Zb 14- 28 Me CH ₂ CH (Me) H 4-iPrO-Ph O 4-Zb 14- 29 Me CH ₂ CH (Me) H 4-MeS-Ph O 4-Zb 14- 30 Me CH ₂ CH (Me) H 4-EtS-Ph O 4-Zb 14- 31 Me CH ₂ CH (Me) H 4-iPrS-Ph O 4-Zb 14- 32 Me CH ₂ CH (Me) H 4-MeSO ₂ -Ph O 4-Zb 14- 33 Me CH ₂ CH (Me) H 4-EtSO ₂ -Ph O 4-Zb 14- 34 Me CH ₂ CH (Me) H 4-iPrSO ₂ -Ph O 4-Zb ──────────────────────────────────.

[0104]

[Table 15] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 15- 1 H CH (Me) CH (Me) H 4-Et-Ph O 4-Zb 15- 2 H CH (Me) CH (Me) H 4-iPr-Ph O 4-Zb 15- 3 H CH (Me) CH (Me) H 3-Ph-Ph O 4-Zb 15- 4 H CH (Me) CH (Me) H 4-Ph-Ph O 4-Zb 15- 5 H CH (Me) CH (Me) H 3-Pyr O 4-Zb 15-6 H CH (Me) CH (Me) H 5-Me-3-Pyr O 4-Zb 15- 7 H CH (Me) CH (Me) H 5-Et-3-Pyr O 4-Zb 15-8 H CH ( Me) CH (Me) H 5-Ph-3-Pyr O 4-Zb 15- 9 H CH (Me) CH (Me) H 6-Me-3-Pyr O 4-Zb 15-10 H CH (Me) CH (Me) H 6-Et-3-Pyr O 4-Zb 15-11 H CH (Me) CH (Me) H 6-Ph-3-Pyr O 4-Zb 15-12 H CH (Me) CH ( Me) H 6-MeO-3-Pyr O 4-Zb 15-13 H CH (Me) CH (Me) H 6-EtO-3-Pyr O 4-Zb 15-14 H CH (Me) CH (Me) H 6-iPrO-3-Pyr O 4-Zb 15-15 H CH (Me) CH (Me) H 6-MeS-3-Pyr O 4-Zb 15-16 H CH (Me) CH (Me) H 6 -EtS-3-Pyr O 4-Zb 15-17 H CH (Me) CH (Me) H 6-iPrS-3-Pyr O 4-Zb 15-18 H CH (Me) CH (Me) H 6-MeSO ₂ -3-Pyr O 4-Zb 15-19 H CH (Me) CH (Me) H 6-EtSO ₂ -3-Pyr O 4-Zb 15-20 H CH (Me) CH (Me) H 6-iPrSO ₂ -3-Pyr O 4-Zb 15- 21 H CH (Me) CH (Me) H 6-Bz-3-Pyr O 4-Zb 15-22 H CH (Me) CH (Me) H 6-PhO-3-Pyr O 4-Zb 15-23 H CH (Me) CH (Me) H 6-PhS-3-Pyr O 4-Zb 15-24 H CH (Me) CH (Me ) H 6-PhSO ₂ -3-Pyr O 4-Zb 15- 25 H CH (Me) CH (Me) H 2-Quin O 4-Zb 15- 26 H CH (Me) CH (Me) H 4-MeO -Ph O 4-Zb 15- 27 H CH (Me) CH (Me) H 4-EtO-Ph O 4-Zb 15- 28 H CH (Me) CH (Me) H 4-iPrO-Ph O 4-Zb 15- 29 H CH (Me) CH (Me) H 4-MeS-Ph O 4-Zb 15-30 H CH (Me) CH (Me) H 4-EtS-Ph O 4-Zb 15- 31 H CH ( Me) CH (Me) H 4-iPrS-Ph O 4-Zb 15- 32 H CH (Me) CH (Me) H 4-MeSO ₂ -Ph O 4-Zb 15-33 H CH (Me) CH (Me ) H 4-EtSO ₂ -Ph O 4-Zb 15- 34 H CH (Me) CH (Me) H 4-iPrSO ₂ -Ph O 4-Zb ─────────────── ───────────────────.

[0105]

[Table 16] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 16- 1 Me CH (Me) CH (Me) H 4-Et-Ph O 4-Zb 16- 2 Me CH (Me) CH (Me) H 4-iPr-Ph O 4-Zb 16- 3 Me CH (Me) CH (Me) H 3-Ph-Ph O 4-Zb 16- 4 Me CH (Me) CH (Me) H 4-Ph-Ph O 4-Zb 16- 5 Me CH (Me) CH (Me) H 3-Pyr O 4-Zb 16-6 Me CH (Me) CH (Me) H 5-Me-3-Pyr O 4-Zb 16-7 Me CH (Me) CH (Me) H 5-Et-3-Pyr O 4-Zb 16-8 Me CH ( Me) CH (Me) H 5-Ph-3-Pyr O 4-Zb 16-9 Me CH (Me) CH (Me) H 6-Me-3-Pyr O 4-Zb 16-10 Me CH (Me) CH (Me) H 6-Et-3-Pyr O 4-Zb 16-11 Me CH (Me) CH (Me) H 6-Ph-3-Pyr O 4-Zb 16-12 Me CH (Me) CH ( Me) H 6-MeO-3-Pyr O 4-Zb 16-13 Me CH (Me) CH (Me) H 6-EtO-3-Pyr O 4-Zb 16-14 Me CH (Me) CH (Me) H 6-iPrO-3-Pyr O 4-Zb 16-15 Me CH (Me) CH (Me) H 6-MeS-3-Pyr O 4-Zb 16-16 Me CH (Me) CH (Me) H 6 -EtS-3-Pyr O 4-Zb 16-17 Me CH (Me) CH (Me) H 6-iPrS-3-Pyr O 4-Z b 16-18 Me CH (Me) CH (Me) H 6-MeSO ₂ -3-Pyr O 4-Zb 16-19 Me CH (Me) CH (Me) H 6-EtSO ₂ -3-Pyr O 4- Zb 16-20 Me CH (Me) CH (Me) H 6-iPrSO ₂ -3-Pyr O 4-Zb 16-21 Me CH (Me) CH (Me) H 6-Bz-3-Pyr O 4-Zb 16- 22 Me CH (Me) CH (Me) H 6-PhO-3-Pyr O 4-Zb 16- 23 Me CH (Me) CH (Me) H 6-PhS-3-Pyr O 4-Zb 16- 24 Me CH (Me) CH (Me) H 6-PhSO ₂ -3-Pyr O 4-Zb 16- 25 Me CH (Me) CH (Me) H 2-Quin O 4-Zb 16- 26 Me CH (Me ) CH (Me) H 4-MeO-Ph O 4-Zb 16- 27 Me CH (Me) CH (Me) H 4-EtO-Ph O 4-Zb 16- 28 Me CH (Me) CH (Me) H 4-iPrO-Ph O 4-Zb 16- 29 Me CH (Me) CH (Me) H 4-MeS-Ph O 4-Zb 16-30 Me CH (Me) CH (Me) H 4-EtS-Ph O 4-Zb 16- 31 Me CH (Me) CH (Me) H 4-iPrS-Ph O 4-Zb 16- 32 Me CH (Me) CH (Me) H 4-MeSO ₂ -Ph O 4-Zb 16- 33 Me CH (Me) CH (Me) H 4-EtSO ₂ -Ph O 4-Zb 16- 34 Me CH (Me) CH (Me) H 4-iPrSO ₂ -Ph O 4-Zb ────── ────────────────────────────.

[0106]

[Table 17] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 17- 1 Me (CH ₂ ) ₂ H 4- Et-Ph S 4-Zb 17- 2 Me (CH ₂ ) ₂ H 4-iPr-Ph S 4-Zb 17- 3 Me (CH ₂ ) ₂ H 3-Ph-Ph S 4-Zb 17- 4 Me ( CH ₂ ) ₂ H 4-Ph-Ph S 4-Zb 17-5 Me (CH ₂ ) ₂ H 3-Pyr S 4-Zb 17-6 Me (CH ₂ ) ₂ H 5-Me-3-Pyr S 4 -Zb 17- 7 Me (CH ₂ ) ₂ H 5-Et-3-Pyr S 4-Zb 17- 8 Me (CH ₂ ) ₂ H 5-Ph-3-Pyr S 4-Zb 17- 9 Me (CH ₂ ) ₂ H 6-Me-3-Pyr S 4-Zb 17-10 Me (CH ₂ ) ₂ H 6-Et-3-Pyr S 4-Zb 17-11 Me (CH ₂ ) ₂ H 6-Ph- 3-Pyr S 4-Zb 17-12 Me (CH ₂ ) ₂ H 6-MeO-3-Pyr S 4-Zb 17-13 Me (CH ₂ ) ₂ H 6-EtO-3-Pyr S 4-Zb 17 -14 Me (CH ₂ ) ₂ H 6-iPrO-3-Pyr S 4-Zb 17-15 Me (CH ₂ ) ₂ H 6-MeS-3-Pyr S 4-Zb 17-16 Me (CH ₂ ) ₂ H 6-EtS-3-Pyr S 4-Zb 17-17 Me (CH ₂ ) ₂ H 6-iPrS-3-Pyr S 4-Zb 17-18 Me (CH ₂ ) ₂ H 6-MeSO ₂ -3- Pyr S 4-Zb 17- 19 Me (CH ₂ ) ₂ H 6-EtSO ₂ -3-Pyr S 4-Zb 17-20 Me (CH ₂ ) ₂ H 6-iPrSO ₂ -3-Pyr S 4-Zb 17- 21 Me (CH ₂ ) _{2 H 6-Bz-3-} Pyr S 4-Zb 17- 22 Me (CH 2) 2 H 6-PhO-3-Pyr S 4-Zb 17- 23 Me (CH 2) 2 H 6-PhS-3- Pyr S 4-Zb 17- 24 Me (CH ₂ ) ₂ H 6-PhSO ₂ -3-Pyr S 4-Zb 17- 25 Me (CH ₂ ) ₂ H 2-Quin S 4-Zb 17- 26 Me (CH ₂ ) ₂ H 4-MeO-Ph S 4-Zb 17- 27 Me (CH ₂ ) ₂ H 4-EtO-Ph S 4-Zb 17- 28 Me (CH ₂ ) ₂ H 4-iPrO-Ph S 4- Zb 17- 29 Me (CH ₂ ) ₂ H 4-MeS-Ph S 4-Zb 17-30 Me (CH ₂ ) ₂ H 4-EtS-Ph S 4-Zb 17- 31 Me (CH ₂ ) ₂ H 4 -iPrS-Ph S 4-Zb 17- 32 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph S 4-Zb 17- 33 Me (CH ₂ ) ₂ H 4-EtSO ₂ -Ph S 4-Zb 17- 34 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph S 4-Zb ──────────────────────────────── ──.

[0107]

[Table 18] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 18- 1 Me (CH ₂ ) ₂ H 4- Et-Ph NMe 4-Zb 18- 2 Me (CH ₂ ) ₂ H 4-iPr-Ph NMe 4-Zb 18- 3 Me (CH ₂ ) ₂ H 3-Ph-Ph NMe 4-Zb 18- 4 Me ( CH ₂ ) ₂ H 4-Ph-Ph NMe 4-Zb 18-5 Me (CH ₂ ) ₂ H 3-Pyr NMe 4-Zb 18-6 Me (CH ₂ ) ₂ H 5-Me-3-Pyr NMe 4 -Zb 18- 7 Me (CH ₂ ) ₂ H 5-Et-3-Pyr NMe 4-Zb 18- 8 Me (CH ₂ ) ₂ H 5-Ph-3-Pyr NMe 4-Zb 18- 9 Me (CH ₂ ) ₂ H 6-Me-3-Pyr NMe 4-Zb 18-10 Me (CH ₂ ) ₂ H 6-Et-3-Pyr NMe 4-Zb 18-11 Me (CH ₂ ) ₂ H 6-Ph- 3-Pyr NMe 4-Zb 18-12 Me (CH ₂ ) ₂ H 6-MeO-3-Pyr NMe 4-Zb 18-13 Me (CH ₂ ) ₂ H 6-EtO-3-Pyr NMe 4-Zb 18 -14 Me (CH ₂ ) ₂ H 6-iPrO-3-Pyr NMe 4-Zb 18-15 Me (CH ₂ ) ₂ H 6-MeS-3-Pyr NMe 4-Zb 18-16 Me (CH ₂ ) ₂ H 6-EtS-3-Pyr NMe 4-Zb 18-17 Me (CH ₂ ) ₂ H 6-iPrS-3-Pyr NMe 4-Zb 18-18 Me (CH ₂ ) ₂ H 6-MeSO ₂ -3-Pyr NMe 4-Zb 18-19 Me (CH ₂ ) ₂ H 6-EtSO ₂ -3-Pyr NMe 4-Zb 18-20 Me (CH ₂ ) ₂ H 6-iPrSO ₂ -3-Pyr NMe 4-Zb 18-21 Me (CH ₂ ) ₂ H 6-Bz-3-Pyr NMe 4-Zb 18-22 Me (CH ₂ ) ₂ H 6-PhO-3-Pyr NMe 4- _{Zb 18- 23 Me (CH 2)} 2 H 6-PhS-3-Pyr NMe 4-Zb 18- 24 Me (CH 2) 2 H 6-PhSO 2 -3-Pyr NMe 4-Zb 18- 25 Me (CH ₂ ) ₂ H 2-Quin NMe 4-Zb 18- 26 Me (CH ₂ ) ₂ H 4-MeO-Ph NMe 4-Zb 18- 27 Me (CH ₂ ) ₂ H 4-EtO-Ph NMe 4-Zb 18 -28 Me (CH ₂ ) ₂ H 4-iPrO-Ph NMe 4-Zb 18-29 Me (CH ₂ ) ₂ H 4-MeS-Ph NMe 4-Zb 18-30 Me (CH ₂ ) ₂ H 4-EtS -Ph NMe 4-Zb 18- 31 Me (CH ₂ ) ₂ H 4-iPrS-Ph NMe 4-Zb 18- 32 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph NMe 4-Zb 18- 33 Me ( CH ₂ ) ₂ H 4-EtSO ₂ -Ph NMe 4-Zb 18- 34 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph NMe 4-Zb ─────────────── ───────────────────.

[0108]

[Table 19] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 19- 1 Me (CH ₂ ) ₂ H 4- Et-Ph NAc 4-Zb 19- 2 Me (CH ₂ ) ₂ H 4-iPr-Ph NAc 4-Zb 19- 3 Me (CH ₂ ) ₂ H 3-Ph-Ph NAc 4-Zb 19- 4 Me ( CH ₂ ) ₂ H 4-Ph-Ph NAc 4-Zb 19-5 Me (CH ₂ ) ₂ H 3-Pyr NAc 4-Zb 19-6 Me (CH ₂ ) ₂ H 5-Me-3-Pyr NAc 4 -Zb 19- 7 Me (CH ₂ ) ₂ H 5-Et-3-Pyr NAc 4-Zb 19- 8 Me (CH ₂ ) ₂ H 5-Ph-3-Pyr NAc 4-Zb 19- 9 Me (CH ₂ ) ₂ H 6-Me-3-Pyr NAc 4-Zb 19-10 Me (CH ₂ ) ₂ H 6-Et-3-Pyr NAc 4-Zb 19-11 Me (CH ₂ ) ₂ H 6-Ph- 3-Pyr NAc 4-Zb 19-12 Me (CH ₂ ) ₂ H 6-MeO-3-Pyr NAc 4-Zb 19-13 Me (CH ₂ ) ₂ H 6-EtO-3-Pyr NAc 4-Zb 19 -14 Me (CH ₂ ) ₂ H 6-iPrO-3-Pyr NAc 4-Zb 19-15 Me (CH ₂ ) ₂ H 6-MeS-3-Pyr NAc 4-Zb 19-16 Me (CH ₂ ) ₂ H 6-EtS-3-Pyr NAc 4-Zb 19-17 Me (CH ₂ ) ₂ H 6-iPrS-3-Pyr NAc 4-Zb 19-18 Me (CH ₂ ) ₂ H 6-MeSO ₂ -3-Pyr NAc 4-Zb 19-19 Me (CH ₂ ) ₂ H 6-EtSO ₂ -3-Pyr NAc 4-Zb 19-20 Me (CH ₂ ) ₂ H 6-iPrSO ₂ -3-Pyr NAc 4-Zb 19-21 Me (CH ₂ ) ₂ H 6-Bz-3-Pyr NAc 4-Zb 19-22 Me (CH ₂ ) ₂ H 6-PhO-3-Pyr NAc 4- _{Zb 19- 23 Me (CH 2)} 2 H 6-PhS-3-Pyr NAc 4-Zb 19- 24 Me (CH 2) 2 H 6-PhSO 2 -3-Pyr NAc 4-Zb 19- 25 Me (CH ₂ ) ₂ H 2-Quin NAc 4-Zb 19- 26 Me (CH ₂ ) ₂ H 4-MeO-Ph NAc 4-Zb 19- 27 Me (CH ₂ ) ₂ H 4-EtO-Ph NAc 4-Zb 19 -28 Me (CH ₂ ) ₂ H 4-iPrO-Ph NAc 4-Zb 19-29 Me (CH ₂ ) ₂ H 4-MeS-Ph NAc 4-Zb 19-30 Me (CH ₂ ) ₂ H 4-EtS -Ph NAc 4-Zb 19- 31 Me (CH ₂ ) ₂ H 4-iPrS-Ph NAc 4-Zb 19- 32 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph NAc 4-Zb 19- 33 Me ( CH ₂ ) ₂ H 4-EtSO ₂ -Ph NAc 4-Zb 19- 34 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph NAc 4-Zb ─────────────── ───────────────────.

[0109]

[Table 20] 例 示 Examples R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 20- 1 Me (CH ₂ ) ₂ 2-Cl 4-Et-Ph O 4-Zb 20- 2 Me (CH ₂ ) ₂ 2-Cl 4-iPr-Ph O 4-Zb 20- 3 Me (CH ₂ ) ₂ 2-Cl 3-Ph-Ph O 4- Zb 20- 4 Me (CH ₂ ) ₂ 2-Cl 4-Ph-Ph O 4-Zb 20- 5 Me (CH ₂ ) ₂ 2-Cl 3-Pyr O 4-Zb 20- 6 Me (CH ₂ ) ₂ 2-Cl 5-Me-3-Pyr O 4-Zb 20- 7 Me (CH ₂ ) ₂ 2-Cl 5-Et-3-Pyr O 4-Zb 20- 8 Me (CH ₂ ) ₂ 2-Cl 5 -Ph-3-Pyr O 4-Zb 20- 9 Me (CH ₂ ) ₂ 2-Cl 6-Me-3-Pyr O 4-Zb 20- 10 Me (CH ₂ ) ₂ 2-Cl 6-Et-3 -Pyr O 4-Zb 20- 11 Me (CH ₂ ) ₂ 2-Cl 6-Ph-3-Pyr O 4-Zb 20- 12 Me (CH ₂ ) ₂ 2-Cl 6-MeO-3-Pyr O 4 -Zb 20- 13 Me (CH ₂ ) ₂ 2-Cl 6-EtO-3-Pyr O 4-Zb 20- 14 Me (CH ₂ ) ₂ 2-Cl 6-iPrO-3-Pyr O 4-Zb 20- _{15 Me (CH 2) 2 2} -Cl 6-MeS-3-Pyr O 4-Zb 20- 16 Me (CH 2) 2 2-Cl 6-EtS-3-Pyr O 4-Zb 20- 17 Me (CH ₂ ) ₂ 2-Cl 6-iPrS-3-Pyr O 4-Z b 20-18 Me (CH ₂ ) ₂ 2-Cl 6-MeSO ₂ -3-Pyr O 4-Zb 20-19 Me (CH ₂ ) ₂ 2-Cl 6-EtSO ₂ -3-Pyr O 4-Zb 20 -20 Me (CH ₂ ) ₂ 2-Cl 6-iPrSO ₂ -3-Pyr O 4-Zb 20- 21 Me (CH ₂ ) ₂ 2-Cl 6-Bz-3-Pyr O 4-Zb 20- 22 Me _{(CH 2) 2 2-Cl} 6-PhO-3-Pyr O 4-Zb 20- 23 Me (CH 2) 2 2-Cl 6-PhS-3-Pyr O 4-Zb 20- 24 Me (CH 2) ₂ 2-Cl 6-PhSO ₂ -3-Pyr O 4-Zb 20- 25 Me (CH ₂ ) ₂ 2-Cl 2-Quin O 4-Zb 20- 26 Me (CH ₂ ) ₂ 2-Cl 4-MeO -Ph O 4-Zb 20- 27 Me (CH ₂ ) ₂ 2-Cl 4-EtO-Ph O 4-Zb 20- 28 Me (CH ₂ ) ₂ 2-Cl 4-iPrO-Ph O 4-Zb 20- 29 Me (CH ₂ ) ₂ 2-Cl 4-MeS-Ph O 4-Zb 20- 30 Me (CH ₂ ) ₂ 2-Cl 4-EtS-Ph O 4-Zb 20- 31 Me (CH ₂ ) ₂ 2 -Cl 4-iPrS-Ph O 4-Zb 20- 32 Me (CH ₂ ) ₂ 2-Cl 4-MeSO ₂ -Ph O 4-Zb 20- 33 Me (CH ₂ ) ₂ 2-Cl 4-EtSO _2- Ph O 4-Zb 20- 34 Me (CH ₂ ) ₂ 2-Cl 4-iPrSO ₂ -Ph O 4-Zb ─────────────────────── ───────────.

[0110]

[Table 21] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 21- 1 Me (CH ₂ ) ₂ 3-Cl 4-Et-Ph O 4-Zb 21- 2 Me (CH ₂ ) ₂ 3-Cl 4-iPr-Ph O 4-Zb 21- 3 Me (CH ₂ ) ₂ 3-Cl 3-Ph-Ph O 4- Zb 21- 4 Me (CH ₂ ) ₂ 3-Cl 4-Ph-Ph O 4-Zb 21- 5 Me (CH ₂ ) ₂ 3-Cl 3-Pyr O 4-Zb 21- 6 Me (CH ₂ ) ₂ 3-Cl 5-Me-3-Pyr O 4-Zb 21- 7 Me (CH ₂ ) ₂ 3-Cl 5-Et-3-Pyr O 4-Zb 21- 8 Me (CH ₂ ) ₂ 3-Cl 5 -Ph-3-Pyr O 4-Zb 21-9 Me (CH ₂ ) ₂ 3-Cl 6-Me-3-Pyr O 4-Zb 21-10 Me (CH ₂ ) ₂ 3-Cl 6-Et-3 -Pyr O 4-Zb 21- 11 Me (CH 2) 2 3-Cl 6-Ph-3-Pyr O 4-Zb 21- 12 Me (CH 2) 2 3-Cl 6-MeO-3-Pyr O 4 _{-Zb 21- 13 Me (CH 2)} 2 3-Cl 6-EtO-3-Pyr O 4-Zb 21- 14 Me (CH 2) 2 3-Cl 6-iPrO-3-Pyr O 4-Zb 21- _{15 Me (CH 2) 2 3} -Cl 6-MeS-3-Pyr O 4-Zb 21- 16 Me (CH 2) 2 3-Cl 6-EtS-3-Pyr O 4-Zb 21- 17 Me (CH ₂ ) ₂ 3-Cl 6-iPrS-3-Pyr O 4-Z b 21-18 Me (CH ₂ ) ₂ 3-Cl 6-MeSO ₂ -3-Pyr O 4-Zb 21-19 Me (CH ₂ ) ₂ 3-Cl 6-EtSO ₂ -3-Pyr O 4-Zb 21 -20 Me (CH ₂ ) ₂ 3-Cl 6-iPrSO ₂ -3-Pyr O 4-Zb 21-21 Me (CH ₂ ) ₂ 3-Cl 6-Bz-3-Pyr O 4-Zb 21-22 Me _{(CH 2) 2 3-Cl} 6-PhO-3-Pyr O 4-Zb 21- 23 Me (CH 2) 2 3-Cl 6-PhS-3-Pyr O 4-Zb 21- 24 Me (CH 2) ₂ 3-Cl 6-PhSO ₂ -3-Pyr O 4-Zb 21-25 Me (CH ₂ ) ₂ 3-Cl 2-Quin O 4-Zb 21- 26 Me (CH ₂ ) ₂ 3-Cl 4-MeO -Ph O 4-Zb 21- 27 Me (CH 2) 2 3-Cl 4-EtO-Ph O 4-Zb 21- 28 Me (CH 2) 2 3-Cl 4-iPrO-Ph O 4-Zb 21- 29 Me (CH ₂ ) ₂ 3-Cl 4-MeS-Ph O 4-Zb 21-30 Me (CH ₂ ) ₂ 3-Cl 4-EtS-Ph O 4-Zb 21- 31 Me (CH ₂ ) ₂ 3 -Cl 4-iPrS-Ph O 4-Zb 21- 32 Me (CH ₂ ) ₂ 3-Cl 4-MeSO ₂ -Ph O 4-Zb 21- 33 Me (CH ₂ ) ₂ 3-Cl 4-EtSO _2- Ph O 4-Zb 21- 34 Me (CH ₂ ) ₂ 3-Cl 4-iPrSO ₂ -Ph O 4-Zb ─────────────────────── ───────────.

[0111]

[Table 22] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 22- 1 Me (CH ₂ ) ₂ 2-MeO 4-Et-Ph O 4-Zb 22- 2 Me (CH ₂ ) ₂ 2-MeO 4-iPr-Ph O 4-Zb 22- 3 Me (CH ₂ ) ₂ 2-MeO 3-Ph-Ph O 4- Zb 22- 4 Me (CH ₂ ) ₂ 2-MeO 4-Ph-Ph O 4-Zb 22-5 Me (CH ₂ ) ₂ 2-MeO 3-Pyr O 4-Zb 22-6 Me (CH ₂ ) ₂ 2-MeO 5-Me-3-Pyr O 4-Zb 22-7 Me (CH ₂ ) ₂ 2-MeO 5-Et-3-Pyr O 4-Zb 22-8 Me (CH ₂ ) ₂ 2-MeO 5 -Ph-3-Pyr O 4-Zb 22-9 Me (CH ₂ ) ₂ 2-MeO 6-Me-3-Pyr O 4-Zb 22-10 Me (CH ₂ ) ₂ 2-MeO 6-Et-3 -Pyr O 4-Zb 22- 11 Me (CH ₂ ) ₂ 2-MeO 6-Ph-3-Pyr O 4-Zb 22-12 12 Me (CH ₂ ) ₂ 2-MeO 6-MeO-3-Pyr O 4 -Zb 22- 13 Me (CH ₂ ) ₂ 2-MeO 6-EtO-3-Pyr O 4-Zb 22- 14 Me (CH ₂ ) ₂ 2-MeO 6-iPrO-3-Pyr O 4-Zb 22- _{15 Me (CH 2) 2 2} -MeO 6-MeS-3-Pyr O 4-Zb 22- 16 Me (CH 2) 2 2-MeO 6-EtS-3-Pyr O 4-Zb 22- 17 Me (CH ₂ ) ₂ 2-MeO 6 -iPrS-3-Pyr O 4-Zb 22-18 Me (CH ₂ ) ₂ 2-MeO 6-MeSO ₂ -3-Pyr O 4-Zb 22-19 Me (CH ₂ ) ₂ 2-MeO 6-EtSO ₂ -3-Pyr O 4-Zb 22- 20 Me (CH 2) 2 2-MeO 6-iPrSO 2 -3-Pyr O 4-Zb 22- 21 Me (CH 2) 2 2-MeO 6-Bz-3- Pyr O 4-Zb 22- 22 Me (CH 2) 2 2-MeO 6-PhO-3-Pyr O 4-Zb 22- 23 Me (CH 2) 2 2-MeO 6-PhS-3-Pyr O 4- Zb 22-24 Me (CH ₂ ) ₂ 2-MeO 6-PhSO ₂ -3-Pyr O 4-Zb 22-25 Me (CH ₂ ) ₂ 2-MeO 2-Quin O 4-Zb 22- 26 Me (CH _{2) 2 2-MeO 4-} MeO-Ph O 4-Zb 22- 27 Me (CH 2) 2 2-MeO 4-EtO-Ph O 4-Zb 22- 28 Me (CH 2) 2 2-MeO 4- iPrO-Ph O 4-Zb 22- 29 Me (CH 2) 2 2-MeO 4-MeS-Ph O 4-Zb 22- 30 Me (CH 2) 2 2-MeO 4-EtS-Ph O 4-Zb 22 _{- 31 Me (CH 2) 2} 2-MeO 4-iPrS-Ph O 4-Zb 22- 32 Me (CH 2) 2 2-MeO 4-MeSO 2 -Ph O 4-Zb 22- 33 Me (CH 2) ₂ 2-MeO 4-EtSO ₂ -Ph O 4-Zb 22- 34 Me (CH ₂ ) ₂ 2-MeO 4-iPrSO ₂ -Ph O 4-Zb ────────────── ────────────────────.

[0112]

[Table 23] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 23- 1 Me (CH ₂ ) ₂ 3-MeO 4-Et-Ph O 4- Zb 23- 2 Me (CH 2) 2 3-MeO 4-iPr-Ph O 4-Zb 23- 3 Me (CH 2) 2 3-MeO 3-Ph-Ph O 4- Zb 23- 4 Me (CH ₂ ) ₂ 3-MeO 4-Ph-Ph O 4-Zb 23- 5 Me (CH ₂ ) ₂ 3-MeO 3-Pyr O 4-Zb 23-6 Me (CH ₂ ) ₂ 3-MeO 5-Me-3 -Pyr O 4-Zb 23- 7 Me (CH 2) 2 3-MeO 5-Et-3-Pyr O 4-Zb 23- 8 Me (CH 2) 2 3-MeO 5 -Ph-3-Pyr O 4- Zb 23- 9 Me (CH 2) 2 3-MeO 6-Me-3-Pyr O 4-Zb 23- 10 Me (CH 2) 2 3-MeO 6-Et-3 -Pyr O 4-Zb 23- 11 Me (CH 2) 2 3-MeO 6-Ph-3-Pyr O 4-Zb 23- 12 Me (CH 2) 2 3-MeO 6-MeO-3-Pyr O 4 _{-Zb 23- 13 Me (CH 2)} 2 3-MeO 6-EtO-3-Pyr O 4-Zb 23- 14 Me (CH 2) 2 3-MeO 6-iPrO-3-Pyr O 4-Zb 23- _{15 Me (CH 2) 2 3} -MeO 6-MeS-3-Pyr O 4-Zb 23- 16 Me (CH 2) 2 3-MeO 6-EtS-3-Pyr O 4-Zb 23- 17 Me (CH ₂ ) ₂ 3-MeO 6 -iPrS-3-Pyr O 4-Zb 23-18 Me (CH ₂ ) ₂ 3-MeO 6-MeSO ₂ -3-Pyr O 4-Zb 23-19 Me (CH ₂ ) ₂ 3-MeO 6-EtSO ₂ -3-Pyr O 4-Zb 23- 20 Me (CH 2) 2 3-MeO 6-iPrSO 2 -3-Pyr O 4-Zb 23- 21 Me (CH 2) 2 3-MeO 6-Bz-3- Pyr O 4-Zb 23- 22 Me (CH 2) 2 3-MeO 6-PhO-3-Pyr O 4-Zb 23- 23 Me (CH 2) 2 3-MeO 6-PhS-3-Pyr O 4- _{Zb 23- 24 Me (CH 2)} 2 3-MeO 6-PhSO 2 -3-Pyr O 4-Zb 23- 25 Me (CH 2) 2 3-MeO 2-Quin O 4-Zb 23- 26 Me (CH _{2) 2 3-MeO 4-} MeO-Ph O 4-Zb 23- 27 Me (CH 2) 2 3-MeO 4-EtO-Ph O 4-Zb 23- 28 Me (CH 2) 2 3-MeO 4- iPrO-Ph O 4-Zb 23- 29 Me (CH 2) 2 3-MeO 4-MeS-Ph O 4-Zb 23- 30 Me (CH 2) 2 3-MeO 4-EtS-Ph O 4-Zb 23 _{- 31 Me (CH 2) 2} 3-MeO 4-iPrS-Ph O 4-Zb 23- 32 Me (CH 2) 2 3-MeO 4-MeSO 2 -Ph O 4-Zb 23- 33 Me (CH 2) ₂ 3-MeO 4-EtSO ₂ -Ph O 4-Zb 23- 34 Me (CH ₂ ) ₂ 3-MeO 4-iPrSO ₂ -Ph O 4-Zb ────────────── ────────────────────.

[0113]

[Table 24] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 24- 1 Me (CH ₂ ) ₂ H 4- Et-Ph O 4-Za 24- 2 Me (CH ₂ ) ₂ H 4-iPr-Ph O 4-Za 24- 3 Me (CH ₂ ) ₂ H 3-Ph-Ph O 4-Za 24- 4 Me ( CH ₂ ) ₂ H 4-Ph-Ph O 4-Za 24- 5 Me (CH ₂ ) ₂ H 3-Pyr O 4-Za 24- 6 Me (CH ₂ ) ₂ H 5-Me-3-Pyr O 4 -Za 24- 7 Me (CH ₂ ) ₂ H 5-Et-3-Pyr O 4-Za 24- 8 Me (CH ₂ ) ₂ H 5-Ph-3-Pyr O 4-Za 24- 9 Me (CH ₂ ) ₂ H 6-Me-3-Pyr O 4-Za 24- 10 Me (CH ₂ ) ₂ H 6-Et-3-Pyr O 4-Za 24- 11 Me (CH ₂ ) ₂ H 6-Ph- 3-Pyr O 4-Za 24- 12 Me (CH ₂ ) ₂ H 6-MeO-3-Pyr O 4-Za 24- 13 Me (CH ₂ ) ₂ H 6-EtO-3-Pyr O 4-Za 24 -14 Me (CH ₂ ) ₂ H 6-iPrO-3-Pyr O 4-Za 24- 15 Me (CH ₂ ) ₂ H 6-MeS-3-Pyr O 4-Za 24- 16 Me (CH ₂ ) ₂ H 6-EtS-3-Pyr O 4-Za 24-17 Me (CH ₂ ) ₂ H 6-iPrS-3-Pyr O 4-Za 24- 18 Me (CH ₂ ) ₂ H 6-MeSO ₂ -3- Pyr O 4-Za 24- 19 Me (CH ₂ ) ₂ H 6-EtSO ₂ -3-Pyr O 4-Za 24- 20 Me (CH ₂ ) ₂ H 6-iPrSO ₂ -3-Pyr O 4-Za 24- 21 Me (CH ₂ ) _{2 H 6-Bz-3-} Pyr O 4-Za 24- 22 Me (CH 2) 2 H 6-PhO-3-Pyr O 4-Za 24- 23 Me (CH 2) 2 H 6-PhS-3- Pyr O 4-Za 24-24 Me (CH ₂ ) ₂ H 6-PhSO ₂ -3-Pyr O 4-Za 24- 25 Me (CH ₂ ) ₂ H 2-Quin O 4-Za 24- 26 Me (CH ₂ ) ₂ H 4-MeO-Ph O 4-Za 24-27 Me (CH ₂ ) ₂ H 4-EtO-Ph O 4-Za 24-28 Me (CH ₂ ) ₂ H 4-iPrO-Ph O 4- Za 24-29 Me (CH ₂ ) ₂ H 4-MeS-Ph O 4-Za 24- 30 Me (CH ₂ ) ₂ H 4-EtS-Ph O 4-Za 24-31 Me (CH ₂ ) ₂ H 4 -iPrS-Ph O 4-Za 24-32 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Za 24-33 Me (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4-Za 24- 34 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Za ──────────────────────────────── ──.

