JP2003212864A - 5-(m-cyanobenzylamino)thiazole derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new fungicide which is used for agriculture and horticulture and can control Phytophthora infestans and Plasmopara viticola at a low dose. <P>SOLUTION: This 5-(m-cyanobenzylamino)thiazole derivative represented by general formula (1) [R<SP>1</SP>is an alkyl, an aliphatic acyl, phenyl, a heterocyclic group or an alkylamino; R<SP>2</SP>is H or an alkyl; R<SP>3</SP>is a halogen atom, an alkyl, a cycloalkyl, phenyl, an alkoxy, phenoxy, a heterocyclic oxy, an alkylthio, phenylthio, heterocyclic thio, cyclic amino or amino; X is O or S; Y is an alkyl, an alkoxy, cyano, nitro, a halogen atom or an alkoxycarbonyl; (n) is an integer of 0 to 4, provided that, when (n) is 2 to 4, Y groups may be the same or different each other] or its salt, and an agrichemical containing the compound as an active ingredient. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a 5- (m-cyanobenzylamino) thiazole derivative and a salt thereof, and an agricultural chemical containing the same as an active ingredient.

[0002]

2. Description of the Related Art Heretofore, a 5- (m-cyanobenzylamino) thiazole derivative having a 5-amino group bonded to an m-cyanobenzyl group has not been known at all. Further, it is not known that the 5- (substituted amino) thiazole derivative can be used as an agricultural / horticultural fungicide.

[0003]

The object of the present invention is tomato late blight (Phytophthora infestans), which often causes serious damage to agricultural and horticultural crops among mold diseases of plants.
And against downy mildew (Plasmopara viticola),
It is to develop a new agricultural and horticultural fungicide that can be controlled with a low dosage.

As a result of earnest studies on the 5-aminothiazole derivative, the present inventors have found that the 5-amino group has m
The present inventors have completed the present invention by finding that a 5- (m-cyanobenzylamino) thiazole derivative having a -cyanobenzyl group bonded thereto has extremely excellent bactericidal activity against various plant diseases.

[0005]

The present invention has the general formula

[0006]

[Chemical 2]

[Where R¹Is C which may be substituted₁~ C₆
Alkyl group (the substituent is selected from the following substituent group A)
It ), C₂~ C₇Aliphatic acyl group, optionally substituted phenyl
Nyl group (the substituent is selected from the following substituent group B
It ), A heterocyclic group which may be substituted (the substituent is as follows:
It is selected from the substituent group C. ) Or C₁~ C₆Alkylami
Represents a no group, R²Is a hydrogen atom or optionally substituted C₁~
C₆Alkyl group (the substituent is a halogen atom)
It ), R³Is a halogen atom, which may be substituted
C₁~ C₆Alkyl group (whether the substituent is the following substituent group D
Chosen from. ), C₃~ C₇Cycloalkyl group, substituted
A phenyl group (the substituent is selected from the following substituent group B)
To be elected. ), Optionally substituted C₁~ C₆Alkoxy group
(The substituent is C₁~ C₆It is an alkoxy group. ),
A phenoxy group which may be replaced (the substituent is the following substituent
Selected from Group B. ), Optionally substituted heterocyclic oxy group
(The substituent is selected from the following substituent group C.),
C that may be exchanged₁~ C₆Alkylthio group (the substituent is
Cyano group, phenyl group or C₁~ C₆An alkoxy group
It ), A phenylthio group which may be substituted (the substituent
Is selected from the following substituent group B. ), May be replaced
Heterocyclic thio group (the substituent is selected from the following substituent group C)
Be done. ), A cyclic amino group which may be substituted (the cyclic amino group
The no group may be interrupted by one oxygen atom. The location
The substituent is C ₁~ C₆Alkyl group and C₂~ C₇Alkoxyca
It is selected from the group consisting of rubonyl groups. ) Or replaced
A good amino group (the substituent is selected from the following substituent group E)
Be done. ), X represents an oxygen atom or a sulfur atom,
Y is C₁~ C₆Alkyl group, C₁~ C₆Alkoxy group,
Ano group, nitro group, halogen atom or C₂~ C₇Arcoki
Represents a carbonyl group, n represents an integer of 0 to 4,
However, when n is 2 to 4, each Y may be the same or different.
Well, the substituent group A may be substituted with a halogen atom.
C₃~ C₇Cycloalkyl group (the cycloalkyl group is
It may be interrupted by one oxygen atom. The substituent is
C₁~ C₆Selected from the group consisting of alkyl groups and halogen atoms
Be exposed. ), The substituent group B is
May be C₁~ C₆Alkyl group (the substituent is a halogen atom)
Is a child. ), C₁~ C₆Alkoxy group, cyano group, nit
Group, halogen atom, C₂~ C₇Alkoxy carbonyl
Base, C₂~ C₇Alkylcarbonylamino group and C ₁~ C₃
Substituent group C, which is a group consisting of alkylenedioxy groups
Is C which may be substituted₁~ C₆Alkyl group (the substituent
Is a halogen atom. ), C₁~ C₆An alkoxy group,
Cyano group, phenyl group, halogen atom, C₂~ C₇Arco
A group consisting of an oxycarbonyl group and an oxo group, which is substituted
Group D is a halogen atom, hydroxyl group, C₁~ C₆Alkoxy
Group, optionally substituted C₂~ C₇Aliphatic acyloxy group (this
The substituent is C₃~ C₇Cycloalkyl group, C₁~ C₆Al
Selected from the group consisting of coroxy groups and halogen atoms
It ), An optionally substituted phenoxy group (the substituent is
It is selected from the above substituent group B. ), A complex that may be replaced
Ring oxy group (the substituent is selected from the above substituent group C)
It ), Optionally substituted C₁~ C₆Alkylthio group
The substituents are cyano group, phenyl group and C₁~ C₆Arcoki
Selected from the group consisting of Si groups. ), Which may be replaced
Nylthio group (the substituent is selected from the above substituent group B)
It ), An optionally substituted heterocyclic thio group (the substituent is
It is selected from the above substituent group C. ), C₂~ C₇Aliphatic reed
A ruthio group, an optionally substituted phenyl group (the substituent is
It is selected from the above substituent group B. ) And a compound that may be substituted
Elementary ring group (the substituent is selected from the above substituent group C)
It ), The substituent group E is
I C₁~ C₆Alkyl group (the substituent is a cyano group, a halo group
Gen atom, phenyl group and C₁~ C₆From an alkoxy group
Selected from the group. ), C₃~ C₆Alkenyl group, C₃~
C₆Alkynyl group, C₃~ C₇Cycloalkyl group, hydroxy
Group, optionally substituted C₁~ C₆Alkoxy group {the relevant substituent
Is a phenyl group which may be substituted (the substituent is
It is selected from the substituent group B. ). }, C₃~ C₆Arche
Nyloxy group, phenyl group which may be substituted (the substituent
Is selected from the above substituent group B. ), May be replaced
A heterocyclic group (the substituent is selected from the above substituent group C)
It ), Optionally substituted C₂~ C₇Aliphatic acyl group
The substituent is a halogen atom. ) And may be replaced
Benzoyl group (the substituent is selected from the above substituent group B)
Be done. ) Is a group consisting of. ] 5- (m-si represented by
Anobenzylamino) thiazole derivative or salt thereof, and
And an agricultural chemical containing it as an active ingredient.

In the present invention, "C ₁ -C ₆ alkyl group"
Is a linear or branched alkyl group having 1 to 6 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a s-butyl group, and t.
-Butyl group, pentyl group, isopentyl group, 2-methylbutyl group, neopentyl group, 1-ethylpropyl group, hexyl group, 4-methylpentyl group, 3-methylpentyl group, 2-methylpentyl group, 1-methylpentyl group Base,
3,3-dimethylbutyl group, 2,2-dimethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group or 2- It may be an ethylbutyl group, preferably a linear or branched alkyl group having 1 to 5 carbon atoms (C _{1 to} C ₅
Alkyl), more preferably R ¹ is a linear or branched alkyl group having 4 or 5 carbon atoms (C ₄ -C ₅ alkyl), and even more preferably 4 or 5 carbon atoms. 5 branched-chain alkyl groups, particularly preferably an isobutyl group or a neopentyl group, most preferably an isobutyl group, and other more preferably a carbon number of 1
To 4 linear or branched alkyl groups (C ₁ -C ₄ alkyl), and even more preferably, linear or branched alkyl groups having 1 to 3 carbon atoms, and particularly preferably Is an alkyl group having 1 or 2 carbon atoms (C ₁ -C ₂ alkyl),
Most preferably, it is a methyl group.

In the present invention, the "halogen atom" is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom,
Preferably, it is a fluorine atom, a chlorine atom or a bromine atom,
Of the substituents on the heterocyclic ring, a bromine atom is more preferable, a fluorine atom or a chlorine atom is more preferable, and a fluorine atom is still more preferable.

In the present invention, "C₃~ C₇Cycloalk
Group "means a cyclopropyl group, a cyclobutyl group, a cyclo group.
A pentyl group, a cyclohexyl group or a cycloheptyl group
And preferably a cycloalkyl group having 3 to 6 carbon atoms
(C₃~ C₆Cycloalkyl) and R¹At
More preferably, it is a cycloalkyl group having 4 to 6 carbon atoms (C
_Four~ C₆Cycloalkyl), and even more preferably charcoal
Cycloalkyl group having 4 or 5 primes (C_Four~ C_FiveCycloa
And a cyclopentyl group is particularly preferable.
In other respects, more preferably, it has 3 to 5 carbon atoms.
Cycloalkyl group (C₃~ C_FiveCycloalkyl)
And even more preferably, cycloalkyl having 3 or 4 carbon atoms
Kill group (C₃~ C_FourCycloalkyl), particularly preferably
Is a cyclopropyl group, and in the present invention, "substituted
C may be done₃~ C₇Cycloalkyl group (the cycloalkyl
The kill group may be interrupted by one oxygen atom. Concerned
The substituent is C₁~ C₆Consisting of alkyl groups and halogen atoms
Selected from the group. ) ”Is the above“ C₃~ C₇Cycloal
"Kill group" or carbon with one oxygen atom inserted in the carbocycle
A cycloalkyl group having the number of 3 to 7, wherein the above-mentioned “C₁
~ C₆Consisting of an "alkyl group" and the above "halogen atom"
1 to 4 substituents which are the same or different and are selected from the group
Is a functional group which may be substituted,₃~ C₇Shiku
In addition to the “alkyl group”, for example, an oxetanyl group,
Solanyl group, oxanyl group (tetrahydropyranyl
Group), oxepanyl group, oxocanyl group, methylcyclo
Pentyl group, dimethylcyclopentyl group, trimethylsilane
Clopentyl group, tetramethylcyclopentyl group, ethyl
Rucyclopentyl group, chlorocyclopentyl group, dichloro
Rocyclopentyl group, trichlorocyclopentyl group, te
Trachlorocyclopentyl group, fluorocyclopentyl
Group, difluorocyclopentyl group, trifluorocyclo
Pentyl group, bromocyclopentyl group or methylchloro
It may be a cyclopentyl group, preferably C₁~ C_FourArchi
Group, fluorine atom, chlorine atom and bromine atom
Be substituted with the same 1-3 substituents selected from
Yes, C₃~ C₆1 oxygen in a cycloalkyl group or carbocycle
C with an atom inserted₃~ C₆It's a cycloalkyl group,
More preferably, C_Four~ C₆1 on cycloalkyl or carbocycle
C with one oxygen atom inserted _Four~ C₆With a cycloalkyl group
Yes, and even more preferably, C_Four~ C_FiveWith a cycloalkyl group
And particularly preferably a cyclopentyl group.

In the present invention, "C ₁ -which may be substituted"
"C ₆ alkyl group (the substituent is selected from the substituent group A)" means the "halogen atom" and the "optionally substituted C ₃ -C ₇ cycloalkyl group (the cycloalkyl group is 1 ₁ to ₆ substituents selected from the group consisting of C _{1 to} C ₆ alkyl groups and halogen atoms). The aforementioned "C which may be substituted by a group
₁ -C ₆ alkyl group ", for example, trifluoromethyl group, trichloromethyl group, difluoromethyl group, dichloromethyl group, dibromomethyl group, fluoromethyl group,
Chloromethyl group, bromomethyl group, iodomethyl group,
2,2,2-trichloroethyl group, 2,2,2-trifluoroethyl group, 2-bromoethyl group, 2-chloroethyl group, 2-fluoroethyl group, 3-chloropropyl group,
3,3,3-trifluoropropyl group, 4-fluorobutyl group, 3-fluoro-2-methylpropyl group, 3,
3,3-trifluoro-2-methylpropyl group, 6,
6,6-trichlorohexyl group, cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group,
It may be a cyclohexylmethyl group, a cycloheptylmethyl group, a cyclobutylethyl group, a cyclopentylethyl group or a tetrahydropyran-4-ylmethyl group, preferably a fluorine atom, a chlorine atom, a bromine atom and optionally substituted C ₃ -C. ₆ cycloalkyl group (the cycloalkyl group may be interrupted by an oxygen atom. The substituent is C
₁ -C ₄ alkyl group, a fluorine atom, selected from the group consisting of chlorine and bromine. And a C ₁ -C ₆ alkyl group which may be substituted with 1 to 4 substituents which are the same or different from each other and are more preferably fluorine atom, chlorine atom and C ₄ -C ₆ cyclo group. An alkyl group (the cycloalkyl group may be interrupted by an oxygen atom), which is a C ₁ -C ₅ alkyl group optionally substituted by 1 to 3 substituents which are the same or different and are selected from the group consisting of: Still more preferably, it is a C ₄ -C ₅ alkyl group which may be substituted by 1 to 3 fluorine atoms or a methyl group which may be substituted by 1 C ₄ -C ₅ cycloalkyl group, and particularly preferably Is an isobutyl group, neopentyl group, 3,3,3-
It is a trifluoro-2-methylpropyl group or a cyclopentylmethyl group.

In the present invention, "C ₂ -C ₇ aliphatic acyl group" means, for example, acetyl group, propionyl group, butyryl group, isobutyryl group, pentanoyl group, isopentanoyl group, 2-methylbutanoyl group, pivaloyl group. Group, straight-chain or branched-chain aliphatic acyl group having 2 to 7 carbon atoms such as hexanoyl group; cycloaliphatic group having 4 to 7 carbon atoms such as cyclopropylcarbonyl group, cyclobutylcarbonyl group and cyclopentylcarbonyl group Group acyl group; or 2
An unsaturated aliphatic acyl group having 4 to 7 carbon atoms such as a methyl-1-butenoyl group and a 2-methyl-2-butenoyl group, and preferably a straight chain or a branched chain having 2 to 6 carbon atoms. Branched chain aliphatic acyl group, cyclic aliphatic acyl group having 4 to 6 carbon atoms or unsaturated aliphatic acyl group having 4 to 6 carbon atoms (C
_{2 to} C ₆ aliphatic acyl), and more preferably having 2 carbon atoms.
To 4 linear or branched aliphatic acyl groups, and even more preferably an isobutyryl group.

In the present invention, "C ₁ -which may be substituted"
C ₆ alkyl group (the substituent is a halogen atom.), "Is located by the which may be substituted the same or different 1 to 6 wherein the" halogen atom "," C ₁ -C ₆ alkyl group " , For example, trifluoromethyl group, trichloromethyl group, difluoromethyl group, dichloromethyl group,
Dibromomethyl group, fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, 2,2,2-trichloroethyl group, 2,2,2-trifluoroethyl group, 2-bromoethyl group, 2-chloroethyl group , 2-fluoroethyl group, 3-chloropropyl group, 3,3,3-
Trifluoropropyl group, 4-fluorobutyl group, 3-
It may be a fluoro-2-methylpropyl group, a 3,3,3-trifluoro-2-methylpropyl group or a 6,6,6-trichlorohexyl group, preferably consisting of a fluorine atom, a chlorine atom and a bromine atom. A C ₁ -C ₄ alkyl group which may be substituted with ₁ to ₄ substituents which are the same or different from the group, and more preferably the same or different from the group consisting of a fluorine atom and a chlorine atom. A C ₁ -C ₂ alkyl group which may be substituted by 1 to 3 substituents, and more preferably, R ² is a methyl group which may be substituted by 1 to 3 fluorine atoms, Of these, a methyl group is preferable, and among them, a C ₁ -C ₂ alkyl group is still more preferable, and a methyl group is particularly preferable.

In the present invention, the "C ₁ -C ₆ alkoxy group" is a straight or branched chain alkoxy group having 1 to 6 carbon atoms, for example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group. , Butoxy group, isobutoxy group, s-butoxy group, t-butoxy group, pentyloxy group, isopentyloxy group, 2-methylbutoxy group, neopentyloxy group, 1-ethylpropoxy group, hexyloxy group, (4- Methylpentyl) oxy group, (3-
Methylpentyl) oxy group, (2-methylpentyl) oxy group, (1-methylpentyl) oxy group, 3,3-dimethylbutoxy group, 2,2-dimethylbutoxy group, 1,
It may be a 1-dimethylbutoxy group, a 1,2-dimethylbutoxy group, a 1,3-dimethylbutoxy group, a 2,3-dimethylbutoxy group or a 2-ethylbutoxy group, and preferably has 1 to 4 carbon atoms. A straight-chain or branched-chain alkoxy group (C ₁ -C ₄ alkoxy), more preferably a straight-chain or branched-chain alkoxy group having 1 to 3 carbon atoms (C ₁ -C ₃ alkoxy), Even more preferably, the carbon number is 1 or 2.
Is an alkoxy group (C ₁ -C ₂ alkoxy), particularly preferably a methoxy group.

In the present invention, the "C ₂ -C ₇ alkoxycarbonyl group" is a carbonyl group to which one "" is bonded, and examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group and an isopropoxycarbonyl group. Group, butoxycarbonyl group, isobutoxycarbonyl group, s-butoxycarbonyl group, t-butoxycarbonyl group, pentyloxycarbonyl group, isopentyloxycarbonyl group, 2-methylbutoxycarbonyl group, neopentyloxycarbonyl group, 1-ethyl Propoxycarbonyl group, hexyloxycarbonyl group,
(4-methylpentyl) oxycarbonyl group, (3-methylpentyl) oxycarbonyl group, (2-methylpentyl) oxycarbonyl group, (1-methylpentyl) oxycarbonyl group, 3,3-dimethylbutoxycarbonyl group, 2 , 2-dimethylbutoxycarbonyl group, 1,1
-Dimethylbutoxycarbonyl group, 1,2-dimethylbutoxycarbonyl group, 1,3-dimethylbutoxycarbonyl group, 2,3-dimethylbutoxycarbonyl group or 2
It may be an -ethylbutoxycarbonyl group, preferably a linear or branched alkoxycarbonyl group having 2 to 5 carbon atoms (C ₂ -C ₅ alkoxycarbonyl), and more preferably ₂ to ₅ carbon atoms. 4 straight-chain or branched-chain alkoxycarbonyl groups, and even more preferably 2 or 3 carbon atoms
Is an alkoxycarbonyl group, particularly preferably a methoxycarbonyl group.