[0114]

[Table 25] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 25- 1 Me (CH ₂ ) ₂ H 4- Et-Ph O 4-Zd 25- 2 Me (CH ₂ ) ₂ H 4-iPr-Ph O 4-Zd 25- 3 Me (CH ₂ ) ₂ H 3-Ph-Ph O 4-Zd 25- 4 Me ( CH ₂ ) ₂ H 4-Ph-Ph O 4-Zd 25-5 Me (CH ₂ ) ₂ H 3-Pyr O 4-Zd 25- 6 Me (CH ₂ ) ₂ H 5-Me-3-Pyr O 4 -Zd 25- 7 Me (CH ₂ ) ₂ H 5-Et-3-Pyr O 4-Zd 25- 8 Me (CH ₂ ) ₂ H 5-Ph-3-Pyr O 4-Zd 25- 9 Me (CH ₂ ) ₂ H 6-Me-3-Pyr O 4-Zd 25-10 Me (CH ₂ ) ₂ H 6-Et-3-Pyr O 4-Zd 25-11 Me (CH ₂ ) ₂ H 6-Ph- 3-Pyr O 4-Zd 25-12 Me (CH ₂ ) ₂ H 6-MeO-3-Pyr O 4-Zd 25-13 Me (CH ₂ ) ₂ H 6-EtO-3-Pyr O 4-Zd 25 -14 Me (CH ₂ ) ₂ H 6-iPrO-3-Pyr O 4-Zd 25-15 Me (CH ₂ ) ₂ H 6-MeS-3-Pyr O 4-Zd 25-16 Me (CH ₂ ) ₂ H 6-EtS-3-Pyr O 4-Zd 25-17 Me (CH ₂ ) ₂ H 6-iPrS-3-Pyr O 4-Zd 25-18 Me (CH ₂ ) ₂ H 6-MeSO ₂ -3- Pyr O 4-Zd 25- 19 Me (CH ₂ ) ₂ H 6-EtSO ₂ -3-Pyr O 4-Zd 25-20 Me (CH ₂ ) ₂ H 6-iPrSO ₂ -3-Pyr O 4-Zd 25- 21 Me (CH ₂ ) _{2 H 6-Bz-3-} Pyr O 4-Zd 25- 22 Me (CH 2) 2 H 6-PhO-3-Pyr O 4-Zd 25- 23 Me (CH 2) 2 H 6-PhS-3- Pyr O 4-Zd 25- 24 Me (CH ₂ ) ₂ H 6-PhSO ₂ -3-Pyr O 4-Zd 25- 25 Me (CH ₂ ) ₂ H 2-Quin O 4-Zd 25- 26 Me (CH ₂ ) ₂ H 4-MeO-Ph O 4-Zd 25- 27 Me (CH ₂ ) ₂ H 4-EtO-Ph O 4-Zd 25- 28 Me (CH ₂ ) ₂ H 4-iPrO-Ph O 4- Zd 25- 29 Me (CH ₂ ) ₂ H 4-MeS-Ph O 4-Zd 25-30 Me (CH ₂ ) ₂ H 4-EtS-Ph O 4-Zd 25- 31 Me (CH ₂ ) ₂ H 4 -iPrS-Ph O 4-Zd 25- 32 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 4-Zd 25- 33 Me (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 4-Zd 25- 34 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 4-Z
d ──────────────────────────────────.

[0115]

[Table 26] Example R ¹ R ² R ³ XYZ Compound number ──────────────────────────────────── 26- 1 Me (CH ₂ ) ₂ H 4- Et-Ph O 3-Zb 26- 2 Me (CH ₂ ) ₂ H 4-iPr-Ph O 3-Zb 26- 3 Me (CH ₂ ) ₂ H 3-Ph-Ph O 3-Zb 26- 4 Me ( CH ₂ ) ₂ H 4-Ph-Ph O 3-Zb 26-5 Me (CH ₂ ) ₂ H 3-Pyr O 3-Zb 26-6 Me (CH ₂ ) ₂ H 5-Me-3-Pyr O 3 -Zb 26- 7 Me (CH ₂ ) ₂ H 5-Et-3-Pyr O 3-Zb 26- 8 Me (CH ₂ ) ₂ H 5-Ph-3-Pyr O 3-Zb 26- 9 Me (CH ₂ ) ₂ H 6-Me-3-Pyr O 3-Zb 26-10 Me (CH ₂ ) ₂ H 6-Et-3-Pyr O 3-Zb 26-11 Me (CH ₂ ) ₂ H 6-Ph- 3-Pyr O 3-Zb 26-12 Me (CH ₂ ) ₂ H 6-MeO-3-Pyr O 3-Zb 26-13 Me (CH ₂ ) ₂ H 6-EtO-3-Pyr O 3-Zb 26 -14 Me (CH ₂ ) ₂ H 6-iPrO-3-Pyr O 3-Zb 26-15 Me (CH ₂ ) ₂ H 6-MeS-3-Pyr O 3-Zb 26-16 Me (CH ₂ ) ₂ H 6-EtS-3-Pyr O 3-Zb 26-17 Me (CH ₂ ) ₂ H 6-iPrS-3-Pyr O 3-Zb 26-18 Me (CH ₂ ) ₂ H 6-MeSO ₂ -3- Pyr O 3-Zb 26 _{- 19 Me (CH 2) 2} H 6-EtSO 2 -3-Pyr O 3-Zb 26- 20 Me (CH 2) 2 H 6-iPrSO 2 -3-Pyr O 3-Zb 26- 21 Me (CH 2 _{) 2 H 6-Bz-3} -Pyr O 3-Zb 26- 22 Me (CH 2) 2 H 6-PhO-3-Pyr O 3-Zb 26- 23 Me (CH 2) 2 H 6-PhS-3 -Pyr O 3-Zb 26- 24 Me (CH ₂ ) ₂ H 6-PhSO ₂ -3-Pyr O 3-Zb 26- 25 Me (CH ₂ ) ₂ H 2-Quin O 3-Zb 26- 26 Me ( CH ₂ ) ₂ H 4-MeO-Ph O 3-Zb 26- 27 Me (CH ₂ ) ₂ H 4-EtO-Ph O 3-Zb 26- 28 Me (CH ₂ ) ₂ H 4-iPrO-Ph O 3 -Zb 26- 29 Me (CH ₂ ) ₂ H 4-MeS-Ph O 3-Zb 26-30 Me (CH ₂ ) ₂ H 4-EtS-Ph O 3-Zb 26- 31 Me (CH ₂ ) ₂ H 4-iPrS-Ph O 3-Zb 26- 32 Me (CH ₂ ) ₂ H 4-MeSO ₂ -Ph O 3-Zb 26- 33 Me (CH ₂ ) ₂ H 4-EtSO ₂ -Ph O 3-Zb 26 -34 Me (CH ₂ ) ₂ H 4-iPrSO ₂ -Ph O 3-Zb ─────────────────────────────── ───.

In Tables 1 to 26, abbreviations indicate the following groups. Ac: acetyl, tBu: t-butyl, Bmid: benzimidazolyl, Boxa: benzoxazolyl, B
thiz: benzthiazolyl, Bz: benzyl, Et:
Ethyl, Fur: furyl, Imid: imidazolyl, I
nd: indolyl, Isox: isoxazolyl, Md
O: methylenedioxy, Me: methyl, Np: naphthyl, Oxa: oxazolyl, Ph: phenyl, iPr:
Isopropyl, Pym: pyrimidinyl, Pyr: pyridyl, Pyrr: pyrrolyl, Pyza: pyrazolyl, Qu
in: quinolyl, iQuin: isoquinolyl, Thi:
Thienyl, Thiz: thiazolyl, Za: 2, 4-dioxothiazolidine-5-yridenylmethyl, Zb: 2,
4-dioxothiazolidine-5-ylmethyl, Zc:
2,4-dioxooxazolidin-5-ylmethyl, Z
d: 3,5-dioxooxadiazolidine-2-ylmethyl.

In the above table, (1) preferably exemplified compound numbers 1-1, 1-2, 1-3, 1-4, 1-5, 1-7, 1
-10, 1-11, 1-14, 1-15, 1-16, 1
-17, 1-18, 1-19, 1-20, 1-21, 1
-22, 1-23, 1-24, 1-25, 1-26, 1
-27, 1-28, 1-29, 1-30, 1-31, 1
-32, 1-33, 1-34, 1-35, 1-36, 1
-37, 1-38, 1-39, 1-40, 1-41, 1
-42, 1-43, 1-44, 1-45, 1-53, 1
-56, 1-58, 1-60, 1-66, 1-70, 1
-72, 1-78, 1-80, 1-87, 1-88, 1
-89, 1-90, 1-91, 1-92, 1-93, 1
-94, 1-95, 1-96, 1-97, 1-98, 1
-99, 1-100, 1-101, 1-102, 1-1
03, 1-104, 1-105, 1-106, 1-10
7, 1-108, 1-109, 1-110, 1-11
1, 1-112, 1-144, 1-145, 1-14
6, 1-147, 1-148, 1-149, 1-15
0, 1-155, 1-156, 1-157, 1-15
8, 1-161, 1-162, 1-163, 1-16
4, 1-165, 1-166, 1-167, 1-16
8, 1-169, 1-170, 1-171, 1-17
2, 1-175, 1-176, 1-180, 1-18
1, 1-182, 1-183, 1-184, 1-18
5, 1-186, 1-187, 1-188, 1-18
9, 1-190, 1-191, 1-192, 1-19
3, 1-194, 1-195, 1-196, 1-19
7, 1-198, 1-199, 1-200, 1-20
1, 1-202, 1-203, 2-1, 2-2, 2-
3, 2-4, 2-5, 2-7, 2-10, 2-11, 2
-14, 2-15, 2-16, 2-17, 2-18, 2
-19, 2-20, 2-21, 2-22, 2-23, 2
-24, 2-25, 2-26, 2-27, 2-28, 2
-29, 2-30, 2-31, 2-32, 2-33, 2
-34, 2-35, 2-36, 2-37, 2-38, 2
-39, 2-40, 2-41, 2-42, 2-43, 2
-44, 2-45, 2-53, 2-56, 2-58, 2
-60, 2-66, 2-70, 2-72, 2-78, 2
-80, 2-87, 2-88, 2-89, 2-90, 2
-91, 2-92, 2-93, 2-94, 2-95, 2
-96, 2-97, 2-98, 2-99, 2-100,
2-101, 2-102, 2-103, 2-104, 2
-105, 2-106, 2-107, 2-108, 2-
109, 2-110, 2-111, 2-112, 2-1
44, 2-145, 2-146, 2-147, 2-14
8, 2-149, 2-150, 2-155, 2-15
6, 2-157, 2-158, 2-161, 2-16
2, 2-163, 2-164, 2-165, 2-16
6, 2-167, 2-168, 2-169, 2-17
0, 2-171, 2-172, 2-175, 2-17
6, 2-180, 2-181, 2-182, 2-18
3, 2-184, 2-185, 2-186, 2-18
7, 2-188, 2-189, 2-190, 2-19
1, 2-192, 2-193, 2-194, 2-19
5, 2-196, 2-197, 2-198, 2-19
9, 2-200, 2-201, 2-202, 2-20
3, 3-1, 3-2, 3-3, 3-4, 3-5, 3-
7, 3-10, 3-11, 3-14, 3-15, 3-1
6, 3-17, 3-18, 3-19, 3-20, 3-2
1, 3-22, 3-23, 3-24, 3-25, 3-2
6, 3-27, 3-28, 3-29, 3-30, 3-3
1, 3-32, 3-33, 3-34, 3-35, 3-3
6, 3-37, 3-38, 3-39, 3-40, 3-4
1, 3-42, 3-43, 3-44, 3-45, 3-5
3, 3-56, 3-58, 3-60, 3-66, 3-7
0, 3-72, 3-78, 3-80, 3-87, 3-8
8, 3-89, 3-90, 3-91, 3-92, 3-9
3, 3-94, 3-95, 3-96, 3-97, 3-9
8, 3-99, 3-100, 3-101, 3-102,
3-103, 3-104, 3-105, 3-106, 3
-107, 3-108, 3-109, 3-110, 3-
111, 3-112, 3-144, 3-145, 3-1
46, 3-147, 3-148, 3-149, 3-15
0, 3-155, 3-156, 3-157, 3-15
8, 3-161, 3-162, 3-163, 3-16
4, 3-165, 3-166, 3-167, 3-16
8, 3-169, 3-170, 3-171, 3-17
2, 3-175, 3-176, 3-180, 3-18
1, 3-182, 3-183, 3-184, 3-18
5, 3-186, 3-187, 3-188, 3-18
9, 3-190, 3-191, 3-192, 3-19
3, 3-194, 3-195, 3-196, 3-19
7, 3-198, 3-199, 3-200, 3-20
1, 3-202, 3-203, 4-1 4-2, 4-
3, 4-4, 4-5, 4-7, 4-10, 4-11, 4
-14, 4-15, 4-16, 4-17, 4-18, 4
-19, 4-20, 4-21, 4-22, 4-23, 4
-24, 4-25, 4-26, 4-27, 4-28, 4
-29, 4-30, 4-31, 4-32, 4-33, 4
-34, 4-35, 4-36, 4-37, 4-38, 4
-39, 4-40, 4-41, 4-42, 4-43, 4
-44, 4-45, 4-53, 4-56, 4-58, 4
-60, 4-66, 4-70, 4-72, 4-78, 4
-80, 4-87, 4-88, 4-89, 4-90, 4
-91, 4-92, 4-93, 4-94, 4-95, 4
-96, 4-97, 4-98, 4-99, 4-100,
4-101, 4-102, 4-103, 4-104, 4
-105, 4-106, 4-107, 4-108, 4-
109, 4-110, 4-111, 4-112, 4-1
44, 4-145, 4-146, 4-147, 4-14
8, 4-149, 4-150, 4-155, 4-15
6, 4-157, 4-158, 4-161, 4-16
2, 4-163, 4-164, 4-165, 4-16
6, 4-167, 4-168, 4-169, 4-17
0, 4-171, 4-172, 4-175, 4-17
6, 4-180, 4-181, 4-182, 4-18
3, 4-184, 4-185, 4-186, 4-18
7, 4-188, 4-189, 4-190, 4-19
1, 4-192, 4-193, 4-194, 4-19
5, 4-196, 4-197, 4-198, 4-19
9, 4-200, 4-201, 4-202, 4-20
3, 5-1, 5-2, 5-3, 5-4, 5-5, 5-
7, 5-10, 5-11, 5-14, 5-15, 5-1
6, 5-17, 5-18, 5-19, 5-20, 5-2
1, 5-22, 5-23, 5-24, 5-25, 5-2
6, 5-27, 5-28, 5-29, 5-30, 5-3
1, 5-32, 5-33, 5-34, 5-35, 5-3
6, 5-37, 5-38, 5-39, 5-40, 5-4
1, 5-42, 5-43, 5-44, 5-45, 5-5
3, 5-56, 5-58, 5-60, 5-66, 5-7
0, 5-72, 5-78, 5-80, 5-87, 5-8
8, 5-89, 5-90, 5-91, 5-92, 5-9
3, 5-94, 5-95, 5-96, 5-97, 5-9
8, 5-99, 5-100, 5-101, 5-102,
5-103, 5-104, 5-105, 5-106, 5
-107, 5-108, 5-109, 5-110, 5-
111, 5-112, 5-144, 5-145, 5-1
46, 5-147, 5-148, 5-149, 5-15
0, 5-155, 5-156, 5-157, 5-15
8, 5-161, 5-162, 5-163, 5-16
4, 5-165, 5-166, 5-167, 5-16
8, 5-169, 5-170, 5-171, 5-17
2, 5-175, 5-176, 5-180, 5-18
1, 5-182, 5-183, 5-184, 5-18
5, 5-186, 5-187, 5-188, 5-18
9, 5-190, 5-191, 5-192, 5-19
3, 5-194, 5-195, 5-196, 5-19
7, 5-198, 5-199, 5-200, 5-20
1, 5-202, 5-203, 6-1, 6-2, 6
3, 6-4, 6-5, 6-7, 6-10, 6-11, 6
-14, 6-15, 6-16, 6-17, 6-18, 6
-19, 6-20, 6-21, 6-22, 6-23, 6
-24, 6-25, 6-26, 6-27, 6-28, 6
-29, 6-30, 6-31, 6-32, 6-33, 6
-34, 6-35, 6-36, 6-37, 6-38, 6
-39, 6-40, 6-41, 6-42, 6-43, 6
-44, 6-45, 6-53, 6-56, 6-58, 6
-60, 6-66, 6-70, 6-72, 6-78, 6
-80, 6-87, 6-88, 6-89, 6-90, 6
-91, 6-92, 6-93, 6-94, 6-95, 6
-96, 6-97, 6-98, 6-99, 6-100,
6-101, 6-102, 6-103, 6-104, 6
-105, 6-106, 6-107, 6-108, 6
109, 6-110, 6-111, 6-112, 6-1
44, 6-145, 6-146, 6-147, 6-14
8, 6-149, 6-150, 6-155, 6-15
6, 6-157, 6-158, 6-161, 6-16
2, 6-163, 6-164, 6-165, 6-16
6, 6-167, 6-168, 6-169, 6-17
0, 6-171, 6-172, 6-175, 6-17
6, 6-180, 6-181, 6-182, 6-18
3, 6-184, 6-185, 6-186, 6-18
7, 6-188, 6-189, 6-190, 6-19
1, 6-192, 6-193, 6-194, 6-19
5, 6-196, 6-197, 6-198, 6-19
9, 6-200, 6-201, 6-202, 6-20
3, 7-1, 7-2, 7-3, 7-4, 7-5, 7-
7, 7-10, 7-11, 7-14, 7-15, 7-1
6, 7-17, 7-18, 7-19, 7-20, 7-2
1, 7-22, 7-23, 7-24, 7-25, 7-2
6, 7-27, 7-28, 7-29, 7-30, 7-3
1, 7-32, 7-33, 7-34, 7-35, 7-3
6, 7-37, 7-38, 7-39, 7-40, 7-4
1, 7-42, 7-43, 7-44, 7-45, 7-5
3, 7-56, 7-58, 7-60, 7-66, 7-7
0, 7-72, 7-78, 7-80, 7-87, 7-8
8, 7-89, 7-90, 7-91, 7-92, 7-9
3, 7-94, 7-95, 7-96, 7-97, 7-9
8, 7-99, 7-100, 7-101, 7-102,
7-103, 7-104, 7-105, 7-106, 7
-107, 7-108, 7-109, 7-110, 7-
111, 7-112, 7-144, 7-145, 7-1
46, 7-147, 7-148, 7-149, 7-15
0, 7-155, 7-156, 7-157, 7-15
8, 7-161, 7-162, 7-163, 7-16
4, 7-165, 7-166, 7-167, 7-16
8, 7-169, 7-170, 7-171, 7-17
2, 7-175, 7-176, 7-180, 7-18
1, 7-182, 7-183, 7-184, 7-18
5, 7-186, 7-187, 7-188, 7-18
9, 7-190, 7-191, 7-192, 7-19
3, 7-194, 7-195, 7-196, 7-19
7, 7-198, 7-199, 7-200, 7-20
1, 7-202, 7-203, 8-1, 8-2, 8-
3, 8-4, 8-5, 8-7, 8-10, 8-11, 8
-14, 8-15, 8-16, 8-17, 8-18, 8
-19, 8-20, 8-21, 8-22, 8-23, 8
-24, 8-25, 8-26, 8-27, 8-28, 8
-29, 8-30, 8-31, 8-32, 8-33, 8
-34, 8-35, 8-36, 8-37, 8-38, 8
-39, 8-40, 8-41, 8-42, 8-43, 8
-44, 8-45, 8-53, 8-56, 8-58, 8
-60, 8-66, 8-70, 8-72, 8-78, 8
-80, 8-87, 8-88, 8-89, 8-90, 8
-91, 8-92, 8-93, 8-94, 8-95, 8
-96, 8-97, 8-98, 8-99, 8-100,
8-101, 8-102, 8-103, 8-104, 8
-105, 8-106, 8-107, 8-108, 8-
109, 8-110, 8-111, 8-112, 8-1
44, 8-145, 8-146, 8-147, 8-14
8, 8-149, 8-150, 8-155, 8-15
6, 8-157, 8-158, 8-161, 8-16
2, 8-163, 8-164, 8-165, 8-16
6, 8-167, 8-168, 8-169, 8-17
0, 8-171, 8-172, 8-175, 8-17
6, 8-180, 8-181, 8-182, 8-18
3, 8-184, 8-185, 8-186, 8-18
7, 8-188, 8-189, 8-190, 8-19
1, 8-192, 8-193, 8-194, 8-19
5, 8-196, 8-197, 8-198, 8-19
9, 8-200, 8-201, 8-202, 8-20
3,9-1,9-2,9-3,9-4,9-5,9-
7, 9-10, 9-11, 9-14, 9-15, 9-1
6, 9-17, 9-18, 9-19, 9-20, 9-2
1, 9-22, 9-23, 9-24, 9-25, 9-2
6, 9-27, 9-28, 9-29, 9-30, 9-3
1, 9-32, 9-33, 9-34, 9-35, 9-3
6, 9-37, 9-38, 9-39, 9-40, 9-4
1, 9-42, 9-43, 9-44, 9-45, 9-5
3, 9-56, 9-58, 9-60, 9-66, 9-7
0, 9-72, 9-78, 9-80, 9-87, 9-8
8, 9-89, 9-90, 9-91, 9-92, 9-9
3, 9-94, 9-95, 9-96, 9-97, 9-9
8, 9-99, 9-100, 9-101, 9-102,
9-103, 9-104, 9-105, 9-106, 9
-107, 9-108, 9-109, 9-110, 9-
111, 9-112, 9-144, 9-145, 9-1
46, 9-147, 9-148, 9-149, 9-15
0, 9-155, 9-156, 9-157, 9-15
8, 9-161, 9-162, 9-163, 9-16
4, 9-165, 9-166, 9-167, 9-16
8, 9-169, 9-170, 9-171, 9-17
2, 9-175, 9-176, 9-180, 9-18
1, 9-182, 9-183, 9-184, 9-18
5, 9-186, 9-187, 9-188, 9-18
9, 9-190, 9-191, 9-192, 9-19
3, 9-194, 9-195, 9-196, 9-19
7, 9-198, 9-199, 9-200, 9-20
1, 9-202, 9-203, 10-1, 10-2, 1
0-3, 10-4, 10-5, 10-7, 10-10,
10-11, 10-14, 10-15, 10-16, 1
0-17, 10-18, 10-19, 10-20, 10
-21, 10-22, 10-23, 10-24, 10-
25, 10-26, 10-27, 10-28, 10-2
9, 10-30, 10-31, 10-32, 10-3
3, 10-34, 10-35, 10-36, 10-3
7, 10-38, 10-39, 10-40, 10-4
1, 10-42, 10-43, 10-44, 10-4
5, 10-53, 10-56, 10-58, 10-6
0, 10-66, 10-70, 10-72, 10-7
8, 10-80, 10-87, 10-88, 10-8
9, 10-90, 10-91, 10-92, 10-9
3, 10-94, 10-95, 10-96, 10-9
7, 10-98, 10-99, 10-100, 10-1
01, 10-102, 10-103, 10-104, 1
0-105, 10-106, 10-107, 10-10
8, 10-109, 10-110, 10-111, 10
-112, 10-144, 10-145, 10-14
6, 10-147, 10-148, 10-149, 10
-150, 10-155, 10-156, 10-15
7, 10-158, 10-161, 10-162, 10
-163, 10-164, 10-165, 10-16
6, 10-167, 10-168, 10-169, 10
-170, 10-171, 10-172, 10-17
5, 10-176, 10-180, 10-181, 10
-182, 10-183, 10-184, 10-18
5, 10-186, 10-187, 10-188, 10
-189, 10-190, 10-191, 10-19
2, 10-193, 10-194, 10-195, 10
-196, 10-197, 10-198, 10-19
9, 10-200, 10-201, 10-202, 10
−203.

(2) More preferably, Exemplified Compound Nos. 1-1, 1-2, 1-3, 1-10, 1-11, 1-1
4, 1-15, 1-16, 1-17, 1-18, 1-1
9, 1-20, 1-21, 1-22, 1-23, 1-2
5, 1-29, 1-31, 1-33, 1-34, 1-3
5, 1-36, 1-37, 1-38, 1-39, 1-4
1, 1-43, 1-45, 1-87, 1-88, 1-8
9, 1-90, 1-91, 1-92, 1-93, 1-9
4, 1-95, 1-96, 1-97, 1-98, 1-9
9, 1-100, 1-101, 1-102, 1-10
3, 1-104, 1-105, 1-106, 1-10
7, 1-108, 1-109, 1-110, 1-11
1, 1-112, 1-149, 1-150, 1-15
6, 1-158, 1-162, 1-164, 1-16
6, 1-168, 1-170, 1-172, 1-17
5, 1-176, 1-180, 1-181, 1-18
2, 1-183, 1-184, 1-185, 1-18
6, 1-187, 1-188, 1-189, 1-19
0, 1-191, 1-192, 1-193, 1-19
4, 1-195, 1-196, 1-197, 1-19
8, 1-199, 1-200, 1-201, 1-20
2, 1-203, 2-1, 2-2, 2-3, 2-10,
2-11, 2-14, 2-15, 2-16, 2-17,
2-18, 2-19, 2-20, 2-21, 2-22,
2-23, 2-25, 2-29, 2-31, 2-33,
2-34, 2-35, 2-36, 2-37, 2-38,
2-39, 2-41, 2-43, 2-45, 2-87,
2-88, 2-89, 2-90, 2-91, 2-92,
2-93, 2-94, 2-95, 2-96, 2-97,
2-98, 2-99, 2-100, 2-101, 2-1
02, 2-103, 2-104, 2-105, 2-10
6, 2-107, 2-108, 2-109, 2-11
0, 2-111, 2-112, 2-149, 2-15
0, 2-156, 2-158, 2-162, 2-16
4, 2-166, 2-168, 2-170, 2-17
2, 2-175, 2-176, 2-180, 2-18
1, 2-182, 2-183, 2-184, 2-18
5, 2-186, 2-187, 2-188, 2-18
9, 2-190, 2-191, 2-192, 2-19
3, 2-194, 2-195, 2-196, 2-19
7, 2-198, 2-199, 2-200, 2-20
1, 2-202, 2-203, 3-1, 3-2, 3-
3, 3-10, 3-11, 3-14, 3-15, 3-1
6, 3-17, 3-18, 3-19, 3-20, 3-2
1, 3-22, 3-23, 3-25, 3-29, 3-3
1, 3-33, 3-34, 3-35, 3-36, 3-3
7, 3-38, 3-39, 3-41, 3-43, 3-4
5, 3-87, 3-88, 3-89, 3-90, 3-9
1, 3-92, 3-93, 3-94, 3-95, 3-9
6, 3-97, 3-98, 3-99, 3-100, 3-
101, 3-102, 3-103, 3-104, 3-1
05, 3-106, 3-107, 3-108, 3-10
9, 3-110, 3-111, 3-112, 3-14
9, 3-150, 3-156, 3-158, 3-16
2, 3-164, 3-166, 3-168, 3-17
0, 3-172, 3-175, 3-176, 3-18
0, 3-181, 3-182, 3-183, 3-18
4, 3-185, 3-186, 3-187, 3-18
8, 3-189, 3-190, 3-191, 3-19
2, 3-193, 3-194, 3-195, 3-19
6, 3-197, 3-198, 3-199, 3-20
0, 3-201, 3-202, 3-203, 6-1, 6
-2, 6-3, 6-10, 6-11, 6-14, 6-1
5, 6-16, 6-17, 6-18, 6-19, 6-2
0, 6-21, 6-22, 6-23, 6-25, 6-2
9, 6-31, 6-33, 6-34, 6-35, 6-3
6, 6-37, 6-38, 6-39, 6-41, 6-4
3, 6-45, 6-87, 6-88, 6-89, 6-9
0, 6-91, 6-92, 6-93, 6-94, 6-9
5, 6-96, 6-97, 6-98, 6-99, 6-1
00, 6-101, 6-102, 6-103, 6-10
4, 6-105, 6-106, 6-107, 6-10
8, 6-109, 6-110, 6-111, 6-11
2, 6-149, 6-150, 6-156, 6-15
8, 6-162, 6-164, 6-166, 6-16
8, 6-170, 6-172, 6-175, 6-17
6, 6-180, 6-181, 6-182, 6-18
3, 6-184, 6-185, 6-186, 6-18
7, 6-188, 6-189, 6-190, 6-19
1, 6-192, 6-193, 6-194, 6-19
5, 6-196, 6-197, 6-198, 6-19
9, 6-200, 6-201, 6-202, 6-20
3, 8-1, 8-2, 8-3, 8-10, 8-11, 8
-14, 8-15, 8-16, 8-17, 8-18, 8
-19, 8-20, 8-21, 8-22, 8-23, 8
-25, 8-29, 8-31, 8-33, 8-34, 8
-35, 8-36, 8-37, 8-38, 8-39, 8
-41, 8-43, 8-45, 8-87, 8-88, 8
-89, 8-90, 8-91, 8-92, 8-93, 8
-94, 8-95, 8-96, 8-97, 8-98, 8
-99, 8-100, 8-101, 8-102, 8-1
03, 8-104, 8-105, 8-106, 8-10
7, 8-108, 8-109, 8-110, 8-11
1, 8-112, 8-149, 8-150, 8-15
6, 8-158, 8-162, 8-164, 8-16
6, 8-168, 8-170, 8-172, 8-17
5, 8-176, 8-180, 8-181, 8-18
2, 8-183, 8-184, 8-185, 8-18
6, 8-187, 8-188, 8-189, 8-19
0, 8-191, 8-192, 8-193, 8-19
4, 8-195, 8-196, 8-197, 8-19
8, 8-199, 8-200, 8-201, 8-20
2, 8-203, 10-1, 10-2, 10-3, 10
-10, 10-11, 10-14, 10-15, 10-
16, 10-17, 10-18, 10-19, 10-2
0, 10-21, 10-22, 10-23, 10-2
5, 10-29, 10-31, 10-33, 10-3
4, 10-35, 10-36, 10-37, 10-3
8, 10-39, 10-41, 10-43, 10-4
5, 10-87, 10-88, 10-89, 10-9
0, 10-91, 10-92, 10-93, 10-9
4, 10-95, 10-96, 10-97, 10-9
8, 10-99, 10-100, 10-101, 10-
102, 10-103, 10-104, 10-105,
10-106, 10-107, 10-108, 10-1
09, 10-110, 10-111, 10-112, 1
0-149, 10-150, 10-156, 10-15
8, 10-162, 10-164, 10-166, 10
-168, 10-170, 10-172, 10-17
5, 10-176, 10-180, 10-181, 10
-182, 10-183, 10-184, 10-18
5, 10-186, 10-187, 10-188, 10
-189, 10-190, 10-191, 10-19
2, 10-193, 10-194, 10-195, 10
-196, 10-197, 10-198, 10-19
9, 10-200, 10-201, 10-202, 10
−203.

(3) More preferably, Exemplified Compound Nos. 1-14, 1-15, 1-16, 1-17, 1-18,
1-19, 1-20, 1-21, 1-22, 1-23,
1-29, 1-31, 1-33, 1-34, 1-35,
1-36, 1-37, 1-38, 1-39, 1-41,
1-43, 1-45, 1-88, 1-90, 1-91,
1-92, 1-93, 1-94, 1-95, 1-96,
1-97, 1-98, 1-99, 1-100, 1-10
1, 1-102, 1-103, 1-104, 1-10
5, 1-106, 1-107, 1-108, 1-10
9, 1-110, 1-181, 1-182, 1-18
3, 1-184, 1-185, 1-186, 1-18
7, 1-188, 1-189, 1-192, 1-19
3, 1-195, 2-14, 2-15, 2-16, 2-
17, 2-18, 2-19, 2-20, 2-21, 2-
22, 2-23, 2-29, 2-31, 2-33, 2-
34, 2-35, 2-36, 2-37, 2-38, 2-
39, 2-41, 2-43, 2-45, 2-88, 2-
90, 2-91, 2-92, 2-93, 2-94, 2-
95, 2-96, 2-97, 2-98, 2-99, 2-
100, 2-101, 2-102, 2-103, 2-1
04, 2-105, 2-106, 2-107, 2-10
8, 2-109, 2-110, 2-181, 2-18
2, 2-183, 2-184, 2-185, 2-18
6, 2-187, 2-188, 2-189, 2-19
2, 2-193, 2-195, 3-14, 3-15, 3
-16, 3-17, 3-18, 3-19, 3-20, 3
-21, 3-22, 3-23, 3-29, 3-31,3
-33, 3-34, 3-35, 3-36, 3-37,
-38, 3-39, 3-41, 3-43, 3-45, 3
-88, 3-90, 3-91, 3-92, 3-93, 3
-94, 3-95, 3-96, 3-97, 3-98, 3
-99, 3-100, 3-101, 3-102, 3-1
03, 3-104, 3-105, 3-106, 3-10
7, 3-108, 3-109, 3-110, 3-18
1, 3-182, 3-183, 3-184, 3-18
5, 3-186, 3-187, 3-188, 3-18
9, 3-192, 3-193, 3-195.

(4) More preferably, Exemplified Compound Nos. 1-15, 1-17, 1-19, 1-21, 1-23,
1-35, 1-37, 1-39, 1-95, 1-96,
1-97, 1-98, 1-99, 1-100, 1-10
1, 1-102, 1-103, 1-104, 1-10
5, 1-108, 1-183, 1-185, 1-18
7, 1-189, 1-195, 2-15, 2-17, 2
-19, 2-21, 2-23, 2-35, 2-37, 2
-39, 2-95, 2-96, 2-97, 2-98, 2
-99, 2-100, 2-101, 2-102, 2-1
03, 2-104, 2-105, 2-108, 2-18
3, 2-185, 2-187, 2-189, 2-19
5, 3-15, 3-17, 3-19, 3-21, 3-2
3, 3-35, 3-37, 3-39, 3-95, 3-9
6, 3-97, 3-98, 3-99, 3-100, 3-
101, 3-102, 3-103, 3-104, 3-1
05, 3-108, 3-183, 3-185, 3-18
7, 3-189, 3-195.

(5) More preferably, Exemplified Compound Nos. 2-15, 2-17, 2-19, 2-21, 2-23,
2-35, 2-37, 2-39, 2-95, 2-96,
2-97, 2-98, 2-99, 2-100, 2-10
1, 2-102, 2-103, 2-104, 2-10
5, 2-108, 2-183, 2-185, 2-18
7, 2-189, 2-195, 3-15, 3-17, 3
-19, 3-21, 3-23, 3-35, 3-37, 3
-39, 3-95, 3-96, 3-97, 3-98, 3
-99, 3-100, 3-101, 3-102, 3-1
03, 3-104, 3-105, 3-108, 3-18
3, 3-185, 3-187, 3-189, 3-19
5.

(6) More preferably, Exemplified Compound Nos. 2-15, 2-23, 2-35, 2-37, 2-39,
2-95, 2-96, 2-97, 2-98, 2-10
5, 3-15, 3-23, 3-35, 3-37, 3-3
9, 3-95, 3-96, 3-97, 3-98, 3-1
05.

(7) More preferably, Exemplified Compound No. 2-15) 5- [4- [2-[[[1- (4-biphenylyl) ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4 -Dione 2-23) 5- [4- [2-[[[1- (4-phenylsulfonylphenyl) ethylidene] amino] oxy]
Ethoxy] benzyl] thiazolidine-2,4-dione 2-35) 5- [4- [2-[[[1- [4- (2-
Pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2-37) 5- [4- [2-[[[1- [4- (3-
Pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2-39) 5- [4- [2-[[[1- [4- (4-
Pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2-95) 5- [4- [2-[[1- (2-phenyl-5-pyridyl) ethylidene] amino ] Oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2-96) 5- [4- [2-[[[1- (2-methoxy-5-pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] Thiazolidine-2,4-dione 2-97) 5- [4- [2-[[[1- (2-ethoxy-5-pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2-98) 5- [4- [2-[[[1- (2-isopropoxy-5-pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2; - a - [[[[1- (2-benzyl-5-pyridyl) ethylidene] amino] oxy] ethoxy] benzyl 4- [2] thiazolidine-2,4-dione dione 2-105) 5-.

[0124]

BEST MODE FOR CARRYING OUT THE INVENTION The oxime derivative having the above general formula (I) or a salt thereof of the present invention can be easily produced according to the following Method A.

<< Method A >>

[0126]

Embedded image

In the above formula, R ¹ , R ² , R ³ , X and Y
Has the same meaning as described above. U has a hydroxyl group, a halogen atom (preferably a chlorine atom, a bromine atom, an iodine atom) or -O-SO ₂ -R ⁵ group (wherein, R ⁵ is methyl, six C 1 -C such as ethyl Alkyl group; halogenated alkyl group having 1 to 4 carbon atoms such as trifluoromethyl; or phenyl, p-tolyl, p
Alkyl having 1 to 4 carbons as a substituent such as -nitrophenyl, p-bromophenyl, nitro or halogen having 6 to 10 carbons which may be substituted;
Aryl group).

Za-d is Za, Zb, Zc or Zd
Is shown.

Z'a-d is Za, Zb, Zc or Z
In d,> NH group contained in these groups is protected by a conventional method, for example, a group protected by a triphenylmethyl group (hereinafter abbreviated as trityl group) (that is,> N
-CPh ₃ ).

Step A1 Step A1 is a step of producing a compound having the general formula (IV), and reacting a compound having the general formula (II) with a compound having the general formula (III). Manufactured by

When U is a hydroxyl group, the usual Mitsunobu reaction [O. Mitsunobu, Synthesis, p.
Year)].