In the present invention, the "C ₂ -C ₇ alkylcarbonylamino group" is an amino group substituted by one of the above "C ₂ -C ₇ alkylcarbonyl" and has 2 to 5 carbon atoms.
Linear or branched alkoxycarbonylamino groups, more preferably linear or branched alkoxycarbonylamino groups having 2 to 4 carbon atoms, and even more preferably 2 or carbon atoms. Three alkoxycarbonylamino groups, particularly preferably a methoxycarbonylamino group.

In the present invention, the "C ₁ -C ₃ alkylenedioxy group" is a linear or branched alkylenedioxy group having 1 to 3 carbon atoms, for example, methylenedioxy group, ethylenedioxy group. Group or trimethylenedioxy group, preferably an alkylenedioxy group having 1 or 2 carbon atoms, and more preferably a methylenedioxy group.

In the present invention, "a phenyl group which may be substituted (the substituent is selected from the substituent group B)".
Are the above-mentioned "C ₁ -C ₆ alkyl group which may be substituted (the substituent is a halogen atom)", the "C ₁ -C ₆ alkoxy group", a cyano group, a nitro group, the "halogen atom". ], The above “C _{2 to} C ₇ alkoxycarbonyl group”, the above “C _{2 to} C ₇ alkylcarbonylamino group” and the above “C
₁ -C ₃ an alkylene same or different 1 to 5 substituents may phenyl group substituted selected from the group consisting of oxy group ", for example, a phenyl group, methylphenyl group, ethylphenyl group, propyl Phenyl group, isopropylphenyl group, dimethylphenyl group, trimethylphenyl group, trifluoromethylphenyl group, methoxyphenyl group, dimethoxyphenyl group, trimethoxyphenyl group, ethoxyphenyl group, isopropoxyphenyl group,
Methylenedioxyphenyl group, ethylenedioxyphenyl group, cyanophenyl group, nitrophenyl group, chlorophenyl group, dichlorophenyl group, fluorophenyl group,
It may be a difluorophenyl group, a chloro-methylphenyl group, a fluoro-methylphenyl group, a methoxycarbonylphenyl group, a chloro-methoxyphenyl group or an acetylaminophenyl group, preferably C ₁ -which may be substituted.
A C ₄ alkyl group (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom), a C _{1 to} C ₄ alkoxy group, a cyano group, a nitro group, a fluorine atom, a chlorine atom, a bromine atom, C ₂ -C ₅ alkoxycarbonyl group, C ₂
To C ₅ alkylcarbonylamino groups and C _{1 to} C ₂ alkylenedioxy groups are phenyl groups which may be substituted with 1 to 3 same or different substituents, more preferably methyl. A phenyl group which may be substituted with the same or different 1 to 2 substituents selected from the group consisting of a group, a cyano group, a fluorine atom and a chlorine atom, and a phenyl group is particularly preferable.

In the present invention, "heterocycle which may be substituted"
A group (the substituent is selected from the substituent group C) "
The above "C which may be substituted"₁~ C₆Alkyl group (the substituent
Is a halogen atom. ) ”, The above“ C₁~ C₆Arco
Xy group ", cyano group, phenyl group, the above-mentioned" halogen source "
Child ", above-mentioned" C₂~ C₇Alkoxycarbonyl group "and
Identical or different 1-4 selected from the group consisting of xo groups
Saturated or unsaturated compounds which may be substituted by
A cyclic group, for example, 2-pyridyl group, 3-pyridyl group
Group, 4-pyridyl group, 4-chloro-3-pyridyl group, 4
-Methyl-3-pyridyl group, 2-furyl group, 2-thienyl
Group, 2-quinolyl group, 3-quinolyl group, 4-quinolyl group
Group, 2-methyl-3-quinolyl group, 6-chloro-2-pi
It may be a lysyl group or a 2-thiazolyl group, R¹smell
And preferably C which may be substituted₁~ C _FourAlkyl group (this
The substituent is composed of a fluorine atom, a chlorine atom and a bromine atom.
Selected from the group. ), C₁~ C_FourAlkoxy group, cyano
Group, phenyl group, fluorine atom, chlorine atom, bromine atom, C
₂~ C_FiveGroup consisting of alkoxycarbonyl group or oxo group
By the same or different 1 to 3 substituents selected from
It may be substituted and the hetero atom in the ring is a nitrogen atom or a sulfur atom.
And the same or different selected from the group consisting of oxygen atoms
A 5- or 6-membered heterocyclic group having 1 to 3 hetero atoms,
More preferably, it is composed of a methyl group, a fluorine atom and a chlorine atom.
The same or different 1 or 2 substituents selected from the group
More substituted, nitrogen having 1 to 2 heteroatoms in the ring
A 6-membered heterocyclic group which is an atom, and even more preferably,
It is a lysyl group, and in the substituent group D, it is preferably substituted.
C may be done₁~ C_FourAlkyl group (the substituent is fluorine
Selected from the group consisting of atoms, chlorine atoms and bromine atoms
It ), C₁~ C_FourAlkoxy group, cyano group, phenyl
Group, fluorine atom, chlorine atom, bromine atom, C₂~ C_FiveArco
Selected from the group consisting of a oxycarbonyl group and an oxo group
Be substituted with 1 to 3 same or different substituents
The heteroatoms in the ring are nitrogen, sulfur and oxygen.
Same or different 1 to 3 compounds selected from the group consisting of
It is a 5- or 6-membered heterocyclic group which is an elementary atom, and more preferably,
C₁~ C₂Alkyl group, cyano group, fluorine atom, chlorine source
Same selected from the group consisting of a child, a bromine atom and an oxo group
Or may be substituted by 1 to 2 different substituents,
5-membered heterocycle in which the heteroatoms in the ring are 1-2 nitrogen atoms
A group, even more preferably substituted by a bromine atom
A pyrazolyl group which may be
A group of the substituent group E, which is preferably substituted
Good C₁~ C_FourAlkyl group (the substituent is a fluorine atom,
It is selected from the group consisting of chlorine atom and bromine atom. ), C
₁~ C_FourAlkoxy, cyano, phenyl, fluorogen
Child, chlorine atom, bromine atom, C₂~ C_FiveAlkoxy Carboni
The same or different selected from the group consisting of
May be substituted by only 1 to 3 substituents,
Is the elementary atom a group consisting of nitrogen atom, sulfur atom and oxygen atom?
Same or different 1 to 3 heteroatoms selected from
A 4- to 6-membered heterocyclic group which may be condensed with a benzene ring.
More preferably, the heteroatoms in the ring are nitrogen and sulfur.
1-2 identical or different atoms selected from the group consisting of atoms
5 to 6-membered heteroatom which may be condensed with the benzene ring
A heterocyclic group, and even more preferably a quinolyl group or a dicyclic group.
A hydrothiazolyl group, particularly preferably 4,5-di
It is a hydrothiazolyl group.

In the present invention, the "C ₁ -C ₆ alkylamino group" is an amino group substituted by one of the above "C ₁ -C ₆ alkyl group", for example, methylamino group,
It may be an ethylamino group, a propylamino group, an isopropylamino group, a butylamino group, an isobutylamino group, a t-butylamino group, a pentylamino group or a hexylamino group, and preferably one C _{1 to} C ₄ alkyl. The group is a substituted amino group, more preferably a methylamino group or an isobutylamino group, and even more preferably an isobutylamino group.

In the present invention, "C which may be substituted"₂~
C₇Aliphatic acyloxy group (the substituent is C₃~ C₇Shi
Chloroalkyl group, C₁~ C₆Alkoxy group and halogen source
Selected from the group of children. ) ”Is the above“ C₃~ C₇Shi
A chloroalkyl group ", the above" C₁~ C₆An alkoxy group "and
The same or selected from the group consisting of the above "halogen atom"
The above "C₂~
C₇It is an oxygen atom to which an "aliphatic acyl group" is bonded.
For example, acetoxy, propionyloxy, butyryl
Xy, isobutyryloxy, pentanoyloxy
Group, isobutyryloxy group, isopentanoyloxy
Group, 2-methylbutanoyloxy group, pivaloyloxy
Groups, such as hexanoyloxy groups, having 2 to 7 carbon atoms
Linear or branched aliphatic acyloxy group; cyclopropyl
Carbonyloxy group, cyclobutylcarbonyloxy,
4 carbon atoms such as cyclopentylcarbonyloxy group
Up to 7 cycloaliphatic acyloxy groups; acryloxy
Group, 2-methylacryloxy group, 2-methyl-1-bu
Thenoyloxy group, 2-methyl-2-butenoyloxy
Group, carbon such as 3-methyl-2-butenoyloxy group
4 to 7 unsaturated aliphatic acyloxy groups; or
Loloacetoxy group, dichloroacetoxy group, trichloro
Acetoxy group, fluoroacetoxy group, difluoroacetate
Toxy group, trifluoroacetoxy group, 2- (triflu
2 to 7 carbon atoms such as oromethyl) acryloxy group
Haloaliphatic acyloxy groups, preferably C
₃~ C₆Cycloalkyl group, C₁~ C_FourAlkoxy group,
Selected from the group consisting of elementary atom, chlorine atom and bromine atom
Be substituted by 1 to 4 substituents which are the same or different
I C₂~ C_FiveAn aliphatic acyloxy group, more preferably
Is a group selected from the group consisting of a fluorine atom and a chlorine atom.
May be substituted by 1 or 3 different 1 to 3 substituents
C ₂~ C_FiveAn aliphatic acyloxy group, and even more preferably
Is C₂~ C_FourAn aliphatic acyloxy group, particularly preferably
Is an acetoxy group.

In the present invention, "a phenoxy group which may be substituted (the substituent is selected from the substituent group B)".
Is an oxygen atom to which one of the above-mentioned “optionally substituted phenyl group (the substituent is selected from the substituent group B)” is bonded, and is, for example, a phenoxy group, a methylphenoxy group, an ethylphenoxy group, Propylphenoxy group, isopropylphenoxy group, dimethylphenoxy group, trimethylphenoxy group, trifluoromethylphenoxy group,
Methoxyphenoxy group, dimethoxyphenoxy group, trimethoxyphenoxy group, ethoxyphenoxy group, isopropoxyphenoxy group, methylenedioxyphenoxy group, ethylenedioxyphenoxy group, cyanophenoxy group, nitrophenoxy group, chlorophenoxy group, dichlorophenoxy group, Fluorophenoxy group, difluorophenoxy group, chloro-methylphenoxy group, fluoro-
It may be a methylphenoxy group, a methoxycarbonylphenoxy group, a chloro-methoxyphenoxy group or an acetylaminophenoxy group, preferably C ₁ which may be substituted.
To C ₄ alkyl group (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom), C _{1 to} C ₄
Alkoxy group, cyano group, nitro group, fluorine atom, chlorine atom, bromine atom, C ₂ -C ₅ alkoxycarbonyl group, C
A ₂ -C ₅ alkylcarbonylamino group and C ₁ -C ₂ alkylene same or different 1-3 is substituted by a substituent which may be a phenoxy group selected from the group consisting of an oxy group, more preferably, A phenoxy group which may be substituted with the same or different 1 to 2 substituents selected from the group consisting of a methyl group, a cyano group, a fluorine atom and a chlorine atom, and more preferably a phenoxy group, 3-fluoro. Phenoxy group, 2,4-dichlorophenoxy group or 3
-Cyanophenoxy group, more preferably 3-fluorophenoxy group or 2,4-fluorophenoxy group.

In the present invention, "heterocyclic oxy group which may be substituted (the substituent is selected from the substituent group C)" means one "heterocyclic group which may be substituted (the substituent is Is selected from Substituent Group C.) ”is bonded to an oxygen atom, and examples thereof include a 2-pyridyloxy group and 3-
Pyridyloxy group, 4-pyridyloxy group, 4-chloro-3-pyridyloxy group, 4-methyl-3-pyridyloxy group, 2-furyloxy group, 2-thienyloxy group,
2-quinolyloxy group, 3-quinolyloxy group, 4-quinolyloxy group, 2-methyl-3-quinolyloxy group,
It may be a 6-chloro-2-pyridyloxy group or a 2-thiazolyloxy group, and is preferably C ₁ -C ₄ which may be substituted.
An alkyl group (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom), a C ₁ -C ₄ alkoxy group, a cyano group, a phenyl group, a fluorine atom, a chlorine atom, a bromine atom, C ₂ ~ The same or different 1 to 3 selected from the group consisting of C ₅ alkoxycarbonyl group and oxo group
5- or 6-membered heterocyclic oxy, which may be substituted with 3 substituents and the heteroatoms in the ring are 1 to 3 heteroatoms which are the same or different and are selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom. And R ³ is more preferably C ₁
~ C ₂ alkyl group, cyano group, fluorine atom, chlorine atom,
A 6-membered heterocyclic oxy group which may be substituted with 1 or 2 identical or different substituents selected from the group consisting of a bromine atom and an oxo group, wherein the hetero atom in the ring is 1 or 2 nitrogen atoms. And even more preferably a pyridinyloxy group, and more preferably Substituent Group D from the group consisting of C ₁ -C ₂ alkyl groups, cyano groups, fluorine atoms, chlorine atoms, bromine atoms and oxo groups. It may be substituted by 1 or 2 same or different selected substituents, and the hetero atom in the ring is 1 or 2 same or different hetero atom selected from the group consisting of nitrogen atom and oxygen atom. To a 6-membered heterocyclic oxy group, and even more preferably a pyridyloxy group which may be substituted with a methyl group.

In the present invention, "C ₁ -which may be substituted"
A C ₆ alkylthio group (the substituent is selected from the group consisting of a cyano group, a phenyl group and a C ₁ -C ₆ alkoxy group.) Means a cyano group, a phenyl group and the above-mentioned “C ₁ -C ₆ alkoxy group”. The same or different 1 or 2 substituents selected from the group consisting of may be a linear or branched alkylthio group having 1 to 6 carbon atoms which may be substituted, and examples thereof include a methylthio group, a benzylthio group and a methoxymethylthio group. Group, ethoxymethylthio group, hexyloxymethylthio group, ethylthio group, phenethylthio group, 2-methoxyethylthio group, 2-ethoxyethylthio group, propylthio group, isopropylthio group, butylthio group, isobutylthio group, t
It may be a butylthio group or a hexylthio group, and is preferably selected from the group consisting of a cyano group, a phenyl group and a C ₁ -C ₄ alkoxy group. Is a cyano group, a phenyl group, and a straight chain having 1 to 4 carbon atoms which may be substituted with 1 to 2 substituents which are the same or different and are selected from the group consisting of the above-mentioned "C ₁ -C ₆ alkoxy group". A chain or branched chain alkylthio group, more preferably, in R ³ , a straight chain or branched chain alkylthio group having 1 to 4 carbon atoms, even more preferably a methylthio group, a substituent In Group D, more preferably, it has 1 carbon atom which may be substituted by 1 cyano group.
Or two alkylthio groups, and even more preferably,
It is a cyanomethylthio group.

In the present invention, "a phenyl group which may be substituted"
A ruthio group (the substituent is selected from the substituent group B)
It ) ”Is one of the“ optionally substituted phenyl groups ”
(The substituent is selected from the substituent group B.) "
Sulfur atom, for example, phenylthio group, methyl
Phenylthio group, ethylphenylthio group, propylphene
Nylthio group, isopropylphenylthio group, dimethyl group
Phenylthio group, trimethylphenylthio group, trifluor
Romethylphenylthio group, methoxyphenylthio group, di
Methoxyphenylthio group, trimethoxyphenylthio
Group, ethoxyphenylthio group, isopropoxyphenyl
Thio group, methylenedioxyphenylthio group, ethylenedi
Oxyphenylthio group, cyanophenylthio group, nitro
Phenylthio group, chlorophenylthio group, dichlorophen
Nylthio group, fluorophenylthio group, difluorofe
Nylthio group, chloro-methylphenylthio group, fluoro
-Methylphenylthio group, methoxycarbonylphenyl
Thio group, chloro-methoxyphenylthio group or acetyl
May be an aminophenylthio group, preferably substituted
Good C ₁~ C_FourAlkyl group (the substituent is a fluorine atom,
It is selected from the group consisting of chlorine atom and bromine atom. ), C
₁~ C_FourAlkoxy, cyano, nitro, fluorogen
Child, chlorine atom, bromine atom, C₂~ C_FiveAlkoxy Carboni
Lu group, C₂~ C_FiveAlkylcarbonylamino group and C₁~
C₂The same selected from the group consisting of alkylenedioxy groups
Or optionally substituted by 1 to 3 different substituents
Phenylthio group, more preferably a methyl group or cyano
A group selected from the group consisting of a group, a fluorine atom and a chlorine atom.
May be substituted by one or different 1-2 substituents
A phenylthio group, and even more preferably a phenylthio group.
O group, 3-fluorophenylthio group, 2,4-dichloro
A phenylthio group or a 3-cyanophenylthio group,
More preferably, a 3-fluorophenylthio group or 2,4
A fluorophenylthio group.

In the present invention, "a heterocyclic thio group which may be substituted (the substituent is selected from the substituent group C)".
Is a sulfur atom to which one of the “heterocyclic group which may be substituted (the substituent is selected from the substituent group C)” is bonded, and is, for example, a 2-pyridylthio group, a 3-pyridylthio group, 4-pyridylthio group, 4-chloro-3-pyridylthio group, 4-methyl-3-pyridylthio group, 2-furylthio group, 2-thienylthio group, 2-quinolylthio group, 3
-Quinolylthio group, 4-quinolylthio group, 2-methyl-
It may be a 3-quinolylthio group, a 6-chloro-2-pyridylthio group or a 2-thiazolylthio group, and is preferably a C ₁ -C ₄ alkyl group which may be substituted (the substituent is a fluorine atom, a chlorine atom and a bromine atom). Selected from the group consisting of atoms), a C _{1 to} C ₄ alkoxy group, a cyano group, a phenyl group, a fluorine atom, a chlorine atom, a bromine atom, a C _{2 to} C ₅ alkoxycarbonyl group, and an oxo group. It may be substituted with the same or different 1 to 3 substituents, and the heteroatom in the ring is the same or different 1 to 3 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom. It is a 5- or 6-membered heterocyclic thio group, and in R ³ , more preferably a 6-membered heterocyclic oxy group in which the heteroatoms in the ring are 1 to 2 nitrogen atoms, and even more preferably, With a pyridinylthio group Ri, the substituent group D, more preferably, C ₁ -C ₂ alkyl group, a cyano group, a fluorine atom, a chlorine atom, the same or different one to two selected from the group consisting of bromine and oxo group It is a 5-membered heterocyclic thio group which may be substituted with a substituent, and the heteroatoms in the ring are 1 or 2 heteroatoms which are the same or different and are selected from the group consisting of a nitrogen atom and a sulfur atom, and further more preferably Has
It is a thiadiazolylthio group which may be substituted with a methyl group.

In the present invention, the “C ₂ -C ₇ aliphatic acylthio group” is a sulfur atom to which one “C ₂ -C ₇ aliphatic acyl group” is bonded, and examples thereof include acetylthio group and propionylthio group. Group, butyrylthio group, isobutyrylthio group, pentanoylthio group, isopentanoylthio group, 2
-A linear or branched aliphatic acylthio group having 2 to 7 carbon atoms such as methylbutanoylthio group, pivaloylthio group, and hexanoylthio group; cyclopropylcarbonylthio group, cyclobutylcarbonylthio group, cyclopentylcarbonylthio group A cyclic aliphatic acylthio group having 4 to 7 carbon atoms such as a group; or an unsaturated aliphatic group having 4 to 7 carbon atoms such as a 2-methyl-1-butenoylthio group and a 2-methyl-2-butenoylthio group An acylthio group, preferably a linear or branched aliphatic acylthio group having 2 to 5 carbon atoms, a cyclic aliphatic acylthio group having 4 or 5 carbon atoms, or an unsaturated fat having 4 or 5 carbon atoms Group acylthio group (C _2-
C ₅ aliphatic acylthio), more preferably a linear or branched aliphatic acylthio group having 2 to 4 carbon atoms, and even more preferably an isobutyrylthio group.

In the present invention, "C ₁ -which may be substituted"
A C ₆ alkyl group (the substituent is selected from the substituent group D) "means the above-mentioned“ halogen atom ”, hydroxyl group, the above-mentioned“ C
₁ -C ₆ alkoxy group ", the" optionally substituted C ₂ -C ₇
Aliphatic acyloxy group (the substituent is selected from the group consisting of a C _{3 to} C ₇ cycloalkyl group, a C _{1 to} C ₆ alkoxy group and a halogen atom), ”the above-mentioned“ an optionally substituted phenoxy group (the said substitution The group is selected from Substituent group B.) ", the above-mentioned" heterocyclic oxy group which may be substituted (the substituent is selected from Substituent group C) ", and the" optionally substituted C _1- ". A C ₆ alkylthio group (the substituent is selected from the group consisting of a cyano group, a phenyl group, and a C ₁ -C ₆ alkoxy group), ”the“ optionally substituted phenylthio group (the substituent is a group of substituents. B)) ”, the above-mentioned“ optionally substituted heterocyclic thio group (the substituent is selected from the substituent group C) ”, and the above“ C _2-
A C ₇ aliphatic acylthio group ", the above-mentioned" phenyl group which may be substituted (the substituent is selected from the substituent group B) ".
And the same or different 1 to 6 substituents selected from the group consisting of the "optionally substituted heterocyclic group (the substituent is selected from the substituent group C)" a C ₁ -C ₆ alkyl group ", preferably a fluorine atom, a chlorine atom, a bromine atom, a hydroxyl group, C ₁ -C ₄ alkoxy group, may be substituted C ₂ -C ₅ aliphatic acyloxy group (the substituent The group is selected from the group consisting of a C ₃ -C ₆ cycloalkyl group, a C ₁ -C ₄ alkoxy group, a fluorine atom, a chlorine atom and a bromine atom, and an optionally substituted phenoxy group (the substituent is as follows: Substituent group B1), optionally substituted 5- or 6-membered heterocyclic oxy group (the heterocyclic ring is the same or different 1 to 3 selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom). And has the following hetero atom. Substituent group C1), an optionally substituted C ₁ -C ₄ alkylthio group (the substituent is selected from the group consisting of a cyano group, a phenyl group and a C ₁ -C ₄ alkoxy group), a substituent A phenylthio group which may be substituted (the substituent is selected from the following substituent group B1), and a 5- to 6-membered heterocyclic thio group which may be substituted (the heterocycle comprises a nitrogen atom, a sulfur atom and an oxygen atom) It has the same or different 1 to 3 hetero atoms selected from the group. The substituent is selected from the following substituent group C1), C _{2 to} C ₅ aliphatic acylthio group, and optionally substituted phenyl group. (The substituent is selected from the following substituent group B1) and an optionally substituted 5- or 6-membered heterocyclic group (the heterocycle is the same or selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom). 1 to 3 different heteroatoms To. The substituents may be substituted with same or different 1 to 4 substituents selected from the group consisting chosen.) From the following substituent group C1 C
_{1 to} C ₅ alkyl group, more preferably a fluorine atom,
Chlorine atom, hydroxyl group, C ₁ -C ₂ alkoxy group, optionally substituted C ₂ -C ₅ aliphatic acyloxy group (the substituent is selected from the group consisting of fluorine atom and chlorine atom), and may be substituted. Phenoxy group (the substituent is selected from the following Substituent group B2), optionally substituted 5- or 6-membered heterocyclic oxy group (the heterocycle is the same or selected from the group consisting of a nitrogen atom and an oxygen atom). It has 1 to 2 different heteroatoms, and the substituent is selected from the following substituent group C2) and an optionally substituted C ₁ -C ₂ alkylthio group (the substituent is a cyano group). ), An optionally substituted phenylthio group (the substituent is selected from the following substituent group B2), an optionally substituted 5-membered heterocyclic thio group (the heterocycle is selected from the group consisting of a nitrogen atom and a sulfur atom). Same or different selected It has 1 to 3 hetero atoms, the substituent is selected from the following substituent group C2, and optionally substituted 5 heterocyclic group (the hetero ring has 1 to 2 nitrogen atoms). The substituents are the same or different 1 to 3 selected from the group consisting of the following substituent group C2).
C are optionally substituted C ₁ -C ₄ alkyl groups,
Even more preferably, it is substituted with a hydroxyl group, a methoxy group, a C ₂ -C ₄ aliphatic acyloxy group, a phenoxy group which may be substituted (the substituent is selected from the group consisting of a cyano group and a fluorine atom). A good pyridyloxy group (the substituent is a methyl group), a cyanomethylthio group, an optionally substituted thiadiazolylthio group (the substituent is a methyl group), and an optionally substituted pyrazolyl group ( The said substituent is a bromine atom.) C ₁ which may be substituted with 1 or 2 same or different substituents selected from the group consisting of
To C ₂ alkyl group, particularly preferably methyl group, hydroxymethyl group, methoxymethyl group, acetoxymethyl group, and (bromopyrazolyl) methyl group.

In the present invention, "C which may be substituted"₁~
C₆Alkoxy group (the substituent is C ₁~ C₆Alkoxy
It is a base. ) ”Is a single“ C₁~ C₆Alkoxy
"C" may be substituted₁~ C₆An alkoxy group "
, For example, methoxymethoxy group, ethoxymethoxy
Group, propoxymethoxy group, isopropoxymethoxy
Group, butoxymethoxy group, isobutoxymethoxy group, s
-Butoxymethoxy group, t-butoxymethoxy group, pen
Tyloxymethoxy group, isopentyloxymethoxy
Group, 2-methylbutoxymethoxy group, neopentyloxy
Cymethoxy group, 1-ethylpropoxymethoxy group, hex
Syloxymethoxy group, (4-methylpentyl) oxy
Methoxy group, (3-methylpentyl) oxymethoxy
Group, (2-methylpentyl) oxymethoxy group, (1-
Methylpentyl) oxymethoxy group, 3,3-dimethyl
Butoxymethoxy group, 2,2-dimethylbutoxymethoxy
Si group, 1,1-dimethylbutoxymethoxy group, 1,2-
Dimethylbutoxymethoxy group, 1,3-dimethylbutoxy
Simethoxy group, 2,3-dimethylbutoxymethoxy group,
2-ethylbutoxymethoxy group, methoxyethoxy group,
Ethoxy ethoxy group, propoxy ethoxy group, isopro
Poxyethoxy group, butoxyethoxy group, isobutoxy
Ethoxy group, s-butoxyethoxy group, t-butoxy group
Toxy group, pentyloxyethoxy group or isopentyl group
It may be an oxyethoxy group, preferably one C₁~ C_Four
C which may be substituted by an alkoxy group₁~ C_FourAn alkoxy group
More preferably one C₁~ C₂Alkoxy group is substituted
You may do C₁~ C_FourAn alkoxy group, and even more preferably
Is C₁~ C₂It is an alkoxy group.

In the present invention, "a cyclic group which may be substituted is
Mino group (the cyclic amino group is
You may be refused. The substituent is C₁~ C₆Alkyl group and
C₂~ C₇Selected from the group consisting of alkoxycarbonyl groups
It ) ”Is the above“ C₁~ C ₆An alkyl group "and the above-mentioned" C
₂~ C₇Selected from the group consisting of "alkoxycarbonyl groups"
Substituted with one or two identical or different substituents
Well, cyclic amino where one oxygen atom may be inserted in the ring
Group, for example, 1-azetidinyl group, 1-pyrrolidi
Nyl group, 3-methyl-1-pyrrolidinyl group, 3-methoxy group
Cycarbonyl-1-pyrrolidinyl group, 1-piperidinyl
Group or morpholino group, preferably C₁~ C_FourAl
Kill group and C₂~ C_FiveGroup consisting of alkoxycarbonyl groups
By the same or different 1 or 2 substituents selected from
May be substituted, the ring being interrupted by one oxygen atom
A good 4- to 6-membered cyclic amino group, and more preferably a ring
4- to 5-membered cyclic amides which may be interrupted by one oxygen atom
And more preferably a 1-azetidinyl group or
Is a morpholino group, particularly preferably 1-azetidinii
It is a ru basis.

In the present invention, "C which may be substituted"₁~
C₆Alkyl group (the substituent is a cyano group, a halogen atom
Child, phenyl group and C₁~ C₆Is it a group consisting of alkoxy groups?
Chosen from. ) ”Is a cyano group,
Child ”, a phenyl group and the aforementioned“ C₁~ C₆"Alkoxy group"
1-6 identical or different substitutions selected from the group consisting of
The aforementioned "C which may be substituted by a group₁~ C₆With an alkyl group
Yes, preferably a cyano group, a fluorine atom, a chlorine atom, an odor
Elementary atom, phenyl group and C₁~ C_FourConsisting of an alkoxy group
By the same or different 1 to 5 substituents selected from the group
C which may be replaced ₁~ C_FourAlkyl group, more preferred
Include cyano group, fluorine atom, chlorine atom, phenyl group and
And C₁~ C₂The same or selected from the group consisting of alkoxy groups
Is C which may be substituted by 1 to 3 different substituents₁
~ C_FourAn alkyl group, and even more preferably phenyl
The same or different selected from the group consisting of
C optionally substituted by only 1 to 2 substituents₁~ C₂A
And a benzyl group or a methoxy group.
It is a cyethyl group.

In the present invention, the "C ₃ -C ₆ alkenyl group" is a straight chain or branched chain alkenyl group having 3 to 6 carbon atoms, such as allyl group, 1-propenyl group, 2-
It may be a methyl-1-propenyl group, a 2-methyl-2-propenyl group, a 3-butenyl group, a 2-methyl-2-butenyl group or a 4-pentenyl group, and is preferably a direct group having 3 or 4 carbon atoms. It is a chain or branched alkenyl group, and more preferably an allyl group.

In the present invention, the "C ₃ -C ₆ alkynyl group" is a straight or branched chain alkynyl group having 3 to 6 carbon atoms, for example, 2-propynyl group, 1-propynyl group, 3- Butynyl group, 2-butynyl group, 1-methyl-3
It may be a butynyl group, a 1-methyl-2-butynyl group or a 4-pentynyl group, preferably a linear or branched alkynyl group having 3 or 4 carbon atoms, and more preferably 2-
It is a propynyl group.

In the present invention, "C ₁ -which may be substituted"
C ₆ alkoxy group (the substituent is a phenyl group which may be substituted (the substituent is selected from the substituent group B). }] Is the above-mentioned “C ₁ -C ₆ alkoxy group” which may be substituted by _{one of the} above-mentioned “optionally substituted phenyl group (the said substituent is selected from the substituent group B)”,
For example, a benzyloxy group, a methylbenzyloxy group,
Ethylbenzyloxy group, propylbenzyloxy group,
Isopropylbenzyloxy group, dimethylbenzyloxy group, trimethylbenzyloxy group, trifluoromethylbenzyloxy group, methoxybenzyloxy group, dimethoxybenzyloxy group, trimethoxybenzyloxy group, ethoxybenzyloxy group, isopropoxybenzyloxy group, methylene Dioxybenzyloxy group, ethylenedioxybenzyloxy group, cyanobenzyloxy group, nitrobenzyloxy group, chlorobenzyloxy group, dichlorobenzyloxy group, fluorobenzyloxy group, difluorobenzyloxy group, chloro-methylbenzyloxy group, A fluoro-methylbenzyloxy group,
It may be a methoxycarbonylbenzyloxy group, a chloro-methoxybenzyloxy group, an acetylaminobenzyloxy group, a 1-phenylethoxy group, a 2-phenylethoxy group or a 3-phenylpropoxy group, preferably 1
C ₁ which may be substituted with phenyl groups which may be substituted (the substituents are selected from the following Substituent Group B1).
To C ₄ alkoxy groups, more preferably benzyloxy groups.

In the present invention, the "C ₃ -C ₆ alkenyloxy group" is an oxygen atom to which one "C ₃ -C ₆ alkenyl group" is bonded, such as an allyloxy group, 1-
It may be a propenyloxy group, a 2-methyl-1-propenyloxy group, a 2-methyl-2-propenyloxy group, a 3-butenyloxy group, a 2-methyl-2-butenyloxy group or a 4-pentenyloxy group, preferably , Carbon number 3
Or four linear or branched alkenyloxy groups,
More preferably, it is an allyloxy group.

In the present invention, "C which may be substituted"₂~
C₇Aliphatic acyl group (the substituent is a halogen atom
It ) ”Is the same or different 1-6 above“ halogens ”.
"C atom" may be substituted by the above "C₂~ C₇Aliphatic
And a chloroacetyl group, dichloro, etc.
Acetyl group, trichloroacetyl group, fluoroacetyl
Group, difluoroacetyl group, trifluoroacetyl group or
May be a 2- (trifluoromethyl) acryl group,
Suitably, a group consisting of fluorine atom, chlorine atom and bromine atom
By the same or different 1 to 3 substituents selected from
C that may be substituted ₂~ C_FiveIt is an aliphatic acyl group,
Suitably, C₂~ C_FiveIt is an aliphatic acyl group.

In the present invention, "a benzoyl group which may be substituted (the substituent is selected from the substituent group B)".
Are the above-mentioned "C ₁ -C ₆ alkyl group which may be substituted (the substituent is a halogen atom)", the "C ₁ -C ₆ alkoxy group", a cyano group, a nitro group, the "halogen atom". ], The above “C _{2 to} C ₇ alkoxycarbonyl group”, the above “C _{2 to} C ₇ alkylcarbonylamino group” and the above “C
₁ -C ₃ are the same or different 1 to 5 substituents may benzoyl group which is substituted by a group selected from the group consisting alkylenedioxy group ", for example, benzoyl group, methylbenzoyl group, ethylbenzoyl group, propyl Benzoyl group, isopropylbenzoyl group, dimethylbenzoyl group, trimethylbenzoyl group, trifluoromethylbenzoyl group, methoxybenzoyl group, dimethoxybenzoyl group, trimethoxybenzoyl group, ethoxybenzoyl group, isopropoxybenzoyl group, methylenedioxybenzoyl group, ethylene Dioxybenzoyl group, cyanobenzoyl group, nitrobenzoyl group, chlorobenzoyl group, dichlorobenzoyl group, fluorobenzoyl group, difluorobenzoyl group, chloro-methylbenzoyl group,
It may be a fluoro-methylbenzoyl group, a methoxycarbonylbenzoyl group, a chloro-methoxybenzoyl group or an acetylaminobenzoyl group, and is preferably a C ₁ -C ₄ alkyl group which may be substituted (the substituent is a fluorine atom,
It is selected from the group consisting of chlorine atom and bromine atom. ), C
₁ -C ₄ alkoxy group, a cyano group, a nitro group, a fluorine atom, a chlorine atom, a bromine atom, C ₂ -C ₅ alkoxycarbonyl group, C ₂ -C ₅ alkylcarbonylamino group, and C ₁ ~
A benzoyl group which may be substituted with 1 to 3 same or different substituents selected from the group consisting of C ₂ alkylenedioxy groups, more preferably a methyl group, a cyano group, a fluorine atom and a chlorine atom. It is a benzoyl group which may be substituted with 1 to 2 substituents which are the same or different and are selected from the group consisting of, and particularly preferably a benzoyl group.