The reaction is usually carried out by bringing an azo compound into contact with a phosphine in the presence of a solvent.
As the azo compounds of the reaction reagent, diethyl azodicarboxylate, 1,1 '-(azodicarbonyl) dipiperidine and the like are used. As the phosphines, triphenylphosphine, tributylphosphine and the like are used.

The reaction is generally and preferably effected in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not affect the reaction, and examples thereof include hydrocarbons such as benzene, toluene, xylene, hexane, and heptane; chloroform, methylene chloride, carbon tetrachloride, and 1,2- Halogenated hydrocarbons such as dichloroethane; ethers such as diethyl ether, tetrahydrofuran, and dioxane; amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; or a mixed solvent thereof is preferably used.

The reaction is carried out at a temperature of from 10 ° C to 100 ° C, preferably from 20 ° C to 80 ° C.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 1 hour to 3 days, preferably 5 hours to 3 days.

U is a halogen atom or —O—SO ₂ —
R ⁵ groups (wherein, R ⁵ has the same meaning as described above.)
In the case of, the reaction is carried out in an inert solvent in the presence of a base.

The base used is preferably an alkali metal carbonate such as sodium carbonate or potassium carbonate; an alkali metal hydride such as sodium hydride, potassium hydride or lithium hydride; sodium methoxide; Sodium ethoxide, potassium t-butoxide,
Alkali metal alkoxides such as lithium methoxide; alkyl lithiums such as butyl lithium and methyl lithium; lithium amides such as lithium diethylamide, lithium diisopropylamide, lithium bis (trimethylsilyl) amide; sodium hydrogen carbonate;
Alkali metal bicarbonates such as potassium bicarbonate;
1,5-diazabicyclo [4.3.0] non-5-ene, 1,8-diazabicyclo [5.4.0] undeca-
Tertiary organic amines such as 7-ene, N, N-diisopropylethylamine; preferably alkali metal carbonates, alkali metal hydrides and alkali metal alkoxides.

The inert solvent used in the reaction is not particularly limited as long as it does not participate in the reaction. Examples thereof include hydrocarbons such as benzene and toluene; ethers such as tetrahydrofuran and dioxane; methanol, ethanol, and t.
Alcohols such as butanol; amides such as dimethylformamide, dimethylacetamide, N-methylpyrrolidinone; ketones such as acetone and 2-butanone; nitriles such as acetonitrile; sulfoxides such as dimethylsulfoxide; Or a mixed solvent thereof, preferably an ether, an amide, a ketone or a sulfoxide.

When this reaction is carried out in the presence of a phase transfer catalyst such as benzyltriethylammonium iodide or tetrabutylammonium iodide, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide is used as a base. It is carried out in a two-layer solvent of water and halogenated hydrocarbons such as methylene chloride and chloroform.

The reaction temperature is from -10 ° C to 120 ° C, preferably from 10 ° C to 100 ° C.

The reaction time varies depending on the reagent used, the reaction temperature and the like, but is 30 minutes to 48 hours, preferably 1 hour to 16 hours.

Step A2 Step A2 is a step for producing an oxime derivative having the general formula (I), and by removing a protecting group such as a trityl group of the compound having the general formula (IV). Done.

This step is carried out in the presence or absence of a solvent in the presence of formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, hydrochloric acid, sulfuric acid, or the like. It is carried out by reacting with an acid.

In the present reaction, when a solvent is used, it is not particularly limited as long as it does not affect the reaction, and examples thereof include hydrocarbons such as benzene, toluene, xylene, hexane and heptane; chloroform, methylene chloride, and the like. Halogenated hydrocarbons such as carbon tetrachloride; ethers such as diethyl ether, tetrahydrofuran and dioxane; alcohols such as methanol and ethanol;
Amides such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; esters such as methyl acetate and ethyl acetate; water; and a mixed solvent thereof are preferably used.

The reaction temperature varies depending on the acid used, but is from -10 ° C to 120 ° C, preferably from 0 ° C to 100 ° C.

The reaction time varies depending on the acid used, the reaction temperature and the like, but is usually from 10 minutes to 24 hours.
Preferably it is 30 minutes to 16 hours.

Alternatively, this step can also be carried out by subjecting the compound having the general formula (IV) to a catalytic hydrogenation reaction. As the catalyst used, for example, palladium-
Examples thereof include carbon, palladium black, platinum oxide, and platinum black. Palladium-carbon is preferred.

The reaction is generally and preferably effected in the presence of a solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and examples thereof include hydrocarbons such as benzene, toluene, xylene, hexane, and heptane; and halogenated carbons such as chloroform, methylene chloride, and carbon tetrachloride. Hydrogens; ethers such as diethyl ether, tetrahydrofuran and dioxane; alcohols such as methanol, ethanol and isopropanol; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; carboxylic acids such as formic acid and acetic acid Acids; or a mixed solvent thereof is preferably used.

The reaction temperature is between 10 ° C. and 140 ° C.
Preferably it is 20 ° C to 120 ° C.

In this reaction, the reaction may be promoted by adding a carboxylic acid such as formic acid, acetic acid or trifluoroacetic acid; or a mineral acid such as hydrochloric acid or sulfuric acid.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 30 minutes to 3 days, preferably 1 hour to 1 day.

The intermediate represented by the above general formula (I) which is an intermediate in the method A
The compound having V) can also be produced according to Method B.

<< Method B >>

[0154]

Embedded image

In the above formula, R ¹ , R ² , R ³ , U, X, Y
And Z'a-d have the same meaning as described above.

Step B1 in Method B is a step of producing a compound having the general formula (IV), and reacting a compound having the general formula (V) with a compound having the general formula (VI). This is done by:

This reaction is carried out in the same manner as in Step A1 of Method A described in detail above.

The oxime derivative having the general formula (I) and the compound having the general formula (IV) as an intermediate of the present invention can also be produced according to the following Method C.

<< Method C >>

[0160]

Embedded image

In the above formula, R ¹ , R ² , R ³ , U, X,
Y, Za-d and Z'a-d have the same meaning as described above.

R ⁶ and R ⁷ represent a hydrogen atom or an amino-protecting group.

The amino-protecting groups represented by R ⁶ and R ⁷ are well-known in organic synthetic chemistry, for example, aralkyl groups such as benzyl, diphenylmethyl and trityl; formyl, trifluoroacetyl An alkoxycarbonyl group such as t-butoxycarbonyl; an aralkyloxycarbonyl group such as benzyloxycarbonyl and p-nitrobenzyloxycarbonyl; or a phthaloyl group; and preferably benzyl. , Trityl, trifluoroacetyl, t-butoxycarbonyl, benzyloxycarbonyl or phthaloyl.

Z ″ a-d represents Za-d or Z′a-d described above.

Step C1 Step C1 is a step of producing a compound having the general formula (VIII), and reacting a compound having the general formula (VII) with a compound having the general formula (III). Done by

This step is performed in the same manner as in step A1 of method A.

Step C2 Step C2 is a step for producing a compound having the general formula (IX), wherein the amino-protecting groups R ⁶ and / or R ^{7 in the} compound having the general formula (VIII) are included. And, if desired, removing the protecting group of Z'a-d to convert it to Za-d.

The deprotection of a group in which the protecting group R ⁶ can be removed by catalytic reduction such as an aralkyl group or an aralkyloxycarbonyl group, or a group such as a trityl group or t-butoxycarbonyl group which can be removed by an acid can be carried out by the method described in Method A. No. A
It is performed in the same manner as in the two steps. When the compound having the above general formula (IV) as an intermediate is produced, the reaction is carried out under a reaction condition in which a group in which the> NH group in Z'a-d is protected by a conventional method, for example, a trityl group, is not eliminated. There is a need.

When the protecting group R ⁶ is an aliphatic acyl group such as formyl or trifluoroacetyl, it is removed under basic conditions.

Examples of the base used include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide; and alkali metal carbonates such as sodium carbonate and potassium carbonate.

This reaction is suitably carried out in an inert solvent such as an alcohol such as methanol or ethanol; water; an ether such as tetrahydrofuran or dioxane; or a mixed solvent thereof.

The reaction temperature is between 0 ° C. and 100 ° C.
Preferably it is 10 ° C to 80 ° C.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 16 hours.

When the protecting groups R ⁶ and / or R ⁷ are phthaloyl groups, the protecting groups can be removed by treating with hydrazines or primary amines.

The hydrazines used include, for example, hydrazine, methylhydrazine, phenylhydrazine and the like. The primary amines used include, for example, methylamine, ethylamine, propylamine, butylamine, isobutylamine, pentylamine , Hexylamine and the like.

In this reaction, an inert agent such as methanol is used.
Alcohols such as ethanol; ethers such as tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride and chloroform; or mixed solvents thereof are preferably used.

The reaction temperature is between 0 ° C. and 100 ° C.
Preferably it is 10 ° C to 80 ° C.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 16 hours.

Further, if desired, the reaction of removing the protecting group of Z'a-d to convert it to Za-d is carried out in the same manner as in the above-mentioned Step A2 of Method A.

Step C3 Step C3 is a step for producing a compound having the general formula (IV), wherein the amino compound having the general formula (IX) and the carbonyl compound having the general formula (X) are dehydrated. This is performed by a condensation reaction.

This step is performed in an inert solvent. The inert solvent used is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, benzene and xylene; methylene chloride, chloroform, 1, 2
Halogenated hydrocarbons such as dichloroethane; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol and ethanol; esters such as ethyl acetate and butyl acetate; amides such as dimethylformamide and dimethylacetamide. And preferably hydrocarbons, halogenated hydrocarbons, ethers or alcohols.

The reaction temperature is between 0 ° C. and 120 ° C.
Preferably it is 10 ° C to 100 ° C.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 16 hours.

In the method A, the starting material represented by the general formula (I)
The compound having I) can be produced, for example, according to Method D.

<< Method D >>

[0186]

Embedded image

In the above formula, R ¹ , R ² and X have the same meaning as described above.

U 'is a halogen atom in U or
-O-SO ₂ -R ⁵ group (wherein, R ⁵ is. Showing the same meanings as defined above) shows a.

The formula (IIa) produced by the present method
Is a compound in which U in the general formula (II) is a hydroxyl group, and a compound having the general formula (IIb) is a compound in which U in the general formula (II) is a halogen atom or
It is a compound which is a —O—SO ₂ —R ⁵ group (wherein, R ⁵ has the same meaning as described above).

Step D1 Step D1 is a step for producing a compound having the general formula (XII), wherein the compound represented by the general formula (V) and the compound represented by the general formula (XI) are combined. It is performed by reacting.

In this reaction, U described in Method A and Step A1 is a halogen atom or —O—SO ₂ —R ⁵
The reaction is performed in the same manner as in the case of a group (wherein, R ⁵ has the same meaning as described above).

Step D2 Step D2 is a step for producing a compound having the general formula (IIa), and is carried out by removing a tetrahydropyranyl group of the compound having the general formula (XII).

This reaction is carried out in the same manner as in the method for deprotection with an acid described in Method A and Step A2.

Step D3 Step D3 is a step for producing a compound having the general formula (IIb), wherein the hydroxyl group in the compound having the general formula (IIa) is replaced with a halogen atom or —O—SO _2.
The conversion is carried out by converting into a —R ⁵ group (wherein R ⁵ has the same meaning as described above).

When U 'in the compound having the general formula (IIa) is a halogen atom, the reaction is carried out by reacting the compound with a halogenating agent in the presence of a solvent.

Examples of the halogenating agent used include thionyl halides such as thionyl chloride and thionyl bromide; phosphorus pentahalides such as phosphorus pentachloride and phosphorus pentabromide; phosphorus oxychloride and phosphorus oxybromide. Such as phosphorus oxyhalide; oxalyl chloride; and preferably thionyl halide and oxalyl chloride.

The inert solvent used is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, benzene, toluene and xylene; methylene chloride, chloroform and 1,2-dichloroethane Halogenated hydrocarbons; ethers such as tetrahydrofuran and dioxane; esters such as ethyl acetate and butyl acetate; and preferred are halogenated hydrocarbons and ethers.

The reaction temperature is from -10 ° C to 100 ° C, preferably from 10 ° C to 80 ° C.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 16 hours.

Alternatively, the reaction is carried out according to the above general formula (IIa)
Is reacted with a halogenating agent such as carbon tetrachloride, carbon tetrabromide, N-bromosuccinimide or N-chlorosuccinimide in the presence of phosphines such as triphenylphosphine and tributylphosphine. Is also performed. The reaction conditions for this reaction are A
The conditions are the same as those of the Mitsunobu reaction described in the step A1 of the method.

When U ′ in the compound having the general formula (IIa) is —O—SO ₂ —R ⁵ group (wherein R ⁵ has the same meaning as described above), it is inactive. In a solvent in the presence of a base, R ⁵ —SO ₂ —Cl (where
⁵ has the same meaning as described above. ) Or (R ⁵ -S
O ₂ ) ₂ O (wherein R ⁵ has the same meaning as described above).

The base used is preferably a tertiary amine such as triethylamine, N-methylmorpholine, N, N-diisopropylethylamine.

The inert solvent used is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, benzene, toluene and xylene; methylene chloride, chloroform and 1,2-dichloroethane Halogenated hydrocarbons; ethers such as tetrahydrofuran and dioxane; esters such as ethyl acetate and butyl acetate; and preferred are halogenated hydrocarbons and ethers.

The reaction temperature is from -10 ° C to 100 ° C, preferably from 0 ° C to 60 ° C.

The reaction time varies depending on the reaction reagent, reaction temperature, solvent and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 16 hours.

After completion of the reaction, the desired compound obtained in each of the above steps can be purified, if necessary, by a conventional method, for example, column chromatography, recrystallization, reprecipitation or the like. For example, a solvent is added to the reaction mixture for extraction, and the solvent is distilled off from the extract. The obtained residue is purified by subjecting it to column chromatography using silica gel or the like, whereby a pure product of the target compound can be obtained.

The oxime derivative having the above general formula (I) or a salt thereof according to the present invention may be used in the form of hyperlipidemia, hyperglycemia, obesity, glucose intolerance, insulin-resistant non-glucose intolerance, insulin resistance. , Cachexia, psoriasis, diabetic complications,
Arteriosclerosis, hypertension, osteoporosis, polycystic ovary syndrome,
It improves fatty liver and gestational diabetes, and has an aldose reductase inhibitory effect.

That is, the oxime derivative having the above general formula (I) or a salt thereof according to the present invention can be used for hyperlipidemia, hyperglycemia,
Obesity, glucose intolerance, insulin resistant non-glucose intolerance,
Insulin resistance, cachexia, psoriasis, diabetic complications (eg, retinopathy, nephropathy, neuropathy, cataract, coronary artery disease, etc.), arteriosclerosis, also hypertension, osteoporosis, polycystic ovary syndrome, fatty liver and It is useful as a prophylactic and / or therapeutic drug for gestational diabetes mellitus and the like.

The oxime derivative having the general formula (I) or a salt thereof of the present invention is administered in various forms. As the administration form, for example, tablets, capsules, granules,
Oral administration by powders, syrups and the like or parenteral administration by injections (intravenous, intramuscular, subcutaneous), drops, suppositories and the like can be mentioned. These various preparations are commonly used in the pharmaceutical preparation technical field such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizing agents, suspending agents, coating agents, and the like, in accordance with the usual methods for the main drug. It can be formulated using known adjuvants. The dose varies depending on symptoms, age, body weight, administration method, dosage form, etc., but is usually 0.001 mg (preferably 0.01 mg, more preferably 0.1 mg) as a lower limit per adult per day. 2,000 mg as an upper limit (preferably 200 mg
g, more preferably 20 mg).

[0210]

EXAMPLES The present invention will be described in more detail with reference to Examples, Reference Examples, Test Examples and Formulation Examples, but the present invention is not limited to these.

Example 1 5- [4- [2-[(benzylideneamino) oxy] e
Toxi] benzyl] thiazolidine-2,4-dione (Exemplary Compound No. 1-1) (a) 5- [4- [2-[(benzylideneamino) oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine
383 mg of 2-, 4 -dione 2-[(benzylideneamino) oxy] ethanol (compound of Reference Example 1), 1.00 g of 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione and triphenyl Phosphine 629m
g of tetrahydrofuran in a 10 ml solution of tetrahydrofuran in 450 mg of diethyl azodicarboxylate.
The solution was added dropwise at room temperature and stirred at room temperature for 16 hours. The reaction mixture was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain 0.53 g of the target compound as a gum.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.07 (1H, d, d, J = 8.5, 14Hz), 3.44 (1H, d, d, J = 4,
14Hz), 4.26 (2H, t, J = 4.5Hz), 4.36 (1H, d, d, J = 4, 8.
5Hz), 4.52 (2H, t, J = 4.5Hz), 6.88 (2H, d, J = 8.5Hz),
7.12 (2H, d, J = 8.5Hz), 7.17-7.59 (20H, m), 8.14 (1H,
s).

(B) 5- [4- [2-[(benzylidene)
Amino) oxy] ethoxy] benzyl] thiazolidine-
2,4-dione 5- [4- [2-[(benzylideneamino) oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione obtained in Example 1 (a) 0.53 g of dioxane A mixed solution of 10 ml, 7 ml of acetic acid and 3 ml of water was stirred at 80 ° C. for 2 hours. The reaction mixture was concentrated and the remaining acetic acid and water were removed by azeotropic distillation with toluene. The obtained residue is subjected to silica gel column chromatography (hexane: ethyl acetate =
2: 1 → 1: 1) to give a crystalline powder, which was suspended in isopropyl ether and collected by filtration to give a melting point of 126.
215 mg of the desired compound having a temperature of -129 ° C. were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.10 (1H, d, d, J = 9, 14Hz), 3.45 (1H, d, d, J = 4, 14H
z), 4.26 (2H, t, J = 4.5Hz), 4.47-4.53 (3H, m), 6.90 (2
H, d, J = 8.5Hz), 7.14 (2H, d, J = 8.5Hz), 7.36-7.38 (3H,
m), 7.56-7.59 (2H, m), 8.02 (1H, brs), 8.14 (1H, s).

Example 2 5- [4- [2-[(2-quinolylmethyleneamino) o]
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (Exemplified Compound No. 1-149) (a) 5- [4- [2-[(2- quinolylmethyleneamido)
No) oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[(2 -quinolylmethyleneamino ) oxy] ethanol (compound of Reference Example 2) 478 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,
4-dione 1.00 g, triphenylphosphine 6
38 mg and 423 mg of diethyl azodicarboxylate
When the reaction and after-treatment were carried out in the same manner as in Example 1 (a), 1.12 g of a crystalline powdery target compound having a melting point of 127 to 130 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.06 (1H, d, d, J = 8.5, 14Hz), 3.41 (1H, d, d, J = 4, 1
4Hz), 4.29-4.38 (3H, m), 4.61 (2H, t, J = 4.5Hz), 6.90
(2H, d, J = 8.5Hz), 7.11-7.44 (17H, m), 7.56 (1H, t, J =
8Hz), 7.72 (1H, t, J = 8Hz), 7.82 (1H, d, J = 8Hz), 7.96
(1H, d, J = 8.5Hz), 8.09 (1H, d, J = 8.5Hz), 8.13 (1H, d,
J = 8Hz), 8.39 (1H, s).

(B) 5- [4- [2-[(2-quinolyl)
Methyleneamino) oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione 5- [4- [2-[(2-quinolylmethyleneamino) oxy] ethoxy] benzyl] obtained in Example 2 (a).
-3-tritylthiazolidine-2,4-dione 1.00
Using g, the reaction and after-treatment were carried out according to Example 1 (b), to obtain 522 mg of the target compound as a crystalline powder having a melting point of 164-166 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H, d, d, J = 4.5,
14Hz), 4.30 (2H, t, J = 4.5Hz), 4.56 (2H, t, J = 4.5Hz),
4.87 (1H, d, d, J = 4.5, 9Hz), 6.94 (2H, d, J = 8.5H
z), 7.17 (2H, d, J = 8.5Hz), 7.66 (1H, t, J = 8Hz), 7.8
0 (1H, t, J = 8Hz), 7.95-8.06 (3H, m), 8.37 (1H, s),
8.42 (1H, d, J = 8.5Hz).

Example 3 5- [4- [2-[(3-quinolylmethyleneamino) o]
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (Exemplified Compound No. 1-150) (a) 5- [4- [2-[(3- quinolylmethyleneamido)
No) oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[(3 -quinolylmethyleneamino ) oxy] ethanol (compound of Reference Example 3) 0.60 g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,
1.10 g of 4-dione and tributylphosphine
To a suspension of 0.72 ml of 30 ml of tetrahydrofuran was added dropwise a solution of 0.73 g of 1,1 '-(azodicarbonyl) dipiperazine in 10 ml of toluene at room temperature, and the mixture was stirred for 16 hours. The reaction mixture was subjected to silica gel column chromatography (hexane: ethyl acetate = 1: 1).
By subjecting it to 1), 1.45 g of a crystalline powder of the target compound having a melting point of 127-130 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14
Hz), 4.30 (2H, t, J = 4.5Hz), 4.36 (1H, d, d, J = 4, 9H
z), 4.60 (2H, t, J = 4.5Hz), 6.91 (2H, d, J = 8.5Hz),
7.12-7.44 (17H, m), 7.57 (1H, t, J = 7.5Hz), 7.75 (1H,
t, J = 7.5Hz), 7.83 (1H, d, J = 8.5Hz), 8.12 (1H, d, J =
8.5Hz), 8.18 (1H, s), 8.27 (1H, s), 9.21 (1H, s).

(B) 5- [4- [2-[(3-quinolyl)
Methyleneamino) oxy] ethoxy ] benzyl] thiazo
Lysine-2,4-dione 5- [4- [2-[(3-quinolylmethyleneamino) oxy] ethoxy] benzyl] obtained in Example 3 (a).
-3-Tritylthiaziridine-2,4-dione 0.89
Using g, the reaction and post-treatment were carried out according to Example 1 (b), to obtain 0.47 g of a crystalline powder of the target compound having a melting point of 182-184 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H, d, d, J = 4, 14H
z), 4.28 (2H, t, J = 4.5Hz), 4.52 (2H, t, J = 4.5Hz), 4.87
(1H, d, d, J = 4, 9Hz), 6.94 (2H, d, J = 8.5Hz), 7.17 (2
H, d, J = 8.5Hz), 7.66 (1H, t, J = 7.5Hz), 7.81 (1H, t,
J = 7.5Hz), 8.05 (2H, d, J = 8.5Hz), 8.53 (2H, s), 9.18
(1H, s).

Example 4 5- [4- [2-[(2-pyridylmethyleneamino) o]
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (Exemplified Compound No. 1-87) (a) 5- [4- [2-[(2-pyridylmethyleneamido )
No) oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[(2-pyridylmethyleneamino) oxy] ethanol (compound of Reference Example 4) 498 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,
1.13 g of 4-dione, tributylphosphine
Using 75 ml and 693 mg of 1,1 '-(azodicarbonyl) dipiperazine, the reaction and post-treatment were carried out according to Example 3 (a) to give the target compound as a foamy solid.
82 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 3.42 (1H, d, d, J = 4, 14H
z), 4.27 (2H, t, J = 5Hz), 4.37 (1H, d, d, J = 4, 9Hz),
4.58 (2H, t, J = 5Hz), 6.89 (2H, d, J = 8.5Hz), 7.11-7.33
(18H, m), 7.69-7.77 (2H, m), 8.24 (1H, s), 8.63 (1H,
d, J = 5Hz).

(B) 5- [4- [2-[(2-pyridyl)
Methyleneamino) oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione 5- [4- [2-[(2-pyridylmethyleneamino) oxy] ethoxy] benzyl] obtained in Example 4 (a).
-3-Tritylthiazolidine-2,4-dione 0.82
Using g, the reaction and post-treatment were carried out according to Example 1 (b) to obtain 0.42 g of a crystalline powder of the target compound having a melting point of 161-163 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H, d, d, J = 4, 14H
z), 4.26 (2H, t, J = 4.5Hz), 4.49 (2H, t, J = 4.5Hz), 4.88
(1H, d, d, J = 4, 9Hz), 6.92 (2H, d, J = 8.5Hz), 7.16 (2
H, d, J = 8.5Hz), 7.40-7.45 (1H, m), 7.79-7.89 (2H,
m), 8.22 (1H, s), 8.61 (1H, d, J = 5Hz), 11.98 (1H, s)
.

Example 5 5- [4- [2-[(3-pyridylmethyleneamino) OH]
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (Exemplified Compound No. 1-88) (a) 5- [4- [2-[(3-pyridylmethyleneamido )
No) oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[(3-pyridylmethyleneamino) oxy] ethanol (compound of Reference Example 5) 0.90 g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,
2.00 g of 4-dione, tributylphosphine
Using 32 ml and 1.23 g of 1,1 ′-(azodicarbonyl) dipiperazine, the reaction and work-up were carried out according to Example 3 (a) to give the desired compound 1 as a crystalline powder having a melting point of 155-157 ° C. .37 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14H
z), 4.26 (2H, t, J = 4.5Hz), 4.36 (1H, d, d, J = 4, 9H
z), 4.54 (2H, t, J = 4.5Hz), 6.88 (2H, d, J = 8.5Hz),
7.11-7.37 (18H, m), 7.93 (1H, d, J = 8Hz), 8.13 (1H,
s), 8.60 (1H, d, d, J = 1.5, 5Hz), 8.73 (1H, d, J = 2H
z).

(B) 5- [4- [2-[(3-pyridyl)
Methyleneamino) oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione 5- [4- [2-[(3-pyridylmethyleneamino) oxy] ethoxy] benzyl] obtained in Example 5 (a).
-3-tritylthiazolidine-2,4-dione 1.27
Using g, the reaction and work-up were carried out according to Example 1 (b), to obtain 0.75 g of a crystalline powder of the target compound having a melting point of 157-159 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 4.32 (1H, d, d, J = 4, 14H
z), 4.24 (2H, t, J = 4.5Hz), 4.46 (2H, t, J = 4.5Hz), 4.87
(1H, d, d, J = 4, 9Hz), 6.92 (2H, d, J = 8.5Hz), 7.16 (2
H, d, J = 8.5Hz), 7.45 (1H, d, d, J = 5, 8Hz), 8.02 (1H,
d, J = 8Hz), 8.37 (1H, s), 8.60 (1H, d, J = 5Hz), 8.78 (1
H, s).

Example 6 5- [4- [2-[(4-pyridylmethyleneamino) o]
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (exemplified compound number 1-89) (a) 5- [4- [2-[(4-pyridylmethyleneamido )
No) oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[(4-pyridylmethyleneamino) oxy] ethanol (compound of Reference Example 6) 0.88 g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,
2.00 g of 4-dione, tributylphosphine
When 32 ml and 1.23 g of 1,1 '-(azodicarbonyl) dipiperazine are used for the reaction and post-treatment according to Example 3 (a), the target compound as a foamy solid is obtained.
10 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.08 (1H, d, d, J = 9, 14Hz), 3.40 (1H, d, d, J = 4, 14H
z), 4.26 (2H, t, J = 4.5Hz), 4.37 (1H, d, d, J = 4, 9Hz),
4.57 (2H, t, J = 4.5Hz), 6.88 (2H, d, J = 8.5Hz), 7.13 (2
H, d, J = 8.5Hz), 7.17-7.33 (15H, m), 7.43 (1H, d, J = 6
Hz), 8.07 (1H, s), 8.62 (1H, d, J = 6Hz).

(B) 5- [4- [2-[(4-pyridyl)
Methyleneamino) oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione 5- [4- [2-[(4-pyridylmethyleneamino) oxy] ethoxy] benzyl] obtained in Example 6 (a).
-3-tritylthiazolidine-2,4-dione 1.10
Using g, the reaction and post-treatment were carried out according to Example 1 (b), to obtain 0.42 g of a crystalline powder of the target compound having a melting point of 221 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 3.32 (1H, d, d, J = 4, 14H
z), 4.25 (2H, t, J = 4.5Hz), 4.50 (2H, t, J = 4.5Hz), 4.87
(1H, d, d, J = 4, 9Hz), 6.92 (2H, d, J = 8.5Hz), 7.16 (2
H, d, J = 8.5Hz), 7.57 (2H, d, J = 6Hz), 8.35 (1H, s),
8.63 (2H, d, J = 6Hz).

Example 7 5- [4- [2-[(2-naphthylmethyleneamino) o]
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (exemplified compound number 1-3) (a) 5- [4- [2-[(2-naphthylmethyleneamido )
No) oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[(2-naphthylmethyleneamino) oxy] ethanol (compound of Reference Example 7) 430 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,
4-dione 716 mg, triphenylphosphine 5
25 mg and 348 mg of diethyl azodicarboxylate
When the reaction and post-treatment were carried out according to Example 1 (a) using, 712 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.07 (1H, d, d, J = 9, 14Hz), 3.40 (1H, d, d, J = 4, 14
Hz), 4.29 (2H, t, J = 4.5Hz), 4.36 (1H, d, d, J = 4, 9H
z), 4.56 (2H, t, J = 4.5Hz), 6.91 (2H, d, J = 8.5Hz),
7.11-7.32 (17H, m), 7.46-7.54 (2H, m), 7.79-7.87 (5H, m
m), 8.28 (1H, s).

(B) 5- [4- [2-[(2-naphthyl)
Methyleneamino) oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione 5- [4- [2-[(2-naphthylmethyleneamino) oxy] ethoxy] benzyl] obtained in Example 7 (a).
-3-m-Tritylthiazolidine-2,4-dione 712m
Using g, the reaction and post-treatment were carried out according to Example 1 (b), to obtain 374 mg of the target compound as a foamy solid having a melting point of 108 to 111 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.09 (1H, d, d, J = 9.5, 14Hz), 3.45 (1H, d, d, J = 4, 1
4Hz), 4.29 (2H, t, J = 4.5Hz), 4.49 (1H, d, d, J = 4, 9.5
Hz), 4.56 (2H, t, J = 4.5Hz), 6.92 (2H, d, J = 8.5Hz), 7.
14 (2H, d, J = 8.5Hz), 7.47-7.54 (2H, m), 7.80-7.89 (5
H, m), 8.29 (1H, s).

Embodiment 85- [4- [2-[(3-phenylbenzylideneami
No) oxy] ethoxy] benzyl] thiazolidine-2,
4-dione (Exemplary Compound No. 1-14) (a)5- [4- [2-[(3-phenylbenzylidene)
Amino) oxy] ethoxy] benzyl] -3-trityl
Thiazolidine-2,4-dione 2-[(3-phenylbenzylideneamino) oxy] d
Tanol (compound of Reference Example 8) 483 mg, 5- (4
-Hydroxybenzyl) -3-tritylthiazolidine-
716 mg of 2,4-dione, triphenylphosphine
 525 mg and diethyl azodicarboxylate 348
The reaction and work-up were carried out according to Example 1 (a) using mg
Is carried out to obtain 807 mg of the target compound as a foamy solid.
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.06 (1H, d, d, J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14H
z), 4.27 (2H, t, J = 4.5Hz), 4.36 (1H, d, d, J = 4, 9Hz),
4.54 (2H, t, J = 4.5Hz), 6.90 (2H, d, J = 8.5Hz), 7.11
-7.61 (25H, m), 7.80 (1H, s), 8.20 (1H, s).

(B) 5- [4- [2-[(3-phenyl)
Benzylideneamino) oxy] ethoxy] benzyl] thio
Azolidine-2,4-dione 5- [4- [2-[(3-phenylbenzylideneamino) oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione obtained in Example 8 (a) 8
When the reaction and after-treatment were carried out according to Example 1 (b) using 00 mg, 344 mg of the target compound as crystalline powder having a melting point of 128 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.09 (1H, d, d, J = 9, 14Hz), 3.44 (1H, d, d, J = 4, 14
Hz), 4.27 (2H, t, J = 4.5Hz), 4.49 (1H, d, d, J = 4, 9H
z), 4.53 (2H, t, J = 4.5Hz), 6.91 (2H, d, J = 8.5Hz),
7.14 (2H, d, J = 8.5Hz), 7.34-7.61 (8H, m), 7.81 (1H,
s), 8.20 (1H, s).

Embodiment 95- [4- [2-[(4-phenylbenzylideneamido)
No) oxy] ethoxy] benzyl] thiazolidine-2,
4-dione (Exemplary Compound No. 1-15) (a)5- [4- [2-[(4-phenylbenzylidene)
Amino) oxy] ethoxy] benzyl] -3-trityl
Thiazolidine-2,4-dione 2-[(4-phenylbenzylideneamino) oxy] d
Tanol (compound of Reference Example 9) 483 mg, 5- (4
-Hydroxybenzyl) -3-tritylthiazolidine-
716 mg of 2,4-dione, triphenylphosphine
 525 mg and diethyl azodicarboxylate 348
The reaction and work-up were carried out according to Example 1 (a) using mg
Is performed, a crystalline powder having a melting point of 157-159 ° C.
914 mg of the desired compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.08 (1H, d, d, J = 9, 14Hz), 3.42 (1H, d, d, J = 4, 14H
z), 4.29 (2H, t, J = 4.5Hz), 4.37 (1H, d, d, J = 4, 9H
z), 4.55 (2H, t, J = 4.5Hz), 6.91 (2H, d, J = 8.5Hz),
7.12-7.68 (26H), 8.19 (1H, s).

(B) 5- [4- [2-[(4-phenyl)
Benzylideneamino) oxy] ethoxy] benzyl] thio
Azolidine-2,4-dione 5- [4- [2-[(4-phenylbenzylideneamino) oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione obtained in Example 9 (a) 9
When the reaction and after-treatment were carried out according to Example 1 (b) using 07 mg, 442 mg of the target compound as a crystalline powder having a melting point of 124 to 127 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.11 (1H, d, d, J = 9, 14Hz), 3.45 (1H, d, d, J = 4, 14H
z), 4.28 (2H, t, J = 4.5Hz), 4.50 (1H, d, d, J = 4,9H
z), 4.53 (2H, t, J = 4.5Hz), 6.92 (2H, d, J = 8.5Hz), 7.1
5 (2H, d, J = 8.5Hz), 7.27-7.68 (9H, m), 8.18 (1H, s)
.

Example 10 5- [4- [2-[[(2-phenyl-5-pyridyl)
Methyleneamino] oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione (Exemplary Compound No. 1-95) (a) 5- [4- [2-[[(2-phenyl-5-pyri)
Jyl) methyleneamino] oxy] ethoxy] benzyl]
-3-Tritylthiazolidine-2,4-dione 2-[[(2-phenyl-5-pyridyl) methyleneamino] oxy] ethanol (compound of Reference Example 10) 39
Using 0 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione (576 mg), triphenylphosphine (422 mg) and diethyl azodicarboxylate (280 mg), the reaction and post-treatment were carried out according to Example 1 (a). This gave 671 mg of a crystalline powder of the target compound having a melting point of 146-148 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.08 (1H, d, d, J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14H
z), 4.28 (2H, t, J = 4.5Hz), 4.37 (1H, d, d, J = 4,9Hz),
4.56 (2H, t, J = 4.5Hz), 6.90 (2H, d, J = 8.5Hz), 7.12-7.
33 (17H, m), 7.44-7.53 (3H, m), 7.74 (1H, d, J = 8.5Hz),
7.99-8.03 (3H, m), 8.18 (1H, s), 8.77 (1H, d, J = 2H
z).

(B)5- [4- [2-[[(2-phenyl
Ru-5-pyridyl) methyleneamino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[(2
-Phenyl-5-pyridyl) methyleneamino] oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine-
Using 600 mg of 2,4-dione, in Example 1 (b)
When the reaction and post-treatment are carried out according to the above,
312 mg of a crystalline powder of the target compound having a
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.14 (1H, d, d, J = 9, 14Hz), 3.42 (1H, d, d, J = 4, 14
Hz), 4.29 (2H, t, J = 4.5Hz), 4.48-4.58 (3H, m), 6.91
(2H, d, J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz), 7.44-7.53
(3H, m), 7.75 (1H, d, J = 8.5Hz), 8.00-8.03 (3H, m),
8.18 (1H, s), 8.43 (1H, brs), 8.76 (1H, d, J = 2 Hz).