In the present invention, "optionally substituted amino"
A group (the substituent is selected from the substituent group E) "
The above "C which may be substituted"₁~ C₆Alkyl group (the substituent
Is a cyano group, a halogen atom, a phenyl group and C₁~ C₆
It is selected from the group consisting of alkoxy groups. ) ”, The above“ C
₃~ C₆An alkenyl group ”, the above“ C₃~ C₆Alkynyl
Group ", the above-mentioned" C₃~ C₇Cycloalkyl group ", hydroxyl group, before
Note "C which may be replaced₁~ C₆Alkoxy group {the relevant substituent
Is a phenyl group which may be substituted (the substituent is a substituent
Selected from Group B. ). } ”, The above“ C₃~ C₆A
"Lukenyloxy group", the above-mentioned "phenyl group which may be substituted"
(The substituent is selected from the substituent group B.) "
“A heterocyclic group which may be substituted (the substituent is a substituent group C
Chosen from. ) ”, Said“ optionally substituted C₂~ C₇Fat
Aliphatic acyl group (the substituent is a halogen atom)
It ) ”And the above“ optionally substituted benzoyl group (wherein
The substituent is selected from the substituent group B. ) ”
The same or different 1 or 2 substituents selected from
An amino group which may be substituted, preferably substituted.
I C ₁~ C_FourAlkyl group (the substituent is a cyano group or a fluorine group)
Elemental atom, chlorine atom, bromine atom, phenyl group and C₁~ C_Four
It is selected from the group consisting of alkoxy groups. ), C₃~ C_FourA
Lucenyl group, C₃~ C_FourAlkynyl group, C₃~ C_FiveCycloa
Alkyl group, hydroxyl group, optionally substituted C₁~ C_FourAlkoxy
Group {the substituent is an optionally substituted phenyl group (the
The substituent is selected from the following substituent group B1. )
It }, C₃~ C_FourAlkenyloxy group, which may be substituted
Phenyl group (the substituent is selected from the following substituent group B1
Be done. ), A 4- to 6-membered heterocyclic group which may be substituted (the heterocyclic group
The ring is selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.
Having the same or different 1 to 3 heteroatoms selected,
It may be condensed with a benzene ring. The substituent is the following substituent
Selected from group C1. ), Optionally substituted C₂~ C_Fivefat
Group acyl group (the substituent is a fluorine atom, a chlorine atom and
It is selected from the group consisting of bromine atoms. ) And be replaced
A benzoyl group (the substituent is selected from the following substituent group B1
To be elected. ) The same or different selected from the group consisting of
An amino group which may be substituted by 1 to 2 substituents
And more preferably C which may be substituted₁~ C_FourAlkyl group
(The substituent is a cyano group, a fluorine atom, a chlorine atom,
Phenyl group and C₁~ C₂Selected from the group consisting of alkoxy groups
Be done. ), C₃~ C_FourAlkenyl group, C₃~ C_FourAlkynyl
Base, C₃~ C_FourCycloalkyl group, hydroxyl group, benzyloxy
Shi group, C₃~ C_FourAlkenyloxy group, phenyl group, 5
6-membered heterocyclic group (whether the heterocyclic ring is a nitrogen atom or a sulfur atom)
1 or 2 same or different complex selected from the group consisting of
It has an atom and may be condensed with the benzene ring. ), C₂~ C_Five
Selected from the group consisting of an aliphatic acyl group and a benzoyl group
Substituted with one or two identical or different substituents
A good amino group, and even more preferably, substituted.
I C₁~ C₂Alkyl group (the substituent is a phenyl group and
It is selected from the group consisting of methoxy groups. ) And allyl groups
1-2 identical or different substitutions selected from the group consisting of
An amino group which may be substituted with a group, particularly preferably
Is an amino group.

(1) In the present invention, R ¹ is preferably a C ₁ -C ₆ alkyl group which may be substituted (the substituent is a fluorine atom, a chlorine atom, a bromine atom and a C _{3 group} which may be substituted). A C ₆ cycloalkyl group (the cycloalkyl group may be interrupted by an oxygen atom.
₁ -C ₄ alkyl group, a fluorine atom, selected from the group consisting of chlorine and bromine. ) Is selected from the group consisting of. }, A C ₂ -C ₆ aliphatic acyl group, a phenyl group which may be substituted (the substituent is an optionally substituted C ₁ -C ₄ alkyl group (the substituent is a fluorine atom, a chlorine atom and a bromine atom). A C _{1 to} C ₄ alkoxy group, a cyano group, a nitro group, a fluorine atom, a chlorine atom, a bromine atom, a C _{2 to} C ₅ alkoxycarbonyl group, a C _{2 to} C ₅ alkylcarbonylamino group, and It is selected from the group consisting of C ₁ -C ₂ alkylenedioxy groups. }, 5 which may be substituted
6-membered heterocyclic group (the heterocyclic ring has the same or different 1 to 5 atoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom)
It has 3 heteroatoms. The substituent is a C ₁ -C ₄ alkyl group which may be substituted (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom), C ₁
-C ₄ alkoxy group, a cyano group, a phenyl group, a fluorine atom, a chlorine atom, a bromine atom, selected from C ₂ -C ₅ alkoxyalkyl group consisting carbonyl group and oxo group. } Or C ₁
To C ₄ alkylamino group, more preferably a C _{1 to} C ₅ alkyl group which may be substituted (the substituent is a fluorine atom, a chlorine atom and a C _{4 to} C ₆ cycloalkyl group (the cycloalkyl group). May be interrupted by an oxygen atom). }, A phenyl group which may be substituted (the substituent is selected from the group consisting of a methyl group, a cyano group, a fluorine atom and a chlorine atom) or a 6-membered heterocyclic group which may be substituted (the heterocycle is 1 To a nitrogen atom, the substituent is selected from the group consisting of a methyl group, a fluorine atom and a chlorine atom, and more preferably a C ₄ -C ₅ alkyl group which may be substituted. (the substituent is a fluorine atom.) or which may be substituted methyl group (the substituent is a C ₄ -C ₅ cycloalkyl group.)
And particularly preferably an isobutyl group, a neopentyl group, a 3,3,3-trifluoro-2-methylpropyl group or a cyclopentylmethyl group.

(2) In the present invention, R ² is preferably a hydrogen atom or an optionally substituted C ₁ -C ₄ alkyl group (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom). And more preferably a C ₁ -C ₂ alkyl group which may be substituted (the substituent is selected from the group consisting of a fluorine atom and a chlorine atom),
More preferably, it is a methyl group which may be substituted (the substituent is a fluorine atom), and particularly preferably, it is a methyl group.

(3) In the present invention, R³Is preferably
Is a chlorine atom, optionally substituted C₁~ C_FiveAlkyl group (this
The substituent is selected from the following substituent group D1. ), C₃
~ C₆Cycloalkyl group, optionally substituted phenyl group
(The substituent is selected from the following substituent group B1),
C that may be substituted₁~ C_FourAlkoxy group (the substituent is
C ₁~ C_FourIt is an alkoxy group. ), Which may be replaced
A nonoxy group (the substituent is selected from the following substituent group B1)
It ), A 5- or 6-membered heterocyclic oxy group which may be substituted (wherein
Heterocycle is a group consisting of nitrogen atom, sulfur atom and oxygen atom.
Having 1 to 3 different or identical heteroatoms selected from
To do. The substituent is selected from the following substituent group C1.
It ), Optionally substituted C₁~ C_FourAlkylthio group
The substituents are cyano group, phenyl group and C₁~ C_FourArcoki
Selected from the group consisting of Si groups. ), Which may be replaced
Nylthio group (the substituent is selected from the following substituent group B1
Be done. ), An optionally substituted 5- or 6-membered heterocyclic thio group (wherein
Heterocycle is a group consisting of nitrogen atom, sulfur atom and oxygen atom.
Having 1 to 3 different or identical heteroatoms selected from
To do. The substituent is selected from the following substituent group C1.
It ), A 4- to 6-membered cyclic amino group which may be substituted (the ring
Amino groups may be interrupted by one oxygen atom.
The substituent is C₁~ C_FourAlkyl group and C₂~ C_FiveArco
It is selected from the group consisting of oxycarbonyl groups. ) Or replacement
Optionally substituted amino group (the substituent is the following substituent group E1
Chosen from. ) And the substituent group B1 is substituted
Good C₁~ C_FourAlkyl group (the substituent is a fluorine atom,
It is selected from the group consisting of chlorine atom and bromine atom. ), C
₁~ C_FourAlkoxy, cyano, nitro, fluorogen
Child, chlorine atom, bromine atom, C₂~ C_FiveAlkoxy Carboni
Lu group, C₂~ C_FiveAlkylcarbonylamino group and C₁~
C₂A group consisting of alkylenedioxy groups, a group of substituents
C1 may be substituted C₁~ C_FourAlkyl group (substitution
Is the group a group consisting of fluorine, chlorine and bromine atoms?
Chosen from. ), C₁~ C_FourAlkoxy group, cyano group,
Phenyl group, fluorine atom, chlorine atom, bromine atom, C₂~ C_Five
A group consisting of an alkoxycarbonyl group and an oxo group
Substituent group D1 is a fluorine atom, a chlorine atom, or a bromine atom.
Child, hydroxyl group, C₁~ C_FourAlkoxy group, optionally substituted C
₂~ C_FiveAliphatic acyloxy group (the substituent is C₃~ C₆
Cycloalkyl group, C₁~ C_FourAlkoxy group, Fluorogen
Selected from the group consisting of children, chlorine atoms and bromine atoms.
It ), An optionally substituted phenoxy group (the substituent is
It is selected from the above substituent group B1. ), Optionally substituted 5
~ 6-membered heterocyclic oxy group (the heterocyclic ring is a nitrogen atom, sulfur
Same or different selected from the group consisting of atom and oxygen atom
It has only 1 to 3 heteroatoms. The substituent is the above
It is selected from the substituent group C1. ), Optionally substituted C₁~
C_FourAlkylthio group (the substituent is a cyano group, a phenyl group
Ru radical and C₁~ C_FourSelected from the group consisting of alkoxy groups
It ), A phenylthio group which may be substituted (the substituent
Is selected from the above substituent group B1. ), Please be replaced
A 5- or 6-membered heterocyclic thio group (the heterocyclic ring is a nitrogen atom, a sulfur
The same or different selected from the group consisting of yellow atom and oxygen atom
It has 1 to 3 heteroatoms. The substituent is
It is selected from the above substituent group C1. ), C₂~ C_FiveAliphatic reed
A ruthio group, an optionally substituted phenyl group (the substituent is
It is selected from the above substituent group B1. ) And may be replaced
5- or 6-membered heterocyclic group (the heterocycle is a nitrogen atom, a sulfur atom
And the same or different selected from the group consisting of oxygen atoms
It has 1 to 3 heteroatoms. The substituent is the above-mentioned substituent
It is selected from the base group C1. ), The group of substituents
E1 is C which may be substituted₁~ C_FourAlkyl group (substitution
The group includes a cyano group, a fluorine atom, a chlorine atom, a bromine atom, and a fluorine atom.
Phenyl group and C₁~ C_FourSelected from the group consisting of alkoxy groups
Be done. ), C₃~ C_FourAlkenyl group, C₃~ C_FourAlkynyl
Base, C ₃~ C_FiveCycloalkyl group, hydroxyl group, please be replaced
I C₁~ C_FourAlkoxy group {The substituent should be substituted.
A phenyl group (the substituent is selected from the above substituent group B1)
Be exposed. ). }, C₃~ C_FourAlkenyloxy group,
A phenyl group which may be substituted (the substituent is the above-mentioned substituent
Selected from group B1. ), A 4-6 membered complex that may be substituted
A cyclic group (the heterocyclic ring is a nitrogen atom, a sulfur atom or an oxygen atom)
Same or different 1 to 3 compounds selected from the group consisting of
It has an elementary atom and may be condensed with a benzene ring. The substituent
Is selected from the above substituent group C1. ), Please be replaced
I C₂~ C_FiveAliphatic acyl group (the substituent is a fluorine atom)
Selected from the group consisting of a child, a chlorine atom and a bromine atom. )
And a benzoyl group which may be substituted (the substituent is the above
It is selected from the substituent group B1. ), And more
Suitably C which may be substituted₁~ C_FourAlkyl group
The substituent is selected from the following substituent group D2. ), C₃~ C_Five
A cycloalkyl group, an optionally substituted phenyl group (the
The substituent is selected from the following substituent group B2. ), Replaced
May be C₁~ C_FourAlkoxy group (the substituent is C₁~ C₂
It is an alkoxy group. ), Optionally substituted phenoxy group
(The substituent is selected from the following substituent group B2),
A 6-membered heterocyclic oxy group which may be substituted (the heterocyclic group is 1
Has ˜2 nitrogen atoms. The substituent is the following substituent
Selected from group C2. ), C₁~ C_FourAlkylthio group, 6
Membered heterocyclic thio group (the heterocyclic ring has 1 to 2 nitrogen atoms)
Have. ) 4- to 5-membered cyclic amino group (the cyclic amino group
May be interrupted by one oxygen atom. ) Or replacement
An amino group which may be substituted (the substituent is represented by the following substituent group E2
Chosen from. ) And the substituent group B2 is C₁~ C₂A
Alkyl group, cyano group, fluorine atom, chlorine atom and bromine source
And the substituent group C2 is C₁~ C₂Archi
Group, cyano group, fluorine atom, chlorine atom, bromine atom and
Substituent group D2 is a group consisting of oxo groups,
Child, chlorine atom, hydroxyl group, C₁~ C₂Alkoxy group, substituted
May be C₂~ C_FiveAliphatic acyloxy group (the substituent
Is selected from the group consisting of a fluorine atom and a chlorine atom.
It ), An optionally substituted phenoxy group (the substituent is
It is selected from the above substituent group B2. ), Optionally substituted 5
~ 6-membered heterocyclic oxy group (the heterocyclic ring is a nitrogen atom and an acid
The same or different 1-2 selected from the group consisting of elementary atoms
Has 4 heteroatoms. The said substituent is the said substituent group C
Selected from 2. ), Optionally substituted C₁~ C₂Alkyl
A thio group (the substituent is a cyano group), substituted
A phenylthio group (the substituent is the above-mentioned substituent group B)
Selected from 2. ), Optionally substituted 5-membered heterocyclic thio group
(The heterocycle is selected from the group consisting of nitrogen atom and sulfur atom.
Have 1 to 3 heteroatoms selected, identical or different
It The substituent is selected from the above substituent group C2. )
And 5 heterocyclic groups which may be substituted (the heterocyclic group is 1-2
It has nitrogen atoms. The said substituent is the said substituent group C
Selected from 2. ), And the substituent group E2
Is C which may be substituted₁~ C_FourAlkyl group (the substituent
Is a cyano group, a fluorine atom, a chlorine atom, a phenyl group and
C₁~ C₂It is selected from the group consisting of alkoxy groups. ), C
₃~ C_FourAlkenyl group, C₃~ C_FourAlkynyl group, C₃~ C_Four
Cycloalkyl group, hydroxyl group, benzyloxy group, C₃~
C_FourAlkenyloxy group, phenyl group, 5-6 membered heterocycle
A group (whether the heterocycle is a group consisting of a nitrogen atom and a sulfur atom)
Having one or two heteroatoms selected from the same or different
However, it may be condensed with a benzene ring. ), C₂~ C_FiveAliphatic
A group consisting of a silyl group and a benzoyl group,
Suitably C which may be substituted₁~ C₂Alkyl group (substitution
The group is selected from the following substituent group D3. ), C₃~ C_FourShi
Chloroalkyl group, C₁~ C₂Alkoxy group, pyridinyl
An oxy group or an optionally substituted amino group (the substituent is
It is selected from the substituent group E3. ), And the substituent group D3
Is a hydroxyl group, methoxy group, C₂~ C_FourAliphatic acyloxy
Group, an optionally substituted phenoxy group (the substituent is a sialic group
No group and a fluorine atom. ), Replace
May be a pyridyloxy group (the substituent is a methyl group
Is. ), Cyanomethylthio group, optionally substituted thia
Diazolylthio group (the substituent is a methyl group.)
And an optionally substituted pyrazolyl group (the substituent is bromine
Is an atom. ), The substituent group E3 is
C that may be exchanged₁~ C₂Alkyl group (the substituent is
It is selected from the group consisting of a nyl group and a methoxy group. )as well as
A group consisting of an allyl group, particularly preferably a methyl group,
Hydroxymethyl group, methoxymethyl group, acetoxime
Cyl group, (bromopyrazolyl) methyl group, cyclopropyi
Group or amino group.

(4) In the present invention, X is preferably an oxygen atom.

(5) In the present invention, Y is preferably a methyl group, a fluorine atom or a chlorine atom, and n is
It is 0 or 1, and more preferably n is 0.

When the compound (I) of the present invention has a hydroxyl group in the molecule, it can be converted into, for example, an alkali metal salt, an alkaline earth metal salt or an ammonium salt, and has a basic moiety in the molecule. In this case, for example, salts such as sulfate, hydrochloride, nitrate and phosphate can be used.
These salts are included in the present invention as long as they can be used as fungicides for agriculture and horticulture.

In the present invention, the "alkali metal salt" includes, for example, sodium salt, potassium salt and lithium salt, and preferably sodium salt or potassium salt.

In the present invention, "alkaline earth metal salt"
Examples of the salt include a calcium salt and a magnesium salt, and a calcium salt is preferable.

A hydrate of the compound of the present invention is also included in the present invention.

Among the compounds of the present invention, there are compounds having an asymmetric carbon, and in this case, the present invention includes one kind of optically active substance and a mixture of several kinds of optically active substance in any ratio. .