Example 11 5- [4- [2-[[(3-phenyl-5-pyridyl)
Methyleneamino] oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione (Exemplary Compound No. 1-92) (a) 5- [4- [2-[[(3-phenyl-5-pyri)
Jyl) methyleneamino] oxy] ethoxy] benzyl]
-3-Tritylthiazolidine-2,4-dione 2-[[(3-phenyl-5-pyridyl) methyleneamino] oxy] ethanol (compound of Reference Example 11) 35
Using 4 mg, 510 mg of 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione, 383 mg of triphenylphosphine and 255 mg of diethyl azodicarboxylate, the reaction and post-treatment were carried out according to Example 1 (a). When done, the target compound 5 as a foamy solid
50 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14
Hz), 4.28 (2H, t, J = 4.5Hz), 4.36 (1H, d, d, J = 4, 9H
z), 4.57 (2H, t, J = 4.5Hz), 6.89 (2H, d, J = 8.5Hz),
7.11-7.33 (17H, m), 7.40-7.53 (3H, m), 7.59-7.62 (2H,
m), 8.12 (1H, t, J = 2Hz), 8.20 (1H, s), 8.69 (1H, d,
J = 2Hz), 8.84 (1H, d, J = 2Hz).

(B)5- [4- [2-[[(3-phenyl
Ru-5-pyridyl) methyleneamino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[(3
-Phenyl-5-pyridyl) methyleneamino] oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine-
Using 550 mg of 2,4-dione, in Example 1 (b)
When the reaction and after-treatment are carried out according to the above, melting point 160-161.
287 mg of a crystalline powder of the target compound having a
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in deuterated chloroform and deuterated dimethyl sulfoxide (trace amount), TMS (tetramethylsilane) as internal standard
¹ H-nuclear magnetic resonance spectrum (270
MHz) is as follows. 3.05 (1H, d, d, J = 9, 14Hz), 3.44 (1H, d, d, J = 4, 14
Hz), 4.28 (2H, t, J = 4.5Hz), 4.44 (1H, d, d, J = 4, 9H
z), 4.56 (2H, t, J = 4.5Hz), 6.90 (2H, d, J = 8.5Hz),
7.15 (2H, d, J = 8.5Hz), 7.43-7.53 (3H, m), 7.61-7.64
(2H, m), 8.15 (1H, t, J = 2Hz), 8.23 (1H, s), 8,70 (1
H, d, J = 2 Hz), 8.83 (1H, d, J = 2 Hz).

Example 12 5- [4- [2-[[(2-ethoxy-5-pyridyl)
Methyleneamino] oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione (Exemplary Compound No. 1-97) (a) 5- [4- [2-[[(2-ethoxy-5-pyri)
Jyl) methyleneamino] oxy] ethoxy] benzyl]
-3-Tritylthiazolidine-2,4-dione 2-[[(2-ethoxy-5-pyridyl) methyleneamino] oxy] ethanol (compound of Reference Example 12) 57
Using 0 mg, 1.20 g of 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione, 695 mg of triphenylphosphine, and 462 mg of diethyl azodicarboxylate, the reaction was carried out according to Example 1 (a). After the treatment, the target compound as a foamy solid
1.27 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.40 (3H, t, J = 7Hz), 3.07 (1H, d, d, J = 9, 14Hz), 3.42
(1H, d, d, J = 4, 14Hz), 4.25 (2H, t, J = 4.5Hz), 4.36 (1
H, d, d, J = 4, 9Hz), 4.38 (2H, q, J = 7Hz), 4.49 (2H,
t, J = 4.5Hz), 6.72 (1H, d, J = 8.5Hz), 6.89 (2H, d, J = 8.
5Hz), 7.11-7.53 (17H, m), 7.90 (1H, d, d, J = 2, 8.5H
z), 8.08 (1H, s), 8.17 (1H, d, J = 2Hz).

(B)5- [4- [2-[[(2-ethoxy
C-5-pyridyl) methyleneamino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[(2) obtained in Example 12 (a)
-Ethoxy-5-pyridyl) methyleneamino] oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine-
Using 1.27 g of 2,4-dione, in Example 1 (b)
When the reaction and after-treatment are carried out according to the above, melting point 127-129
572 mg of a crystalline powder of the target compound having a
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 1.32 (3H, t, J = 7Hz), 3.05 (1H, d, d, J = 9, 14Hz), 3.31
(1H, d, d, J = 4, 14Hz), 4.22 (2H, t, J = 4.5Hz), 4.33
(2H, q, J = 7Hz), 4.41 (2H, t, J = 4.5Hz), 4.87 (1H, d,
d, J = 4, 9Hz), 6.84 (1H, d, J = 8.5Hz), 6.91 (2H, d, J =
8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.95 (1H, d, d, J = 2,
8.5Hz), 8.28 (1H, s), 8.31 (1H, d, J = 2Hz), 12.00 (1
H, brs).

Example 13 5- [4- [2-[[[1- (2-naphthyl) ethylide]
[Amino] oxy] ethoxy] benzyl] thiazolidy
Down-2,4-dione (Compound No. 2-3) (a) 5- [4- [2 - [[[1- (2- naphthyl) et
Chiriden] amino] Oki shea] ethoxy] benzyl] -3
-Tritylthiazolidine-2,4-dione 2-[[[1- (2-naphthyl) ethylidene] amino]
Oxy] ethanol (compound of Reference Example 13)
g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione (716 mg), triphenylphosphine (525 mg) and diethyl azodicarboxylate (348 mg) were subjected to the reaction and post-treatment according to Example 1 (a). When this is done, the target compound as a foamy solid is 858 m
g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.35 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.31 (2H, t, J = 5Hz), 4.36 (1H, d,
d, J = 4, 9Hz), 4.59 (2H, t, J = 5Hz), 6.91 (2H, d, J = 8.5
Hz), 7.11-7.33 (17H, m), 7.46-7.52 (2H, m), 7.79-7.93
(4H, m), 7.99 (1H, s).

(B) 5- [4- [2-[[[1- (2-
Naphthyl) ethylidene] amino] oxy] ethoxy] b
Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1
-(2-naphthyl) ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4
The reaction and after-treatment were carried out according to Example 1 (b) using 854 mg of -dione to obtain 442 mg of the target compound as a crystalline powder having a melting point of 138 to 139 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.36 (3H, s), 3.10 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.31 (2H, t, J = 5Hz), 4.50 (1H, d,
d, J = 4, 9Hz), 4.58 (2H, t, J = 5Hz), 6.93 (2H, d, J = 8.5
Hz), 7.15 (2H, d, J = 8.5Hz), 7.46-7.53 (2H, m), 7.80-
7.93 (4H, m), 8.00 (1H, s), 8.12 (1H, brs).

Example 14 5- [4- [2-[[[1- (2-quinolyl) ethylide]
[Amino] oxy] ethoxy] benzyl] thiazolidy
2-a, 4-dione (Exemplified Compound No. 2-149) (a) 5- [4- [2-[[[1- (2-quinolyl) e
Chiriden] amino] Oki shea] ethoxy] benzyl] -3
-Tritylthiazolidine-2,4-dione 2-[[[1- (2-quinolyl) ethylidene] amino]
Oxy] ethanol (compound of Reference Example 14) 461 m
g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione (716 mg), triphenylphosphine (525 mg) and diethyl azodicarboxylate (348 mg) were subjected to the reaction and post-treatment according to Example 1 (a). When done, the target compound is 911 m as a foamy solid
g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.49 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.32 (2H, t, J = 4.5Hz), 4.36 (1H,
d, d, J = 4, 9Hz), 4.62 (2H, t, J = 4.5Hz), 6.90 (2H, d,
J = 8.5Hz), 7.11-7.33 (17H, m), 7.51 (1H, d, t, J = 1,
7.5Hz), 7.70 (1H, d, t, J = 1.5, 7Hz), 7.80 (1H, d, d,
J = 1, 7.5Hz), 8.06 (2H, s), 8.10 (1H, d, J = 8Hz).

(B) 5- [4- [2-[[[1- (2-
Quinolyl) ethylidene] amino] oxy] ethoxy] b
Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1
-(2-quinolyl) ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4
When 904 mg of -dione was used for the reaction and post-treatment according to Example 1 (b), 402 mg of a crystalline powder of the target compound having a melting point of 162-163 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.46 (3H, s), 3.11 (1H, d, d, J = 9, 14Hz), 3.43 (1H,
d, d, J = 4, 14Hz), 4.32 (2H, t, J = 4.5Hz), 4.50 (1H,
d, d, J = 4, 9Hz), 4.62 (2H, t, J = 4.5Hz), 6.92 (2H, d,
J = 8.5Hz), 7.14 (2H, d, J = 8.5Hz), 7.54 (1H, t, J = 7.5
Hz), 7.70 (1H, t, J = 7.5Hz), 7.80 (1H, d, J = 8Hz), 8.
04-8.11 (3H, m).

Embodiment 155- [4- [2-[[[1- (4-biphenylyl) ethyl
[Ridene] amino] oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione (Exemplified Compound No. 2-15) (a)5- [4- [2-[[[1- (4-biphenyli
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] -3-Tritylthiazolidine-2,4-dione 2-[[[1- (4-biphenylyl) ethylidene] amido
[No] oxy] ethanol (compound of Reference Example 15) 17
0 mg, 5- (4-hydroxybenzyl) -3-triti
238 mg of luthiazolidine-2,4-dione, trif
Phenylphosphine 175 mg and azodicarboxylic acid
According to Example 1 (a) using 116 mg of diethyl
Upon reaction and after-treatment, crystals having a melting point of 145 ° C.
As a result, 257 mg of a target compound as a neutral powder was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.27 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 4.5Hz), 4.36 (1H,
d, d, J = 4, 9Hz), 4.55 (2H, d, J = 4.5Hz), 6.90 (2H, d,
J = 8.5Hz), 7.11-7.48 (20H, m), 7.58-7.62 (4H, m),
7.72 (2H, d, J = 8.5Hz).

(B)5- [4- [2-[[[1- (4-
Biphenylyl) ethylidene] amino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1] obtained in Example 15 (a)
-(4-Biphenylyl) ethylidene] amino] oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine-
Example 1 (b) using 254 mg of 2,4-dione
When the reaction and after-treatment are carried out in accordance with the above, the melting point is 164-166.
139 mg of a crystalline powder of the target compound having a
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.28 (3H, s), 3.10 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 4.5Hz), 4.50 (1H,
d, d, J = 4, 9Hz), 4.55 (2H, t, J = 4.5Hz), 6.92 (2H, d,
J = 8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.33-7.48 (3H, m),
7.60 (4H, d, d, J = 2, 8.5Hz), 7.73 (2H, d, J = 8.5Hz),
8.05 (1H, brs).

Embodiment 165- [4- [2-[[[1- (3-biphenylyl) ethyl
[Ridene] amino] oxy] ethoxy] benzyl] thiazo
Lysine-2,4-dione (Exemplary Compound No. 2-14) (a)5- [4- [2-[[[1- (3-biphenyli
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] -3-Tritylthiazolidine-2,4-dione 2-[[[1- (3-biphenylyl) ethylidene] amido
[No] oxy] ethanol (compound of Reference Example 16) 51
1 mg, 5- (4-hydroxybenzyl) -3-triti
716 mg of luthiazolidine-2,4-dione, trif
525 mg of phenylphosphine and azodicarboxylic acid
According to Example 1 (a) using 348 mg of diethyl
After the reaction and post-treatment, the target compound is an amorphous solid
916 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.29 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 4.5Hz), 4.36 (1H,
d, d, J = 4, 9Hz), 4.55 (2H, d, J = 4.5Hz), 6.90 (2H, d,
J = 8.5Hz), 7.10-7.39 (17H, m), 7.41-7.48 (3H, m),
7.58-7.63 (4H, m), 7.85 (2H, d, J = 8.5Hz).

(B)5- [4- [2-[[[1- (3-
Biphenylyl) ethylidene] amino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1] obtained in Example 16 (a)
-(3-Biphenylyl) ethylidene] amino] oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine-
Using 912 mg of 2,4-dione, and in Example 1 (b)
Perform the reaction and post-treatment in accordance with
Lamb tomatography (hexane: ethyl acetate = 2:
Purification according to 1) gives a gummy compound of interest 540.
mg was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.29 (3H, s), 3.11 (1H, d, d, J = 9.5, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 5Hz), 4.49 (1H, d,
d, J = 4, 9.5Hz), 4.55 (2H, t, J = 5Hz), 6.92 (2H, d, J =
8.5Hz), 7.14 (2H, d, J = 8.5Hz), 7.34-7.48 (4H, m), 7.5
7-7.63 (4H, m), 7.85 (2H, d, J = 2Hz), 8.07 (1H, brs)
.

Example 17 5- [4- [2-[[[1- (2-phenyl-5-pyri)
Jill) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (exemplary compound number
2-95) (a) 5- [4- [2-[[[1- (2-phenyl-5
-Pyridyl) ethylidene] amino] oxy] ethoxy]
[Benzyl] -3-tritylthiazolidine-2,4-dio
Down 2 - [[[1- (2-phenyl-5-pyridyl) ethylidene] amino] oxy] ethanol (Compound of Reference Example 17) 384mg, 5- (4- hydroxybenzyl) -
3-tritylthiazolidine-2,4-dione 537m
g, 393 mg of triphenylphosphine and 261 mg of diethyl azodicarboxylate.
When the reaction and post-treatment were carried out according to (a), 698 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.29 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 4.5Hz), 4.37 (1H,
d, d, J = 4, 9Hz), 4.57 (2H, d, J = 4.5Hz), 6.90 (2H, d,
J = 8.5Hz), 7.12-7.36 (17H, m), 7.43-7.52 (3H, m),
7.72 (1H, d, J = 8Hz), 8.00-8.04 (3H, m), 8.94 (1H, d,
J = 2.5Hz).

(B)5- [4- [2-[[[1- (2-
Phenyl-5-pyridyl) ethylidene] amino] oxo
[Ethoxy] benzyl] thiazolidine-2,4-di
N 5- [4- [2-[[[1] obtained in Example 17 (a)
-(2-Phenyl-5-pyridyl) ethylidene] ami
[No] oxy] ethoxy] benzyl] -3-tritylthia
Example using 695 mg of zolidine-2,4-dione
When the reaction and post-treatment are carried out according to 1 (b), the melting point is 18
Target compound 3 as crystalline powder having 6-187 ° C
80 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.29 (3H, s), 3.16 (1H, d, d, J = 9, 14Hz), 3.40 (1H,
d, d, J = 4, 14Hz), 4.31 (2H, t, J = 4.5Hz), 4.49-4.59 (3
H, m), 6.91 (2H, d, J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz),
7.43-7.52 (3H, m), 7.73 (1H, d, J = 8.5Hz), 7.99-8.03 (3
H, m), 8.87 (1H, d, J = 2Hz).

Example 18 5- [4- [2-[[[1- (3-phenyl-5-pyri)
Jill) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (exemplary compound number
2-92) (a) 5- [4- [2-[[[1- (3-phenyl-5
-Pyridyl) ethylidene] amino] oxy] ethoxy]
[Benzyl] -3-tritylthiazolidine-2,4-dio
Down 2 - [[[1- (3-phenyl-5-pyridyl) ethylidene] amino] oxy] ethanol (the compound of Reference Example 18) 419mg, 5- (4- hydroxybenzyl) -
3-tritylthiazolidine-2,4-dione 585m
g, 429 mg of triphenylphosphine and 285 mg of diethyl azodicarboxylate.
When the reaction and post-treatment were carried out according to (a), 522 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.30 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.40 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 4.5Hz), 4.35 (1H,
d, d, J = 4, 9Hz), 4.57 (2H, t, J = 4.5Hz), 6.88 (2H, d,
J = 8.5Hz), 7.10-7.32 (17H, m), 7.41-7.51 (3H, m),
7.58-7.61 (2H, m), 8.12 (1H, t, J = 2Hz), 8.88-8.90 (2
H, m).

(B)5- [4- [2-[[[1- (3-
Phenyl-5-pyridyl) ethylidene] amino] oxo
[Ethoxy] benzyl] thiazolidine-2,4-di
N 5- [4- [2-[[[1] obtained in Example 18 (a)
-(3-Phenyl-5-pyridyl) ethylidene] ami
[No] oxy] ethoxy] benzyl] -3-tritylthia
Example 1 Using 516 mg of Zolidine-2,4-dione
When the reaction and post-treatment are carried out according to 1 (b), the melting point is 15
The target compound 3 as a crystalline powder having a temperature of 0-153 ° C 3
03 mg was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in deuterated chloroform and deuterated dimethyl sulfoxide (trace amount), TMS (tetramethylsilane) as internal standard
¹ H-nuclear magnetic resonance spectrum (270
MHz) is as follows. 2.31 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 4.5Hz), 4.43 (1H,
d, d, J = 4, 9Hz), 4.57 (2H, t, J = 4.5Hz), 6.90 (2H, d,
J = 8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.43-7.53 (3H, m),
7.60-7.63 (2H, m), 8.13 (1H, t, J = 2Hz), 8.82 (2H, m
d, J = 2Hz).

Example 19 5- [4- [2-[[[1- (2-ethoxy-5-pyri)
Jill) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (exemplary compound number
2-97) (a) 5- [4- [2-[[[1- (2-ethoxy-5)
-Pyridyl) ethylidene] amino] oxy] ethoxy]
[Benzyl] -3-tritylthiazolidine-2,4-dio
Down 2 - [[[1- (2-ethoxy-5-pyridyl) ethylidene] amino] oxy] ethanol (Compound of Reference Example 19) 410mg, 5- (4- hydroxybenzyl) -
3-tritylthiazolidine-2,4-dione 655m
g, 480 mg of triphenylphosphine and 319 mg of diethyl azodicarboxylate.
When the reaction and post-treatment were carried out according to (a), 763 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.40 (3H, t, J = 7Hz), 2.21 (3H, s), 3.07 (1H, d, d,
J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14Hz), 4.25 (2H, t,
J = 4.5Hz), 4.33-4.41 (3H, m), 4.51 (2H, t, J = 4.5Hz),
6.70 (1H, d, J = 9Hz), 6.88 (2H, d, J = 8.5Hz), 7.11-
7.33 (17H, m), 7.91 (1H, d, d, J = 2.5, 9Hz), 8.35 (1H,
d, J = 2.5Hz).

(B)5- [4- [2-[[[1- (2-
Ethoxy-5-pyridyl) ethylidene] amino] oxo
[Ethoxy] benzyl] thiazolidine-2,4-di
N 5- [4- [2-[[[1 obtained in Example 19 (a)
-(2-ethoxy-5-pyridyl) ethylidene] amido
[No] oxy] ethoxy] benzyl] -3-tritylthia
Example using 508 mg of zolidine-2,4-dione
When the reaction and post-treatment are carried out according to 1 (b), the melting point is 13
The target compound 2 as a crystalline powder having a temperature of 5-138 ° C.
19 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.40 (3H, t, J = 7Hz), 2.21 (3H, s), 3.13 (1H, d, d,
J = 9, 14Hz), 3.43 (1H, d, d, J = 4, 14Hz), 4.27 (2H, t,
J = 4.5Hz), 4.37 (2H, q, J = 7Hz), 4.48-4.53 (3H, m),
6.71 (1H, d, J = 9Hz), 6.90 (2H, d, J = 8.5Hz), 7.15 (2H,
d, J = 8.5Hz), 7.91 (1H, d, d, J = 2.5, 9Hz), 8.32 (1H,
d, J = 2.5Hz).

Embodiment 205- [4- [2-[[[1- [4- (imidazole-1
-Yl) phenyl] ethylidene] amino] oxy] eth
[Xy] benzyl] thiazolidine-2,4-dione (Example
Compound number 2-25)(A) 5- [4- [2-[[[1- [4- (imidazo
Ru-1-yl) phenyl] ethylidene] amino] oxo
[Ethoxy] benzyl] -3-tritylthiazolidine
-2,4-dione 2-[[[1- [4- (imidazol-1-yl) fe
Nyl] ethylidene] amino] oxy] ethanol (reference
Compound of Example 20) 490 mg, 5- (4-hydroxy
(Benzyl) -3-tritylthiazolidine-2,4-dio
907 mg, triphenylphosphine 550 mg
And 365 mg of ethyl azodicarboxylate
When the reaction and post-treatment are performed according to Example 1 (a),
830 mg of the target compound were obtained as a solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.26 (3H, s), 3.08 (1H, d, d, J = 9, 14Hz), 3.40 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 5Hz), 4.37 (1H, d,
d, J = 4, 9Hz), 4.56 (2H, t, J = 5Hz), 6.89 (2H, d, J = 8.5
Hz), 7.10-7.39 (21H, m), 7.75 (2H, d, J = 8.5Hz), 7.87
(1H, s).

(B)5- [4- [2-[[[1- [4-
(Imidazol-1-yl) phenyl] ethylidene] A
[Mino] oxy] ethoxy] benzyl] thiazolidine-
2,4-dione 5- [4- [2-[[[1 obtained in Example 20 (a)
-[4- (imidazol-1-yl) phenyl] ethyl
Den] amino] oxy] ethoxy] benzyl] -3-to
Lityl thiazolidine-2,4-dione 830mg
The reaction and post-treatment are performed according to Example 1 (b).
Of crystalline powder having a melting point of 192 to 200 ° C.
465 mg of the compound were obtained. 1)¹H-nuclear magnetic resonance spectrum: δ ppm: heavy dime
In tyl sulfoxide, TMS (tetramethyl
Silane)¹H-nuclear magnetic resonance spectrum
(270 MHz) is as follows. 2.22 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H,
d, d, J = 4.5, 14Hz), 4.27 (2H, t, J = 4.5Hz), 4.47 (2H,
t, J = 4.5Hz), 4.87 (1H, d, d, J = 4.5, 9Hz), 6.93 (2H,
d, J = 8.5Hz), 7.13 (1H, s), 7.16 (2H, d, J = 8.5Hz), 7.7
1 (2H, d, J = 8.5Hz), 7.80 (2H, d, J = 8.5Hz), 7.81 (1H,
s), 8.33 (1H, s).

Embodiment 215- [4- [2-[[[1- [4- (2-pyridyl) fu]
[Enyl] ethylidene] amino] oxy] ethoxy] ben
Jill] thiazolidine-2,4-dione (Example compound number
 2-35) (a)5- [4- [2-[[[1- [4- (2-pyridi
Ru) phenyl] ethylidene] amino] oxy] ethoxy
[B] benzyl] -3-tritylthiazolidine-2,4-
Zeon 2-[[[1- [4- (2-pyridyl) phenyl] ethyl
Riden] amino] oxy] ethanol (Chemical Example 21
Compound) 7.00 g, 5- (4-hydroxybenzyl)
-3-tritylthiazolidine-2,4-dione
39 g, 7.51 g of triphenylphosphine and
Example 1 was prepared using 4.99 g of diethyl zodicarboxylate.
When the reaction and post-treatment are carried out according to (a), the melting point is 117.
Crystalline powder of target compound having -119 ° C 16.1
5 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.29 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 4.5Hz), 4.37 (1H,
d, d, J = 4, 9Hz), 4.56 (2H, t, J = 4.5Hz), 6.90 (2H,
d, J = 8.5Hz), 7.11-7.34 (18H, m), 7.75-7.78 (3H,
m), 8.01 (2H, d, J = 8.5Hz), 8.71 (1H, d, J = 5Hz).

(B) 5- [4- [2-[[[1- [4-
(2-pyridyl) phenyl] ethylidene] amino] oki
[Ethoxy] benzyl] thiazolidine-2,4-di
Obtained in emissions Example 21 (a) 5- [4- [ 2 - [[[1
Using 16.00 g of-[4- (2-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, the reaction and reaction were carried out according to Example 1 (b). When processed, melting point 1
The target compound as a crystalline powder having 76-179 ° C
9.17 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.28 (3H, s), 3.13 (1H, d, d, J = 9, 14Hz), 3.44 (1H,
d, d, J = 4, 14Hz), 4.30 (2H, t, J = 5Hz), 4.51 (1H, d,
d, J = 4, 14Hz), 4.56 (2H, t, J = 5Hz), 6.92 (2H, d, J =
8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.23-7.28 (1H, m),
7.74-7.81 (4H, m), 7.99 (2H, d, J = 8.5Hz), 8.70 (1H,
d, J = 4.5Hz).

(C) 5- [4- [2-[[[1- [4-
(2-pyridyl) phenyl] ethylidene] amino] oki
[Ethoxy] benzyl] thiazolidine-2,4-di
Obtained in emissions hydrochloride Example 21 (b) 5- [4- [ 2-
Ethyl acetate containing 500 mg of [[[1- [4- (2-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2
To a mixed solution of 0 ml and 20 ml of dioxane was added 1 ml of a 4N hydrogen chloride / dioxane solution, followed by concentration. The obtained crystalline powder was suspended in ethyl acetate-diethyl ether and collected by filtration to obtain 540 mg of a hydrochloride of the target compound as a crystalline powder having a melting point of 187.5 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.25 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H,
d, d, J = 4.5, 14Hz), 4.28 (2H, t, J = 4.5Hz), 4.50 (2
H, t, J = 4.5Hz), 4.88 (1H, d, d, J = 4.5, 9Hz), 6.94 (2
H, d, J = 8.5Hz), 7.17 (2H, d, J = 8.5Hz), 7.67 (1H, d,
d, J = 2, 6Hz), 7.87 (2H, d, J = 8.5Hz), 8.15 (2H, d, J =
8.5Hz), 8.20-8.28 (2H, m), 8.79 (1H, d, J = 5Hz).

Embodiment 225- [4- [2-[[[1- [4- (3-pyridyl) fu]
[Enyl] ethylidene] amino] oxy] ethoxy] ben
Jill] thiazolidine-2,4-dione (Example compound number
 2-37) (a)5- [4- [2-[[[1- [4- (3-pyridi
Ru) phenyl] ethylidene] amino] oxy] ethoxy
[B] benzyl] -3-tritylthiazolidine-2,4-
Zeon 2-[[[1- [4- (3-pyridyl) phenyl] ethyl
Riden] amino] oxy] ethanol (Chemical Example 22
Compound) 512 mg, 5- (4-hydroxybenzyl)
-3-tritylthiazolidine-2,4-dione 907
mg, triphenylphosphine 550 mg and azo
Example 1 Using 365 mg of diethyl dicarboxylate
When the reaction and post-treatment are performed according to (a),
1.16 g of the expected compound are obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.28 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 4.5Hz), 4.37 (1H,
d, d, J = 4, 9Hz), 4.56 (2H, t, J = 4.5Hz), 6.90 (2H, d,
J = 8.5Hz), 7.11-7.41 (18H, m), 7.58 (2H, d, J = 8.5H
z), 7.76 (2H, d, J = 8.5Hz), 7.88 (1H, d, t, J = 1.5, 8H
z), 8.61 (1H, d, d, J = 2, 5Hz), 8.86 (1H, d, J = 1.5
Hz).

(B) 5- [4- [2-[[[1- [4-
(3-pyridyl) phenyl] ethylidene] amino] oki
[Ethoxy] benzyl] thiazolidine-2,4-di
Obtained in emissions Example 22 (a) 5- [4- [ 2 - [[[1
Using 1.16 g of-[4- (3-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione and reacting it according to Example 1 (b), When processed, melting point 18
696 mg of the target compound as crystalline powder having a temperature of 2 ° C.
was gotten.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.23 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4.5, 14Hz), 4.27 (2H, t, J = 4.5Hz), 4.48 (2H,
t, J = 4.5Hz), 4.87 (1H, d, d, J = 4.5, 9Hz), 6.93 (2H,
d, J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz), 7.51 (1H.d, d,
J = 5, 8Hz), 7.80 (4H, s), 8.12 (1H, d, t, J = 2, 8H
z), 8.59 (1H, d, d, J = 1.5, 5Hz), 8.94 (1H, d, J = 2Hz)
.

Embodiment 235- [4- [2-[[[1- [4- (4-pyridyl) fu]
[Enyl] ethylidene] amino] oxy] ethoxy] ben
Jill] thiazolidine-2,4-dione (Example compound number
 2-39) (a)5- [4- [2-[[[1- [4- (4-pyridi
Ru) phenyl] ethylidene] amino] oxy] ethoxy
[B] benzyl] -3-tritylthiazolidine-2,4-
Zeon 2-[[[1- [4- (4-pyridyl) phenyl] ethyl
Ridene] amino] oxy] ethanol (formation of Reference Example 23
Compound) 769 mg, 5- (4-hydroxybenzyl)
-3-Tritylthiazolidine-2,4-dione 1.5
3 g, 866 mg of triphenylphosphine and azo
Example 1 using 575 mg of diethyl dicarboxylate
When the reaction and post-treatment are performed according to (a),
2.00 g of the desired compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.28 (3H, s), 3.08 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 5Hz), 4.37 (1H, d,
d, J = 4, 9Hz), 4.57 (1H, t, J = 5Hz), 6.90 (2H, d, J = 8.
5Hz), 7.11-7.33 (17H, m), 7.51 (2H, d, d, J = 1.5, 4.5
Hz), 7.64 (2H, d, J = 8.5Hz), 7.77 (2H, d, J = 8.5Hz),
8.67 (2H, d, d, J = 1.5, 4.5Hz).

(B) 5- [4- [2-[[[1- [4-
(4-pyridyl) phenyl] ethylidene] amino] oki
[Ethoxy] benzyl] thiazolidine-2,4-di
Obtained in emissions Example 23 (a) 5- [4- [ 2 - [[[1
Using 1.34 g of-[4- (4-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, the reaction and reaction were carried out according to Example 1 (b). When processed, melting point 23
Crystalline powder of target compound having 4-235 ° C 630
mg was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.23 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 4.31 (1H,
d, d, J = 4, 14Hz), 4.27 (2H, t, J = 4.5Hz), 4.48 (2H,
t, J = 4.5Hz), 4.88 (1H, d, d, J = 4, 9Hz), 6.93 (2H, d,
J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz), 7.75 (2H.d, J = 6
Hz), 7.82 (2H, d, J = 8.5Hz), 7.86 (2H, d, J = 8.5Hz),
8.66 (2H, d, J = 6Hz).

Example 24 5- [4- [2-[[(1,4-dimethyl-2-phenyl)
Imidazol-5-yl) methyleneamino] oxy] d
Toxi] benzyl] thiazolidine-2,4-dione (Exemplary Compound No. 1-176) (a) 5- [4- [2-[[(1,4-dimethyl-2-)
Phenylimidazol-5-yl) methyleneamino] o
[Xy] ethoxy] benzyl] -3-tritylthiazolidi
-2,4-dione 2-[[(1,4-dimethyl-2-phenylimidazol-5-yl) methyleneamino] oxy] ethanol (compound of Reference Example 24) 420 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4
-580 g of dione, 42 of triphenylphosphine
When the reaction and post-treatment were carried out according to Example 1 (a) using 5 mg and diethyl azodicarboxylate 282 mg, 646 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.33 (3H, s), 3.08 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 3.76 (3H, s), 4.26 (2H, t, J = 5H
z), 4.37 (1H, d, d, J = 4, 9Hz), 4.49 (2H, d, J = 5Hz),
6.90 (2H, d, J = 8.5Hz), 7.13-7.32 (18H, m), 7.42-7.47
(3H, m), 7.56-7.60 (2H, m), 8.22 (1H, s).

(B) 5- [4- [2-[[(1,4-di
Methyl-2-phenylimidazol-5-yl) methyl
Amino] oxy] ethoxy] benzyl] thiazolidine
-2,4-dione 5- [4- [2-] obtained in Example 24 (a)
[[(1,4-Dimethyl-2-phenylimidazole-
5-yl) methyleneamino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione 6
When the reaction and post-treatment were carried out according to Example 1 (b) using 40 mg, 354 mg of the target compound was obtained as an amorphous powder.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.32 (3H, s), 3.11 (1H, d, d, J = 9, 14Hz), 3.43 (1H,
d, d, J = 4, 14Hz), 3.83 (3H, s), 4.25 (2H, t, J = 5H
z), 4.46-4.51 (3H, m), 6.90 (2H, d, J = 8.5Hz), 7.15
(2H, d, J = 8.5Hz), 7.43-7.50 (3H, m), 7.58-7.62 (2H,
m), 8.21 (1H, s).

Embodiment 255- [4- [2-[[[1- (1-methyl-2-phenyl)
Louisimidazol-4-yl) ethylidene] amino] oxo
[Ethoxy] benzyl] thiazolidine-2,4-di
N (Exemplary Compound No. 2-175) (a)5- [4- [2-[[[1- (1-methyl-2-
Phenylimidazol-4-yl) ethylidene] ami
[No] oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[[[1- (1-methyl-2-phenylimidazo)
Ru-4-yl) ethylidene] amino] oxy] ethanol
(Compound of Reference Example 25) 396 mg, 5- (4-H
Droxybenzyl) -3-tritylthiazolidine-2,
694 mg of 4-dione, triphenylphosphine 44
0 mg and 292 mg of diethyl azodicarboxylate
The reaction and post-treatment are carried out according to Example 1 (a).
Thus, 866 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.27 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.42 (1H,
d, d, J = 4, 14Hz), 3.70 (3H, s), 4.25 (2H, t, J = 5H
z), 4.36 (1H, d, d, J = 4, 9Hz), 4.52 (2H, d, J = 5Hz),
6.89 (2H, d, J = 8.5Hz), 7.12 (2H, d, J = 8.5Hz), 7.15
7.34 (15H, m), 7.41-7.49 (3H, m), 7.59-7.64 (2H, m)
.

(B) 5- [4- [2-[[[1- (1-
Methyl-2-phenylimidazol-4-yl) ethyl
Den] amino] oxy] ethoxy] benzyl] thiazoly
Gin-2,4-dione 5- [4- [2-[[[1
-(1-Methyl-2-phenylimidazol-4-yl) ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione 8
The reaction and after-treatment were carried out according to Example 1 (b) using 66 mg to obtain 444 mg of the desired compound as an amorphous powder.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.15 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H,
d, d, J = 4.5, 14Hz), 3.75 (3H, s), 4.22 (2H, t, J =
4.5Hz), 4.37 (2H, d, J = 4.5Hz), 4.88 (1H, d, d, J = 4.
5, 9Hz), 6.93 (2H, d, J = 8.5Hz), 7.16 (2H, d, J = 8.5H
z), 7.46-7.53 (3H, m), 7.63-7.72 (2H, m).

Example 26 5- [4- [2-[[[1- (4'-methylbiphenyl)
-4-yl) ethylidene] amino] oxy] ethoxy]
Benzyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-189) (a) 5- [4- [2-[[[1- (4′-methylbifu)
Enyl-4-yl) ethylidene] amino] oxy] eth
[Xy] benzyl] -3-tritylthiazolidine-2,4
-Dione 2-[[[1- (4'-methylbiphenyl-4-yl)
[Ethylidene] amino] oxy] ethanol (Reference Example 26)
539 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione 9
When 31 mg, 577 mg of triphenylphosphine and 366 mg of diethyl azodicarboxylate were reacted and worked up according to Example 1 (a), 1.24 g of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.27 (3H, s), 2.40 (3H, s), 3.07 (1H, d, d, J = 9, 1
4Hz), 3.41 (1H, d, d, J = 4, 14Hz), 4.28 (2H, t, J = 4.5
Hz), 4.36 (1H, d, d, J = 4, 9Hz), 4.55 (2H, t, J = 4.5H
z), 6.90 (2H, d, J = 8.5Hz), 7.11-7.33 (19H, m), 7.50 (2
H, d, J = 8Hz), 7.57 (2H, d, J = 8.5Hz), 7.70 (2H, d,
J = 8.5Hz).

(B) 5- [4- [2-[[[1- (4 '
-Methylbiphenyl-4-yl) ethylidene] amino]
[Oxy] ethoxy] benzyl] thiazolidine-2,4-
Dione The 5- [4- [2-[[[1] obtained in Example 26 (a)
-(4'-methylbiphenyl-4-yl) ethylidene]
Using 1.24 g of amino [oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, the reaction and post-treatment were carried out according to Example 1 (b), and the melting point was 1.
Crystalline powder target compound having 84-186 ° C 67
0 mg was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in deuterated chloroform and deuterated dimethyl sulfoxide (trace amount), TMS (tetramethylsilane) as internal standard
¹ H-nuclear magnetic resonance spectrum (270
MHz) is as follows. 2.27 (3H, s), 2.40 (3H, s), 3.06 (1H, d, d, J = 9, 1
4Hz), 3.46 (1H, d, d, J = 4, 14Hz), 4.28 (2H, t, J = 4.5
Hz), 4.43 (1H, d, d, J = 4, 9Hz), 4.54 (2H, t, J = 4.5H
z), 6.90 (2H, d, J = 8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.2
6 (2H, d, J = 8Hz), 7.50 (2H, d, J = 8Hz), 7.58 (2H, d,
J = 8.5Hz), 7.71 (2H, d, J = 8.5Hz).

Embodiment 275- [4- [2-[[[1- (4'-fluorobiphenyl)
Ru-4-yl) ethylidene] amino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione (Example
Compound number 2-190) (a)5- [4- [2-[[[1- (4'-fluorobi
Phenyl-4-yl) ethylidene] amino] oxy] d
Toxy] benzyl] -3-tritylthiazolidine-2,
4-dione 2-[[[1- (4'-fluorobiphenyl-4-i
Le) Ethylidene] amino] oxy] ethanol (Reference example)
Compound 27) 547 mg, 5- (4-hydroxybe)
Benzyl) -3-tritylthiazolidine-2,4-dione
 931 mg, triphenylphosphine 577 mg
And 366 mg of diethyl azodicarboxylate
When the reaction and post-treatment are performed according to Example 1 (a),
1.29 g of the solid target compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.27 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 5Hz), 4.36 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.90 (2H, d, J = 8.
5Hz), 7.10-7.33 (19H, m), 7.52-7.58 (4H, m), 7.71 (2
H, d, J = 8.5Hz).

(B)5- [4- [2-[[[1- (4 ′
-Fluorobiphenyl-4-yl) ethylidene] amido
[No] oxy] ethoxy] benzyl] thiazolidine-2,
4-dione 5- [4- [2-[[[1] obtained in Example 27 (a)
-(4'-Fluorobiphenyl-4-yl) ethylide
[Amino] oxy] ethoxy] benzyl] -3-tri
1.29 g of thithiazolidine-2,4-dione
The reaction and post-treatment are performed according to Example 1 (b).
Of crystalline powder having a melting point of 155 to 156 ° C.
695 mg of the compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.27 (3H, s), 3.11 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 5Hz), 4.50 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.92 (2H, d, J = 8.
5Hz), 7.14 (2H, t, J = 8.5Hz), 7.15 (2H, d, J = 8.5H
z), 7.53-7.60 (4H, m), 7.72 (2H, d, J = 8.5Hz).

Embodiment 285- [4- [2-[[[1- (4'-trifluoromethyl
Rubiphenyl-4-yl) ethylidene] amino] oxo
[Ethoxy] benzyl] thiazolidine-2,4-di
N (Exemplary Compound No. 2-191) (a)5- [4- [2-[[[1- (4'-trifluoro)
Romethylbiphenyl-4-yl) ethylidene] amino]
[Oxy] ethoxy] benzyl] -3-tritylthiazoly
Gin-2, 4-dione 2-[[[1- (4'-trifluoromethylbiphenyl
-4-yl) ethylidene] amino] oxy] ethanol
(Compound of Reference Example 28) 647 mg, 5- (4-hydr)
Roxybenzyl) -3-tritylthiazolidine-2,4
-931 mg of dione, 577 triphenylphosphine
mg and 366 mg of diethyl azodicarboxylate
The reaction and post-treatment are carried out according to Example 1 (a).
And 1.35 g of the target compound as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.28 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 5Hz), 4.36 (1H, d,
d, J = 4, 9Hz), 4.56 (2H, t, J = 5Hz), 6.90 (2H, d, J = 8.
5Hz), 7.11-7.33 (17H, m), 7.59 (2H, d, J = 8.5Hz), 7.
70 (4H, s), 7.75 (2H, d, J = 8.5Hz).

(B) 5- [4- [2-[[[1- (4 ′
-Trifluoromethylbiphenyl-4-yl) ethylide
[Amino] oxy] ethoxy] benzyl] thiazolidy
2-, 4 -dione 5- [4- [2-[[[1
-(4'-trifluoromethylbiphenyl-4-yl)
[Ethylidene] amino] oxy] ethoxy] benzyl]-
3-tritylthiazolidine-2,4-dione 1.35
Using g, the reaction and post-treatment were carried out according to Example 1 (b), to obtain 781 mg of the desired compound as a crystalline powder having a melting point of 165 to 166 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in deuterated chloroform and deuterated dimethyl sulfoxide (trace amount), TMS (tetramethylsilane) as internal standard
¹ H-nuclear magnetic resonance spectrum (270
MHz) is as follows. 2.28 (3H, s), 3.05 (1H, d, d, J = 9, 14Hz), 3.46 (1H,
d, d, J = 4, 14Hz), 4.29 (2H, t, J = 5Hz), 4.43 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.90 (2H, d, J = 8.
5Hz), 7.15 (2H, t, J = 8.5Hz), 7.61 (2H, d, J = 8.5H
z), 7.71 (4H, s), 7.76 (2H, d, J = 8.5Hz).

Example 29 5- [4- [2-[[[1- (4-ethoxyphenyl)]
Ethylidene] amino] oxy] ethoxy] benzyl] thio
Azolidine-2,4-dione (Exemplary Compound No. 2-15
8) (a) 5- [4- [2-[[[1- (4-ethoxyfe
Nyl) ethylidene] amino] oxy] ethoxy] benzyl
] -3-tritylthiazolidine-2,4-dione 2-[[[1- (4-ethoxyphenyl) ethylidene]
Amino] oxy] ethanol (compound of Reference Example 29)
Using 447 mg, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione 931 mg, triphenylphosphine 577 mg and diethyl azodicarboxylate 366 mg, the reaction and post-treatment were carried out according to Example 1 (a). This gave 1.34 g of the target compound as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.41 (3H, t, J = 7Hz), 2.21 (3H, s), 3.06 (1H, d, d,
J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14Hz), 4.04 (2H,
q, J = 7Hz), 4.26 (2H, t, J = 5Hz), 4.36 (1H, d, d, J = 4,
9Hz), 4.50 (2H, t, J = 5Hz), 6.87 (2H, d, J = 9Hz), 6.
89 (2H, d, J = 8.5Hz), 7.10-7.33 (17H, m), 7.57 (2H, d,
J = 9Hz).

(B) 5- [4- [2-[[[1- (4-
Ethoxyphenyl) ethylidene] amino] oxy] eth
[Xy] benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1
Example 1 (b) using 1.34 g of-(4-ethoxyphenyl) ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione
When the reaction and after-treatment are carried out according to
517 mg of a crystalline powder of the target compound having a temperature of 31 ° C. are obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.42 (3H, t, J = 7Hz), 2.21 (3H, s), 3.10 (1H, d, d,
J = 9, 14Hz), 3.46 (1H, d, d, J = 4, 14Hz), 4.05 (2H, q,
J = 7Hz), 4.26 (2H, t, J = 5Hz), 4.49 (1H, d, d, J = 4, 9
Hz), 4.51 (2H, t, J = 5Hz), 6.88 (2H, d, J = 8.5Hz), 6.
91 (2H, t, J = 8.5Hz), 7.41 (2H, d, J = 8.5Hz), 7.58 (2H,
d, J = 9Hz).

Example 30 5- [4- [2-[[[1- (3 ', 4'-methylenedi
Oxybiphenyl-4-yl) ethylidene] amino] o
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
ON (Exemplified Compound No. 2-180) (a) 5- [4- [2-[[[1- (3 ′, 4′-methyl)
Rangeoxybiphenyl-4-yl) ethylidene] ami
[No] oxy] ethoxy] benzyl] -3-tritylthia
Zolidine-2,4-dione 2-[[[1- (3 ', 4'-methylenedioxybiphenyl-4-yl) ethylidene] amino] oxy] ethanol (compound of Reference Example 30) 600 mg, 5- ( 4-
(Hydroxybenzyl) -3-tritylthiazolidine-
907 mg of 2,4-dione, triphenylphosphine
550 mg and diethyl azodicarboxylate 365 m
Using g, the reaction and post-treatment were carried out according to Example 1 (a) to obtain 1.12 g of the target compound as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.26 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 5Hz), 4.37 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.01 (2H, s),
6.89 (2H, d, J = 8.5Hz), 6.90 (1H, d, J = 8.5Hz), 7.06-
7.33 (19H, m), 7.51 (2H, d, J = 8.5Hz), 7.68 (2H, d,
J = 8.5Hz).

(B)5- [4- [2-[[[1-
(3 ', 4'-methylenedioxybiphenyl-4-i
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione 5- [4- [2-[[[1] obtained in Example 30 (a)
-(3 ', 4'-methylenedioxybiphenyl-4-i
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] -3-Tritylthiazolidine-2,4-dione
Using 1.12 g, according to Example 1 (b), the reaction and
After post-treatment, crystals with a melting point of 137-139 ° C
As a result, 646 mg of a target compound as a neutral powder was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.26 (3H, s), 3.10 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.28 (2H, t, J = 5Hz), 4.47-4.56 (3
H, m), 6.01 (2H, s), 6.89 (1H, d, J = 8.5Hz), 6.92 (2
H, d, J = 8.5Hz), 7.06-7.09 (2H, m), 7.14 (2H, d, J = 8.
5Hz), 7.52 (2H, d, J = 8.5Hz), 7.69 (2H, d, J = 8.5Hz).

Example 31 5- [4- [2-[[[1- (2-methoxy-5-pyri)
Jill) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (exemplary compound number
2-96) (a) 5- [4- [2-[[[1- (2-methoxy-5
-Pyridyl) ethylidene] amino] oxy] ethoxy]
[Benzyl] -3-tritylthiazolidine-2,4-dio
Down 2 - [[[1- (2-methoxy-5-pyridyl) ethylidene] amino] oxy] ethanol (the compound of Reference Example 31) 346mg, 5- (4- hydroxybenzyl) -
3-tritylthiazolidine-2,4-dione 766m
g, 475 mg of triphenylphosphine and 301 mg of diethyl azodicarboxylate.
When the reaction and post-treatment were carried out according to (a), 846 mg of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.21 (3H, s), 3.05 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 3.95 (3H, s), 4.25 (2H, t, J = 5H
z), 4.36 (1H, d, d, J = 4, 9Hz), 4.51 (2H, t, J = 5Hz),
6.72 (1H, d, J = 8.5Hz), 6.88 (2H, d, J = 8.5Hz), 7.11-
7.33 (17H, m), 7.92 (1H, d, d, J = 2.5, 8.5Hz), 8.37 (1
H, d, J = 2Hz).

(B)5- [4- [2-[[[1- (2-
Methoxy-5-pyridyl) ethylidene] amino] oki
[Ethoxy] benzyl] thiazolidine-2,4-di
N 5- [4- [2-[[[1] obtained in Example 31 (a)
-(2-methoxy-5-pyridyl) ethylidene] ami
[No] oxy] ethoxy] benzyl] -3-tritylthia
Example using 840 mg of zolidine-2,4-dione
When the reaction and post-treatment are carried out according to 1 (b), the melting point is 1
Crystalline powder target compound having 48-149 ° C 43
6 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.22 (3H, s), 3.09 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 3.95 (3H, s), 4.26 (2H, t, J = 5H
z), 4.45 (1H, d, d, J = 4, 9Hz), 4.51 (2H, t, J = 5Hz),
6.73 (1H, d, J = 9Hz), 6.89 (2H, d, J = 8.5Hz), 7.15 (2
H, d, J = 8.5Hz), 7.93 (1H, d, d, J = 2.5, 9Hz), 8.36 (1
H, d, J = 2.5Hz).

Example 32 5- [4- [2-[[[1- (2-Isopropoxy-5)
-Pyridyl) ethylidene] amino] oxy] ethoxy]
Benzyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-98) (a) 5- [4- [2-[[[1- (2-isopropoxy)
C-5-pyridyl) ethylidene] amino] oxy] eth
[Xy] benzyl] -3-tritylthiazolidine-2,4
-Dione 2-[[[1- (2-isopropoxy-5-pyridyl)
[Ethylidene] amino] oxy] ethanol (Reference Example 32)
1.02 g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione
When the reaction and post-treatment were carried out according to Example 1 (a) using 2.00 g, 1.24 g of triphenylphosphine and 784 mg of diethyl azodicarboxylate, 2.39 g of the target compound as a foamy solid was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.35 (6H, d, J = 6Hz), 2.21 (3H, s), 3.06 (1H, d, d,
J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14Hz), 4.25 (2H, t,
J = 5Hz), 4.36 (1H, d, d, J = 4,9Hz), 4.51 (2H, t, J = 5
Hz), 5.32 (1H, septet, J = 6Hz), 6.65 (1H, d, J = 8.5H
z), 6.88 (2H, d, J = 8.5Hz), 7.11-7.33 (17H, m), 7.89 (1
H, d, d, J = 2.5, 8.5Hz), 8.35 (1H, d, J = 2.5Hz).

(B) 5- [4- [2-[[[1- (2-
Isopropoxy-5-pyridyl) ethylidene] amino]
[Oxy] ethoxy] benzyl] thiazolidine-2,4-
Dione 5- [4- [2-[[[1
-(2-Isopropoxy-5-pyridyl) ethylidene]
Amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, having a melting point of 143-144 ° C., when subjected to the reaction and the after-treatment according to Example 1 (b) using 2.39 g. Target compound of crystalline powder
1.32 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.35 (6H, d, J = 6Hz), 2.21 (3H, s), 3.12 (1H, d, d,
J = 9, 14Hz), 3.44 (1H, d, d, J = 4, 14Hz), 4.27 (2H, t,
J = 5Hz), 4.48-4.52 (3H, m), 5.30 (1H, septet, J = 6H
z), 6.67 (1H, d, J = 9Hz), 6.90 (2H, d, J = 8.5Hz), 7.1
5 (2H, d, J = 8.5Hz), 7.89 (1H, d, d, J = 2.5, 9Hz), 8.3
3 (1H, d, J = 2.5Hz).

Embodiment 335- [4- [2-[[[1- (2-phenylsulfonyl)
-5-pyridyl) ethylidene] amino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione (Example
Compound number 2-108) (a)5- [4- [2-[[[1- (2-phenylsulfur
Honyl-5-pyridyl) ethylidene] amino] oxy]
[Ethoxy] benzyl] -3-tritylthiazolidine-
2,4-dione 2-[[[1- (2-phenylsulfonyl-5-pyridi
Le) Ethylidene] amino] oxy] ethanol (Reference example)
640 mg, 5- (4-hydroxybe)
Benzyl) -3-tritylthiazolidine-2,4-dione
 907 mg, triphenylphosphine 550 mg
And 365 mg of diethyl azodicarboxylate
When the reaction and post-treatment are performed according to Example 1 (a),
500 mg of the solid target compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.22 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.39 (1H,
d, d, J = 4, 14Hz), 4.24 (2H, t, J = 5Hz), 4.35 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.85 (2H, d, J =
8.5Hz), 7.09-7.33 (17H, m), 7.39-7.63 (3H, m), 8.04
-8.16 (4H, m), 8.89 (1H, d, J = 1.5Hz).

(B) 5- [4- [2-[[[1- (2-
Phenylsulfonyl-5-pyridyl) ethylidene] amido
[No] oxy] ethoxy] benzyl] thiazolidine-2,
4-dione 5- [4- [2-[[[1
Using 500 mg of-(2-phenylsulfonyl-5-pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, the reaction and post-treatment were carried out according to Example 1 (b). This gave 260 mg of the desired compound as a crystalline powder.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.23 (3H, s), 3.14 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.50 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.87 (2H, d, J =
8.5Hz), 7.14 (2H, d, J = 8.5Hz), 7.51-7.65 (3H, m),
8.05-8.20 (4H, m), 8.88 (1H, d, J = 2Hz).

Example 34 5- [4- [2-[[[1- [2- [N- (4-methyl
Phenylsulfonyl) -N-methylamino] pyridine-
5-yl] ethylidene] amino] oxy] ethoxy] be
Ndyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-192) (a) 5- [4- [2-[[[1- [2- [N- (4-
Methylphenylsulfonyl) -N-methylamino] pyri
Zin-5-yl] ethylidene] amino] oxy] ethoxy
[B] benzyl] -3-tritylthiazolidine-2,4-
Dione 2-[[[1- [2- [N- (4-methylphenylsulfonyl) -N-methylamino] pyridin-5-yl] ethylidene] amino] oxy] ethanol (Compound of Reference Example 34) 1.22 g , 5- (4-hydroxybenzyl)
-3-Tritylthiazolidine-2,4-dione 1.5
Example 1 was prepared using 2 g, 0.97 g of triphenylphosphine and 0.63 g of diethyl azodicarboxylate.
When the reaction and post-treatment were carried out according to (a), 2.33 g of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.22 (3H, s), 2.38 (3H, s), 3.07 (1H, d, d, J = 9, 14
Hz), 3.29 (3H, s), 3.41 (1H, d, d, J = 4, 14Hz), 4.27
(2H, t, J = 5Hz), 4.37 (1H, d, d, J = 4, 9Hz), 4.54 (2H,
t, J = 5Hz), 6.88 (2H, d, J = 8.5Hz), 7.11-7.36 (19H,
m), 7.48 (2H, t, J = 8Hz), 7.71 (1H, d, J = 8.5Hz), 7.9
6 (1H, d, d, J = 2.5, 8.5Hz), 8.51 (1H, d, J = 2.5Hz).

(B) 5- [4- [2-[[[1- [2-
[N- (4-methylphenylsulfonyl) -N-methyl
Amino] pyridin-5-yl] ethylidene] amino] o
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
On 5- [4- [2-[[[1 obtained in Example 34 (a)
-[2- [N- (4-methylphenylsulfonyl) -N
-Methylamino] pyridin-5-yl] ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, using 2.33 g according to Example 1 (b) and after After the treatment, 1.48 g of the target compound as a foamy solid was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.22 (3H, s), 2.39 (3H, s), 3.13 (1H, d, d, J = 9, 14
Hz), 3.28 (3H, s), 3.43 (1H, d, d, J = 4, 14Hz), 4.27
(2H, t, J = 5Hz), 4.50 (1H, d, d, J = 4, 9Hz), 4.53 (2H,
t, J = 5Hz), 6.89 (2H, d, J = 8.5Hz), 7.15 (2H, d, J = 8.
5Hz), 7.22 (2H, d, J = 8Hz), 7.49 (2H, d, J = 8Hz), 7.7
1 (1H, d, J = 8.5Hz), 7.96 (1H, d, d, J = 2.5, 8.5Hz),
8.49 (1H, d, J = 2.5Hz).

Example 35 5- [4- [2-[[[1- (4-phenylsulfonyl)
Phenyl) ethylidene] amino] oxy] ethoxy] b
Ndyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-23) (a) 5- [4- [2-[[[1- (4-phenylsulfur)
Honylphenyl) ethylidene] amino] oxy] ethoxy
[B] benzyl] -3-tritylthiazolidine-2,4-
Dione 2-[[[1- (4-phenylsulfonylphenyl) ethylidene] amino] oxy] ethanol (compound of Reference Example 35) 1.006 g, 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4 -Zeon
Using 1.40 g, 866 mg of triphenylphosphine and 549 mg of diethyl azodicarboxylate, the reaction and post-treatment were carried out according to Example 1 (a) to obtain 2.05 g of the target compound as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.22 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.37 (1H,
d, d, J = 4, 14Hz), 4.24 (2H, t, J = 5Hz), 4.36 (1H, d,
d, J = 4, 9Hz), 4.54 (2H, t, J = 5Hz), 6.86 (2H, d, J =
8.5Hz), 7.10-7.33 (17H, m), 7.46-7.56 (3H, m), 7.74
(2H, d, J = 8.5Hz), 7.90-7.95 (4H, m).

(B) 5- [4- [2-[[[1- (4-
Phenylsulfonylphenyl) ethylidene] amino] o
[Xy] ethoxy] benzyl] thiazolidine-2,4-di
On 5- [4- [2-[[[1] obtained in Example 35 (a)
Using 2.04 g of-(4-phenylsulfonylphenyl) ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione, the reaction and post-treatment were carried out according to Example 1 (b). This gave 1.09 g of the target compound as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.23 (3H, s), 3.11 (1H, d, d, J = 9, 14Hz), 3.44 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.50 (1H, d,
d, J = 4, 9Hz), 4.54 (2H, t, J = 5Hz), 6.88 (2H, d, J =
8.5Hz), 7.14 (2H, d, J = 8.5Hz), 7.47-7.60 (2H, d, J =
8.5Hz), 7.47-7.60 (3H, s), 7.76 (2H, d, J = 8.5Hz),
7.92-7.97 (4H, m).

Embodiment 365- [4- [2-[[[1- (4-phenylthiopheni
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (Example compound number
2-21) (a)5- [4- [2-[[[1- (4-phenylthio
Phenyl) ethylidene] amino] oxy] ethoxy] b
Ndyl] -3-tritylthiazolidine-2,4-dione 2-[[[1- (4-phenylthiophenyl) ethylide
[Amino] oxy] ethanol (compound of Reference Example 36)
Compound) 862 mg, 5- (4-hydroxybenzyl)-
3-tritylthiazolidine-2,4-dione 1.40
g, 866 mg of triphenylphosphine and azodi
Example 1 using 549 mg of diethyl carboxylate
When the reaction and post-treatment are performed according to (a),
1.95 g of the target compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.21 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.40 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.36 (1H, d,
d, J = 4, 9Hz), 4.52 (2H, t, J = 5Hz), 6.88 (2H, d, J =
8.5Hz), 7.10-7.46 (24H, m), 7.56 (2H, d, J = 8.5Hz)
.

(B) 5- [4- [2-[[[1- (4-
Phenylthiophenyl) ethylidene] amino] oxy]
Ethoxy] benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1
-(4-phenylthiophenyl) ethylidene] amino]
Example 1 using 1.95 g of [oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione
When the reaction and post-treatment were carried out according to (b), 1.24 g of a glassy target compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.21 (3H, s), 3.09 (1H, d, d, J = 9, 14Hz), 3.45 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.46-4.53 (3
H, m), 6.89 (2H, d, J = 8.5Hz), 7.13 (2H, d, J = 8.5Hz),
7.26-7.40 (7H, m), 7.56 (2H, d, J = 8.5Hz).

Embodiment 375- [4- [2-[[[1- [4- [N- (phenyls
Ruphonyl) -N-methylamino] phenyl] ethylide
[Amino] oxy] ethoxy] benzyl] thiazolidy
-2,4-dione (Exemplary Compound No. 2-181) (a)5- [4- [2-[[[1- [4- [N- (Fe
Nylsulfonyl) -N-methylamino] phenyl] ethy
Ridene] amino] oxy] ethoxy] benzyl] -3-
Trityl thiazolidine-2,4-dione 2-[[[1- [4- [N- (phenylsulfonyl)-
N-methylamino] phenyl] ethylidene] amino] o
[Xy] ethanol (compound of Reference Example 37) 667 mg,
5- (4-hydroxybenzyl) -3-tritylthiazo
1.02 g of lysine-2,4-dione,
577 mg of sphine and diethyl azodicarboxylate
 Using 383 mg, the reaction and
After post-treatment, a crystal having a melting point of 143-145 ° C is obtained.
As a result, 554 mg of a target compound as a neutral powder was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.22 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.17 (3
H, s), 3.41 (1H, d, d, J = 4, 14Hz), 4.26 (2H, t, J = 4.
5Hz), 4.37 (1H, d, d, J = 4, 9Hz), 4.53 (2H, t, J = 5H
z), 6.88 (2H, d, J = 8.5Hz), 7.06-7.33 (21H, m), 7.44 (1
H, t, J = 8Hz), 7.54-7.60 (4H, m).

(B) 5- [4- [2-[[[1- [4-
[N- (phenylsulfonyl) -N-methylamino]
[Enyl] ethylidene] amino] oxy] ethoxy] ben
Zyl] thiazolidine-2,4-dione 5- [4- [2-[[[1
-[4- [N- (phenylsulfonyl) -N-methylamino] phenyl] ethylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-
When 554 mg of dione is used for the reaction and post-treatment according to Example 1 (b), the desired compound as an amorphous powder is obtained.
266 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.23 (3H, s), 3.12 (1H, d, d, J = 9, 14Hz), 3.18 (3H
H, s), 3.45 (1H, d, d, J = 4, 14Hz), 4.26 (2H, t, J = 5H
z), 4.48-4.54 (3H, m), 6.90 (2H, d, J = 8.5Hz), 7.11
(2H, d, J = 8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.46 (2H,
t, J = 8Hz), 7.51-7.65 (5H, m).

Embodiment 385- [4- [2-[[[1- (4-biphenylyl) pro]
Pyridene] amino] oxy] ethoxy] benzyl] thia
Zolidine-2,4-dione (Exemplified Compound No. 3-31) (a)5- [4- [2-[[[1- (4-biphenyli
Le) propylidene] amino] oxy] ethoxy] benzyl
Ru] -3-Tritylthiazolidine-2,4-dione 2-[[[[1- (4-biphenylyl) propylidene] a
[Mino] oxy] ethanol (compound of Reference Example 38) 5
39 mg, 5- (4-hydroxybenzyl) -3-tri
1.02 g of thithiazolidine-2,4-dione, tri
Phenylphosphine 577mg and azodicarbon
According to Example 1 (a) using 383 mg of diethyl acidate
When the reaction and post-treatment are carried out, the target compound
1.09 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.22 (3H, t, J = 7.5Hz), 2.86 (2H, q, J = 7.5Hz), 3.13 (1
(H, d, d, J = 9, 14Hz), 3.48 (1H, d, d, J = 4, 14Hz), 4.3
4 (2H, t, J = 5Hz), 4.43 (1H, d, d, J = 4, 9Hz), 4.61
(2H, t, J = 5Hz), 6.96 (2H, d, J = 8.5Hz), 7.18-7.54 (20
H, m), 7.65-7.74 (4H, m), 7.78 (2H, d, J = 8.5Hz).

(B) 5- [4- [2-[[[1- (4-
Biphenylyl) propylidene] amino] oxy] ethoxy
[Benzyl] thiazolidine-2,4-dione 5- [4- [2-[[[1
Example 1 (b) using 1.09 g of-(4-biphenylyl) propylidene] amino] oxy] ethoxy] benzyl] -3-tritylthiazolidine-2,4-dione
When the reaction and after-treatment are carried out according to
585 mg of a crystalline powder of the target compound having a temperature of 4.degree.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 1.06 (3H, t, J = 7.5Hz), 2.74 (2H, q, J = 7.5Hz), 3.05 (1
H, d, d, J = 9, 14Hz), 3.31 (1H, d, d, J = 4, 14Hz), 4.
26 (2H, t, J = 5Hz), 4.46 (2H, t, J = 5Hz), 4.87 (1H,
d, d, J = 4, 9Hz), 6.93 (2H, d, J = 8.5Hz), 7.16 (2H, d,
J = 8.5Hz), 7.39 (1H, d, J = 8.5Hz), 7.49 (2H, t, J = 7.
5Hz), 7.69-7.78 (6H, m).

Example 39 5- [4- [2-[[[1- (5-Phenyl-2-pyridyl)
Jill) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (exemplary compound number
2-110) (a) 5- [4- [2-[[[1- (5-phenyl-2
-Pyridyl) ethylidene] amino] oxy] ethoxy]
[Benzyl] -3-tritylthiazolidine-2,4-dio
Down 2 - [[[1- (5-phenyl-2-pyridyl) ethylidene] amino] oxy] ethanol (Compound of Reference Example 39) 513 mg, 5- (4-hydroxybenzyl) -
3-tritylthiazolidine-2,4-dione 1.02
g, 577 mg of triphenylphosphine and 383 mg of diethyl azodicarboxylate.
When the reaction and post-treatment were carried out according to (a), 1.40 g of the target compound was obtained as a foamy solid.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.39 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.41 (1H,
d, d, J = 4, 14Hz), 4.30 (2H, t, J = 5Hz), 4.36 (1H, d,
d, J = 4, 9Hz), 4.59 (2H, d, J = 5Hz), 6.90 (2H, d, J =
8.5Hz), 7.12-7.33 (17H, m), 7.38-7.55 (3H, m), 7.60
(2H, d, J = 8Hz), 7.84 (1H, d, d, J = 2, 8Hz), 7.96 (1H,
d, J = 8Hz), 8.83 (1H, d, J = 2Hz).

(B)5- [4- [2-[[[1- (5-
Phenyl-2-pyridyl) ethylidene] amino] oxo
[Ethoxy] benzyl] thiazolidine-2,4-di
N 5- [4- [2-[[[1] obtained in Example 39 (a)
-(5-Phenyl-2-pyridyl) ethylidene] ami
[No] oxy] ethoxy] benzyl] -3-tritylthia
Example using 1.40 g of Zolidine-2,4-dione
When the reaction and post-treatment are carried out according to 1 (b), the melting point is 13
Crystalline powder of target compound having a temperature of 6-138 ° C. 590
mg was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.35 (3H, s), 3.13 (1H, d, d, J = 9, 14Hz), 3.43 (1H,
d, d, J = 4, 14Hz), 4.30 (2H, t, J = 5Hz), 4.50 (1H, d,
d, J = 4,9Hz), 4.58 (2H, t, J = 5Hz), 6.91 (2H, d, J = 8.5
Hz), 7.15 (2H, d, J = 8.5Hz), 7.39-7.52 (3H, m), 7.61
(2H, d, J = 8.5Hz), 7.87 (1H, d, d, J = 2.5, 8.5Hz), 7.
97 (1H, d, J = 8.5Hz), 8.28 (1H, brs), 8.83 (1H, d, J
= 2.5Hz).

Example 40 5- [4- [2-[[[1- (2-hydroxy-5-pi
Lysyl) ethylidene] amino] oxy] ethoxy] ben
Zyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-193) (a) N- [2-[(tetrahydropyran-2-yl)
[Oxy] ethoxy] phthalimide 2- (2-bromoethoxy) tetrahydropyran 1
A 100 ml suspension of dimethylformamide containing 0.8 g, 7.0 g of N-hydroxyphthalimide and 11.1 g of potassium carbonate was stirred at 80 ° C. for 2.5 hours. The reaction solution was dissolved in ethyl acetate and water, the ethyl acetate layer was separated, and the extract was dried over anhydrous magnesium sulfate. After the ethyl acetate was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give 8.62 g of the desired compound in the form of a syrup.
was gotten.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.35-1.73 (6H, m), 3.46-3.53 (1H, m), 3.80-3.89 (2
H, m), 4.00-4.08 (1H, m), 4.51-4.35 (2H, m), 4.66 (1
H, brs), 7.72-7.78 (2H, m), 7.81-7.87 (2H, m).

(B) N- (2-hydroxyethoxy ) phenyl
Talimide p-Toluenesulfonic acid monohydrate was added to a solution of 8.62 g of N- [2-[(tetrahydropyran-2-yl) oxy] ethoxy] phthalimide obtained in Example 40 (a) in 86 ml of methanol. Add 56 g and add 2 g at room temperature.
After stirring for an hour, the reaction solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and water, and aqueous sodium bicarbonate was added to neutralize the mixture. The ethyl acetate layer was separated and dried over anhydrous magnesium sulfate. The dried extract was concentrated under reduced pressure to give a crystalline powder of the target compound, which was washed with isopropyl ether to give 4.10 g of a pure target compound having a melting point of 82-85 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.48 (1H, t, J = 6Hz), 3.78-3.84 (2H, m), 4.30-4.33
(2H, m), 7.74-7.82 (2H, m), 7.85-7.91 (2H, m).

(C) 5- [4- [2-[(N-phthalyl)
Mido) oxy] ethoxy] benzyl] -3-tritylthio
Azolidine-2,4-dione 2.0 g of N- (2-hydroxyethoxy) phthalimide obtained in Example 40 (b), 5- (4-hydroxybenzyl) -3-tritylthiazolidine-2,4-dione
When 4.4 g, 2.53 g of triphenylphosphine and 1.68 g of diethyl azodicarboxylate are used and subjected to the reaction and the post-treatment according to Example 1 (a), 5.00 g of the target compound as a foamy solid is obtained. Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.03 (1H, d, d, J = 9, 14Hz), 3.41 (1H, d, d, J = 4, 14
Hz), 4.31-4.38 (3H, m), 4.56-4.60 (2H, m), 6.77 (2
H, d, J = 8.5Hz), 7.09 (2H, d, J = 8.5Hz), 7.15-7.34 (15
H, m), 7.72-7.78 (2H, m), 7.80-7.86 (2H, m).

(D)5- [4- [2-[(N-phthalyl
Mido) oxy] ethoxy] benzyl] thiazolidine-
2,4-dione 5- [4- [2-[(N-
Phthalimido) oxy] ethoxy] benzyl] -3-to
Lithium thiazolidine-2,4-dione 5.00g
The reaction and post-treatment are performed according to Example 1 (b).
Of crystalline powder having a melting point of 146-147 ° C.
2.74 g of the compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.10 (1H, d, d, J = 9, 14Hz), 3.44 (1H, d, d, J = 4, 14
Hz), 4.33-4.36 (2H, m), 4.49 (1H, d, d, J = 4, 9Hz),
4.56-4.60 (2H, m), 6.79 (1H, d, J = 8.5Hz), 7.12 (2H,
d, J = 8.5Hz), 7.74-7.80 (2H, m), 7.81-7.86 (2H, m),
8.08 (1H, brs).

(E) 5- [4- [2- (aminooxy)
[Ethoxy] benzyl] thiazolidine-2,4-dione.
Hydrochloride 5- [4- [2-[(N-) obtained in Example 40 (d).
Phthalimido) oxy] ethoxy] benzyl] thiazolidine-2,4-dione 2.64 g ethanol 30
To the resulting suspension was added 0.32 ml of hydrazine monohydrate, followed by stirring at 80 ° C. for 2 hours. The reaction solution was cooled, and the precipitated phthalhydrazide was removed by filtration, and then the reaction solution was concentrated. The residue was subjected to silica gel column chromatography (methanol: dichloromethane = 1: 20),
5- [4- [2- (aminooxy) ethoxy] benzyl] thiazolidine-2,4-dione in syrup form 1.9
3 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 3.10 (1H, d, d, J = 9, 14Hz), 3.44 (1H, d, d, J = 4, 14
Hz), 4.02 (2H, t, J = 5Hz), 4.15 (2H, t, J = 5Hz), 4.4
9 (1H, d, d, J = 4, 9Hz), 6.89 (2H, d, J = 8.5Hz), 7.15
(2H, d, J = 8.5Hz).

This was dissolved in 20 ml of ethyl acetate, and 4
3 ml of N hydrogen chloride / dioxane solution was added, and 20 ml of ethyl ether was further added, followed by stirring for 16 hours. The precipitated target substance / hydrochloride is collected by filtration to obtain an amorphous solid.
1.27 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 3.07 (1H, d, d, J = 9, 14Hz), 3.31 (1H, d, d, J = 4.5,
14Hz), 4.19-4.23 (2H, m), 4.31-4.34 (2H, m), 4.88 (1
H, d, d, J = 4.5, 9Hz), 6.91 (2H, d, J = 8.5Hz), 7.18 (2
H, d, J = 8.5Hz).

(F) 5- [4- [2-[[[1- (2-
Hydroxy-5-pyridyl) ethylidene] amino] oki
[Ethoxy] benzyl] thiazolidine-2,4-di
Down 3-acetyl-6-hydroxy-pyridine 100mg
And 5- [4- [2- (aminooxy) ethoxy] benzyl] thiazolidine-2 obtained in Example 40 (e);
4-dione hydrochloride 232mg ethanol 10m
After adding 124 μl of pyridine to the suspension at room temperature,
The mixture was stirred under reflux for an hour. After the reaction, the reaction solution was cooled to room temperature, and the precipitated target product was collected by filtration.
183 mg of the desired product as a crystalline powder having a temperature of 42 ° C. were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.05 (3H, s), 3.05 (1H, d, d, J = 9, 14Hz), 3.31 (1H,
d, d, J = 4, 14Hz), 4.22 (2H, t, J = 5Hz), 4.38 (2H, t,
J = 5Hz), 4.86 (1H, d, d, J = 4, 9Hz), 6.35 (1H, d, J =
9.5Hz), 6.91 (2H, d, J = 8.5Hz), 7.15 (2H, d, J = 8.5H
z), 7.59 (1H, d, J = 2.5Hz), 7.84 (1H, d, d, J = 2.5, 9.
5Hz).

Example 41 5- [4- [2-[[[1- (2-benzyloxy-5)
-Pyridyl) ethylidene] amino] oxy] ethoxy]
Benzyl] thiazolidine-2,4-dione (exemplified compound number 2-194) 5-acetyl-2-benzyloxypyridine 130 m
g and 5- [4- [2-] obtained in Example 40 (e).
(Aminooxy) ethoxy] benzyl] thiazolidine-
Example 4 using 182 mg of 2,4-dione hydrochloride
The reaction was carried out according to 0 (f), the product was extracted with ethyl acetate, washed with water, and the solvent was distilled off under reduced pressure.
219 mg of the target compound having a 161 ° C. are obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.18 (3H, s), 3.05 (1H, d, d, J = 9, 14Hz), 3.31 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.43 (2H,
t, J = 5Hz), 4.86 (1H, d, d, J = 4, 9Hz), 5.39 (2H, s),
6.91 (1H, d, J = 8.5Hz), 6.92 (2H, d, J = 8.5Hz), 7.15
(2H, d, J = 8.5Hz), 7.32-7.47 (5H, m), 8.02 (1H, d,
d, J = 2.5, 8.5Hz), 8.43 (1H, d, J = 2.5Hz).