In the compound (I) of the present invention, preferably
Is (a1) R¹Is C which may be substituted₁~ C₆Archi
Group (the relevant substituent is a fluorine atom, a chlorine atom, a bromine atom)
And C which may be substituted₃~ C₆Cycloalkyl group
The chloroalkyl group may be interrupted by an oxygen atom. This
The substituent is C₁~ C_FourAlkyl group, fluorine atom, chlorine source
Selected from the group consisting of a child and a bromine atom. Group consisting of
Chosen from. }, C₂~ C₆Aliphatic acyl group, substituted
A phenyl group which may be substituted (the substituent is optionally substituted C₁
~ C_FourAlkyl group (The substituent is a fluorine atom, chlorine atom
Selected from the group consisting of a child and a bromine atom. ), C₁~ C_Four
Alkoxy group, cyano group, nitro group, fluorine atom, chlorine
Atom, bromine atom, C₂~ C_FiveAlkoxycarbonyl group, C
₂~ C_FiveAlkylcarbonylamino group and C₁~ C₂Archi
It is selected from the group consisting of dioxy groups. }, Replaced
A 5- or 6-membered heterocyclic group which may be
The same or different selected from the group consisting of yellow atom and oxygen atom
It has 1 to 3 heteroatoms. The substituent is
C that may be exchanged₁~ C_FourAlkyl group (the substituent is
Selected from the group consisting of elementary atoms, chlorine atoms and bromine atoms
It ), C₁~ C_FourAlkoxy group, cyano group, phenyl
Group, fluorine atom, chlorine atom, bromine atom, C₂~ C_FiveArco
Selected from the group consisting of a oxycarbonyl group and an oxo group
It } Or C₁~ C_FourAn alkylamino group, (a2)
  R²Is a hydrogen atom or optionally substituted C₁~ C_FourArchi
Group (the relevant substituents are fluorine atom, chlorine atom and bromine atom)
Selected from the group of children. ), And (a3) R³
Is a chlorine atom, optionally substituted C₁~ C_FiveAlkyl group (this
The substituent is selected from the following substituent group D1. ), C₃
~ C₆Cycloalkyl group, optionally substituted phenyl group
(The substituent is selected from the following substituent group B1),
C that may be substituted₁~ C_FourAlkoxy group (the substituent is
C₁~ C_FourIt is an alkoxy group. ), Which may be replaced
A nonoxy group (the substituent is selected from the following substituent group B1)
It ), A 5- or 6-membered heterocyclic oxy group which may be substituted (wherein
Heterocycle is a group consisting of nitrogen atom, sulfur atom and oxygen atom.
Having 1 to 3 different or identical heteroatoms selected from
To do. The substituent is selected from the following substituent group C1.
It ), Optionally substituted C₁~ C_FourAlkylthio group
The substituents are cyano group, phenyl group and C₁~ C_FourArcoki
Selected from the group consisting of Si groups. ), Which may be replaced
Nylthio group (the substituent is selected from the following substituent group B1
Be done. ), An optionally substituted 5- or 6-membered heterocyclic thio group (wherein
Heterocycle is a group consisting of nitrogen atom, sulfur atom and oxygen atom.
Having 1 to 3 different or identical heteroatoms selected from
To do. The substituent is selected from the following substituent group C1.
It ), A 4- to 6-membered cyclic amino group which may be substituted (the ring
Amino groups may be interrupted by one oxygen atom.
The substituent is C₁~ C_FourAlkyl group and C₂~ C_FiveArco
It is selected from the group consisting of oxycarbonyl groups. ) Or replacement
Optionally substituted amino group (the substituent is the following substituent group E1
Chosen from. ) And the substituent group B1 is substituted
Good C₁~ C_FourAlkyl group (the substituent is a fluorine atom,
It is selected from the group consisting of chlorine atom and bromine atom. ), C
₁~ C_FourAlkoxy, cyano, nitro, fluorogen
Child, chlorine atom, bromine atom, C₂~ C_FiveAlkoxy Carboni
Lu group, C₂~ C_FiveAlkylcarbonylamino group and C₁~
C₂A group consisting of alkylenedioxy groups, a group of substituents
C1 may be substituted C₁~ C_FourAlkyl group (substitution
Is the group a group consisting of fluorine, chlorine and bromine atoms?
Chosen from. ), C₁~ C_FourAlkoxy group, cyano group,
Phenyl group, fluorine atom, chlorine atom, bromine atom, C₂~ C_Five
A group consisting of an alkoxycarbonyl group and an oxo group
Substituent group D1 is a fluorine atom, a chlorine atom, or a bromine atom.
Child, hydroxyl group, C₁~ C_FourAlkoxy group, optionally substituted C
₂~ C_FiveAliphatic acyloxy group (the substituent is C₃~ C₆
Cycloalkyl group, C₁~ C_FourAlkoxy group, Fluorogen
Selected from the group consisting of children, chlorine atoms and bromine atoms.
It ), An optionally substituted phenoxy group (the substituent is
It is selected from the above substituent group B1. ), Optionally substituted 5
~ 6-membered heterocyclic oxy group (the heterocyclic ring is a nitrogen atom, sulfur
Same or different selected from the group consisting of atom and oxygen atom
It has only 1 to 3 heteroatoms. The substituent is the above
It is selected from the substituent group C1. ), Optionally substituted C₁~
C_FourAlkylthio group (the substituent is a cyano group, a phenyl group
Ru radical and C₁~ C_FourSelected from the group consisting of alkoxy groups
It ), A phenylthio group which may be substituted (the substituent
Is selected from the above substituent group B1. ), Please be replaced
A 5- or 6-membered heterocyclic thio group (the heterocyclic ring is a nitrogen atom, a sulfur
The same or different selected from the group consisting of yellow atom and oxygen atom
It has 1 to 3 heteroatoms. The substituent is
It is selected from the above substituent group C1. ), C₂~ C_FiveAliphatic reed
A ruthio group, an optionally substituted phenyl group (the substituent is
It is selected from the above substituent group B1. ) And may be replaced
5- or 6-membered heterocyclic group (the heterocycle is a nitrogen atom, a sulfur atom
And the same or different selected from the group consisting of oxygen atoms
It has 1 to 3 heteroatoms. The substituent is the above-mentioned substituent
It is selected from the base group C1. ), The group of substituents
E1 is C which may be substituted₁~ C_FourAlkyl group (substitution
The group includes a cyano group, a fluorine atom, a chlorine atom, a bromine atom, and a fluorine atom.
Phenyl group and C₁~ C_FourSelected from the group consisting of alkoxy groups
Be done. ), C₃~ C_FourAlkenyl group, C₃~ C_FourAlkynyl
Base, C ₃~ C_FiveCycloalkyl group, hydroxyl group, please be replaced
I C₁~ C_FourAlkoxy group {The substituent should be substituted.
A phenyl group (the substituent is selected from the above substituent group B1)
Be exposed. ). }, C₃~ C_FourAlkenyloxy group,
A phenyl group which may be substituted (the substituent is the above-mentioned substituent
Selected from group B1. ), A 4-6 membered complex that may be substituted
A cyclic group (the heterocyclic ring is a nitrogen atom, a sulfur atom or an oxygen atom)
Same or different 1 to 3 compounds selected from the group consisting of
It has an elementary atom and may be condensed with a benzene ring. The substituent
Is selected from the above substituent group C1. ), Please be replaced
I C₂~ C_FiveAliphatic acyl group (the substituent is a fluorine atom)
Selected from the group consisting of a child, a chlorine atom and a bromine atom. )
And a benzoyl group which may be substituted (the substituent is the above
It is selected from the substituent group B1. ), And (a
4) X is an oxygen atom or a sulfur atom, (a5)
Y is a methyl group, a fluorine atom or a chlorine atom, and n
Is 0 or 1, and more preferably (b1) R
¹Is C which may be substituted₁~ C_FiveAlkyl group {the relevant substituent
Is a fluorine atom, a chlorine atom and C_Four~ C₆Cycloalkyl
A group (the cycloalkyl group is interrupted by an oxygen atom)
You may ) Is selected from the group consisting of. }, Be replaced
A phenyl group (the relevant substituents are a methyl group, a cyano group,
It is selected from the group consisting of fluorine atom and chlorine atom. ) Or
6-membered heterocyclic group which may be substituted (the heterocyclic ring is 1-2
Containing nitrogen atoms of. The substituent is a methyl group or a fluorine group.
It is selected from the group consisting of elementary atoms and chlorine atoms. )
R, (b2) R²Is C which may be substituted₁~ C₂Archi
Group (the substituent is composed of a fluorine atom and a chlorine atom)
Selected from the group. ), And (b3) R³Is replaced
May be C₁~ C_FourAlkyl group (The substituent is the following substitution
It is selected from the group D2. ), C₃~ C_FiveCycloalkyl
Group, a phenyl group which may be substituted (the substituent is
It is selected from the substituent group B2. ), Optionally substituted C ₁~ C_Four
Alkoxy group (the substituent is C₁~ C₂With an alkoxy group
is there. ), An optionally substituted phenoxy group (the substituent
Is selected from the following substituent group B2. ), Please be replaced
A 6-membered heterocyclic oxy group (the heterocyclic ring has 1 to 2 nitrogen atoms)
Have atoms. The substituent is selected from the following substituent group C2.
Be exposed. ), C₁~ C_FourAlkylthio group, 6-membered heterocyclic thio
A group (the heterocycle has 1 to 2 nitrogen atoms),
4- to 5-membered cyclic amino group (the cyclic amino group is a single acid
It may be interrupted by elementary atoms. ) Or an optionally substituted
Mino group (the substituent is selected from the following substituent group E2
It ) And the substituent group B2 is C₁~ C₂An alkyl group,
Consists of cyano group, fluorine atom, chlorine atom and bromine atom
And the substituent group C2 is C₁~ C₂Alkyl group, shea
Group, fluorine atom, chlorine atom, bromine atom and oxo group
Substituent group D2 is a group consisting of a fluorine atom and a chlorine atom.
Child, hydroxyl group, C₁~ C₂Alkoxy group, optionally substituted C
₂~ C_FiveAliphatic acyloxy group (the relevant substituent is a fluorogen
Selected from the group consisting of a child and a chlorine atom. ), Replaced
A phenoxy group (the substituent is the above-mentioned Substituent Group B2
Chosen from. ), Optionally substituted 5- or 6-membered heterocyclic oki
Si group (the heterocycle is a group consisting of a nitrogen atom and an oxygen atom
Having 1 to 2 different or identical heteroatoms selected from
To do. The substituent is selected from the above substituent group C2.
It ), Optionally substituted C₁~ C₂Alkylthio group
The substituent is a cyano group. ), Optionally substituted phenyl
Ruthio group (the substituent is selected from the above substituent group B2)
It ), An optionally substituted 5-membered heterocyclic thio group (the heterocyclic ring
Are the same selected from the group consisting of nitrogen atom and sulfur atom.
Or has 1 to 3 different heteroatoms. The substituent
Is selected from the above substituent group C2. ) And replaced
Good 5 heterocyclic groups (the heterocyclic group has 1 to 2 nitrogen atoms)
Have. The substituent is selected from the above substituent group C2.
It ), Wherein the substituent group E2 is substituted
Good C₁~ C_FourAlkyl group (the substituent is a cyano group,
Fluorine atom, chlorine atom, phenyl group and C₁~ C₂Arcoki
Selected from the group consisting of Si groups. ), C₃~ C_FourAlkenyl
Base, C₃~ C_FourAlkynyl group, C₃~ C_FourCycloalkyl
Group, hydroxyl group, benzyloxy group, C₃~ C_FourAlkenyl
Xy group, phenyl group, 5- or 6-membered heterocyclic group (the heterocyclic ring
Are the same selected from the group consisting of nitrogen atom and sulfur atom.
Or having 1 to 2 different heteroatoms and a benzene ring
May be condensed. ), C₂~ C_FiveAliphatic acyl group and benzo
(B4) X is an oxygen atom or
Is a sulfur atom, (b5) n is 0, and
More preferably, (c1) R¹Is C which may be substituted_Four~ C
_FiveAlkyl group (the substituent is a fluorine atom)
Is a methyl group which may be substituted (the substituent is C_Four~ C_FiveShi
It is a chloroalkyl group. ) And (c2) R²Is
A methyl group which may be substituted (the substituent is a fluorine atom)
is there. ), And (c3) R³Is C which may be substituted₁
~ C₂Alkyl group (whether the substituent is the following substituent group D3
Chosen from. ), C₃~ C_FourCycloalkyl group, C₁~ C₂
Alkoxy group, pyridinyloxy group or may be substituted
Amino group (the substituent is selected from the following substituent group E3
It ) And the substituent group D3 is a hydroxyl group, a methoxy group,
C₂~ C_FourAliphatic acyloxy group, optionally substituted pheno
Xy group (the substituent is composed of a cyano group and a fluorine atom)
Selected from the group. ), Optionally substituted pyridyloxy
Group (the substituent is a methyl group), cyanomethyl
Thio group, optionally substituted thiadiazolylthio group (substitute
The substituent is a methyl group. ) And optionally substituted pyrazo
A group consisting of a ryl group (the substituent is a bromine atom).
And the substituent group E3 is C which may be substituted.₁~ C₂Al
Kill group (the substituent is a phenyl group or a methoxy group
Selected from the group. ) And an allyl group
And (c4) X is an oxygen atom, and (c5) n
Is 0, and particularly preferably (d1) R¹Is the
Butyl group, neopentyl group, 3,3,3-trifluoro
2-methylpropyl group or cyclopentylmethyl group
Yes, (d2) R²Is a methyl group, and (d3)
R³Is a methyl group, hydroxymethyl group, methoxymethyl group
Group, acetoxymethyl group, (bromopyrazolyl) methyl
A group, a cyclopropyl group or an amino group, (d4)
  X is an oxygen atom, and (d5) n is 0.

Representative compounds of the present invention are shown in Tables 1 to 11, but the present invention is not limited to these compounds.

Hereinafter, "Me" is a methyl group, "Et" is an ethyl group, "Pr" is a propyl group, "iPr" is an isopropyl group, "cPr" is a cyclopropyl group, and "Bu" is Butyl group, "iBu" is an isobutyl group, "tBu" is a tert-butyl group, "cBu" is a cyclobutyl group, "cPent" is a cyclopentyl group, "cHex" is a cyclohexyl group,
"Ph" represents a phenyl group, a "2-Me-Ph" 2-methylphenyl group, a "2,3-F ₂ -Ph" is 2,3-difluorophenyl group, "Bn" refers to benzyl , "2-Pyr" is a 2-pyridyl group, "3-Isox" is a 3-isoxazolyl group,
"2-Thida" is a 2- (1,3,4-thiadiazolyl) group, "1-Aze" is a 1-azetidinyl group, "1-Pyrd" is a 1-pyrrolidinyl group, and "1-Pip" is Piperidino group,
"4-Mor" is a morpholino group and "5-Me-3-Isox" is 5-
Methyl-3-isoxazolyl group, "1-Pyza" is 1-
A pyrazolyl group, "2-oxo-1-Pyr" is 2-oxo-1-
Pyridyl group, "2-Quino" is 2-quinolyl group, "C
"N" is a cyano group, "Ac" is an acetyl group, "2- (4,5-Dh
thia) "is a 4,5-dihydrothiazol-2-yl group, and in Yn" H "is n = 0. In Yn," 5-Me "is a methyl group at the 5-position of the benzene ring. This is shown respectively.

[0052]

[Table 1]

[0053]

[Chemical 3]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 1-1 Me Me OH 1-2 Me Et OH 1-3 Me Pr OH 1 -4 Me iPr OH 1-5 Me Bu OH 1-6 Me tBu OH 1-7 Me cPr OH 1-8 Me cBu OH 1-9 Me cPent OH 1-10 Me cHex OH 1-11 Me Cl OH 1-12 Me CH ₂ Cl OH 1-13 Me CH ₂ Br OH 1-14 Me CH ₂ FOH 1-15 Me CHCl ₂ OH 1-16 Me CHF ₂ OH 1-17 Me CCl ₃ OH 1-18 Me CF ₃ OH 1- 19 Me Ph OH 1-20 Me 2-Me-Ph OH 1-21 Me 3-Me-Ph OH 1-22 Me 4-Me-Ph OH 1-23 Me 2-OMe-Ph OH 1-24 Me 3- OMe-Ph OH 1-25 Me 4-OMe-Ph OH 1-26 Me 2-Cl-Ph OH 1-27 Me 3-Cl-Ph OH 1-28 Me 4-Cl-Ph OH 1-29 Me 2- F-Ph OH 1-30 Me 3-F-Ph OH 1-31 Me 2-CN-Ph OH 1-32 Me 3-CN-Ph OH 1-33 Me 4-CN-Ph OH 1-34 Me 3- NO ₂ -Ph OH 1-35 Me CH ₂ OH OH 1-36 Me CH (Me) OH OH 1-37 Me CH ₂ CH ₂ OH OH 1-38 Me CH ₂ CH ₂ CH ₂ OH OH 1-39 Me CH ₂ OMe OH 1-40 Me CH (Me) OMe OH 1-41 Me CH ₂ CH ₂ OMe OH 1- 42 Me CH ₂ OEt OH 1-43 Me CH ₂ SMe OH 1-44 Me CH ₂ SEt OH 1-45 Me CH ₂ SCH ₂ CN OH 1-46 Me CH ₂ SCH ₂ OMe OH 1-47 Me CH ₂ CH ₂ SMe OH 1-48 Me CH ₂ OPh OH 1-49 Me CH ₂ O- (2-Me-Ph) OH 1-50 Me CH ₂ O- (3-Me-Ph) OH 1-51 Me CH ₂ O- (4-Me-Ph) OH 1-52 Me CH ₂ O- (2-OMe-Ph) OH 1-53 Me CH ₂ O- (3-OMe-Ph) OH 1-54 Me CH ₂ O- (4 -OMe-Ph) OH 1-55 Me CH ₂ O- (2-Cl-Ph) OH 1-56 Me CH ₂ O- (3-Cl-Ph) OH 1-57 Me CH ₂ O- (4-Cl -Ph) OH 1-58 Me CH ₂ O- (2-F-Ph) OH 1-59 Me CH ₂ O- (3-F-Ph) OH 1-60 Me CH ₂ O- (4-F-Ph ) OH 1-61 Me CH ₂ O- (2,3-F ₂ -Ph) OH 1-62 Me CH ₂ O- (2,4-F ₂ -Ph) OH 1-63 Me CH ₂ O- (3 , 4-F ₂ -Ph) OH 1-64 Me CH ₂ O- (3,5-F ₂ -Ph) OH 1-65 Me CH ₂ O- (2-CN-Ph) OH 1-66 Me CH ₂ O- (3-CN-Ph) OH 1-67 Me CH ₂ O- (4-CN-Ph) OH 1-68 Me CH ₂ O- (3-NO ₂ -Ph) OH 1-69 Me CH ₂ S -(2-F-Ph) OH 1-70 Me CH ₂ S- (3-F-Ph) OH 1-71 Me CH ₂ S- (4-F-Ph) OH 1-72 Me CH ₂ S- ( 4-Cl-Ph) OH 1-73 Me CH ₂ S- (4-CN-Ph) OH 1-74 Me CH ₂ S- (4-Me-Ph) OH 1-75 Me CH ₂ OAc OH 1-76 Me CH ₂ OCOPr OH 1-77 Me CH ₂ OCOcPr OH 1-78 Me CH ₂ OCOcBu OH 1-79 Me CH ₂ O COCH ₂ CH = CH ₂ OH 1-80 Me CH ₂ OCOCH = C (Me) ₂ OH 1-81 Me CH ₂ OCOC (Me) = CH ₂ OH 1-82 Me CH ₂ OCOC (CF ₃ ) = CH ₂ OH 1-83 Me CH ₂ OCOCH ₂ Cl OH 1-84 Me CH ₂ OCOCHCl ₂ OH 1-85 Me CH ₂ OCOCCl ₃ OH 1-86 Me CH ₂ OCOCH ₂ FOH 1-87 Me CH ₂ OCOCHF ₂ OH 1-88 Me CH ₂ SAc OH 1-89 Me CH ₂ O- (2-Pyr) OH 1-90 Me CH ₂ O- (3-Me-2-Pyr) OH 1-91 Me CH ₂ O- (6-Me-2 -Pyr) OH 1-92 Me CH ₂ O- (3-Cl-2-Pyr) OH 1-93 Me CH ₂ O- (5-Cl-2-Pyr) OH 1-94 Me CH ₂ O- (6 -Cl-2-Pyr) OH 1-95 Me CH ₂ O- (6-OMe-2-Pyr) OH 1-96 Me CH ₂ O- (5-Me-3-Isox) OH 1-97 Me CH ₂ S- (5-Me-2-Thida) OH 1-98 Me CH ₂ -1-Pyza OH 1-99 Me CH _2- (4-Br-1-Pyza) OH 1-100 Me CH _2- (4- CH ₃ -1-Pyza) OH 1-101 Me CH _2- (2-oxo-1-Pyr) OH 1-102 Me CH _2- (2-oxo-3-Me-1-Pyr) OH 1-103 Me OMe OH 1-104 Me OEt OH 1-105 Me OPr OH 1-106 Me OBu OH 1-107 Me OtBu OH 1-108 Me OPh OH 1-109 Me O- (4-Me-Ph) OH 1-110 Me O- (4-OMe-Ph) OH 1-111 Me O- (2-F-Ph) OH 1-112 Me O- (3-F-Ph) OH 1-113 Me O- (4-F-Ph ) OH 1-114 Me O- (4-Cl-Ph) OH 1-115 Me O- (3-CN-Ph) OH 1-116 Me O- (4-CN-Ph) OH 1-117 Me O- (4-CF ₃ -Ph) OH 1-118 Me O-2-Pyr OH 1-119 Me O-3-Pyr OH 1-120 Me O- (5-Cl-2-Pyr) OH 1-121 Me O- (6- Cl-2-Pyr) OH 1-122 Me O- (3-Me-2-Pyr) OH 1-123 Me O- (6-Me-2-Pyr) OH 1-124 Me OCH ₂ OMe OH 1-125 Me OCH ₂ OEt OH 1-126 Me OCH ₂ OPr OH 1-127 Me OCH ₂ CH ₂ OMe OH 1-128 Me OCH ₂ CH ₂ OEt OH 1-129 Me OCH ₂ CH ₂ CH ₂ OMe OH 1-130 Me SMe OH 1-131 Me SEt OH 1-132 Me SPr OH 1-133 Me SBu OH 1-134 Me S-iPr OH 1-135 Me StBu OH 1-136 Me SCH ₂ OMe OH 1-137 Me S-2-Pyr OH 1-138 Me S-3-Pyr OH 1-139 Me NH ₂ OH 1-140 Me NHMe OH 1-141 Me NHEt OH 1-142 Me NHiPr OH 1-143 Me NHBu OH 1-144 Me NHiBu OH 1- 145 Me NHtBu OH 1-146 Me NHcPr OH 1-147 Me NHcBu OH 1-148 Me NHPh OH 1-149 Me NHBn OH 1-150 Me NHCH (Me) Ph OH 1-151 Me NHCH (CN) Ph OH 1- 152 Me NHCH ₂ CH = CH ₂ OH 1-153 Me NHCH ₂ C ≡ CH OH 1-154 Me NHCH ₂ CF ₃ OH 1-155 Me NHCH ₂ CH ₂ OMe OH 1-156 Me NHCH ₂ CN OH 1-157 Me NHOH OH 1-158 Me NHOCH ₂ CH = CH ₂ OH 1-159 Me NHOBn OH 1-160 Me 1-Aze OH 1-161 Me 1-Pyrd OH 1-162 Me 3-COOMe-1-Pyrd OH 1-163 Me 1-Pip OH 1-164 Me 4-Mor OH 1 -165 Me NH-2-Quino OH 1-166 Me NH-3-Quino OH 1-167 Me NH-4-Quino OH 1-168 Me NH-2- (4,5-Dhthia) OH 1-169 Me NHAc OH 1-170 Me NHCOPh OH 1-171 H Me OH 1-172 H Et OH 1-173 H Ph OH 1-174 H CH ₂ OH OH 1-175 H CH ₂ OMe OH 1-176 H CH ₂ OPh OH 1 -177 H CH ₂ OAc OH 1-178 H CH ₂ O-2-Pyr OH 1-179 H OMe OH 1-180 H OPh OH 1-181 H O-2-Pyr OH 1-182 H NH ₂ OH 1- 183 CF ₃ Me OH 1-184 Me NH ₂ SH 1-185 Me OPh SH 1-186 Me SPh SH 1-187 Me O-2-Pyr SH 1-188 Me S-2-Pyr SH 1-189 Me Me O 5-Me 1-190 Me Me O 2-OMe 1-191 Me Me O 4-F 1-192 Me Me O 6-Br 1-193 Me Me O 5-CN 1-194 Me Me O 4-NO ₂ ─ ───────────────────────────────────