Example 42 5- [4- [2-[[[1- [4- (2-pyridylsulfur)
Honyl) phenyl] ethylidene] amino] oxy] eth
[ Xy ] benzyl] thiazolidine-2,4-dione (exemplified compound number 2-185) 4 '-(2-pyridylsulfonyl) acetophenone 1
50 mg and the 5- [4- obtained in Example 40 (e).
The reaction was carried out according to Example 40 (f) using 183 mg of [2- (aminooxy) ethoxy] benzyl] thiazolidine-2,4-dione hydrochloride.

The reaction solution was concentrated, the product was extracted with ethyl acetate, washed with water, and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (methanol: dichloromethane = 2: 98) to give a cam-like target compound.
5 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.24 (3H, s), 3.12 (1H, d, d, J = 9, 14Hz), 3.44 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.50 (1H, d,
d, J = 4, 9Hz), 4.55 (2H, t, J = 5Hz), 6.88 (2H, d, J = 8.
5Hz), 7.14 (2H, d, J = 8.5Hz), 7.44-7.49 (1H, m), 7.8
0 (2H, d, J = 8.5Hz), 7.93 (1H, d, t, J = 1.5, 8Hz), 8.0
6 (2H, d, J = 8.5Hz), 8.21 (1H, d, J = 8Hz), 8.66-8.69
(1H, m).

Example 43 5- [4- [2-[[[1- [4- (4-pyridylsulfur)
Honyl) phenyl] ethylidene] amino] oxy] eth
[ Xy ] benzyl] thiazolidine-2,4-dione (exemplary compound number 2-195) 4 '-(4-pyridylsulfonyl) acetophenone 1
50 mg and the 5- [4- obtained in Example 40 (e).
When 183 mg of [2- (aminooxy) ethoxy] benzyl] thiaziridine-2,4-dione hydrochloride was used in the reaction and post-treatment according to Example 40 (f),
173 mg of the target compound having a melting point of 213-215 ° C
was gotten.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.20 (3H, s), 3.05 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 5Hz), 4.48 (2H,
t, J = 5Hz), 4.87 (1H, d, d, J = 4, 9Hz), 6.91 (2H, d, J
= 8.5Hz), 7.14 (2H, d, J = 8.5Hz), 7.91-7.94 (4H, m), 8.
05 (2H, d, J = 8.5Hz), 8.89 (2H, d, J = 6Hz).

Example 44 5- [4- [2-[[[1- [4- (phenylsulfonyl)
Ru)) phenyl] ethylidene] amino] oxy] d
Toxi] benzyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-183) 4 '-(phenylsulfonylamino) acetophenone
170 mg and 5- [4] obtained in Example 40 (e).
Using 197 mg of-[2- (aminooxy) ethoxy] benzyl] thiazolidine-2,4-dione hydrochloride,
The reaction was carried out according to Example 40 (f). The reaction solution was concentrated, and the product was extracted with ethyl acetate. After washing with water, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (methanol: dichloromethane 2:98) to give the target compound 170 having a melting point of 213-215 ° C.
mg was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.17 (3H, s), 3.11 (1H, d, d, J = 9, 14Hz), 3.44 (1H,
d, d, J = 4, 14Hz), 4.24 (2H, t, J = 5Hz), 4.48-4.53 (3
H, m), 6.89 (2H, d, J = 8.5Hz), 7.07 (2H, d, J = 8.5Hz),
7.14 (2H, d, J = 8.5Hz), 7.42-7.57 (5H, m), 7.78 (2H,
d, J = 8Hz).

Example 455- [4- [2-[[[1- (2 ', 4'-dimethoxy
Biphenyl-4-yl) ethylidene] amino] oxy]
[Ethoxy] benzyl] thiazolidine-2,4-dione
 (Exemplified Compound No. 2-196) 4 '-(2,4-dimethoxyphenyl) acetophenone
 256 mg and 5- (5) obtained in Example 40 (e).
[4- [2- (aminooxy) ethoxy] benzyl] thio
Use 382mg of azolidine-2,4-dione hydrochloride
The reaction and post-treatment were carried out according to Example 40 (f).
The target compound having a melting point of 186-188 ° C. 46
7 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.20 (3H, s), 3.06 (1H, d, d, J = 9 _, 14Hz), 3.31 (1H,
d, d, J = 4.5, 14Hz), 3.77 (3H, s), 3.81 (3H, s), 4.2
6 (2H, t, J = 4.5Hz), 4.45 (2H, t, J = 4.5Hz), 4.87 (1H,
d, d, J = 4.5, 9Hz), 6.62 (1H, d, d, J = 2, 8.5Hz), 6.6
7 (1H, d, J = 2Hz), 6.93 (2H, d, J = 8.5Hz), 7.16 (2H,
d, J = 8.5Hz), 7.24 (1H, d, J = 8.5Hz), 7.47 (2H, d, J =
8.5Hz), 7.67 (2H, d, J = 8.5Hz), 11.99 (1H, brs).

Embodiment 465- [4- [2-[[[1- (2 ', 5'-dimethoxy
Biphenyl-4-yl) ethylidene] amino] oxy]
[Ethoxy] benzyl] thiazolidine-2,4-dione
 (Exemplified Compound No. 2-197) 4 '-(2,5-dimethoxyphenyl) acetophenone
 256 mg and 5- (5) obtained in Example 40 (e).
[4- [2- (aminooxy) ethoxy] benzyl] thio
Use 382mg of azolidine-2,4-dione hydrochloride
The reaction was carried out according to Example 40 (f). Reaction liquid
, And the product was extracted with ethyl acetate.
Was distilled off under reduced pressure. The residue is purified by silica gel column chromatography.
Raffy (ethyl acetate: hexane = 2: 3)
Purpose of an amorphous solid having a melting point of 47-52 ° C (softening point)
482 mg of the compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.21 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.31 (1H,
d, d, J = 4.5, 14Hz), 3.70 (3H, s), 3.75 (3H, s), 4.2
6 (2H, t, J = 4.5Hz), 4.46 (2H, t, J = 4.5Hz), 4.87 (1H,
d, d, J = 4.5, 9Hz), 6.88 (1H, d, J = 3Hz), 6.91-6.94
(3H, m), 7.05 (1H, d, J = 8.5Hz), 7.16 (2H, d, J = 8.5H
z), 7.52 (2H, d, J = 8.5Hz), 7.70 (2H, d, J = 8.5Hz), 1
2.00 (1H, brs).

Example 47 5- [4- [2-[[(1-phenylethylidene) amido]
[No] oxy] ethoxy] benzyl] thiazolidine-2,
4-dione (Exemplary Compound No. 2-1) 0.16 ml of acetophenone and Example 40 (e)
The reaction was carried out according to Example 40 (f) using 400 mg of 5- [4- [2- (aminooxy) ethoxy] benzyl] thiazolidine-2,4-dione hydrochloride obtained in the above. The reaction solution was concentrated, and the product was extracted into ethyl acetate. After washing with water, the solvent was distilled off under reduced pressure. The residue was stirred in isopropyl ether and the precipitated powder was collected by filtration.
370 mg of the desired compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.18 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 4.5Hz), 4.45 (2H,
t, J = 4.5Hz), 4.86 (1H, d, d, J = 4, 9Hz), 6.92 (2H,
d, J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz), 7.40-7.68 (5H,
m).

Example 48 5- [4- [2-[[[1- (3-chlorophenyl) e
Tylidene] amino] oxy] ethoxy] benzyl] thia
Zolidine-2,4-dione (Exemplified Compound No. 2-10) 3'-chloroacetophenone 0.18 ml and 5- [4- [2- (aminooxy) ethoxy] benzyl] obtained in Example 40 (e) The reaction was carried out according to Example 40 (f) using 400 mg of thiazolidine-2,4-dione hydrochloride. After concentration of the reaction solution, the product was extracted with ethyl acetate, washed with water, and the solvent was distilled off under reduced pressure. The residue was stirred in ethyl ether-isopropyl ether-hexane, and the precipitated powder was collected by filtration.
290 mg of the desired compound having a temperature of ℃ were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.18 (3H, s), 3.06 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 4.5Hz), 4.47 (2H,
t, J = 4.5Hz), 4.84 (1H, d, d, J = 4, 9Hz), 6.92 (2H, d,
J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz), 7.45-7.69 (4H, m)
.

Example 49 5- [4- [2-[[[1- (4-Chlorophenyl) e]
Tylidene] amino] oxy] ethoxy] benzyl] thia
Zolidine-2,4-dione (Exemplary Compound No. 2-11) 4'-chloroacetophenone 0.18 ml and 5- [4- [2- (aminooxy) ethoxy] benzyl] obtained in Example 40 (e) The reaction was carried out according to Example 40 (f) using 400 mg of thiazolidine-2,4-dione hydrochloride. The reaction solution was concentrated, and the product was extracted with ethyl acetate. After washing with water, the solvent was distilled off under reduced pressure. The residue was stirred in ethyl ether-isopropyl ether-hexane, and the precipitated powder was collected by filtration.
360 mg of the target compound having a temperature of 119 ° C. were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.17 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4, 14Hz), 4.25 (2H, t, J = 4.5Hz), 4.45 (2H,
t, J = 4.5Hz), 4.86 (1H, d, d, J = 4, 9Hz), 6.92 (2H,
d, J = 8.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.47 (2H, d, J =
8.5Hz), 7.69 (2H, d, J = 8.5Hz).

Embodiment 505- [4- [2-[[[1- (3-hydroxyphenyl)
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (Example compound number
2-198) 3'-hydroxyacetophenone 0.33 g and fruit
5- [4- [2- (aminothio) obtained in Example 40 (e)
Xy) ethoxy] benzyl] thiazolidine-2,4-di
Example 40 (f) using 0.70 g of on-hydrochloride
According to the reaction and after-treatment, melting point 133-13
0.74 g of the target compound having a temperature of 5 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.13 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4, 14Hz), 4.24 (2H, t, J = 4.5Hz), 4.43 (2H,
t, J = 4.5Hz), 4.86 (1H, d, d, J = 4, 14Hz), 6.79-6.81
(1H, m), 6.92 (2H, d, J = 8.5Hz), 7.08 −7.23 (5H, m)
.

Embodiment 515- [4- [2-[[[1- (4-hydroxyphenyl)
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (Example compound number
2-199) 0.33 g of 4'-hydroxyacetophenone and fruit
5- [4- [2- (aminothio) obtained in Example 40 (e)
Xy) ethoxy] benzyl] thiazolidine-2,4-di
Example 40 (f) using 0.70 g of on-hydrochloride
According to the reaction and after-treatment, melting point 157-15
0.74 g of the target compound having a temperature of 9 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.12 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.30 (1H,
d, d, J = 4.5, 14Hz), 4.23 (2H, t, J = 4.5Hz), 4.39 (2H,
t, J = 4.5Hz), 4.86 (1H, d, d, J = 4.5, 9Hz), 6.80 (2H,
d, J = 8.5Hz), 6.91 (2H, d, J = 8.5Hz), 7.15 (2H, d,
J = 8.5Hz), 7.50 (2H, d, J = 8.5Hz).

Example 52 5- [4- [2-[[[1- (5-acetoxy-2-hydroxy)
Droxy-3,4,6-trimethylphenyl) ethylide
[Amino] oxy] ethoxy] benzyl] thiazolidy
-2,4-dione (Exemplified Compound No. 2-200) 5'-acetoxy-2'-hydroxy-3 ', 4',
Using 0.32 g of 6'-trimethylacetophenone and 0.40 g of 5- [4- [2- (aminooxy) ethoxy] benzyl] thiazolidine-2,4-dione hydrochloride obtained in Example 40 (e). According to Example 46,
After the reaction and the post-treatment, 0.28 g of an amorphous powdery target compound having a melting point of 60-75 ° C (softening point) was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 1.85 (3H, s), 1.96 (3H, s), 2.02 (3H, s), 2.09 (3H, s)
s), 2.30 (3H, s), 3.07 (1H, d, d, J = 9, 14Hz), 3.30
(1H, d, d, J = 4.5, 9Hz), 4.19 (2H, d, J = 4.5Hz), 4.3
6 (2H, t, J = 4.5Hz), 4.87 (1H, d, d, J = 4.5, 9Hz), 6.9
2 (2H, d, J = 8.5Hz), 7.16 (2H, d, J = 8.5Hz).

Example 53 5- [4- [2-[[[1- (4-hydroxy-3,5-
Dimethylphenyl) ethylidene] amino] oxy] eth
[Xy] benzyl] thiazolidine-2,4-dione (Exemplary Compound No. 2-201) 0.22 g of 4'-hydroxy-3 ', 5'-dimethylacetophenone and 5-
Using 0.40 g of [4- [2- (aminooxy) ethoxy] benzyl] thiazolidine-2,4-dione hydrochloride according to Example 46 and conducting the reaction and post-treatment,
0.30 g of an amorphous powdery target compound having a melting point of 53-65 ° C. (softening point) was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.10 (3H, s), 2.17 (6H, s), 3.06 (1H, d, d, J = 9, 14
Hz), 3.30 (1H, d, d, J = 4.5, 14Hz), 4.22 (2H, t, J = 4.
5Hz), 4.38 (2H, t, J = 4.5Hz), 4.86 (1H, d, d, J = 4.5,
9Hz), 6.91 (2H, d, J = 8.5Hz), 7.15 (2H, d, J = 8.5Hz),
7.24 (2H, s).

Embodiment 545- [4- [2-[[[1- (3-acetoxyphenyl)
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (Example compound number
2-202) 5- [4- [2-[[[1- (3
-Hydroxyphenyl) ethylidene] amino] oxy]
[Ethoxy] benzyl] thiazolidine-2,4-dione
0.30 g, acetic anhydride 0.092 ml and pyridine
 15 ml of the mixture was stirred at room temperature for 1.5 hours. Solvent
After distilling off, water was added to the obtained residue, and ethyl acetate was added.
Extracted. The extract was washed with 1N hydrochloric acid and then with a saline solution.
Then, it was dried over anhydrous sodium sulfate. Ethyl acetate
After distillation, the resulting residue is purified by silica gel column chromatography.
Apply to chromatography (ethyl acetate: hexane = 1: 2)
And a target compound having a melting point of 30-50 ° C (softening point)
0.23 g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.17 (3H, s), 2.28 (3H, s), 3.07 (1H, d, d, J = 9, 14
Hz), 3.30 (1H, d, d, J = 4.5, 14Hz), 4.25 (2H, t, J = 4.
5Hz), 4.45 (2H, t, J = 4.5Hz), 4.86 (1H, d, d, J = 4.5,
9Hz), 6.92 (2H, d, J = 8.5Hz), 7.14-7.56 (6H, m).

Embodiment 555- [4- [2-[[[1- (4-acetoxyphenyi)
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] thiazolidine-2,4-dione (Example compound number
2-203) 5- [4- [2-[[[1- (4
-Hydroxyphenyl) ethylidene] amino] oxy]
[Ethoxy] benzyl] thiazolidine-2,4-dione
0.30 g, acetic anhydride 0.092 ml and pyridine
 The reaction and work-up were carried out according to Example 54 using 15 ml.
The target compound having a melting point of 133-135 ° C.
 0.3 g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.18 (3H, s), 2.28 (3H, s), 3.07 (1H, d, d, J = 9, 14
Hz), 3.30 (1H, d, d, J = 4.5, 14Hz), 4.23 (2H, t, J = 4.
5Hz), 4.44 (2H, t, J = 4.5Hz), 4.86 (1H, d, d, J = 4.5,
9Hz), 6.92 (2H, d, J = 8.5Hz), 7.14 −7.17 (4H, m),
7.70 (2H, d, J = 8.5Hz).

Embodiment 565- [4- [2-[[[1- (4-biphenylyl) ethyl
[Ridene] amino] oxy] ethoxy] benzyl] oxa
Zolidine-2,4-dione (Exemplified Compound No. 6-15) (a)5- [4- [2-[[[1- (4-biphenyli
Le) ethylidene] amino] oxy] ethoxy] benzyl
Ru] -3-Trityloxazolidine-2,4-dione 2-[[[1- (4-biphenylyl) ethylidene] amido
[No] oxy] ethanol (compound of Reference Example 15)
23 g, 5- (4-hydroxybenzyl) -3-triti
Luoxazolidine-2,4-dione 0.40 g, tri
0.40 g of butylphosphine and 1,1 '-(azodi
Example using 0.50 g of carbonyl) dipiperazine
When the reaction and post-treatment are carried out according to 3 (a), the melting point is 19
Crystalline powder target compound having 3-195 ° C. 0.3
1 g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.24 (3H, s), 3.03 (1H, d, d, J = 4.5, 15Hz), 3.19 (1
H, d, d, J = 4.5, 15Hz), 4.20-4.30 (2H, m), 4.50 (2
H, t, J = 4.5Hz), 5.32 (1H, t, J = 4.5Hz), 6.98 (2H,
d, J = 8.5Hz), 7.10-7.20 (17H, m), 7.39 (1H, t, J = 1.5
Hz), 7.48 (2H, t, J = 8Hz), 7.60-7.70 (4H, m), 7.73 (2
H, d, J = 8Hz).

(B)5- [4- [2-[[[1- (4-
Biphenylyl) ethylidene] amino] oxy] ethoxy
[Benzyl] oxazolidine-2,4-dione 5- [4- [2-[[[1] obtained in Example 56 (a)
-(4-Biphenylyl) ethylidene] amino] oxy]
Ethoxy] benzyl] -3-trityloxazolidine-
Using 0.31 g of 2,4-dione, in Example 1 (b)
When the reaction and after-treatment are carried out according to the procedure, the melting point is 177-179.
0.16 g of a crystalline powder of the target compound having a temperature of 0.16 ° C. are obtained.
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in deuterated chloroform and deuterated dimethyl sulfoxide (trace amount), TMS (tetramethylsilane) as internal standard
¹ H-nuclear magnetic resonance spectrum (270
MHz) is as follows. 2.28 (3H, s), 3.07 (1H, d, d, J = 5.5, 15Hz), 3.24 (1H,
d, d, J = 4, 15Hz), 4.28 (2H, t, J = 5Hz), 4.54 (2H,
t, J = 5Hz), 4.97 (1H, d, d, J = 4, 5.5Hz), 6.89 (2H, d,
J = 8.5Hz), 7.17 (2H, d, J = 8.5Hz), 7.30-7.50 (3H, m),
7.60-7.70 (4H, m), 7.74 (2H, d, J = 8.5Hz).

Example 57 5- [4- [2-[[[1- [4- (2-pyridyl) furf]
[Enyl] propylidene] amino] oxy] ethoxy] b
Ndyl] thiazolidine-2,4-dione (Exemplified Compound No. 3-35) 4 ′-(2-pyridyl) propiophenone 211 mg
And 5- [4- [2-] obtained in Example 40 (e).
(Aminooxy) ethoxy] benzyl] thiazolidine-
Example 4 using 319 mg of 2,4-dione hydrochloride
When the reaction and after-treatment are carried out in accordance with No. 7, melting point 171-1
239 m of crystalline powder of the target compound having a temperature of 72.5 ° C.
g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 1.06 (3H, t, J = 7.5Hz), 2.75 (2H, q, J = 7.5Hz), 3.05 (1
H, d, d, J = 9, 14Hz), 3.28 (1H, d, d, J = 4.5, 14Hz),
4.26 (2H, t, J = 4.5Hz), 4.48 (2H, t, J = 4.5Hz), 4.88 (1
H, d, d, J = 4.5, 9Hz), 6.93 (2H, d, J = 8.5Hz), 7.16 (2
H, d, J = 8.5Hz), 7.39 (1H, d, d, J = 4.5, 7Hz), 7.79 (2
H, d, J = 8.5Hz), 7.91 (1H, d, d, J = 7, 8Hz), 8.02 (1H,
d, J = 8Hz), 8.14 (2H, d, J = 8.5Hz), 8.69 (1H, d, J =
4.5Hz).

Reference Example 1 2-[(benzylideneamino) oxy] ethanol (a) benzaldehyde O-2-[(tetrahydropi
Lan-2-yl) oxy] ethylaldoxime 2- (2-bromoethoxy) tetrahydropyran
2.5 g of potassium carbonate was added to a solution of 2 g and benzaldoxime 0.36 g in 10 ml of dimethylacetamide.
Was added and stirred at 80 ° C. for 4 hours. The reaction solution was dissolved in ethyl acetate and water, the ethyl acetate layer was separated, and the extract was dried over anhydrous magnesium sulfate. After evaporating the ethyl acetate under reduced pressure,
The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 7: 1) to give 0.51 g of the syrupy target compound.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.49-1.92 (6H, m), 3.47-3.55 (1H, m), 3.77 (1H, d, t,
J = 5, 11.5Hz), 3.85-3.94 (1H, m), 4.01 (1H, d, t, J =
5, 11.5Hz), 4.36 (2H, t, J = 5Hz), 4.68 (1H, t, J = 3.5H
z), 7.34-7.38 (3H, m), 7.56-7.60 (2H, m), 8.13 (1H, s)
.

(B) 2-[(benzylideneamino) oxo
[B] Ethanol Benzaldehyde O-2- obtained in Reference Example 1 (a)
To a solution of 1.3 g of [(tetrahydropyran-2-yl) oxy] ethylaldoxime in 15 ml of methanol,
100 mg of p-toluenesulfonic acid monohydrate was added,
After stirring at room temperature for 2 hours, the reaction solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain 0.90 g of the syrupy target compound.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.34 (1H, t, J = 6Hz), 3.93-3.95 (2H, m), 4.28-4.31 (2
H, m), 7.38-7.40 (3H, m), 7.56-7.58 (2H, m), 8.13 (1H,
s).

Reference Example 2 2-[(2-quinolylmethyleneamino) oxy] ethano
Lumpur (a) 2-quinoline carboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy]
Ethyl ether 2- (2-bromoethoxy) tetrahydropyran
When 50 g, 1.10 g of 2-quinolinecarboxaldehyde oxime and 2.8 g of potassium carbonate were used for the reaction and post-treatment according to Reference Example 1 (a), 2.00 g of the syrupy target compound was obtained.

(B) 2-[(2-quinolylmethyleneamido )
(No) oxy] ethanol 2-quinolinecarboxaldehyde oxime O-2-[(tetrahydropyran-) obtained in Reference Example 2 (a)
Using 2.00 g of 2-yl) oxy] ethyl ether and 1.50 g of p-toluenesulfonic acid monohydrate to carry out the reaction and post-treatment according to Reference Example 1 (b), it has a melting point of 128 ° C. 0.98 g of the desired compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.34 (1H, t, J = 6Hz), 3.97-4.01 (2H, m), 4.39-4.43
(2H, m), 7.57 (1H, t, J = 8Hz), 7.74 (1H, t, J = 8Hz),
7.83 (1H, d, J = 8.5Hz), 7.95 (1H, d, J = 8.5Hz), 8.10 (1
H, d, J = 8.5Hz), 8.15 (1H, d, J = 8.5Hz), 8.40 (1H, s)
.

Reference Example 3 2-[(3-quinolylmethyleneamino) oxy] ethano
Lumpur (a) 3- quinoline carboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy]
3. ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Using 45 g, 2.60 g of 3-quinolinecarboxaldehyde oxime and 7.30 g of potassium carbonate,
When the reaction and post-treatment were carried out according to Reference Example 1 (a), 4.72 g of a syrup-like target compound was obtained.

(B) 2-[(3-quinolylmethyleneamido )
(No) oxy] ethanol 3-quinolinecarboxaldehyde oxime O-2-[(tetrahydropyran-
When 4.72 g of 2-yl) oxy] ethyl ether and 2.91 g of p-toluenesulfonic acid monohydrate are subjected to a reaction and a post-treatment according to Reference Example 1 (b), they have a melting point of 129 ° C. 1.55 g of the desired compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.17 (1H, brs), 3.97-4.01 (2H, m), 4.36-4.40 (2H,
m), 7.59 (1H, t, J = 8Hz), 7.76 (1H, d, d, J = 1, 8Hz),
7.85 (1H, d, J = 8Hz), 8.13 (1H, d, J = 8.5Hz), 8.24 (1
H, d, J = 2 Hz), 8.31 (1H, s), 9.19 (1H, d, J = 2 Hz).

Reference Example 4 2-[(2-pyridylmethyleneamino) oxy] ethano
Lumpur (a) 2-pyridinecarboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy]
3. ethyl ether 2- (2-bromoethoxy) tetrahydropyran
00g, 2-pyridinecarboxaldehyde oxime 1.22g and potassium carbonate 6.00g,
When the reaction and post-treatment were carried out according to Reference Example 1 (a), 2.30 g of a syrup-like target compound was obtained.

(B) 2-[(2-pyridylmethyleneamido )
(No) oxy] ethanol 2-pyridinecarboxaldehyde oxime O-2-[(tetrahydropyran-
When 2.30 g of 2-yl) oxy] ethyl ether and 2.10 g of p-toluenesulfonic acid monohydrate are subjected to a reaction and a post-treatment according to Reference Example 1 (b), they have a melting point of 45 ° C. 1.29 g of the target compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.34 (1H, brs), 3.93-3.97 (2H, m), 4.35-4.38 (2H,
m), 7.27-7.30 (1H, m), 7.68-7.80 (2H, m), 8.24 (1H,
s), 8.62 (1H, d, J = 4.5Hz).

Reference Example 5 2-[(3-pyridylmethyleneamino) oxy] ethano
Lumpur (a) 3- pyridinecarboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy]
7. Ethyl ether 2- (2-bromoethoxy) tetrahydropyran
When the reaction and post-treatment were carried out according to Reference Example 1 (a) using 00g, 2.44 g of 3-pyridinecarboxaldehyde oxime and 12.00 g of potassium carbonate, 4.18 g of a syrup-like target compound was obtained.

(B) 2-[(3-pyridylmethyleneamido )
(No) oxy] ethanol 3-pyridinecarboxaldehyde oxime O-2-[(tetrahydropyran-
When 4.18 g of 2-yl) oxy] ethyl ether and 3.00 g of p-toluenesulfonic acid monohydrate were subjected to the reaction and post-treatment according to Reference Example 1 (b), the result was a waxy solid. 2.00 g of compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.28 (1H, brs), 3.93-3.97 (2H, m), 4.32-4.35 (2H,
m), 7.32 (1H, d, d, J = 5, 8Hz), 7.95 (1H, d, d, J = 1,
5Hz), 8.14 (1H, s), 8.61 (1H, d, d, J = 1.5, 5Hz), 8.
74 (1H, d, J = 2Hz).

Reference Example 6 2-[(4-pyridylmethyleneamino) oxy] ethano
Lumpur (a) 4-pyridinecarboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy]
3. ethyl ether 2- (2-bromoethoxy) tetrahydropyran
00g, 4-pyridinecarboxaldehyde oxime 1.22g and potassium carbonate 6.00g,
When the reaction and post-treatment were carried out according to Reference Example 1 (a), 2.00 g of the syrupy target compound was obtained.

(B) 2-[(4-pyridylmethyleneamido )
(No) oxy] ethanol 4-pyridinecarboxaldehyde oxime O-2-[(tetrahydropyran-
When 2.10 g of 2-yl) oxy] ethyl ether and 2.00 g of p-toluenesulfonic acid monohydrate were used for the reaction and post-treatment according to Reference Example 1 (b), the melting point was 78-80 ° C. 1.01 g of the desired compound having the formula was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.18 (1H, brs), 3.93-3.97 (2H, m), 4.34-4.37 (2H,
m), 7.45 (2H, d, d, J = 1.5, 4.5Hz), 8.09 (1H, s), 8.64
(2H, d, d, J = 1.5, 4.5Hz).

Reference Example 72-[(2-naphthylmethyleneamino) oxy] ethano
Rule (A)2-Naphthaldehyde oxime O-2-
[(Tetrahydropyran-2-yl) oxy] ethyl
-Tel 2. 2- (2-bromoethoxy) tetrahydropyran
89 g, 2-naphthaldehyde oxime 2.00 g
And Reference Example 1 using 6.46 g of potassium carbonate
When the reaction and post-treatment are carried out according to (a), the melting point is 72-
2.39 g of a crystalline target compound having a temperature of 73 ° C. are obtained.
Was.

(B) 2-[(2-naphthylmethyleneamido )
(No) oxy] ethanol 2.39 g of 2-naphthaldehyde oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 7 (a) and p-toluenesulfonic acid monohydrate Reference Example 1 using 0.20 g of the product
When the reaction and post-treatment are carried out according to (b), the melting point is 87 ° C.
1.17 g of the target compound having the formula were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.35 (1H, t, J = 6Hz), 3.95-4.00 (2H, m), 4.33-4.36
(2H, m), 7.49-7.53 (2H, m), 7.82-7.87 (5H, m), 8.28
(1H, s).

Reference Example 82-[(3-phenylbenzylideneamino) oxy] d
Tanol (A)3-biphenylcarboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2. 2- (2-bromoethoxy) tetrahydropyran
24 g, 3-biphenylcarboxaldehyde oxy
2.00 g of potassium carbonate and 5.61 g of potassium carbonate
The reaction and post-treatment are performed according to Reference Example 1 (a).
And 2.81 g of a syrupy target compound were obtained.

(B) 2-[(3-phenylbenzylidene )
Amino) oxy] ethanol 3-biphenylcarboxaldehyde oxime O-2-[(tetrahydropyran-
2-yl) oxy] ethyl ether 2.14 g and p
Using 200 mg of toluenesulfonic acid monohydrate,
When the reaction and after-treatment were carried out according to Example 1 (b), 1.23 g of the syrupy target compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.30 (1H, t, J = 6Hz), 3.93-3.98 (2H, m), 4.30-4.34
(2H, m), 7.35-7.48 (4H, m), 7.54-7.63 (4H, m), 7.79
(1H, s), 8.20 (1H, s).

Reference Example 92-[(4-phenylbenzylideneamino) oxy] d
Tanol (A)4-biphenylcarboxaldehyde oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2. 2- (2-bromoethoxy) tetrahydropyran
24 g, 4-biphenylcarboxaldehyde oxy
2.00 g of potassium carbonate and 5.61 g of potassium carbonate
The reaction and post-treatment are performed according to Reference Example 1 (a).
As a result, 2.73 g of a syrup-like target compound was obtained.

(B) 2-[(4-phenylbenzylidene )
Amino) oxy] ethanol 4-biphenylcarboxaldehyde oxime O-2-[(tetrahydropyran- obtained in Reference Example 9 (a)
2.73 g of 2-yl) oxy] ethyl ether and p
Using 200 mg of toluenesulfonic acid monohydrate,
When the reaction and post-treatment were carried out according to Reference Example 1 (b), 1.78 g of the target compound having a melting point of 116 to 118 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.32 (1H, t, J = 6Hz), 3.93-3.98 (2H, m), 4.30-4.33
(2H, m), 7.34-7.49 (3H, m), 7.58-7.67 (6H, m), 8.17
(1H, s).

Reference Example 10 2-[[(2-phenyl-5-pyridyl) methyleneamido
[O] oxy] ethanol (a) 2-phenyl-5-pyridinecarboxyaldehyde
De oxime O-2-[(tetrahydropyran-2-
Yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
58 g, 500 mg of 2-phenyl-5-pyridinecarboxaldehyde oxime and potassium carbonate
When the reaction and post-treatment were carried out according to Reference Example 1 (a) using 09 g, 734 mg of the syrupy target compound was obtained.

(B) 2-[[(2-phenyl-5-pyri
Zyl) methyleneamino] oxy] ethanol 2-phenyl-5-pyridinecarboxaldehyde oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 10 (a)
727 mg and p-toluenesulfonic acid monohydrate
When 466 mg of the target compound was subjected to the reaction and post-treatment according to Reference Example 1 (b), 404 mg of the target compound having a melting point of 100 to 101 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.20 (1H, t, J = 5Hz), 3.93-3.97 (2H, m), 4.32-4.36
(2H, m), 7.41-7.53 (3H, m), 7.76 (1H, d, J = 8.5Hz),
8.00-8.05 (3H, m), 8.19 (1H, s), 8.78 (1H, d, J = 2H
z).

Reference Example 11 2-[[(3-phenyl-5-pyridyl) methyleneamido
[N] oxy] ethanol (a) 3-phenyl-5-pyridinecarboxyaldehyde
De oxime O-2-[(tetrahydropyran-2-
Yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
1. 80 g, 3-phenyl-5-pyridinecarboxaldehyde oxime 600 mg and potassium carbonate
When the reaction and post-treatment were carried out according to Reference Example 1 (a) using 50 g, 809 mg of the syrupy target compound was obtained.

(B) 2-[[(3-phenyl-5-pyri
Zyl) methyleneamino] oxy] ethanol 3-phenyl-5-pyridinecarboxaldehyde oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 11 (a)
809 mg and p-toluenesulfonic acid monohydrate
The reaction and after-treatment were carried out according to Reference Example 1 (b) using 750 mg to obtain 529 mg of the desired compound having a melting point of 102 to 104 ° C.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.26 (1H, brs), 3.98-4.02 (2H, m), 4.33-4.37 (2H,
m), 7.40-7.53 (3H, m), 7.59-7.62 (2H, m), 8.13 (1H,
t, J = 2Hz), 8.21 (1H, s), 8.69 (1H, d, J = 2Hz), 8.84
(1H, d, J = 2Hz).

Reference Example 12 2-[[(2-ethoxy-5-pyridyl) methyleneamido
[O] oxy] ethanol (a) 2-ethoxy-5-pyridinecarboxyaldehyde
De oxime O-2-[(tetrahydropyran-2-
1. yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
1.00 g, 1.00 g of 2-ethoxy-5-pyridinecarboxaldehyde oxime and potassium carbonate
When the reaction and post-treatment were carried out according to Reference Example 1 (a) using 50 g, 1.76 g of a syrup-like target compound was obtained.

(B) 2-[[(2-ethoxy-5-pyri
Zyl) methyleneamino] oxy] ethanol 2-ethoxy-5-pyridinecarboxaldehyde oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 12 (a)
1.76 g, p-toluenesulfonic acid monohydrate
When the reaction and the post-treatment are carried out according to Reference Example 1 (b) using 60 g, the target compound having a melting point of 52 to 54 ° C.
0.73 g was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.40 (3H, t, J = 7Hz), 2.20 (1H, t, J = 6Hz), 3.90-3.9
5 (2H, m), 4.26-4.29 (2H, m), 4.39 (2H, q, J = 7Hz),
6.74 (1H, d, J = 8.5Hz), 7.90 (1H, d, d, J = 2, 8.5Hz),
8.08 (1H, s), 8.18 (1H, d, J = 2Hz).

Reference Example 13 2-[[[1- (2-Naphthyl) ethylidene] amino]
Oxy] ethanol (a) 2-acetonaphthone oxime O-2-[(T
3. Trahydropyran-2-yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Using 52 g, 2.00 g of 2-acetonaphthone oxime and 5.97 g of potassium carbonate, Reference Example 1 (a)
The reaction (reaction time: 20 hours) and post-treatment were carried out according to the procedure described in Example 1 to obtain 3.32 g of the target compound in the form of a syrup.

(B) 2-[[[1- (2-naphthyl) d
Tylidene] amino] oxy] ethanol 3.32 g of 2-acetonaphthone oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 13 (a) and p-toluenesulfonic acid / 1 water Reference Example 1 using 0.30 g of Japanese product
When the reaction and post-treatment are carried out according to (b), the melting point is 94-
1.31 g of the target compound having a temperature of 96 ° C. were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.39 (3H, s), 2.58 (1H, brs), 3.97-4.00 (2H, m),
4.36-4.39 (2H, m), 7.47-7.53 (2H, m), 7.79-7.88 (4H, m
m), 8.00 (1H, s).

Reference Example 142-[[[1- (2-quinolyl) ethylidene] amino]
Oxy] ethanol (A)2-acetylquinoline oxime O-2-
[(Tetrahydropyran-2-yl) oxy] ethyl
-Tel 1. 2- (2-bromoethoxy) tetrahydropyran
09 g, 930 mg of 2-acetylquinoline oxime
Reference Example 1 using potassium carbonate and 2.76 g of potassium carbonate
The reaction according to (a) (however, the reaction time is 20 hours) and
After the post-treatment, the target compound in the form of a syrup 1.51
g was obtained.