[0055]

[Table 2]

[0056]

[Chemical 4]

──────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 2-1 Me Me OH 2-2 Me Et OH 2-3 Me Pr OH 2 -4 Me iPr OH 2-5 Me Bu OH 2-6 Me tBu OH 2-7 Me cPr OH 2-8 Me cBu OH 2-9 Me Ph OH 2-10 Me CH ₂ OH OH 2-11 Me CH (Me ) OH OH 2-12 Me C (Me) ₂ OH OH 2-13 Me CH ₂ CH ₂ OH OH 2-14 Me CH ₂ OMe OH 2-15 Me CH (Me) OMe OH 2-16 Me CH ₂ CH ₂ OMe OH 2-17 Me CH ₂ OEt OH 2-18 Me CH ₂ SMe OH 2-19 Me CH ₂ OPh OH 2-20 Me CH ₂ OAc OH 2-21 Me CH ₂ OCOPr OH 2-22 Me CH ₂ OCOcPr OH 2-23 Me CH ₂ OCOCH ₂ CH = CH ₂ OH 2-24 Me CH ₂ OCOCH ₂ Cl OH 2-25 Me CH ₂ OCOCHCl ₂ OH 2-26 Me CH ₂ SAc OH 2-27 Me CH ₂ O- (2 -pyr) OH 2-28 Me CH ₂ O- (5-Me-3-Isox) OH 2-29 Me CH ₂ S- (5-Me-2-Thida) OH 2-30 Me CH ₂ -1-Pyza OH 2-31 Me CH _2- (4-Br-1-Pyza) OH 2-32 Me OMe OH 2-33 Me OEt OH 2-34 Me OPr OH 2-35 Me OBu OH 2-36 Me OtBu OH 2- 37 Me OPh OH 2 -38 Me O-2-Pyr OH 2-39 Me OCH ₂ OMe OH 2-40 Me SMe OH 2-41 Me S-2-Pyr OH 2-42 Me NH ₂ OH 2-43 Me NHMe OH ──── ───────────────────────────────

[0058]

[Table 3]

[0059]

[Chemical 5]

──────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 3-1 Me Me OH 3-2 Me Et OH 3-3 Me Pr OH 3 -4 Me iPr OH 3-5 Me Bu OH 3-6 Me tBu OH 3-7 Me cPr OH 3-8 Me cBu OH 3-9 Me cPent OH 3-10 Me cHex OH 3-11 Me Ph OH 3-12 Me CH ₂ OH OH 3-13 Me CH (Me) OH OH 3-14 Me C (Me) ₂ OH OH 3-15 Me CH ₂ CH ₂ OH OH 3-16 Me CH ₂ CH ₂ CH ₂ OH OH 3- 17 Me CH ₂ OMe OH 3-18 Me CH (Me) OMe OH 3-19 Me CH ₂ CH ₂ OMe OH 3-20 Me CH ₂ OEt OH 3-21 Me CH ₂ SMe OH 3-22 Me CH ₂ OPh OH 3-23 Me CH ₂ OAc OH 3-24 Me CH ₂ OCOPr OH 3-25 Me CH ₂ OCOcPr OH 3-26 Me CH ₂ OCOcBu OH 3-27 Me CH ₂ OCOCH ₂ CH = CH ₂ OH 3-28 Me CH ₂ OCOCH = C (Me) ₂ OH 3-29 Me CH ₂ OCOC (Me) = CH ₂ OH 3-30 Me CH ₂ OCOC (CF ₃ ) = CH ₂ OH 3-31 Me CH ₂ OCOCH ₂ Cl OH 3- 32 Me CH ₂ OCOCHCl ₂ OH 3-33 Me CH ₂ OCOCCl ₃ OH 3-34 Me CH ₂ OCOCH ₂ FOH 3-35 Me CH ₂ OCOCHF ₂ OH 3-36 Me CH ₂ SAc OH 3-37 Me CH ₂ O- (2-pyr) OH 3-38 Me CH ₂ O- (5-Me-3-Isox) OH 3-39 Me CH ₂ S- (5-Me- 2-Thida) OH 3-40 Me CH ₂ -1-Pyza OH 3-41 Me CH _2- (4-Br-1-Pyza) OH 3-42 Me OMe OH 3-43 Me OEt OH 3-44 Me OPr OH 3-45 Me OBu OH 3-46 Me OtBu OH 3-47 Me OPh OH 3-48 Me O- (2-F-Ph) OH 3-49 Me O- (4-F-Ph) OH 3-50 Me O- (3-CN-Ph) OH 3-51 Me O-2-Pyr OH 3-52 Me OCH ₂ OMe OH 3-53 Me SMe OH 3-54 Me S-2-Pyr OH 3-55 Me NH ₂ OH 3-56 Me NHMe OH 3-57 Me NHOBn OH 3-58 Me NH-2- (4,5-Dhthia) OH 3-59 Me NHAc OH ─────────────── ─────────────────────

[0061]

[Table 4]

[0062]

[Chemical 6]

──────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 4-1 Me Me OH 4-2 Me Et OH 4-3 Me iPr OH 4 -4 Me tBu OH 4-5 Me cPr OH 4-6 Me Ph OH 4-7 Me CH ₂ OH OH 4-8 Me CH (Me) OH OH 4-9 Me C (Me) ₂ OH OH 4-10 Me CH ₂ OMe OH 4-11 Me CH ₂ CH ₂ OMe OH 4-12 Me CH ₂ OEt OH 4-13 Me CH ₂ SMe OH 4-14 Me CH ₂ OPh OH 4-15 Me CH ₂ OAc OH 4-16 Me CH ₂ SAc OH 4-17 Me CH ₂ O- (2-pyr) OH 4-18 Me CH ₂ O- (5-Me-3-Isox) OH 4-19 Me CH ₂ S- (5-Me-2 -Thida) OH 4-20 Me CH ₂ -1-Pyza OH 4-21 Me CH _2- (4-Br-1-Pyza) OH 4-22 Me OMe OH 4-23 Me OEt OH 4-24 Me OtBu OH 4-25 Me OPh OH 4-26 Me O-2-Pyr OH 4-27 Me NH ₂ OH ──────────────────────────── ────────

[0064]

[Table 5]

[0065]

[Chemical 7]

──────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 5-1 Me Me OH 5-2 Me Et OH 5-3 Me cPr OH 5 -4 Me cBu OH 5-5 Me cPent OH 5-6 Me cHex OH 5-7 Me Cl OH 5-8 Me CH ₂ Cl OH 5-9 Me CH ₂ Br OH 5-10 Me CH ₂ FOH 5-11 Me CHCl ₂ OH 5-12 Me CHF ₂ OH 5-13 Me CCl ₃ OH 5-14 Me CF ₃ OH 5-15 Me Ph OH 5-16 Me CH ₂ OH OH 5-17 Me CH (Me) OH OH 5- 18 Me C (Me) ₂ OH OH 5-19 Me CH ₂ CH ₂ OH OH 5-20 Me CH ₂ CH ₂ CH ₂ OH OH 5-21 Me CH ₂ OMe OH 5-22 Me CH (Me) OMe OH 5 -23 Me CH ₂ CH ₂ OMe OH 5-24 Me CH ₂ OEt OH 5-25 Me CH ₂ SMe OH 5-26 Me CH ₂ OPh OH 5-27 Me CH ₂ OAc OH 5-28 Me CH ₂ OCOCH ₂ Cl OH 5-29 Me CH ₂ OCOCHCl ₂ OH 5-30 Me CH ₂ SAc OH 5-31 Me CH ₂ O- (2-pyr) OH 5-32 Me CH ₂ O- (5-Me-3-Isox) OH 5-33 Me CH ₂ S- (5-Me-2-Thida) OH 5-34 Me CH ₂ -1-Pyza OH 5-35 Me CH _2- (4-Br-1-Pyza) OH 5-36 Me OMe OH 5-37 Me OEt O H 5-38 Me OPr OH 5-39 Me OtBu OH 5-40 Me OPh OH 5-41 Me O- (4-F-Ph) OH 5-42 Me O- (4-Cl-Ph) OH 5-43 Me O- (4-CN-Ph) OH 5-44 Me O- (4-CH ₃ -Ph) OH 5-45 Me O-2-Pyr OH 5-46 Me OCH ₂ OMe OH 5-47 Me OCH ₂ CH ₂ OMe OH 5-48 Me OCH ₂ CH ₂ OEt OH 5-49 Me OCH ₂ CH ₂ CH ₂ OMe OH 5-50 Me SMe OH 5-51 Me S-2-Pyr OH 5-52 Me NH ₂ OH 5 -53 Me NHMe OH 5-54 Me NHEt OH 5-55 Me NHiPr OH 5-56 Me NHBu OH 5-57 Me NHiBu OH 5-58 Me NHtBu OH 5-59 Me NHcPr OH 5-60 Me NHcBu OH 5-61 Me NHPh OH 5-62 Me NHBn OH 5-63 Me NHCH (Me) Ph OH 5-64 Me NHCH (CN) Ph OH 5-65 Me NHCH ₂ CH = CH ₂ OH 5-66 Me NHCH ₂ C≡CH OH 5-67 Me NHCH ₂ CF ₃ OH 5-68 Me NHCH ₂ CH ₂ OMe OH 5-69 Me NHCH ₂ CN OH 5-70 Me NHOH OH 5-71 Me NHOCH ₂ CH = CH ₂ OH 5-72 Me NHOBn OH 5-73 Me 1-Aze OH 5-74 Me 1-Pyrd OH 5-75 Me 3-COOMe-1-Pyrd OH 5-76 Me 1-Pip OH 5-77 Me 4-Mor OH 5-78 Me NH- 2-Quino OH 5-79 Me NH-3-Quino OH 5-80 Me NH-4-Quino OH 5-81 Me NH-2- (4,5-Dhthia) OH 5-82 Me NHAc OH 5-83 Me NHCOPh OH ─────────────────────── ───────────

[0067]

[Table 6]

[0068]

[Chemical 8]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 6-1 Me Me OH 6-2 Me Et OH 6-3 Me iPr OH 6 -4 Me Ph OH 6-5 Me CH ₂ OH OH 6-6 Me CH ₂ OMe OH 6-7 Me CH ₂ OPh OH 6-8 Me CH ₂ OAc OH 6-9 Me CH ₂ O-2-pyr OH 6 -10 Me OMe OH 6-11 Me OEt OH 6-12 Me OPh OH 6-13 Me O-2-Pyr OH 6-14 Me NH ₂ OH ───────────────── ────────────────────

[0070]

[Table 7]

[0071]

[Chemical 9]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 7-1 Me Me OH 7-2 Me Et OH 7-3 Me Ph OH 7 -4 Me CH ₂ OH OH 7-5 Me CH ₂ OMe OH 7-6 Me CH ₂ OPh OH 7-7 Me CH ₂ OAc OH 7-8 Me CH ₂ O-2-pyr OH 7-9 Me OMe OH 7 -10 Me OEt OH 7-11 Me OPh OH 7-12 Me O-2-Pyr OH 7-13 Me NH ₂ OH ──────────────────────── ─────────────

[0073]

[Table 8]

[0074]

[Chemical 10]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 8-1 Me Me OH 8-2 Me Et OH 8-3 Me Ph OH 8 -4 Me CH ₂ OH OH 8-5 Me CH ₂ OMe OH 8-6 Me CH ₂ OPh OH 8-7 Me CH ₂ OAc OH 8-8 Me CH ₂ O-2-Pyr OH 8-9 Me OMe OH 8 -10 Me OCH ₂ CH ₂ OMe OH 8-11 Me OPh OH 8-12 Me O-2-Pyr OH 8-13 Me NH ₂ OH ─────────────────── ─────────────────

[0076]

[Table 9]

[0077]

[Chemical 11]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 9-1 Me Me OH 9-2 Me Et OH 9-3 Me Ph OH 9 -4 Me CH ₂ OH OH 9-5 Me CH ₂ OMe OH 9-6 Me CH ₂ OPh OH 9-7 Me CH ₂ OAc OH 9-8 Me CH ₂ O-2-pyr OH 9-9 Me OMe OH 9 -10 Me OCH ₂ CH ₂ OMe OH 9-11 Me OPh OH 9-12 Me O-2-Pyr OH 9-13 Me NH ₂ OH ─────────────────── ─────────────────

[0079]

[Table 10]

[0080]

[Chemical 12]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 10-1 Me Me OH 10-2 Me Et OH 10-3 Me Ph OH 10 -4 Me CH ₂ OH OH 10-5 Me CH ₂ OMe OH 10-6 Me CH ₂ OPh OH 10-7 Me CH ₂ OAc OH 10-8 Me CH ₂ O-2-pyr OH 10-9 Me OMe OH 10 -10 Me OPh OH 10-11 Me O-2-Pyr OH 10-12 Me NH ₂ OH ───────────────────────────── ───────

[0082]

[Table 11]

[0083]

[Chemical 13]

─────────────────────────────────── Compound number R ² R ³ XY _n ──── ─────────────────────────────── 11-1 Me Me OH 11-2 Me Et OH 11-3 Me Ph OH 11 -4 Me CH ₂ OH OH 11-5 Me CH ₂ OMe OH 11-6 Me CH ₂ OPh OH 11-7 Me CH ₂ OAc OH 11-8 Me CH ₂ O-2-Pyr OH 11-9 Me OMe OH 11 -10 Me OPh OH 11-11 Me O-2-Pyr OH 11-12 Me NH ₂ OH ───────────────────────────── ──────── Of the above-exemplified compounds, preferred compounds are 1-1 and 1-
5, 1-7, 1-12, 1-19, 1-35, 1-3
9, 1-45, 1-48, 1-59, 1-64, 1-6
6, 1-71, 1-89, 1-91, 1-96, 1-9
7, 1-98, 1-99, 1-101, 1-107, 1
-108, 1-118, 1-139, 1-140, 1-
141, 1-142, 1-148, 1-149, 1-1
50, 1-151, 1-152, 1-153, 1-15
4, 1-155, 1-157, 1-158, 1-15
9, 1-168, 1-169, 1-187, 1-18
8, 2-1, 2-10, 2-14, 2-20, 2-3
2, 3-1, 3-7, 3-12, 3-17, 3-23,
3-25, 3-28, 3-30, 3-31, 3-32,
3-35, 3-42, 3-47, 4-1, 4-7, 4-
10, 4-15, 5-1, 5-3, 5-7, 5-16,
5-27, 5-30, 5-36, 5-41, 5-52,
5-53, 5-54, 5-59, 5-60, 5-61,
5-62, 5-66, 5-67, 5-70, 5-71,
5-72, 5-73, 8-1, 8-9, 8-10, 9-
1 and 11-1 compounds, more preferably 1-
1, 1-7, 1-35, 1-39, 1-45, 1-6
4, 1-66, 1-89, 1-96, 1-97, 1-9
8, 1-99, 1-118, 1-139, 1-149,
1-155, 1-158, 2-1, 2-10, 2-1
4, 2-20, 2-32, 3-1, 3-7, 3-17,
3-23, 3-25, 3-42, 4-7, 4-10, 5
Compounds Nos. -16, 5-27, 5-52, and 5-62, and even more preferably, 1-7, 1-35, 1-9
9, 1-139, 2-1, 2-10, 2-20, 3-1
Compounds Nos. 7, 3-23, and 5-52.

[0085]

BEST MODE FOR CARRYING OUT THE INVENTION The 5- (m-cyanobenzylamino) thiazole derivative of the present invention is obtained by the step A described below.
It can be manufactured by the method of Step F.

In the step A, the 5-position of the thiazole derivative represented by the general formula (III) is nitrated, the nitro group is reduced, the resulting amino group is acetylated, and finally the benzyl group is formed. Of the compound (I) of
It is a step of producing a 5- (m-cyanobenzylamino) thiazole derivative in which R ³ is a methyl group.

(Step A)

[0088]

[Chemical 14]

In the above formula, R¹, R²And Y_nIs the same meaning as above
Indicates R^FourIs a hydrogen atom, optionally substituted C₁~ C_FiveA
Alkyl group (the substituent is selected from the above substituent group A)
It ) Or C which may be substituted₃~ C₇Cycloalkyl group
(The cycloalkyl group is interrupted by one oxygen atom.
May be done. The substituent is C ₁~ C₆Alkyl group and ha
It is selected from the group consisting of rogen atoms. ), And Z is
Halogen atom, C₁~ C₆Alkylsulfonyl group or
Nylsulfonyl group (the phenylsulfonyl groups are the same
Or different halogen atom and C₁~ C₆From an alkyl group
Substituted with 1 to 5 substituents selected from the group consisting of
You may ) (Preferably chlorine atom, bromine atom,
Cylsulfonyl group, phenylsulfonyl group or tolyl
It is a sulfonyl group, more preferably a bromine atom. )
Indicates.

(Step A-1) In step A-1, the compound (I
When R ^{1 of} II) is the group CH ₂ R ⁴ , it has the general formula (I
The 2-acylthiazole derivative represented by I) is reacted with anhydrous hydrazine or hydrazine monohydrate in the presence or absence of a base in an inert solvent, and then heated to reflux to produce the compound (III). Is a process of manufacturing.

The amount of anhydrous hydrazine or hydrazine monohydrate used is usually 1 to 15 mol, preferably 5 to 10 mol, per 1 mol of compound (II).
Is.

When a base is used in this step, the base used is not particularly limited as long as it is used as a base in a normal reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate. Alkali metal hydrogencarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and barium hydroxide; or sodium methoxide, sodium ethoxide, potassium-t. It may be an alkali metal alkoxide such as butoxide, preferably an alkali metal carbonate or alkali metal hydroxide, more preferably potassium carbonate.

The amount of base used depends on the amount of compound (II) 1
It is usually 1 to 10 mol, and preferably 2.0 to 3.0 mol with respect to mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction. For example, alcohols such as methanol, ethanol, propanol and isopropanol; or ethylene glycol, diethylene glycol, triethylene glycol dimethyl ether. And the like, preferably glycols, and more preferably diethylene glycol or triethylene glycol.

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent, etc., but is usually 60 ° C. to 250 ° C.,
It is preferably 120 ° C to 220 ° C.

The reaction time varies depending on the raw material compound, the reaction reagent, the solvent, the reaction temperature and the like, but is usually 10 minutes to 10 minutes.
It is 0 hours, preferably 30 minutes to 48 hours.

The compound (II) used in this step is a known compound, or a known method (for example, tetrahedron Tetrahedron, Vol. 55, No. 12, page 3541 (1999) or Journal of Chemicals. Society, Perkin
Trans 1 J. Chem. Soc., Perkin. Trans. 1,2417
Page (1991)).

(Step A-2) Step A-2 is a process represented by the general formula (I
By reacting the thiazole derivative represented by II) with nitric acid or fuming nitric acid in an acidic solvent,
This is a step of producing a 5-nitrothiazole derivative represented by V).

The amount of nitric acid or fuming nitric acid used is usually 1 to 30 mol, and preferably 10 to 20 mol, relative to 1 mol of compound (III).

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and examples thereof include inorganic acids such as nitric acid and sulfuric acid; organic acids such as acetic acid, propionic acid, butanoic acid and trifluoroacetic acid. Or it may be an acid anhydride such as acetic anhydride, propionic anhydride, or trifluoroacetic anhydride, preferably an inorganic acid, more preferably sulfuric acid.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be -20 ° C to 150 ° C, and is preferably 0 ° C to 90 ° C.

The reaction time varies depending on the raw material compound, the reaction reagent, the solvent, the reaction temperature and the like, but is usually 10 minutes to 24 minutes.
Time, preferably 30 minutes to 10 hours.

The compound (III) used in this step is
The compound produced in step A-1, a known compound, or a known method (for example, Chemical and Pharmaceutical Bulletin Chem. Pharm. Bull., 44
Volume, No. 9, page 1761 (1996)).

(Step A-3) Step A-3 is the same as general formula (I
The 5-nitrothiazole derivative represented by V) is reacted with zinc in the presence of acetic anhydride in an inert solvent to produce a 5-acetamide thiazole derivative represented by the general formula (V). It is a process.

The amount of acetic anhydride used depends on the amount of compound (II
I) 1 mol is usually 1 to 50 mol, and preferably 5 to 30 mol.

The amount of zinc used depends on the amount of compound (III).
It is usually 1 to 20 mol, and preferably 5 to 10 mol per 1 mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and it may be acetic acid, acetic anhydride, methyl acetate, ethyl acetate, propyl acetate, or another acetic acid derivative, and is preferably used. Is acetic acid.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be -20 ° C to 150 ° C, and is preferably 0 ° C to 40 ° C.

The reaction time varies depending on the starting compounds, reaction reagents, solvent, reaction temperature and the like, but is usually 10 minutes to 48 minutes.
Time, preferably 30 minutes to 10 hours.

(Step A-4) In Step A-4, the 5-acetamido thiazole derivative represented by the general formula (V) is
In the presence or absence of a base in an inert solvent, the compound represented by the general formula (V
This is a step of producing a compound (Il) in which R ³ is a methyl group in the compound (I) of the present invention by reacting with a benzylation reagent represented by I).

The amount of compound (VI) used is usually 1 to 3 mol, preferably 1.5 mol, per 1 mol of compound (V).

When a base is used in this step, the base used is not particularly limited as long as it is used as a base in a usual reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate; Alkali metal hydrogen carbonate such as sodium hydrogen, potassium hydrogen carbonate; Alkali metal hydride such as sodium hydride, lithium hydride, potassium hydride; Sodium hydroxide,
Alkali metal hydroxides or alkaline earth metal hydroxides such as potassium hydroxide, barium hydroxide; sodium methoxide, sodium ethoxide, potassium-t.
-Alkali metal alkoxides such as butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-
(N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2. 2.2] Octane (DABCO),
1,8-diazabicyclo [5.4.0] undec-7-
It may be an organic base such as ene (DBU); or an organic metal base such as butyllithium or lithium diisopropylamide, preferably an alkali metal hydroxide, and more preferably sodium hydroxide. Is.

The amount of the base used was 1 m of compound (V).
It is usually 1 to 5 mol relative to ol, and preferably,
It is 1.1 to 2.5 mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and for example, hexane,
Hydrocarbons such as cyclohexane, benzene and toluene;
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloroethane; dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide,
Hexamethylphosphoric triamide (HMPA) and other amides; acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and other ketones; acetonitrile, isobutyronitrile and other nitriles; or methyl acetate, ethyl acetate, propyl acetate, etc. Esters, preferably amides, and more preferably dimethylformamide.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be -20 ° C to 150 ° C, and is preferably 0 ° C to 90 ° C.

The reaction time varies depending on the raw material compound, the reaction reagent, the solvent, the reaction temperature and the like, but is usually 10 minutes to 24 minutes.
Time, preferably 30 minutes to 10 hours.

Step B is a step of producing the compound (I) of the present invention by hydrolyzing the compound (V) under acidic conditions, and then acylating and then 3-cyanobenzylating. (Process B)

[0118]

[Chemical 15]

In the above formula, R ¹ , R ² , R ³ , X, Y _n and Z have the same meanings as described above, and W is a halogen atom (preferably,
It is a chlorine atom or a bromine atom, and more preferably a chlorine atom. ) Is shown.

(Step B-1) In Step B-1, the 5-acetamido thiazole derivative represented by the general formula (V) is added.
This is a step of reacting with hydrochloric acid in an inert solvent to produce an amine hydrochloride derivative represented by the general formula (VII).

The amount of hydrochloric acid used was 1 m of compound (V).
It is usually 1.1 to 100 mol, and preferably 10 to 50 mol with respect to ol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and examples thereof include alcohols such as methanol, ethanol and propanol; ethers such as dioxane, tetrahydrofuran and ethylene glycol; or formic acid. It may be an organic acid such as acetic acid, propionic acid, etc., preferably alcohols, more preferably ethanol.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be 0 ° C. to 150 ° C., and is preferably 20 ° C. to 120 ° C.

The reaction time varies depending on the starting compound, the reaction reagent, the solvent, the reaction temperature and the like, but is usually 1 hour to 48 hours, and preferably 2 hours to 24 hours.

The compound (VII) produced in this step is
Used in the next step B-2 without purification.

(Step B-2) In Step B-2, the compound (V
II) in the presence of a base in the presence of an inert solvent, the compound of general formula (VI
In the step of producing a 5-acylaminothiazole derivative represented by the general formula (X) by reacting with an acyl halide derivative represented by the II) or an acid anhydride derivative represented by the general formula (IX). is there.

The amount of compound (VIII) or compound (IX) used in this step is usually 1 to 4 mol, preferably 1.1 to 1 mol, relative to 1 mol of compound (VII).
It is 2.5 mol.

The base used in this step is not particularly limited as long as it is used as a base in a usual reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate, hydrogen carbonate. Alkali metal hydrogen carbonate such as potassium; Alkali metal hydride such as sodium hydride, lithium hydride, potassium hydride; Alkali metal hydroxide or alkali such as sodium hydroxide, potassium hydroxide, barium hydroxide Earth metal hydroxides; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N- Dimethylamino) pyridine, , N- dimethylaniline, N, N-
Diethylaniline, 1,5-diazabicyclo [4.3.
0] nona-5-ene, 1,4-diazabicyclo [2.
2.2] Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU); or organometallic bases such as butyllithium and lithium diisopropylamide. It may be a class, preferably organic bases, more preferably triethylamine or pyridine.

The amount of the base used depends on the amount of compound (VII).
It is usually 2 to 6 mol, and preferably 2.5 to 4.0 mol, relative to 1 mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction. For example, hexane,
Hydrocarbons such as cyclohexane, benzene and toluene;
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloroethane; dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide,
Amides such as hexamethylphosphoric triamide (HMPA); ketones such as acetone, methylethylketone, methylisobutylketone, cyclohexanone; nitriles such as acetonitrile, isobutyronitrile; or methyl acetate, ethyl acetate, propyl acetate, etc. Esters, preferably halogenated hydrocarbons, more preferably dichloromethane or dichloroethane.

The reaction temperature will differ depending on the raw material compounds, reaction reagents, solvent, etc., but is usually 0 ° C. to 150 ° C., and preferably 0 ° C. to 70 ° C.

The reaction time varies depending on the raw material compounds, reaction reagents, solvent, reaction temperature and the like, but is usually 10 minutes to 24 minutes.
Time, preferably 1 hour to 10 hours.

(Step B-3) In step B-3, compound (X) is treated with an inert solvent in the presence or absence of a base,
This is a step of producing the compound (I) of the present invention by reacting with a benzylation reagent represented by the general formula (VI).

This step can be carried out according to step A-4.

In step C, compound (V) was Nt-butoxycarbonylated, and the resulting compound (XI) was deacetylated with a base to give compound (XII), followed by 3
Cyanobenzylated to give R ³ of the compound (I) of the present invention.
Is a step of producing a compound (Im) in which is a t-butoxy group, and further deriving the compound (I) of the present invention.

(Step C)

[0137]

[Chemical 16]

In the above formula, R ¹ , R ² , R ³ , X, Y _n , W and Z have the same meanings as described above.

(Step C-1) In step C-1, the 5-acetamido thiazole derivative represented by the general formula (V) is
Carbonic acid di-t- in the presence or absence of a base in an inert solvent.
In this step, compound (XI) is produced by reacting with butyl.

The amount of di-t-butyl carbonate used is usually 1 to 10 mol, preferably 1.0 to 3.0 mol, per 1 mol of compound (V).

When a base is used in this step, the base used is not particularly limited as long as it is used as a base in a usual reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate; Alkali metal hydrogen carbonate such as sodium hydrogen, potassium hydrogen carbonate; Alkali metal hydride such as sodium hydride, lithium hydride, potassium hydride; Sodium hydroxide,
Alkali metal hydroxides or alkaline earth metal hydroxides such as potassium hydroxide, barium hydroxide; sodium methoxide, sodium ethoxide, potassium-t.
-Alkali metal alkoxides such as butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-
(N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2. 2.2] Octane (DABCO),
1,8-diazabicyclo [5.4.0] undec-7-
Organic bases such as ene (DBU); or organometallic bases such as butyllithium and lithium diisopropylamide, preferably organic bases, and more preferably 4- (N, N). -Dimethylamino) pyridine.

The amount of base used was 1 m of compound (V).
It is usually 0.05 to 100 mol, and preferably 0.1 to 2.0 mol with respect to ol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and for example, hexane,
Hydrocarbons such as cyclohexane, benzene and toluene;
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloroethane; dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide,
Hexamethylphosphoric triamide (HMPA) and other amides; acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and other ketones; acetonitrile, isobutyronitrile and other nitriles; or methyl acetate, ethyl acetate, propyl acetate, etc. Esters; or triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine,
4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-
Diazabicyclo [4.3.0] non-5-ene, 1,4
-Diazabicyclo [2.2.2] octane (DABC
O), organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), preferably nitriles, and more preferably acetonitrile.

The reaction temperature will differ depending on the raw material compounds, reaction reagents, solvent, etc., but is usually -20 ° C to 100 ° C, and preferably 0 ° C to 40 ° C.

The reaction time varies depending on the raw material compounds, reaction reagents, solvent, reaction temperature and the like, but is usually 10 minutes to 24 minutes.
Time, preferably 30 minutes to 10 hours.

(Step C-2) In Step C-2, the compound (X
I) is reacted with a base in an inert solvent to give compound (XI
It is a process of manufacturing I).

The base used in this step is not particularly limited as long as it is used as a base in a usual reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate and hydrogen carbonate. Alkali metal hydrogen carbonate such as potassium; Alkali metal hydride such as sodium hydride, lithium hydride, potassium hydride; Alkali metal hydroxide or alkali such as sodium hydroxide, potassium hydroxide, barium hydroxide Earth metal hydroxides; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, anhydrous hydrazine, hydrazine monohydrate, Pyridine, 4- N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non -5
-Ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5.4.
0] organic bases such as undec-7-ene (DBU); or organometallic bases such as butyllithium and lithium diisopropylamide, preferably organic bases, more preferably It is anhydrous hydrazine or hydrazine monohydrate.

The amount of the base used is the amount of compound (XI) 1
It is usually 1 to 100 mol, and preferably 3.0 to 7.0 mol with respect to mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction. For example, hexane,
Hydrocarbons such as cyclohexane, benzene and toluene;
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloroethane; dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide,
Hexamethylphosphoric triamide (HMPA) and other amides; acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and other ketones; acetonitrile, isobutyronitrile and other nitriles, methyl acetate,
Esters such as ethyl acetate and propyl acetate; or alcohols such as methanol, ethanol and propanol, preferably alcohols, and more preferably
It is methanol.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be -20 ° C to 100 ° C, and is preferably 0 ° C to 40 ° C.

The reaction time varies depending on the raw material compound, reaction reagent, solvent, reaction temperature and the like, but is usually 1 hour to 48 hours, and preferably 4 hours to 24 hours. (Step C-3) In Step C-3, compound (XII) is prepared by reacting compound (XII) in the presence or absence of a base with general formula (V
This is a step of producing a compound (Im) in which R ³ is a t-butoxy group in the compound (I) of the present invention by reacting with a benzylation reagent represented by I).

This step can be carried out according to step A-4.

(Step C-4) Step C-4 is the same as compound (I
In this step, the t-butyl carbamate derivative represented by m) is reacted with hydrochloric acid in an inert solvent to produce the amine hydrochloride derivative represented by the general formula (XIII).

This step can be carried out according to step B-1.

Compound (XIII) obtained by this step
Can be used in the next step C-5 without purification. (Step C-5) In Step C-5, the compound (XIV) is represented by the acyl halide derivative represented by the general formula (VIII) or the general formula (IX) in the presence of a base in an inert solvent. It is a step of producing the compound (I) of the present invention by reacting with an acid anhydride derivative.

This step can be carried out according to step B-2.

Step D is a step of hydrolyzing the compound (In) having an acetoxy group in R ³ of the compound (I) under basic conditions to deacetylate it.

(Step D)

[0159]

[Chemical 17]

In the above formula, R ¹ , R ² and Y _n have the same meanings as described above.

(Step D-1) In step D-1, the compound (I
In this step, n) is reacted with a base in an inert solvent and hydrolyzed to produce the compound (Io) of the present invention.

The amount of the base used depends on the amount of compound (In) 1
It is usually 1 to 100 mol, and preferably 15 to 50 mol per mol.

The base used in this step may be, for example, an alkali metal carbonate such as sodium carbonate or potassium carbonate; or an alkali metal hydrogen carbonate such as sodium hydrogen carbonate or potassium hydrogen carbonate, and preferably, It is an alkali metal carbonate, and more preferably sodium carbonate.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and for example, dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; alcohols such as methanol, ethanol and propanol; glycols such as ethylene glycol, diethylene glycol and triethylene glycol; water; or a mixed solvent thereof, and preferably alcohol. And a mixed solvent of water and more preferably a mixed solvent of methanol and water.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be -20 ° C to 150 ° C, and is preferably 0 ° C to 40 ° C.

The reaction time varies depending on the raw material compounds, reaction reagents, solvent, reaction temperature and the like, but is usually 10 minutes to 24 minutes.
Time, preferably 30 minutes to 3 hours.