(B) 2-[[[1- (2-quinolyl) e
[Tylidene] amino] oxy] ethanol 2- acetylquinoline oxime O-2-[(tetrahydropyran-2-yl) obtained in Reference Example 14 (a)
Reference Example 1 using 1.51 g of [oxy] ethyl ether
When the reaction and post-treatment are carried out according to (b), the melting point is 89 ° C.
0.85 g of the desired compound having the formula was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.44 (1H, t, J = 6Hz), 2.51 (3H, s), 3.96-4.02 (2H,
m), 4.40-4.43 (2H, m), 7.54 (1H, t, J = 9.5Hz), 7.71
(1H, t, J = 7.5Hz), 7.80 (1H, d, J = 8Hz), 8.01 (1H, d,
J = 8.5Hz), 8.08-8.11 (2H, m).

Reference Example 152-[[[1- (4-biphenylyl) ethylidene] amido
No] oxy] ethanol (A)4-acetylbiphenyl oxime O-2-
[(Tetrahydropyran-2-yl) oxy] ethyl
-Tel 2- (2-bromoethoxy) tetrahydropyran 1
5.8 g, 4-acetylbiphenyl oxime 6.4
0 g and potassium carbonate 20.9 g, Reference Example 1
The reaction according to (a) (however, the reaction time is 16 hours) and
After the post-treatment, the syrupy target compound 10.2
g was obtained.

(B)2-[[[1- (4-biphenyli
Le) Ethylidene] amino] oxy] ethanol 4-acetylbiphenyl obtained in Reference Example 15 (a)
Oxime O-2-[(tetrahydropyran-2-i
L) Oxy] ethyl ether using 10.2 g,
When the reaction and work-up are carried out according to Example 1 (b), the melting point is 1
6.53 g of the desired compound having a temperature of 28-130 ° C. is obtained.
Was.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.30 (3H, s), 2.58 (1H, brs), 3.95-3.99 (2H, m),
4.32-4.36 (2H, m), 7.36-7.48 (3H, m), 7.59-7.62 (4H,
m), 7.71 (2H, d, J = 8.5Hz).

Reference Example 162-[[[1- (3-biphenylyl) ethylidene] amido
No] oxy] ethanol (A)3-acetylbiphenyl oxime O-2-
[(Tetrahydropyran-2-yl) oxy] ethyl
-Tel 2. 2- (2-bromoethoxy) tetrahydropyran
16 g, 3-acetylbiphenyl oxime 1.68
g and potassium carbonate (5.50 g), Reference Example 1
The reaction according to (a) (however, the reaction time is 16 hours) and
After the post-treatment, the target compound in syrup form 2.69
g was obtained.

(B)2-[[[1- (3-biphenyli
Le) Ethylidene] amino] oxy] ethanol 3-acetylbiphenyl obtained in Reference Example 16 (a)
Oxime O-2-[(tetrahydropyran-2-i
2.69 g and p-tol)
Using 0.15 g of ruenesulfonic acid monohydrate for reference
When the reaction and post-treatment were carried out according to Example 1 (b),
1.45 g of the title compound were obtained in the form of a plug.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.32 (3H, s), 2.58 (1H, brs), 3.94-3.98 (2H, m),
4.32-4.36 (2H, m), 7.34-7.48 (4H, m), 7.59-7.62 (4H, m
m), 7.83 (1H, d, J = 1.5Hz).

Reference Example 172-[[[1- (2-phenyl-5-pyridyl) ethyl
Den] amino] oxy] ethanol (A)5-acetyl-2-phenylpyridine oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
48 g, 5-acetyl-2-phenylpyridineoxy
Use 600mg and potassium carbonate 2.30g
The reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
6 hours) and after-treatment, syrup-like target compound
886 mg of the product were obtained.

(B) 2-[[[1- (2-phenylyl-
5-pyridyl) ethylidene] amino] oxy] ethanol
Le Reference Example 17 was obtained in (a) 5-acetyl-2-phenylpyridine oxime O-2 - [(tetrahydropyran-2-yl) oxy] ethyl ether 882mg and p- toluenesulfonic acid monohydrate 542mg When the reaction and after-treatment were carried out according to Reference Example 1 (b) using, 519 mg of the desired compound having a melting point of 76 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.32 (3H, s), 2.42 (1H, brs), 3.96-3.99 (2H, m),
4.35-4.38 (2H, m), 7.44-7.53 (3H, m), 7.75 (1H, d, J =
8Hz), 8.00-8.04 (3H, m), 8.93 (1H, d, d, J = 2, 5Hz).

Reference Example 182-[[[1- (3-phenyl-5-pyridyl) ethyl
Den] amino] oxy] ethanol (A)5-acetyl-3-phenylpyridine oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2- (2-bromoethoxy) tetrahydropyran 98
5 mg, 5-acetyl-3-phenylpyridineoxy
500 mg and potassium carbonate 1.30 g
The reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
6 hours) and after-treatment, syrup-like target compound
641 mg of the product were obtained.

(B) 2-[[[1- (3-phenyl-5
-Pyridyl) ethylidene] amino] oxy] ethanol 641 mg of 5-acetyl-3-phenylpyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 18 (a) and p- When 419 mg of toluenesulfonic acid monohydrate was used for the reaction and post-treatment according to Reference Example 1 (b), 419 mg of the syrupy target compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.34 (3H, s), 2.40 (1H, brs), 3.95-3.99 (2H, m),
4.35-4.39 (2H, m), 7.43-7.52 (3H, m), 7.59-7.62 (2H, m
m), 8.11 (1H, t, J = 2Hz), 8.82 (1H, d, J = 2Hz), 8.83
(1H, d, J = 2Hz).

Reference Example 192-[[[1- (2-ethoxy-5-pyridyl) ethyl
Den] amino] oxy] ethanol (A)5-acetyl-2-ethoxypyridine oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
16 g, 5-acetyl-2-ethoxypyridineoxy
Use 500mg and potassium carbonate 1.53g
The reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
8 hours) and after-treatment, syrup-like target compound
850 mg of the product were obtained.

(B) 2-[[[1- (2-ethoxy-5)
-Pyridyl) ethylidene] amino] oxy] ethanol 903 mg of 5-acetyl-2-ethoxypyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 19 (a) and p- When 580 mg of toluenesulfonic acid monohydrate was used for the reaction and post-treatment according to Reference Example 1 (b), 548 mg of the target compound was obtained in the form of a syrup.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.40 (3H, t, J = 7Hz), 2.24 (3H, s), 2.49 (1H, t, J =
5.5Hz), 3.91-3.96 (2H, m), 4.29-4.32 (2H, m), 4.38
(2H, q, J = 7Hz), 6.72 (1H, d, J = 9Hz), 7.89 (1H, d, d,
J = 2.5, 9Hz), 8.35 (1H, d, J = 2.5Hz).

Reference Example 20 2-[[[1- [4- (imidazol-1-yl) fe
Nyl] ethylidene] amino] oxy] ethanol (a) 4 ′-(imidazol-1-yl) acetopheno
Oxime O-2 [(tetrahydropyran-2-i
1.) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
1. 01 g, 4 '-(imidazol-1-yl) acetophenone oxime 1.00 g and potassium carbonate
When 50 g of the compound were subjected to the reaction (the reaction time was 16 hours) and post-treatment according to Reference Example 1 (a), and 1.14 g of the syrupy target compound was obtained.

(B)2-[[[1- [4- (imidazo
Ru-1-yl) phenyl] ethylidene] amino] oxo
S] Ethanol 4 '-(imidazole-1) obtained in Reference Example 20 (a)
-Yl) acetophenone oxime O-2-[(teto
Lahydropyran-2-yl) oxy] ethyl ether
1.14 g and p-toluenesulfonic acid monohydrate
Using 1.59 g, the reaction was carried out according to Reference Example 1 (b).
After the post-treatment, the product has a melting point of 127-129 ° C.
562 mg of the compound were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: in heavy dimethyl sulfoxide, TMS as internal standard
The ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured using (tetramethylsilane) is as follows. 2.23 (3H, s), 3.68 (2H, q, J = 5.5Hz), 4.17 (2H, t, J
= 5.5Hz), 4.73 (1H, t, J = 5.5Hz), 7.13 (1H, s), 7.70
(2H, d, J = 8.5Hz), 7.79 (2H, d, J = 8.5Hz), 7.80 (1H,
s), 8.33 (1H, s).

Reference Example 21 2-[[[1- [4- (2-pyridyl) phenyl] ethyl]
Ridene] amino] oxy] ethanol (a) 4 ′-(2-pyridyl) acetophenone oxy
O-2-[(tetrahydropyran-2-yl) oxy
2. [Ethyl ether 2- (2-bromoethoxy) tetrahydropyran;
Using 1.20 g of 4 g of 4 ′-(2-pyridyl) acetophenone oxime and 6.00 g of potassium carbonate, the reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
After 6 hours) and post-treatment, 2.01 g of the syrupy target compound was obtained.

(B) 2-[[[1- [4- (2-pyridi
Ru) phenyl] ethylidene] amino] oxy] ethanol
Le obtained in Reference Example 21 4 '- (2-pyridyl) acetophenone oxime O-2 - [(tetrahydropyran -
When 2.01 g of 2-yl) oxy] ethyl ether and 1.30 g of p-toluenesulfonic acid monohydrate were used for the reaction and post-treatment according to Reference Example 1 (b), the melting point was 74-76 ° C. 1.35 g of the target compound having the formula were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.31 (3H, s), 2.57 (1H, t, J = 6Hz), 3.95-3.99 (2H,
m), 4.34-4.36 (2H, m), 7.24-7.27 (1H, m), 7.74-7.77
(4H, m), 8.02 (2H, d, J = 8.5Hz), 8.71 (1H, d, d, J = 1.
5, 5Hz).

Reference Example 22 2-[[[1- [4- (3-pyridyl) phenyl] ethyl]
Riden] amino] oxy] ethanol (a) 4 ′-(3-pyridyl) acetophenone oxy
O-2-[(tetrahydropyran-2-yl) oxy
8. [Ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Using 20 g, 4.76 g of 4 '-(3-pyridyl) acetophenone oxime and 17.4 g of potassium carbonate, the reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
After 6 hours) and post-treatment, 2.60 g of the target compound in the form of a syrup was obtained.

(B) 2-[[[1- [4- (3-pyridi
Ru) phenyl] ethylidene] amino] oxy] ethanol
Obtained in Le Reference Example 22 (a) 4 '- ( 3- pyridyl) acetophenone oxime O-2 - [(tetrahydropyran-2-yl) oxy] ethyl ether 2.60g and p- toluenesulfonic acid water When 1.70 g of the hydrate was used for the reaction and post-treatment according to Reference Example 1 (b), 1.69 g of the desired compound having a melting point of 69-70 ° C.
was gotten.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.31 (3H, s), 2.58 (1H, t, J = 6Hz), 3.95-4.00 (2H,
m), 4.34-4.37 (2H, m), 7.39 (1H, d, d, J = 4.5,8Hz),
7.60 (2H, d, J = 8.5Hz), 7.75 (2H, d, J = 8.5Hz), 7.87
-7.92 (1H, m), 8.61 (1H, d, d, J = 1.5, 4.5Hz), 8.87 (1
H, d, J = 2Hz).

Reference Example 23 2-[[[1- [4- (4-pyridyl) phenyl] ethyl]
Riden] amino] oxy] ethanol (a) 4 ′-(4-pyridyl) acetophenone oxy
O-2-[(tetrahydropyran-2-yl) oxy
1.] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
20 g of 2-butanone containing 30 g of 1.00 g of 4 '-(4-pyridyl) acetophenone oxime and 4.00 g of potassium carbonate was stirred under reflux for 4 hours. Ethyl acetate was added to the reaction solution, washed with brine,
It was dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was subjected to silica gel column chromatography (dichloromethane: methanol = 98: 2 and 95: 5).
Purification by subjecting to 1.5 g of the target compound in the form of a syrup 1.5
8 g were obtained.

(B) 2-[[[1- [4- (4-pyridi
Ru) phenyl] ethylidene] amino] oxy] ethanol
Obtained in Le Reference Example 23 (a) 4 '- ( 4- pyridyl) acetophenone oxime O-2 - [(tetrahydropyran-2-yl) oxy] ethyl ether 1.58g and p- toluenesulfonic acid water When 1.44 g of the hydrate was subjected to the reaction and post-treatment according to Reference Example 1 (b), 1.01 g of the target compound having a melting point of 133 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.31 (3H, s), 2.53 (1H, t, J = 6Hz), 3.95-3.98 (2H,
m), 4.34-4.37 (2H, m), 7.52 (2H, d, d, J = 1.5,5Hz),
7.65 (2H, d, J = 8.5 Hz), 7.76 (2H, d, J = 8.5 Hz), 8.68 (2
H, d, d, J = 1.5, 5Hz).

Reference Example 24 2-[[(1,4-dimethyl-2-phenylimidazoline)
Ru-5-yl) methyleneamino] oxy] ethanol (a) 1,4-dimethyl-2-phenylimidazole-
5-carboxaldehyde oxime O-2-[(te
Trahydropyran-2-yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Reference Example 1 (a) using 46 g, 500 mg of 1,4-dimethyl-2-phenylimidazole-5-carboxaldehyde oxime and 1.93 g of potassium carbonate.
The reaction (reaction time was 5 hours) and post-treatment were carried out according to the procedure described in Example 1 to obtain 716 mg of the target compound in the form of a syrup.

(B) 2-[[((1,4-dimethyl-2-
Phenylimidazol-5-yl) methyleneamino] o
Carboxymethyl] ethanol Reference Example 24 was obtained in (a) 1,4-Dimethyl-2-phenylimidazole-5-carboxaldehyde oxime O-2 - [(tetrahydropyran-2-yl) oxy] ethyl ether 713mg and p- Reference Example 1 using 434 mg of toluenesulfonic acid monohydrate
When the reaction and post-treatment are carried out according to (b), the melting point is 95-
454 mg of the target compound having a temperature of 97 ° C. were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.34 (3H, s), 3.82 (3H, s), 3.91-3.95 (2H, m), 4.2
5-4.28 (2H, m), 7.43-7.51 (3H, m), 7.59-7.62 (2H, m),
8.21 (1H, s).

Reference Example 25 2-[[[1- (1-Methyl-2-phenylimidazo)
Ru-4-yl) ethylidene] amino] oxy] ethanol
Le (a) 4-acetyl-1-methyl-2-Feniruimida
Zol oxime O-2-[(tetrahydropyran-
2-yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
40 g, 673 mg of 4-acetyl-1-methyl-2-phenylimidazole oxime and potassium carbonate
When 2.00 g was used and subjected to the reaction (the reaction time was 16 hours) and post-treatment according to Reference Example 1 (a), 0.78 g of the syrupy target compound was obtained.

(B)2-[[[1- (1-methyl-2-
Phenylimidazol-4-yl) ethylidene] ami
No] oxy] ethanol 4-acetyl-1-methyl obtained in Reference Example 25 (a)
-2-phenylimidazole oxime O-2-
[(Tetrahydropyran-2-yl) oxy] ethyl
0.78 g and p-toluenesulfonic acid / 1
Using 0.50 g of hydrate, the reaction was carried out according to Reference Example 1 (b).
After reaction and after-treatment, it has a melting point of 133-135 ° C
0.42 g of the desired compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.30 (3H, s), 2.75 (1H, brs), 3.73 (3H, s), 3.92-
3.94 (2H, m), 4.28-4.30 (2H, m), 7.27 (1H, s), 7.40-
7.48 (3H, m), 7.60-7.63 (2H, m).

Reference Example 262-[[[1- (4'-methylbiphenyl-4-yl)
Ethylidene] amino] oxy] ethanol (A)4 '-(4-methylphenyl) acetophenone
Oxime O-2-[(tetrahydropyran-2-i
Ru) oxy] ethyl ether 1. 2- (2-bromoethoxy) tetrahydropyran
78 g, 4 '-(4-methylphenyl) acetophenone
 1.20 g of oxime and 3.68 g of potassium carbonate
And the reaction according to Reference Example 1 (a) (however, the reaction time
After 16 hours) and after-treatment, syrupy purpose
1.84 g of the compound were obtained.

(B) 2-[[[1- (4'-methylbifu
Enyl-4-yl) ethylidene] amino] oxy] eta
Obtained in Nord Reference Example 26 (a) 4 '- ( 4- methylphenyl) acetophenone oxime O-2 - [(tetrahydropyran-2-yl) oxy] ethyl ether 1.84
g and p-toluenesulfonic acid monohydrate 0.10
When the reaction and post-treatment are carried out according to Reference Example 1 (b) using g, the target compound having a melting point of 142 to 144 ° C.
1.12 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.30 (3H, s), 2.40 (3H, s), 2.59 (1H, t, J = 6Hz),
3.93-3.99 (2H, m), 4.32-4.40 (2H, m), 7.26 (2H, d, J =
8Hz), 7.50 (2H, d, J = 8Hz), 7.59 (2H, d, J = 8.5Hz),
7.68 (2H, d, J = 8.5Hz).

Reference Example 272-[[[1- (4'-fluorobiphenyl-4-i
Le) Ethylidene] amino] oxy] ethanol (A)4 '-(4-fluorophenyl) acetophenone
Oxime O-2-[(tetrahydropyran-2-i
Ru) oxy] ethyl ether 2. 2- (2-bromoethoxy) tetrahydropyran
42 g, 4 '-(4-fluorophenyl) acetopheno
1.50 g of oxime and 4.52 of potassium carbonate
g and react according to Reference Example 1 (a) (however,
After 20 hours) and after treatment, syrupy eyes
2.33 g of the title compound were obtained.

(B) 2-[[[1- (4'-fluorobi
Phenyl-4-yl) ethylidene] amino] oxy] d
1. 4 ′-(4-Fluorophenyl) acetophenone oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 27 (a) of tanol
33 g and p-toluenesulfonic acid monohydrate
When the reaction and the post-treatment were carried out according to Reference Example 1 (b) using 12 g, 1.42 g of the target compound having a melting point of 133 to 134 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.30 (3H, s), 2.57 (1H, t, J = 5.5Hz), 3.94-3.99 (2H,
m), 4.33-4.36 (2H, m), 7.14 (2H, t, J = 8.5Hz), 7.53
-7.59 (4H, m), 7.70 (2H, d, J = 8.5Hz).

Reference Example 28 2-[[[1- (4'-trifluoromethylbiphenyl)
-4-yl) ethylidene] amino] oxy] ethanol (a) 4 '-(4-trifluoromethylphenyl) ace
Tophenone oxime O-2-[(tetrahydropyran
-2-yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Using 50 g of 4 '-(4-trifluoromethylphenyl) acetophenone oxime 800 mg and potassium carbonate 1.98 g, the reaction (reaction time: 24 hours) and post-treatment were carried out according to Reference Example 1 (a). ,
1.16 g of the desired compound in the form of a syrup were obtained.

(B) 2-[[[1- (4'-trifluoro)
Romethylbiphenyl-4-yl) ethylidene] amino]
Oxy] ethanol 4 '-(4-trifluoromethylphenyl) acetophenone oxime O-2- obtained in Reference Example 28 (a)
1.16 g of [(tetrahydropyran-2-yl) oxy] ethyl ether and p-toluenesulfonic acid / 1
When the reaction and after-treatment were carried out according to Reference Example 1 (b) using 55 mg of the hydrate, 772 mg of the desired compound having a melting point of 108-111 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.31 (3H, s), 2.52 (1H, t, J = 6Hz), 3.94-3.97 (2H,
m), 4.33-4.37 (2H, m), 7.61 (2H, d, J = 8.5Hz), 7.70
(4H, s), 7.74 (2H, d, J = 8.5Hz).

Reference Example 29 2-[[[1- (4-ethoxyphenyl) ethylidene]
Amino] oxy] ethanol (a) 4′-ethoxyacetophenone oxime O—
2-[(tetrahydropyran-2-yl) oxy] ethyl
5. Luether 2- (2-bromoethoxy) tetrahydropyran
42 g, 4'-ethoxyacetophenone oxime
When 2.20 g and 8.48 g of potassium carbonate are used and subjected to the reaction according to Reference Example 1 (a) (the reaction time is 20 hours) and post-treatment, the syrupy target compound is obtained.
3.77 g were obtained.

(B) 2-[[[1- (4-ethoxyfe
Nyl) ethylidene] amino] oxy] ethanol 4′-ethoxyacetophenone oxime O-2-[(tetrahydropyran-2) obtained in Reference Example 29 (a)
-Yl) oxy] ethyl ether 3.77 g and p
Using 0.23 g of toluenesulfonic acid monohydrate,
When the reaction and post-treatment were carried out according to Reference Example 1 (b), 1.88 g of the target compound having a melting point of 51 to 54 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.42 (3H, t, J = 7Hz), 2.24 (3H, s), 2.69 (1H, t, J =
5.5Hz), 3.91-3.95 (2H, m), 4.05 (2H, q, J = 7Hz), 4.2
8-4.31 (2H, m), 6.88 (2H, d, J = 9Hz), 7.56 (2H, d, J = 9
Hz).

Reference Example 302-[[[1- (3 ', 4'-methylenedioxybiphe
Nyl-4-yl) ethylidene] amino] oxy] ethano
Rule (A)3 ', 4'-methylenedioxyacetophenone
Oxime O-2-[(tetrahydropyran-2-i
Ru) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
75 g, 3 ', 4'-methylenedioxyacetophenone
 0.80 g of oxime and 3.40 g of potassium carbonate
And the reaction according to Reference Example 1 (a) (however, the reaction time
6 hours) and after-treatment, syrup-like target
1.12 g of the compound were obtained.

(B) 2-[[[1- (3 ', 4'-methyl
Rangeoxybiphenyl-4-yl) ethylidene] ami
[N] oxy] ethanol 3 ′, 4′-Methylenedioxyacetophenone oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 30 (a) 1.1
2 g and p-toluenesulfonic acid monohydrate 0.0
When the reaction and post-treatment are carried out according to Reference Example 1 (b) using 3 g, the target compound having a melting point of 132 to 134 ° C.
740 mg were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.29 (3H, s), 2.59 (1H, t, J = 6Hz), 3.94-3.98 (2H,
m), 4.32-4.35 (2H, m), 6.01 (2H, s), 6.89 (1H, d, J =
8.5Hz), 7.07-7.09 (2H, m), 7.52 (2H, d, J = 8.5Hz),
7.67 (2H, d, J = 8.5Hz).

Reference Example 312-[[[1- (2-methoxy-5-pyridyl) ethyl
Den] amino] oxy] ethanol (A)5-acetyl-2-methoxypyridine oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
01 g, 5-acetyl-2-methoxypyridineoxy
Use 321 mg of potassium carbonate and 1.33 g of potassium carbonate
The reaction is carried out according to Reference Example 1 (a) (however, the reaction time is 2
0 hours) and post-treatment, the syrupy target compound
560 mg of the product were obtained.

(B) 2-[[[1- (2-methoxy-5
-Pyridyl) ethylidene] amino] oxy] ethanol 560 mg of 5-acetyl-2-methoxypyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 31 (a) and p- When 398 mg of toluenesulfonic acid monohydrate was used for the reaction and post-treatment according to Reference Example 1 (b), 346 mg of the target compound was obtained in the form of a syrup.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.25 (3H, s), 2.45 (1H, t, J = 5.5Hz), 3.92-3.96 (2H,
m), 3.96 (3H, s), 4.29-4.32 (2H, m), 6.74 (1H, d, J
= 9Hz), 7.90 (1H, d, d, J = 2, 9Hz), 8.37 (1H, d, J = 2H
z).

Reference Example 32 2-[[[1- (2-Isopropoxy-5-pyridyl)
Ethylidene] amino] oxy] ethanol (a) 5-acetyl-2-isopropoxypyridine
Kisime O-2-[(tetrahydropyran-2-yl)
[Oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
23 g, 5-acetyl-2-isopropoxypyridine
When 1.20 g of oxime and 4.27 g of potassium carbonate are used and subjected to a reaction according to Reference Example 1 (a) (the reaction time is 15 hours) and post-treatment, 1.99 g of a syrup-like target compound is obtained. Was.

(B) 2-[[[1- (2-isopropoxy)
C-5-pyridyl) ethylidene] amino] oxy] eta
5-5 -acetyl-2-isopropoxypyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether 1.99 obtained in Reference Example 32 (a)
g and p-toluenesulfonic acid monohydrate 1.29
Using g, the reaction and post-treatment were carried out according to Reference Example 1 (b) to obtain 1.02 g of the target compound in the form of a syrup.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.35 (6H, d, J = 6Hz), 2.24 (3H, s), 2.48 (1H, t, J = 6
Hz), 3.91-3.96 (2H, m), 4.28-4.32 (2H, m), 5.32 (1H,
septet, J = 6Hz), 6.67 (1H, d, J = 9Hz), 7.87 (1H, d,
d, J = 2.5, 9Hz), 8.35 (1H, d, J = 2.5Hz).

Reference Example 33 2-[[[1- (2-phenylsulfonyl-5-pyridi)
L) ethylidene] amino] oxy] ethanol (a) 5-acetyl-2- (phenylsulfonyl) pyri
Zin oxime O-2-[(tetrahydropyran-2
-Yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
60 g, 0.80 g of 5-acetyl-2- (phenylsulfonyl) pyridine oxime and potassium carbonate
When the reaction and the post-treatment are carried out according to Reference Example 1 (a) using 3.20 g, 0.97 g of the syrup-like target compound is obtained.
was gotten.

(B) 2-[[[1- (2-phenylsulfur)
Honyl-5-pyridyl) ethylidene] amino] oxy]
Ethanol 0.97 g of 5-acetyl-2- (phenylsulfonyl) pyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 33 (a) and p-toluenesulfonic acid. When 0.40 g of monohydrate was used for the reaction and post-treatment according to Reference Example 1 (b), 0.72 g of the target compound having a melting point of 77-78 ° C was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.01 (1H, t, J = 6Hz), 2.27 (3H, s), 3.91-3.95 (2H,
m), 4.34-4.36 (2H, m), 7.52-7.56 (2H, m), 7.60-7.64
(1H, m), 8.06-8.08 (2H, m), 8.13 (1H, d, d, J = 2, 8.5
Hz), 8.19 (1H, d, J = 8.5Hz), 8.91 (1H, d, J = 2Hz).

Reference Example 342-[[[1- [2- [N- (4-methylphenylsulfur
Honyl) -N-methylamino] pyridin-5-yl] d
Tylidene] amino] oxy] ethanol (A)5-acetyl-2- [N- (4-methylphenyl
Sulfonyl) -N-methylamino] pyridine oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 1. 2- (2-bromoethoxy) tetrahydropyran
61 g, 5-acetyl-2- [N- (4-methylphenyi)
Rusulfonyl) -N-methylamino] pyridine oxime
Using 1.50 g and 5.20 g of potassium carbonate,
Reaction according to Example 1 (a) (however, the reaction time is 14:00
After) and after-treatment, the syrupy target compound
1.93 g were obtained.

(B) 2-[[[1- [2- [N- (4-
Methylphenylsulfonyl) -N-methylamino] pyri
Zin-5-yl] ethylidene] amino] oxy] ethano
Obtained in Lumpur Reference Example 34 (a) 5-Acetyl-2-[N-
(4-Methylphenylsulfonyl) -N-methylamino] pyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether 1.22 g
And 1.00 g of p-toluenesulfonic acid monohydrate
When the reaction and after-treatment were carried out according to Reference Example 1 (b), 1.22 g of the syrupy target compound was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.25 (3H, s), 2.39 (3H, s), 3.29 (3H, s), 3.91-3.9
6 (2H, m), 4.31-4.34 (2H, m), 7.23 (2H, d, J = 8.5Hz),
7.49 (2H, d, J = 8.5Hz), 7.72 (1H, d, J = 8.5Hz), 7.95
(1H, d, d, J = 2.5, 8.5Hz), 8.51 (1H, d, J = 2.5Hz).

Reference Example 352-[[[1- (4-phenylsulfonylphenyl) e
Tylidene] amino] oxy] ethanol (A)4 '-(phenylsulfonyl) acetophenone
Oxime O-2-[(tetrahydropyran-2-i
Ru) oxy] ethyl ether 2. 2- (2-bromoethoxy) tetrahydropyran
46 g, 4 '-(phenylsulfonyl) acetophenone
 2.35 g of oxime and 5.90 g of potassium carbonate
And the reaction according to Example 1 (a) (however, the reaction time
7 hours) and after-treatment, syrup-like target
2.55 g of the compound were obtained.

(B) 2-[[[1- (4-phenylsulfur)
Honylphenyl) ethylidene] amino] oxy] ethano
Obtained in Lumpur Reference Example 35 (a) 4 '- (phenylsulfonyl) acetophenone oxime O-2 - [(tetrahydropyran-2-yl) oxy] ethyl ether 2.55
g and p-toluenesulfonic acid monohydrate 0.20
When the reaction and post-treatment are carried out according to Reference Example 1 (b) using g, the desired compound having a melting point of 87-88 ° C.
72 g were obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.20 (1H, t, J = 6Hz), 2.25 (3H, s), 3.90-3.95 (2H,
m), 4.31-4.35 (2H, m), 7.47-7.60 (3H, m), 7.75 (2H,
d, J = 8.5Hz), 7.92-7.98 (4H, m).

Reference Example 36 2-[[[1- (4-phenylthiophenyl) ethylide
[Amino] oxy] ethanol (a) 4 '-(phenylthio) acetophenone oxy
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Using 2.10 g of 51 g, 4 ′-(phenylthio) acetophenone oxime and 5.96 g of potassium carbonate, the reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
After 6 hours) and post-treatment, 3.20 g of a syrupy target compound was obtained.

(B) 2-[[[1- (4-phenylthio)
Phenyl) ethylidene] amino] oxy] ethanol 3.20 g of 4 ′-(phenylthio) acetophenone oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 36 (a) and p- When 0.17 g of toluenesulfonic acid monohydrate was used for the reaction and post-treatment according to Reference Example 1 (b), 1.69 g of the target compound having a melting point of 56 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.24 (3H, s), 3.91-3.96 (2H, m), 4.29-4.32 (2H, m),
7.26-7.41 (7H, m), 7.54 (2H, d, J = 8.5Hz).

Reference Example 37 2-[[[1- [4- [N- (phenylsulfonyl)-]
N-methylamino] phenyl] ethylidene] amino] o
[Xy] ethanol (a) 4 '-[(N-phenylsulfonyl) -N-methyl
Ruamino] acetophenone oxime O-2-[(T
1. Trahydropyran-2-yl) oxy] ethyl ether 2- (2-bromoethoxy) tetrahydropyran
Reference Example 1 (a) using 78 g, 4 ′-[(N-phenylsulfonyl) -N-methylamino] acetophenone oxime 1.62 g and potassium carbonate 2.20 g
When the reaction (reaction time was 16 hours) and post-treatment were carried out according to the above, 2.15 g of the target compound in the form of a syrup was obtained.

(B) 2-[[[1- [4- [N- (Fe
Nylsulfonyl) -N-methylamino] phenyl] ethy
Isopropylidene] amino] oxy] ethanol Reference Example 37 4 obtained in (a) '- [(N- phenylsulfonyl) -N- methylamino] acetophenone oxime O-2 - [(tetrahydropyran-2-yl) oxy] Reference Example 1 was prepared using 2.15 g of ethyl ether and 0.30 g of p-toluenesulfonic acid monohydrate.
When the reaction and post-treatment are carried out according to (b), the melting point is 76.
1.50 g of the target compound having a temperature of -77 DEG C. are obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.26 (3H, s), 3.18 (3H, s), 3.91-3.97 (2H, m), 4.3
0-4.34 (2H, m), 7.11 (2H, d, J = 8.5Hz), 7.46 (2H, t, J
= 8Hz), 7.55-7.59 (5H, m).

Reference Example 38 2-[[[1- (4-Biphenylyl) propylidene] a
Mino] oxy] ethanol (a) 4-propionylbiphenyl oxime O-2
-[(Tetrahydropyran-2-yl) oxy] ethyl
2. ether 2- (2-bromoethoxy) tetrahydropyran
25 g, 4-propionylbiphenyl oxime
When 40 g and 2.57 g of potassium carbonate are used for the reaction (the reaction time is 24 hours) and post-treatment according to Reference Example 1 (a), the syrupy target compound 2.2
0 g was obtained.

(B)2-[[[1- (4-biphenyli
Le) propylidene] amino] oxy] ethanol 4-propionylbiphenyl obtained in Reference Example 38 (a)
Oxime O-2-[(tetrahydropyran-2-
2.20 g of yl) oxy] ethyl ether and p-
Using 0.15 g of toluenesulfonic acid monohydrate,
When the reaction and the post-treatment are carried out according to Example 1 (b), the melting point
0.77 g of the target compound having a temperature of 76 ° C. was obtained.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 1.19 (3H, t, J = 7.5Hz), 2.59 (1H, t, J = 6Hz), 2.82 (2
H, q, J = 7.5Hz), 3.93-3.98 (2H, m), 4.31-4.34 (2H,
m), 7.36 (1H, t, J = 7Hz), 7.45 (2H, t, J = 7Hz), 7.61
(4H, d, J = 8Hz), 7.70 (2H, d, J = 8.5Hz).

Reference Example 392-[[[1- (5-phenyl-2-pyridyl) ethyl
Den] amino] oxy] ethanol (A)2-acetyl-5-phenylpyridine oxime
O-2-[(tetrahydropyran-2-yl) oxy
[S] ethyl ether 2. 2- (2-bromoethoxy) tetrahydropyran
29 g, 2-acetyl-5-phenylpyridineoxy
1.74 g and potassium carbonate 2.27 g
The reaction was carried out according to Reference Example 1 (a) (however, the reaction time was 1
6 hours) and after-treatment, syrup-like target compound
2.21 g of the product were obtained.

(B) 2-[[[1- (5-Phenyl-2)
-Pyridyl) ethylidene] amino] oxy] ethanol 2.21 g of 2-acetyl-5-phenylpyridine oxime O-2-[(tetrahydropyran-2-yl) oxy] ethyl ether obtained in Reference Example 39 (a) and When 1.23 g of p-toluenesulfonic acid monohydrate is used and subjected to the reaction and the post-treatment according to Reference Example 1 (b), 1.41 g of the target compound having a melting point of 66 to 68 ° C is obtained.
was gotten.

1) ¹ H-nuclear magnetic resonance spectrum: δ p
pm: ¹ H-nuclear magnetic resonance spectrum (270 MHz) measured in deuterated chloroform using TMS (tetramethylsilane) as an internal standard is as follows. 2.41 (3H, s), 2.46 (1H, t, J = 6Hz), 3.95-4.00 (2H,
m), 4.37-4.40 (2H, m), 7.39-7.52 (3H, m), 7.61 (2H,
d, d, J = 1.5, 8.5Hz), 7.85-7.92 (2H, m), 8.84 (1H, d,
J = 2Hz).

[0537]

Test Examples The oxime derivative having the above general formula (I) or a salt thereof according to the present invention has a strong hypoglycemic effect as shown below, and exhibits a preventive and / or therapeutic effect on hyperglycemia. Furthermore, hyperlipidemia, obesity, impaired glucose tolerance, insulin-resistant non-glucose intolerance, insulin resistance, cachexia, psoriasis, diabetic complications (eg, retinopathy, nephropathy, neuropathy, cataract, coronary artery disease) Etc.), arteriosclerosis, also hypertension, osteoporosis, polycystic ovary syndrome, fatty liver and
It is useful as a prophylactic and / or therapeutic drug for gestational diabetes mellitus and the like.

Hypoglycemic action Male KK mice weighing 40 g or more and showing a hyperglycemic state
1 mg / kg of each compound was added to polyethylene glycol 40
0: 0.5% W / V carboxymethylcellulose physiological saline was mixed with a 1: 1 solvent and orally administered, and left for 18 hours under satiety conditions. Next, blood was collected from the tail vein under anesthesia, and the blood glucose level was measured with a glucose analyzer (GL-101 (trade name), manufactured by Mitsubishi Chemical Corporation).

[0539] The blood glucose lowering rate was determined by the following equation. Hypoglycemic rate (%) = [(solvent-administered group blood glucose level−compound-administered group blood glucose level) / solvent-administered group blood glucose level] × 100 Table 27 shows the results of preferred compounds among the obtained results.

[0540]

[Table 27] ──────────────────────────────────── Test compound Hypoglycemic rate (%) ──化合物 Compound 22.1 of Example 2 Compound 20.8 of Example 5 Compound of Example 8 25.1 Compound of Example 9 27.0 Compound of Example 14 19.3 Compound of Example 15 26.7 Compound of Example 18 23.5 Compound of Example 19 28.7 Example Compound of 21 16.6 Compound of Example 23 16.5 Compound of Example 26 27.0 Compound of Example 31 * 49.3 Compound of Example 32 42.2 Compound of Example 33 19.2 Example 35 Compound 25.0 Compound of Example 36 43.2 Compound of Example 37 15.5 Compound 2 of Example 38 7.7 Compound of Example 40 27.0 Compound of Example 47 18.7 Compound of Example 48 17.9 Compound of Example 50 38.1 Compound of Example 51 * 26.4 Compound of Example 55 34. 1 ──────────────────────────────────.

* Shows the blood glucose lowering rate 3 hours after administration of the test compound. Table 27 shows that the compounds of the present invention exhibited excellent hypoglycemic effects.

[0542]

[Formulation Examples] (1) Capsule Compound of Example 21 (b) 10 mg Lactose 110 mg Corn starch 58 mg Magnesium stearate 2 mg 180 mg The powder of each of the above-mentioned components was mixed well, and a 60 mesh mesh was prepared. Pass through a sieve (mesh standard is based on Tyler standard). 180 mg of the obtained powder is weighed and filled into a gelatin capsule (No. 3) to prepare a capsule.

(2) Tablet Compound of Example 15 10 mg Lactose 85 mg Corn starch 34 mg Microcrystalline cellulose 20 mg Magnesium stearate 1 mg 150 mg The powder of each of the above-mentioned components was mixed well and mixed with each other.
Compress to tablets of mg weight. If necessary, these tablets may be coated with sugar or a film.

(3) Granules Compound of Example 35 10 mg Lactose 839 mg Corn starch 150 mg Hydroxypropylcellulose 1 mg 1000 mg The powder of each component shown above was mixed well, wetted with pure water, and basket Granulate with a granulator and dry to obtain granules.

[0545]

EFFECT OF THE INVENTION The oxime derivative having the above general formula (I) or a salt thereof according to the present invention can be used for hyperlipidemia, hyperglycemia, obesity, glucose intolerance, insulin resistance, non-glucose tolerance, insulin resistance. , Cachexia, psoriasis, diabetic complications (eg retinopathy, nephropathy, neuropathy, cataract, coronary artery disease, etc.), arteriosclerosis, further hypertension, osteoporosis, polycystic ovary syndrome, fatty liver, gestational diabetes, etc. It is useful as a prophylactic and / or therapeutic agent for.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/44 ABX A61K 31/44 ABX ACN ACN C07D 263/44 C07D 263/44 271/06 271/06 277/34 277/34 413/12 213 413/12 213 (72) Inventor Takao Yoshioka 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Kunio Wada 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Minoru Oguchi 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Toshihiko Fujiwara 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Daigo Kogoshi 1-258 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (56) References JP-A-5-213913 (JP, A) JP-A-3-170478 (JP, A) Special table Hei 5-508054 JP, A) (58) investigated the field (Int.Cl. ^6, DB name) C07D 417/12 A61K 31/42 A61K 31/425 A61K 31/44 C07D 263/44 C07D 271/06 C07D 277/34 C07D 413 / 12 CA (STN) REGISTRY (STN)

Claims (34)

(57) [Claims] 1. A compound of the general formula [In the formula, R ¹ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. R ² represents a linear or branched alkylene group having 2 to 6 carbon atoms. R ³ is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms,
Linear or branched alkoxy group having 1 to 4 carbon atoms, linear or branched alkylthio group having 1 to 4 carbon atoms, halogen atom, nitro group, amino group, 1 to 4 carbon atoms A straight-chain or branched-chain monoalkylamino group having 4 carbon atoms, a straight-chain or branched-chain dialkylamino group having the same or different alkyl groups each having 1 to 4 carbon atoms, An aryl group having 10 or an aralkyl group having 7 to 12 carbon atoms is shown. X represents an aryl group having 6 to 10 carbon atoms which may have 1 to 3 substituents or a heteroaromatic group which may have 1 to 3 substituents. Examples of the substituent include: 1) a linear or branched alkyl group having 1 to 6 carbon atoms; 2) a linear or branched halogen group having 1 to 4 carbon atoms. Alkyl group, 3) hydroxy group, 4) linear or branched acyloxy group having 1 to 4 carbon atoms, 5) 1 to 4 carbon atoms
Linear or branched alkoxy groups having
6) a linear or branched alkylenedioxy group having 1 to 4 carbon atoms; 7) a 7 to 12 carbon atoms.
8) a linear or branched alkylthio group having 1 to 4 carbon atoms, 9) a linear or branched alkylsulfonyl having 1 to 4 carbon atoms Group) 10) halogen atom, 11) nitro group, 12) amino group, 13) linear or branched monoalkylamino group having 1 to 4 carbon atoms, 14) same or different alkyl groups A linear or branched dialkylamino group having 1 to 4 carbon atoms, 15) an aralkyl group having 7 to 12 carbon atoms, 16) an aryl group having 6 to 10 carbon atoms (the aryl group) Is a linear or branched alkyl having 1 to 6 carbons,
Straight or branched alkyl halide having 1 to 4 carbon atoms, straight or branched alkoxy having 1 to 4 carbon atoms, halogen or having 1 to 4 carbon atoms Linear or branched alkylenedioxy, which may be substituted) 17) aryloxy group having 6 to 10 carbon atoms (the aryl group is a straight-chain having 1 to 6 carbon atoms) Or a branched-chain alkyl, a straight-chain or branched-chain alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched-chain alkoxy having 1 to 4 carbon atoms,
Halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms, which may be substituted); 18) an arylthio group having 6 to 10 carbon atoms (the aryl group may have Linear or branched alkyl having 1 to 6 carbon atoms, 1 to 4 carbon atoms
Linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkyl having 1 to 4 carbon atoms. It may be substituted by a branched alkylenedioxy), 19) C6-C10.
Arylsulfonyl group having 1 to 6 carbon atoms (linear or branched alkyl having 1 to 6 carbons, linear or branched alkyl having 1 to 4 carbons) May be substituted by a straight-chain or branched alkoxy having 1 to 4 carbon atoms, halogen, or a straight-chain or branched alkylenedioxy having 1 to 4 carbon atoms) , 2
0) an arylsulfonylamino group having 6 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbon atoms, and 1 to 4 carbon atoms)
Linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkoxy having 1 to 4 carbon atoms, halogen or linear or branched alkyl having 1 to 4 carbon atoms. It may be substituted with a branched alkylenedioxy. The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), 21) heteroaromatic group, 22) heteroaromatic oxy group, 23) heteroaromatic ring A thio group, 24) a heteroaromatic sulfonyl group, and 25) a heteroaromatic sulfonylamino group (the nitrogen atom may be substituted by a linear or branched alkyl having 1 to 6 carbon atoms) Is shown. Y is an oxygen atom, a sulfur atom or a group>
NR ⁴ is shown. (Wherein R ⁴ represents a hydrogen atom, 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) Z) is a group. Is shown. Or a salt thereof. 2. The oxime derivative according to claim 1, wherein R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms, or a salt thereof. 3. The oxime derivative according to claim 1, wherein R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 3 carbon atoms, or a salt thereof. 4. The method according to claim 1, wherein R ¹ is a hydrogen atom,
An oxime derivative or a salt thereof, which is a methyl group or an ethyl group. 5. The oxime derivative according to claim 1, wherein R ¹ is a methyl group or an ethyl group, or a salt thereof. 6. The oxime derivative according to claim 1, wherein R ² is a linear or branched alkylene group having 2 to 5 carbon atoms, or a salt thereof. 7. The oxime derivative according to claim 1, wherein R ² is a linear or branched alkylene group having 2 to 3 carbon atoms, or a salt thereof. 8. An oxime derivative or a salt thereof according to claim 1, wherein R ² is an ethylene group, a trimethylene group or a methylethylene group. 9. The oxime derivative or a salt thereof according to claim 1, wherein R ² is an ethylene group. 10. The method according to claim 1, wherein R ³ is a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 2 carbon atoms, An oxime derivative which is an alkylthio group or a halogen atom having 1 or 2 or a salt thereof. 11. The oxime derivative or a salt thereof according to claim 1, wherein R ³ is a hydrogen atom. 12. The method according to claim 1, wherein X is 1 to 3
Aryl groups having 6 to 10 carbon atoms which may have 1 to 3 substituents, or 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms which may have 1 to 3 substituents A 5- to 10-membered (single or bicyclic) heteroaromatic ring group having three groups is represented by the following substituents: 1) a linear or branched group having 1 to 6 carbon atoms. Branched alkyl, 2) linear or branched alkyl halide having 1 to 4 carbons, 3) hydroxy, 4) linear or branched having 1 to 4 carbons Acyloxy,
5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) linear or branched alkylenedioxy having 1 to 4 carbon atoms; 7) 7 to 7 carbon atoms. Aralkyloxy having 12; 8)
Linear or branched alkylthio having 1 to 4 carbons, 9) linear or branched alkylsulfonyl having 1 to 4 carbons, 10) halogen atom, 11) carbon number Aralkyl having 7 to 12 carbon atoms, 12) phenyl (the phenyl is a linear or branched alkyl having 1 to 6 carbon atoms,
Straight or branched alkyl halide having 1 to 4 carbon atoms, straight or branched alkoxy having 1 to 4 carbon atoms, halogen or having 1 to 4 carbon atoms 13) phenoxy (the phenyl is a linear or branched alkyl having 1 to 6 carbons, 1 carbon atom) Straight-chain or branched alkyl halide having 1 to 4 carbon atoms, straight-chain or branched alkoxy having 1 to 4 carbon atoms, halogen or straight-chain having 1 to 4 carbon atoms 14) phenylthio (the phenyl is a linear or branched alkyl having 1 to 6 carbon atoms, Number 1 A straight-chain or branched alkyl halide having four, straight-chain or branched alkoxy having 1 to 4 carbon atoms,
Halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms, which may be substituted; 15) phenylsulfonyl (the phenyl is a straight-chain having 1 to 6 carbon atoms) Or a branched alkyl, a straight or branched alkyl halide having 1 to 4 carbons, a straight or branched alkoxy having 1 to 4 carbons, halogen, or Which may be substituted by linear or branched alkylenedioxy having 1 to 4 carbon atoms), 1
6) phenylsulfonylamino (the phenyl has 1 carbon atom)
Linear or branched alkyl having 1 to 4 carbon atoms, linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkyl having 1 to 4 carbon atoms, It may be substituted by a branched alkoxy, a halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms. The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), 17) furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridyl Sulfonyl, 18) imidazolyl (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), and / or
19) pyridylsulfonylamino (the nitrogen atom has 1 carbon atom)
Or an oxime derivative which may be substituted with a straight-chain or branched-chain alkyl having from 6 to 6) or a salt thereof. 13. The method according to claim 1, wherein X is 1 to 3
Aryl groups having 6 to 10 carbon atoms which may have 1 to 3 substituents, or 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms which may have 1 to 3 substituents A 5- to 10-membered (single or bicyclic) heteroaromatic ring group having three groups is represented by the following substituents: 1) a linear or branched group having 1 to 6 carbon atoms. Branched alkyl, 2) linear or branched alkyl halide having 1 to 4 carbons, 3) hydroxy, 4) linear or branched having 1 to 4 carbons Alkanoyloxy, 5) linear or branched alkoxy having 1 to 4 carbons, 6) linear or branched alkylenedioxy having 1 to 4 carbons,
7) aralkyloxy having 7 to 12 carbon atoms;
8) linear or branched alkylthio having 1 to 4 carbons; 9) linear or branched alkylsulfonyl having 1 to 4 carbons;
0) a fluorine atom, a chlorine atom, a bromine atom, 11) an aralkyl having 7 to 12 carbon atoms, 12) phenyl (the phenyl is a linear or branched alkyl having 1 to 6 carbon atoms, carbon A straight-chain or branched alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched alkoxy having 1 to 4 carbon atoms, a halogen or a straight-chain or branched alkoxy having 1 to 4 carbon atoms; 13) phenoxy (the phenyl is a straight-chain or branched alkyl having 1 to 6 carbons, 1 to 6 carbons) Straight or branched alkyl halide having 4 carbon atoms, straight or branched alkoxy having 1 to 4 carbon atoms, halogen or 1 to 4 carbon atoms May be substituted by straight-chain or branched alkylenedioxy having), 1
4) phenylthio (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, 1 carbon Linear or branched alkoxy having 4 to 4 carbon atoms, halogen or linear or branched alkylenedioxy having 1 to 4 carbon atoms), 15) phenyl Sulfonyl (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons,
Straight-chain or branched alkoxy having 1 to 4 carbon atoms, which may be substituted by halogen or straight-chain or branched alkylenedioxy having 1 to 4 carbon atoms), 16) phenylsulfonylamino (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, carbon It may be substituted by a linear or branched alkoxy having 1 to 4 carbon atoms, halogen, or a linear or branched alkylenedioxy having 1 to 4 carbon atoms. May be substituted with linear or branched alkyl having 1 to 6 carbons), 17) furyl, thienyl, oxazolyl, isoxazolyl, thia Zolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (the nitrogen atom may be substituted by straight-chain or branched-chain alkyl having 1 to 6 carbon atoms), and / or 19 ) An oxime derivative optionally having pyridylsulfonylamino (the nitrogen atom may be substituted by a linear or branched alkyl having 1 to 6 carbon atoms) or a salt thereof. 14. The method according to claim 1, wherein X is 1 to 3
A phenyl group, a naphthyl group, an imidazolyl group, an oxazolyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group which may have one or more substituents. Linear or branched alkyl having 1 to 6 carbon atoms; 2) linear or branched alkyl halide having 1 to 4 carbon atoms; 3) hydroxy; 4) 1 to 4 carbon atoms. Linear or branched alkanoyloxy having 1 to 4 carbon atoms; 5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) methylenedioxy; 7) 7 to 12 carbon atoms. 8) linear or branched alkylthio having 1 to 4 carbon atoms; 9) linear or branched alkylthio having 1 to 4 carbon atoms. Alkylsulfonyl, 10) fluorine atom, chlorine atom, bromine atom, 1
1) aralkyl having 7 to 12 carbon atoms, 1
2) phenyl, which may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy; 13) phenoxy, wherein phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy. May be substituted), 1
4) phenylthio (the phenyl may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy), 15) phenylsulfonyl (the phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy) 16) phenylsulfonylamino (the phenyl may be substituted by methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy. The nitrogen atom has 1 to 6 carbon atoms.) Linear or branched alkyl), 17)
Furyl, thienyl, oxazolyl, isoxazolyl,
Thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), and / or 19 ) An oxime derivative optionally having pyridylsulfonylamino (the nitrogen atom may be substituted by a linear or branched alkyl having 1 to 6 carbon atoms) or a salt thereof. 15. The method according to claim 1, wherein X is 1 to 3
A phenyl group, a naphthyl group, an imidazolyl group, an oxazolyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group which may have one or more substituents. Linear or branched alkyl having 1 to 6 carbon atoms; 2) linear or branched alkyl halide having 1 to 4 carbon atoms; 3) hydroxy; 4) 1 to 4 carbon atoms. Linear or branched alkanoyloxy having 1 to 4 carbon atoms, 5) linear or branched alkoxy having 1 to 4 carbon atoms, 6) methylenedioxy, benzyloxy, phenethyloxy, naphthylmethoxy 7) linear or branched alkylthio having 1 to 4 carbons; 8) linear or branched alkylthio having 1 to 4 carbons; Alkylsulfonyl, 9) fluorine atom, chlorine atom, bromine atom, 10)
Benzyl, 11) phenyl (the phenyl may be substituted by methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy), 12) phenoxy (the phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy) Phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonyl Amino, N-methylpyridylsulfonylamino,
And / or 14) an oxime derivative optionally having imidazolyl (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms) or a salt thereof. 16. The method according to claim 1, wherein X is 1 to 3
A phenyl group, a naphthyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group, which may have 1 or 3 substituents, wherein the group is 1) a straight-chain having 1 to 3 carbon atoms. Chain or branched alkyl, 2) trifluoromethyl, difluoromethyl,
Fluoromethyl, hydroxy, formyloxy, acetoxy, 3) linear or branched alkoxy having 1 to 3 carbon atoms, 4) methylenedioxy,
Benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, 5) fluorine, chlorine, bromine, 6) benzyl, phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-fluoro Phenyl, 3,4-methylenedioxyphenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, furyl, thienyl, oxazolyl, thiazolyl, imidazolyl, N-methylimidazolyl, pyridyl, pyridyloxy, pyridylthio ,
An oxime derivative optionally having pyridylsulfonyl, pyridylsulfonylamino and / or N-methylpyridylsulfonylamino, or a salt thereof. 17. The method according to claim 1, wherein X is 1 to 3
A phenyl group, a naphthyl group, a pyridyl group, a quinolyl group or an isoquinolyl group which may have one or more substituents, wherein the group is, as a substituent, methyl, ethyl, isopropyl, trifluoromethyl, hydroxy, acetoxy,
Methoxy, ethoxy, isopropoxy, methylenedioxy, benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, chlorine atom, benzyl,
Oxime optionally having phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino and / or N-methylpyridylsulfonylamino Derivatives or salts thereof. 18. The method according to claim 1, wherein X is 1 to 3
Phenyl group which may have a number of substituents, the group being, as a substituent, methyl, hydroxy, acetoxy,
Chlorine atom, benzyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, pyridyl,
An oxime derivative optionally having pyridyloxy, pyridylthio and / or pyridylsulfonyl, or a salt thereof. 19. The method according to claim 1, wherein X is 1 to 3
Pyridyl group optionally having a substituent, the group being, as a substituent, methoxy, ethoxy, isopropoxy, benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, benzyl, phenyl,
An oxime derivative optionally having phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino and / or N-methylphenylsulfonylamino, or a salt thereof. 20. The method according to claim 1, wherein Y is an oxygen atom,
Sulfur atom or group> NR ⁴ (R ⁴ is a hydrogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms or a linear or branched alkyl group having 2 to 5 carbon atoms An oxime derivative or a salt thereof). 21. The oxime derivative or a salt thereof according to claim 1, wherein Y is an oxygen atom. 22. The method according to claim 1, wherein Z is a 2,4-dioxothiazolidine-5-ylmethyl group, a 2,4-dioxooxazolidin-5-ylmethyl group or 3,5-
An oxime derivative which is a dioxooxadiazolidine-2-ylmethyl group or a salt thereof. 23. The method according to claim 1, wherein Z is 2,4-dioxothiazolidin-5-ylmethyl or 2,4-dioxothiazolidine-5-ylmethyl.
An oxime derivative which is a dioxooxazolidin-5-ylmethyl group or a salt thereof. 24. The oxime derivative according to claim 1, wherein Z is a 2,4-dioxothiazolidin-5-ylmethyl group, or a salt thereof. 25. The method of claim 1, wherein R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms; R ² is a group having 2 to 5 carbon atoms. R ³ is a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched alkylene group having 1 to 4 carbon atoms,
X is an alkoxy group having 1 to 2 carbon atoms, an alkylthio group having 1 to 2 carbon atoms, or a halogen atom;
An aryl group having 6 to 10 carbon atoms which may have 1 to 3 substituents, or a nitrogen atom, an oxygen atom and / or a sulfur atom which may have 1 to 3 substituents. A 5- to 10-membered heteroaromatic group (consisting of one or two rings) having 1 to 3 carbon atoms, and these groups are represented by: 1) a straight-chain having 1 to 6 carbon atoms; Or 2) linear or branched alkyl halide having 1 to 4 carbon atoms; 3) hydroxy; 4) 1 carbon atom.
Linear or branched acyloxy having from 4 to 4 carbon atoms; 5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) linear alkyl having 1 to 4 carbon atoms. Or a branched alkylenedioxy,
7) aralkyloxy having 7 to 12 carbon atoms; 8) linear or branched alkylthio having 1 to 4 carbon atoms; 9) linear or branched alkylthio having 1 to 4 carbon atoms. Chain alkylsulfonyl,
10) a halogen atom, 11) aralkyl having 7 to 12 carbon atoms, 12) phenyl (the phenyl is a linear or branched alkyl having 1 to 6 carbon atoms, and 1 to 4 carbon atoms. Linear or branched alkyl halides having 1 to 4 carbon atoms, straight or branched alkoxy, halogen or linear or branched chains having 1 to 4 carbon atoms May be substituted with alkylenedioxy))
13) Phenoxy (the phenyl is a linear or branched alkyl having 1 to 6 carbons, 1 carbon
Straight-chain or branched alkyl halide having 1 to 4 carbon atoms, straight-chain or branched alkoxy having 1 to 4 carbon atoms, halogen or straight-chain having 1 to 4 carbon atoms Or 14) phenylthio (the phenyl is a linear or branched alkyl having 1 to 6 carbons, 1 to 4 carbons) A straight-chain or branched alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched alkoxy having 1 to 4 carbon atoms, a halogen or a straight-chain or branched alkyl having 1 to 4 carbon atoms 15) phenylsulfonyl (the phenyl is a linear or branched alkyl having 1 to 6 carbons, carbon) A straight-chain or branched alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched alkoxy having 1 to 4 carbon atoms, a halogen or a straight-chain or branched alkoxy having 1 to 4 carbon atoms; 16) phenylsulfonylamino (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a carbon number of 1 to 6) Straight-chain or branched alkyl halide having 1 to 4 carbon atoms, straight-chain or branched alkoxy having 1 to 4 carbon atoms, halogen or straight-chain having 1 to 4 carbon atoms May be substituted with a branched or branched alkylenedioxy.
The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbons), 1
7) furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (where the nitrogen atom is substituted by a linear or branched alkyl having 1 to 6 carbon atoms) And / or
Or 19) may have pyridylsulfonylamino (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms); Y is an oxygen atom, sulfur Atom or group> NR ⁴ (R ⁴
Represents a hydrogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms or a linear or branched alkanoyl group having 2 to 5 carbon atoms)
Z is 2,4-dioxothiazolidine-5-ylmethyl group, 2,4-dioxooxazolidine-5-ylmethyl group or 3,5-dioxooxadiazolidine-
2-ylmethyl group; an oxime derivative or a salt thereof. 26. The method according to claim 1, wherein R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms; R ² is a group having 2 to 5 carbon atoms. R ³ is a hydrogen atom; X is 1 to 3
Aryl groups having 6 to 10 carbon atoms which may have 1 to 3 substituents, or 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms which may have 1 to 3 substituents A 5- to 10-membered (single or bicyclic) heteroaromatic ring group having three groups is represented by the following substituents: 1) a linear or branched group having 1 to 6 carbon atoms. Branched alkyl, 2) linear or branched alkyl halide having 1 to 4 carbons, 3) hydroxy, 4) linear or branched having 1 to 4 carbons Alkanoyloxy, 5) linear or branched alkoxy having 1 to 4 carbons, 6) linear or branched alkylenedioxy having 1 to 4 carbons,
7) aralkyloxy having 7 to 12 carbon atoms;
8) linear or branched alkylthio having 1 to 4 carbons; 9) linear or branched alkylsulfonyl having 1 to 4 carbons;
0) a fluorine atom, a chlorine atom, a bromine atom, 11) an aralkyl having 7 to 12 carbon atoms, 12) phenyl (the phenyl is a linear or branched alkyl having 1 to 6 carbon atoms, carbon A straight-chain or branched alkyl halide having 1 to 4 carbon atoms, a straight-chain or branched alkoxy having 1 to 4 carbon atoms, a halogen or a straight-chain or branched alkoxy having 1 to 4 carbon atoms; 13) phenoxy (the phenyl is a linear or branched alkyl having 1 to 6 carbons, 1 to 6 carbons) Straight or branched alkyl halide having 4 carbon atoms, straight or branched alkoxy having 1 to 4 carbon atoms, halogen or 1 to 4 carbon atoms May be substituted by straight-chain or branched alkylenedioxy having), 1
4) phenylthio (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, 1 carbon Linear or branched alkoxy having 4 to 4 carbon atoms, halogen or linear or branched alkylenedioxy having 1 to 4 carbon atoms), 15) phenyl Sulfonyl (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, 1 to 4 carbons Linear or branched alkoxy having 1 to 4 carbon atoms, which may be substituted by a halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms) 16) phenylsulfonylamino (the phenyl is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl halide having 1 to 4 carbons, carbon It may be substituted by a linear or branched alkoxy having 1 to 4 carbon atoms, halogen, or a linear or branched alkylenedioxy having 1 to 4 carbon atoms. May be substituted by linear or branched alkyl having 1 to 6 carbons), 17) furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (where the nitrogen atom is substituted by straight-chain or branched alkyl having 1 to 6 carbon atoms) And / or 19) pyridylsulfonylamino (the nitrogen atom may be substituted by a linear or branched alkyl having 1 to 6 carbons) Y is an oxygen atom; Z is a 2,4-dioxothiazolidin-5-ylmethyl group or 2,4-
A dioxooxazolidine-5-ylmethyl group; an oxime derivative or a salt thereof. 27. The method of claim 1, wherein R ¹ is a hydrogen atom or a linear or branched alkyl group having 1 to 3 carbon atoms; R ² is a group having 2 to 3 carbon atoms. R ³ is a hydrogen atom; X is 1 to 3
A phenyl group, a naphthyl group, an imidazolyl group, an oxazolyl group, a pyridyl group, an indolyl group, a quinolyl group or an isoquinolyl group which may have one or more substituents. Linear or branched alkyl having 1 to 6 carbon atoms; 2) linear or branched alkyl halide having 1 to 4 carbon atoms; 3) hydroxy; 4) 1 to 4 carbon atoms. Linear or branched alkanoyloxy having 1 to 4 carbon atoms; 5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) methylenedioxy; 7) 7 to 12 carbon atoms. 8) linear or branched alkylthio having 1 to 4 carbon atoms; 9) linear or branched alkylthio having 1 to 4 carbon atoms. Alkylsulfonyl, 10) fluorine atom, chlorine atom, bromine atom, 1
1) aralkyl having 7 to 12 carbon atoms, 1
2) phenyl, which may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy; 13) phenoxy, wherein phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy. May be substituted), 1
4) phenylthio (the phenyl may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy), 15) phenylsulfonyl (the phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy) 16) phenylsulfonylamino (the phenyl may be substituted by methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy. The nitrogen atom has 1 to 6 carbon atoms.) Linear or branched alkyl), 17)
Furyl, thienyl, oxazolyl, isoxazolyl,
Thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, 18) imidazolyl (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbon atoms), and / or 19 ) Pyridylsulfonylamino (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbons);
Y is an oxygen atom; Z is a 2,4-dioxothiazolidin-5-ylmethyl group; an oxime derivative or a salt thereof. 28. A [Claim 1], R ¹ is a hydrogen atom, a methyl group or an ethyl group; R ²
Is an ethylene group, a trimethylene group or a methylethylene group; R ³ is a hydrogen atom; and X is a phenyl group, naphthyl group, imidazolyl group, oxazolyl group, or pyridyl which may have 1 to 3 substituents. A group, an indolyl group, a quinolyl group or an isoquinolyl group, which is substituted as follows: 1) linear or branched alkyl having 1 to 6 carbons, 2) 1 to 4 carbons 3) hydroxy, 4) straight or branched alkanoyloxy having 1 to 4 carbon atoms,
5) linear or branched alkoxy having 1 to 4 carbon atoms; 6) methylenedioxy, benzyloxy, phenethyloxy, naphthylmethoxy; 7)
Linear or branched alkylthio having 1 to 4 carbon atoms, 8) linear or branched alkylsulfonyl having 1 to 4 carbon atoms, 9) fluorine atom, chlorine atom, bromine Atom, 10) benzyl, 1
1) phenyl, wherein the phenyl may be substituted with methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy; 12) phenoxy, wherein the phenyl is methyl, trifluoromethyl, methoxy, fluoro or methylenedioxy. May be substituted), 1
3) phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino,
Furyl, thienyl, oxazolyl, isoxazolyl,
Thiazolyl, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino,
N-methylpyridylsulfonylamino, and / or 14) imidazolyl (the nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbons) Y is an oxygen atom; Z is a 2,4-dioxothiazolidin-5-ylmethyl group; an oxime derivative or a salt thereof. 29. The [claim 1], R ¹ is a hydrogen atom, a methyl group or an ethyl group; R ²
Is an ethylene group, a trimethylene group or a methylethylene group; R ³ is a hydrogen atom; and X is a phenyl group, naphthyl group, pyridyl group, indolyl group, quinolyl which may have 1 to 3 substituents. A group or an isoquinolyl group, wherein the group is substituted with: 1) a linear or branched alkyl having 1 to 3 carbon atoms,
2) trifluoromethyl, difluoromethyl, fluoromethyl, hydroxy, formyloxy, acetoxy,
3) linear or branched alkoxy having 1 to 3 carbon atoms, 4) methylenedioxy, benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, 5) fluorine, chlorine, bromine 6) benzyl, phenyl, 4-methylphenyl,
4-trifluoromethylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 3,4-methylenedioxyphenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, furyl, thienyl, oxazolyl,
Thiazolyl, imidazolyl, N-methylimidazolyl,
Pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino and / or N
-Methylpyridylsulfonylamino; Y is an oxygen atom; Z is a 2,4-dioxothiazolidine-5-ylmethyl group; an oxime derivative or a salt thereof. 30. A [Claim 1], R ¹ is a hydrogen atom, a methyl group or an ethyl group; R ²
Is an ethylene group; R ³ is a hydrogen atom; X is a phenyl group, naphthyl group, pyridyl group, quinolyl group or isoquinolyl group optionally having 1 to 3 substituents, Is methyl, ethyl, isopropyl, trifluoromethyl, hydroxy, acetoxy, methoxy, ethoxy, isopropoxy, methylenedioxy, benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, chlorine atom, benzyl, phenyl, Having phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino, N-methylphenylsulfonylamino, pyridyl, pyridyloxy, pyridylthio, pyridylsulfonyl, pyridylsulfonylamino and / or N-methylpyridylsulfonylamino Well; Y is oxygen atom; Z is a 2,4-dioxo-thiazolidin-5-ylmethyl group; oxime derivative or a salt thereof. 31. The method according to claim 1, wherein R ¹ is a methyl group or an ethyl group; R ² is an ethylene group; R ³ is a hydrogen atom; and X has 1 to 3 substituents. A phenyl group which may be substituted as methyl, hydroxy, acetoxy, chlorine atom, benzyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino,
May have N-methylphenylsulfonylamino, pyridyl, pyridyloxy, pyridylthio and / or pyridylsulfonyl; Y is an oxygen atom; Z is a 2,4-dioxothiazolidine-5-ylmethyl group; Oxime derivatives or salts thereof. 32. The method of claim 1, wherein R ¹ is a methyl group or an ethyl group; R ² is an ethylene group; R ³ is a hydrogen atom; and X has 1 to 3 substituents. A pyridyl group which may be substituted with methoxy, ethoxy, isopropoxy,
Benzyloxy, methylthio, ethylthio, methylsulfonyl, ethylsulfonyl, benzyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfonylamino and / or N-methylphenylsulfonylamino; and Y is an oxygen atom Z is a 2,4-dioxothiazolidin-5-ylmethyl group; an oxime derivative or a salt thereof. 33. The method of claim 1, wherein 1) 5- [4- [2-[[[1- (4-biphenylyl)
[Ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione, 2) 5- [4- [2-[[[1- (4-phenylsulfonylphenyl) ethylidene] amino] oxy] ethoxy] benzyl] Thiazolidine-2,4-dione, 3) 5- [4- [2-[[[1- [4- (2-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 4) 5- [4- [2-[[[1- [4- (3-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione; 5) 5- [4 -[2-[[[1- [4- (4-pyridyl) phenyl] ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione; 6) 5- [4- [2- [ [1- (2-phenyl-5
Pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 7) 5- [4- [2-[[[1- (2-methoxy-5-
Pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 8) 5- [4- [2-[[[1- (2-ethoxy-5-
Pyridyl) ethylidene] amino] oxy] ethoxy] benzyl] thiazolidine-2,4-dione 9) 5- [4- [2-[[[1- (2-isopropoxy-5-pyridyl) ethylidene] amino] oxy ] Ethoxy] benzyl] thiazolidine-2,4-dione or 10) 5- [4- [2-[[[1- (2-benzyl-5)
-Pyridyl) ethylidene] amino] oxy] ethoxy]
Benzyl] thiazolidine-2,4-dione, or an oxime derivative thereof, or a salt thereof. 34. A compound having the general formula (II) And a compound having the general formula (III): And then removing the protecting group to produce an oxime derivative of the above general formula (I). [In the formula, R ¹ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. R ² represents a linear or branched alkylene group having 2 to 6 carbon atoms. R ³ is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms,
Linear or branched alkoxy group having 1 to 4 carbon atoms, linear or branched alkylthio group having 1 to 4 carbon atoms, halogen atom, nitro group, amino group, 1 to 4 carbon atoms A straight-chain or branched-chain monoalkylamino group having 4 carbon atoms, a straight-chain or branched-chain dialkylamino group having the same or different alkyl groups each having 1 to 4 carbon atoms, An aryl group having 10 or an aralkyl group having 7 to 12 carbon atoms is shown. X is an aryl group having 6 to 10 carbon atoms which may have 1 to 3 substituents or 1 which may have 1 to 3 substituents
Or a heteroaromatic group consisting of two rings. Examples of the substituent include: 1) a linear or branched alkyl group having 1 to 6 carbon atoms; 2) a 1 to 4 carbon atoms.
A straight-chain or branched-chain alkyl halide group having 3 carbon atoms; 3) a hydroxy group; 4) a straight-chain or branched-chain acyloxy group having 1 to 4 carbon atoms;
5) a linear or branched alkoxy group having 1 to 4 carbon atoms; 6) a linear or branched alkylenedioxy group having 1 to 4 carbon atoms;
7) an aralkyloxy group having 7 to 12 carbon atoms; 8) a linear or branched alkylthio group having 1 to 4 carbon atoms; 9) a linear or branched alkylthio group having 1 to 4 carbon atoms; Branched alkylsulfonyl group, 10) halogen atom, 11) nitro group, 1
2) an amino group; 13) a linear or branched monoalkylamino group having 1 to 4 carbon atoms;
4) linear or branched dialkylamino groups having the same or different alkyls each having 1 to 4 carbon atoms; 15) aralkyl groups having 7 to 12 carbon atoms; 16) 6 to 10 carbon atoms Aryl groups having 1 to 6 carbon atoms, such as straight-chain or branched alkyl groups, straight-chain or branched alkyl halide groups having 1 to 4 carbon atoms, Straight-chain or branched alkoxy having 1 to 4 carbon atoms, which may be substituted by halogen or straight-chain or branched alkylenedioxy having 1 to 4 carbon atoms), 17) an aryloxy group having 6 to 10 carbon atoms (the aryl group has 1 to 6 carbon atoms)
Linear or branched alkyl having 1 to 4 carbon atoms, linear or branched alkyl halide having 1 to 4 carbon atoms, linear or branched alkyl having 1 to 4 carbon atoms Alkoxy, halogen, or linear or branched alkylenedioxy having 1 to 4 carbon atoms), 18) 6 carbon atoms
An arylthio group having 1 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl having 1 to 4 carbons) Alkyl, linear or branched alkoxy having 1 to 4 carbon atoms, halogen, or linear or branched alkylenedioxy having 1 to 4 carbon atoms may be substituted. ),
19) an arylsulfonyl group having 6 to 10 carbon atoms (the aryl group is a linear or branched alkyl having 1 to 6 carbons, a linear or branched alkyl having 1 to 4 carbons) A branched alkyl halide, a linear or branched alkoxy having 1 to 4 carbon atoms, a halogen or a linear or branched alkylenedioxy having 1 to 4 carbon atoms 20) C6-C10
Arylsulfonylamino group (the aryl group is a straight-chain or branched alkyl having 1 to 6 carbons, a straight-chain or branched halogen having 1 to 4 carbons) Alkyl, linear or branched alkoxy having 1 to 4 carbons, halogen, or linear or branched alkylenedioxy having 1 to 4 carbons may be substituted. .
The nitrogen atom may be substituted by linear or branched alkyl having 1 to 6 carbons), 2
1) heteroaromatic ring group, 22) heteroaromatic oxy group, 2
3) a heteroaromatic thio group, 24) a heteroaromatic sulfonyl group, and 25) a heteroaromatic sulfonylamino group (where the nitrogen atom is substituted by a linear or branched alkyl having 1 to 6 carbon atoms) May be shown). Y
Represents an oxygen atom, a sulfur atom or a group> NR ⁴ .
(Wherein R ⁴ represents a hydrogen atom, 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) U is a hydroxyl group, a halogen atom or —O—SO ₂ —R ⁵ (R
⁵ represents an alkyl group, a halogenated alkyl group or an aryl group which may have an alkyl, nitro or halogen as a substituent), and Za-d represents Za, Zb,
Zc or Zd, Z'a-d is Za, Zb, Zc
Or, in Zd,> NH group contained in these groups represents a protected group]