The compound (In) used in this step can be produced according to the step C-5.

Step E is the same as R ^{3 in the} compound (I) of the present invention.
Is a step of reacting a compound (Ip) in which is a chlorine atom with an alcohol or the like.

(Process E)

[0170]

[Chemical 18]

In the above formula, R ¹ , R ² , X and Y _n have the same meanings as described above, and R ^3a is a C ₁ -C ₆ alkoxy group which may be substituted (the substituent is C _1- A C ₆ alkoxy group), a phenoxy group which may be substituted (the substituent is
It is selected from the above substituent group B. ), A heterocyclic oxy group which may be substituted (the substituent is selected from the substituent group C), a C ₁ -C ₆ alkylthio group which may be substituted (the substituent is a cyano group, a phenyl group or A C ₁ -C ₆ alkoxy group), a phenylthio group that may be substituted (the substituent is selected from the substituent group B), and a heterocyclic thio group that may be substituted (the substituent is the same as those described above). Selected from Substituent group C), optionally substituted cyclic amino group (the cyclic amino group may be interrupted by one oxygen atom.
The substituents are C ₁ -C ₆ alkyl or C ₂ -C ₇ alkoxycarbonyl group. ) Or an optionally substituted amino group (the said substituent is selected from the said Substituent group E).

Step E-1 is the step of treating the compound (Ip) in the presence of a base in the presence of an inert solvent with or without the general formula (XIV).
Is a step of producing the compound (Iq) of the present invention by reacting with alcohols, amines or thiols represented by.

The amount of the compound (XIV) used is usually 1 to 10 mol, preferably 1.0 to 3.0 mol, relative to 1 mol of the compound (Ip).

When a base is used in this step, the base used is not particularly limited as long as it is used as a base in a usual reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate; Alkali metal hydrogen carbonate such as sodium hydrogen, potassium hydrogen carbonate; Alkali metal hydride such as sodium hydride, lithium hydride, potassium hydride; Sodium hydroxide,
Alkali metal hydroxides or alkaline earth metal hydroxides such as potassium hydroxide, barium hydroxide; sodium methoxide, sodium ethoxide, potassium-t.
-Alkali metal alkoxides such as butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-
(N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2. 2.2] Octane (DABCO),
1,8-diazabicyclo [5.4.0] undec-7-
Organic bases such as ene (DBU); or organometallic bases such as butyllithium and lithium diisopropylamide, preferably organic bases, more preferably triethylamine or 4- (N. , N-dimethylamino) pyridine.

The amount of the base used depends on the amount of compound (Ip) 1
It is usually 1 to 10 mol, and preferably 1.0 to 4.0 mol per mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction. For example, hexane,
Hydrocarbons such as cyclohexane, benzene and toluene;
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloroethane; dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide,
Hexamethylphosphoric triamide (HMPA) and other amides; acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and other ketones; acetonitrile, isobutyronitrile and other nitriles; or methyl acetate, ethyl acetate, propyl acetate, etc. Esters, preferably halogenated hydrocarbons, and more preferably dichloromethane.

The reaction temperature will differ depending on the starting compounds, reaction reagents, solvent and the like, but will usually be -20 ° C to 100 ° C, and is preferably 0 ° C to 40 ° C.

The reaction time varies depending on the starting material compound, the reaction reagent, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 minutes.
Time, preferably 1 to 12 hours.

Step F is represented by the general formula (XV)
The acyl thiazole derivative is converted to an oxime derivative (XVI) by reacting with hydroxylamine and the like, and then a rearrangement reaction is carried out with an acid catalyst to convert it to an amide derivative (X), and finally benzylation is carried out. This is a step of producing a 5- (m-cyanobenzylamino) thiazole derivative represented by the general formula (I).

(Step F)

[0181]

[Chemical 19]

In the above formula, R ¹ , R ² , R ³ , Y _n and Z have the same meanings as described above.

(Step F-1) Step F-1 is the same as formula (X).
The 2-acylthiazole derivative represented by V) is reacted with hydroxylamine or hydroxylamine hydrochloride or sulfate in an inert solvent in the presence of a base, and then heated under reflux to be represented by the general formula (XVI). Is a step for producing the oxime derivative.

The amount of hydroxylamine or hydroxylamine hydrochloride or sulfate used in this step is usually 1 to 15 mol, preferably 1.0 to 2.0 mol, per 1 mol of compound (XV). is there.

The base used in this step is not particularly limited as long as it is used as a base in a usual reaction, and examples thereof include alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate and hydrogen carbonate. Alkali metal hydrogen carbonate such as potassium; Alkali metal acetate such as sodium acetate, potassium acetate; Alkali metal hydride such as sodium hydride, lithium hydride, potassium hydride; Sodium hydroxide, potassium hydroxide, Alkali metal hydroxides or alkaline earth metal hydroxides such as barium hydroxide; Alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N -Methylmorpho Emissions, pyridine, 4-(N, N-
Dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-
Diazabicyclo [5.4.0] undec-7-ene (D
BU) or an organic metal base such as butyllithium or lithium diisopropylamide, preferably an alkali metal acetate, and more preferably sodium acetate.

The amount of the base used is the amount of compound (XV) 1
It is usually 1 to 15 mol, and preferably 1.2 to 3.0 mol, relative to mol.

The solvent used in this step is not particularly limited as long as it does not inhibit the reaction, and for example, hexane,
Hydrocarbons such as cyclohexane, benzene and toluene;
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloroethane; dioxane, diethyl ether, tetrahydrofuran (TH
F), ethers such as ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide,
Hexamethylphosphoric triamide (HMPA) and other amides; acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and other ketones; acetonitrile, isobutyronitrile and other nitriles, methyl acetate,
Esters such as ethyl acetate and propyl acetate; or alcohols such as methanol, ethanol and propanol, preferably alcohols, and more preferably
It is ethanol.

The reaction temperature will differ depending on the raw material compounds, reaction reagents, solvent, etc., but is usually 0 ° C. to 150 ° C., and preferably 40 ° C. to 100 ° C.

The reaction time varies depending on the raw material compounds, reaction reagents, solvent, reaction temperature and the like, but is usually 30 minutes to 48 minutes.
Time, preferably 1 to 8 hours.

The compound (XV) used in this step is a known compound or a known method (for example, Justus Liebig's Annalen del Chemie Justus).
Liebigs Ann. Chem., No. 8, p. 1195 (1974), or Pharmacy, Vol. 47, No. 4, p. 298 (1992)).

(Step F-2) Step F-2 is the same as general formula (X
In this step, the oxime derivative represented by VI) is subjected to a rearrangement reaction in an inert solvent or in the absence of a solvent in the presence of an acid catalyst at room temperature or by heating to produce an amide derivative (X).

The catalyst used in this step is, for example, inorganic acids such as nitric acid, sulfuric acid and hydrochloric acid; acetic acid, propionic acid, butanoic acid, trifluoroacetic acid, methanesulfonic acid,
Organic acids such as trifluoromethanesulfonic acid, phosphoric acid and polyphosphoric acid; phosphorus halide reagents such as phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride; or sulfuryl chloride, preferably organic Acids, more preferably,
It is polyphosphoric acid.

When a solvent is used in this step, the solvent used is not particularly limited as long as it does not inhibit the reaction, and examples thereof include hydrocarbons such as hexane, cyclohexane, benzene, toluene; dichloromethane, dichloroethane, chloroform. , Halogenated hydrocarbons such as tetrachloroethane; ethers such as dioxane, diethyl ether, tetrahydrofuran (THF), ethylene glycol dimethyl ether; dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide (HM
Amides such as PA); acetone, methyl ethyl ketone,
Preferred are ketones such as methyl isobutyl ketone and cyclohexanone; nitriles such as acetonitrile and isobutyronitrile; esters such as methyl acetate, ethyl acetate and propyl acetate; or alcohols such as methanol, ethanol and propanol, which are preferable. Alcohols are preferable for the solvent, but solvent-free is more preferable.

The reaction temperature will differ depending on the raw material compounds, reaction reagents, solvent, etc., but is usually 20 ° C. to 250 ° C.,
It is preferably 50 ° C to 180 ° C.

The reaction time varies depending on the starting compounds, reaction reagents, solvent, reaction temperature and the like, but is usually 10 minutes to 24 minutes.
Time, preferably 30 minutes to 10 hours.

(Step F-3) In Step F-3, the amide compound represented by the general formula (X) is represented by the general formula (VI) in an inert solvent in the presence or absence of a base. Is a step of producing the compound (I) of the present invention by reacting with a benzylation reagent.

This step can be carried out according to step A-4.

After completion of each of the above reactions, the target compound of each reaction can be collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, water and an immiscible organic solvent such as ethyl acetate are added, and the mixture is washed with water to form an organic layer containing the target compound. It is obtained by separating, drying over anhydrous magnesium sulfate and the like, and distilling off the solvent.

If necessary, the obtained target compound can be obtained by a conventional method,
It can be further purified by, for example, recrystallization, reprecipitation or chromatography. Of course, it is also possible to stop the purification at any stage of the purification and use the crude product as an active ingredient or a raw material compound for the next reaction.

In the step of producing the salt of compound (I) of the present invention, the extract concentrate of the reaction mixture containing compound (I) of the present invention produced in each step or compound (I) was dissolved in a suitable solvent. This is done by adding acid to the liquor.

The acid used in the reaction is hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydrohalic acid such as hydroiodic acid, inorganic acid such as nitric acid, perchloric acid, sulfuric acid, phosphoric acid; methane. Organic acids such as lower alkyl sulfonic acids such as sulfonic acid, trifluoromethane sulfonic acid, ethane sulfonic acid, benzene sulfonic acid, aryl sulfonic acids such as p-toluene sulfonic acid, succinic acid, oxalic acid; and saccharin Organic acid amide compounds can be mentioned.

The amount of acid used is usually 1 equivalent to 10 equivalents, and preferably 1 equivalent to 5 equivalents, relative to compound (I).

The solvent used in the reaction is not particularly limited as long as it does not inhibit this reaction, but preferably ether, diisopropyl ether, tetrahydrofuran (THF),
Ethers such as dioxane; or alcohols such as methanol and ethanol.

The reaction temperature is generally -20 ° C to 50 ° C, preferably -10 ° C to 30 ° C.

The reaction time will differ depending on the temperature used and the type of solvent, but is usually 10 minutes to 1 hour.

The salt formed is isolated by conventional methods. That is, when it precipitates as crystals, it is isolated by filtration, and when it is a water-soluble salt, it is isolated as an aqueous solution by separating the organic solvent and water.

The compound of the present invention can be used as an active ingredient of a pest control agent. For example, as an agricultural and horticultural fungicide,
It shows an excellent control effect against diseases caused by various plant pathogens. Downy mildew of cucumber and grapes,
It exhibits an excellent control effect against the plague of tomato and potato, and various diseases caused by oomycetes such as Pythium and Aphanomyces. INDUSTRIAL APPLICABILITY The compound of the present invention not only has a long residual effect and an excellent preventive effect, but also has an excellent therapeutic effect and can control diseases by treatment after infection. Also,
The compound of the present invention can also control diseases by soil treatment. The compound of the present invention is effective not only against susceptible bacteria but also against various resistant bacteria (metalaxyl-resistant downy mildew, strobilurin fungicide-resistant downy mildew, etc.).

When the compound of the present invention is used, it may be formulated into various forms such as emulsions, powders, wettable powders, liquids, granules and suspensions together with auxiliary agents, as in the case of conventional pesticide formulations. You can In the actual use of these preparations, they can be used as they are or diluted with a diluent such as water to a predetermined concentration and used.

Examples of the auxiliary agent used include a carrier, an emulsifying agent, a suspending agent, a dispersing agent, a spreading agent, a penetrating agent, a wetting agent, a thickening agent, a stabilizer and the like, which may be appropriately added if necessary. it can.

The carriers used are divided into solid carriers and liquid carriers. The solid carriers include starch, sugar, cellulose powder, cyclodextrin, activated carbon, soybean flour, wheat flour, chaff flour, wood flour, fish meal, milk powder and the like. Animal and plant powders; or may be mineral powders such as talc, kaolin, bentonite, organic bentonite, calcium carbonate, calcium sulfate, sodium bicarbonate, zeolite, diatomaceous earth, white carbon, clay, alumina, silica, sulfur powder, etc.,
Liquid carriers include water; animal and vegetable oils such as soybean oil, cottonseed oil, and corn oil; alcohols such as ethyl alcohol and ethylene glycol; ketones such as acetone and methyl ethyl ketone; ethers such as dioxane and tetrahydrofuran; kerosene, kerosene, Aliphatic hydrocarbons such as liquid paraffin; aromatic hydrocarbons such as xylene, trimethylbenzene, tetramethylbenzene, cyclohexane, solvent naphtha; halogenated hydrocarbons such as chloroform and chlorobenzene; acid amides such as dimethylformamide; It may be ethyl acetate, esters such as glycerin ester of fatty acid; nitriles such as acetonitrile; sulfur-containing compounds such as dimethyl sulfoxide; or N-methylpyrrolidone.

The compounding mass ratio of the compound of the present invention and the auxiliary agent is
Usually, it is 0.05: 99.95 to 90:10, and preferably 0.2: 99.8 to 80:20.

The concentration or amount of the compound of the present invention used varies depending on the target crop, method of use, formulation form, application rate, etc., but in the case of foliar treatment, it is usually
0.1 to 10000 ppm, preferably 1 to 10
It is 00 ppm and is usually 10 to 10 in the case of soil treatment.
0000 g / ha, preferably 200 to 2000
It is 0 g / ha.

If necessary, the compound of the present invention may contain other agricultural chemicals,
For example, insecticides, acaricides, attractants, nematicides, fungicides,
It can be mixed or used in combination with an antiviral agent, a herbicide, a plant growth regulator, etc., and is preferably an insecticide, acaricide, nematicide or fungicide.

The insecticide, acaricide or nematicide used is, for example, O- (4-bromo-2-chlorophenyl).
O-ethyl S-propyl phosphorothioate (generic name:
Prophenophos), O- (2,2-dichlorovinyl)
O, O-dimethyl phosphate (generic name: dichlorvos), O-ethyl O- [3-methyl-4- (methylthio) phenyl] N-isopropylphosphoroamidate (generic name: fenamiphos), O, O-dimethyl O −
(4-Nitro-m-tolyl) phosphorothioate (generic name: fenitrothion), O-ethyl O- (4-nitrophenyl) phenylphosphonothioate (generic name: E
PN), O, O-diethyl O- (2-isopropyl-
6-Methylpyrimidin-4-yl) phosphorothioate (generic name: diazinon), O, O-dimethyl O-
(3,5,6-Trichloro-2-pyridyl) phosphorothioate (generic name: chlorpyrifosmethyl), O, S-
Organic phosphate compounds such as dimethyl N-acetylphosphoramidothioate (generic name: acephate), O- (2,4-dichlorophenyl) O-ethyl S-propyl phosphorodithioate (generic name: prothiophos) 1-naphthyl N-methylcarbamate (generic name: carbaryl), 2-isopropoxyphenyl N
-Methyl carbamate (generic name: propoxur), 2-
Methyl-2- (methylthio) propionaldehyde O
-Methylcarbamoyl oxime (generic name: aldicarb), 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-methylcarbamate (generic name: carbofuran), dimethyl N, N '-[thiobis {(methylimino)] Carbonyloxy}] bisethaneimidothioate (generic name: thiodicarb), S-methyl N- (methylcarbamoyloxy) thioacetimidate (generic name: mesomil), N, N-dimethyl-2-methylcarbamoyloxyimino- 2- (Methylthio) acetamide (generic name: oxamyl), 2- (ethylthiomethyl) phenyl N-methylcarbamate (generic name: etiophencarb), 2-dimethylamino-5,6-dimethylpyrimidin-4-yl N, N -Dimethyl carbamate (generic name: pirimicarb), -sec- butyl phenyl N- methylcarbamate (common name: Fenobucarb) carbamate compounds such as; S, S'-2- dimethylaminotrimethylene-bis (thiocarbamate)
(General name: cartap), N, N-dimethyl-1,2,
Nereistoxin derivatives such as 3-trithian-5-ylamine (generic name: thiocyclam); 2,2,2-trichloro-1,1-bis (4-chlorophenyl) ethanol (generic name: dicofol), 4-chlorophenyl -2
Organochlorine compounds such as 4,5-trichlorophenyl sulfone (generic name: tetradiphone); bis [tris (2
-Methyl-2-phenylpropyl) tin] oxide (generic name: fenbutatin oxide); (RS) -α-cyano-3-phenoxybenzyl (RS) -2- (4-chlorophenyl)- 3-methylbutyrate (generic name: fenvalerate), 3-phenoxybenzyl (1RS) -cis, trans-3- (2,2)
-Dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate (generic name: permethrin), (RS)
-Α-cyano-3-phenoxybenzyl (1RS) -cis, trans-3- (2,2-dichlorovinyl) -2,
2-Dimethylcyclopropanecarboxylate (generic name: cypermethrin), (S) -α-cyano-3-phenoxybenzyl (1R) -cis-3- (2,2-dibromovinyl) -2,2-dimethylcyclo Propane carboxylate (generic name: deltamethrin), (RS) -α-
Cyano-3-phenoxybenzyl (1RS) -cis, trans-3- (2-chloro-3,3,3-trifluoropropenyl) -2,2-dimethylcyclopropanecarboxylate (generic name: cyhalothrin), 4- Methyl-
2,3,5,6-tetrafluorobenzyl-3- (2-
Chloro-3,3,3-trifluoro-1-propenyl)
A pyrethroid-based compound such as -2,2-dimethylcyclopropanecarboxylate (generic name: tefluthrin), 2- (4-ethoxyphenyl) -2-methylpropyl 3-phenoxybenzyl ether (generic name: etofenprox); 1- (4-chlorophenyl) -3-
(2,6-Difluorobenzoyl) urea (generic name: diflubenzuron), 1- [3,5-dichloro-4- (3
-Chloro-5-trifluoromethyl-2-pyridyloxy) phenyl] -3- (2,6-difluorobenzoyl) urea (generic name: chlorfluazuron), 1-
(3,5-dichloro-2,4-difluorophenyl)-
Benzoylurea-based compounds such as 3- (2,6-difluorobenzoyl) urea (generic name: teflubenzuron); isopropyl (2E, 4E) -11-methoxy-3,7,11-trimethyl-2,4-dotecad Juvenile hormone-like compounds such as enoate (generic name: methoprene); 2-t-butyl-5- (4-t-butylbenzylthio) -4-chloro-3 (2H) -pyridazinone (generic name: pyridaben) ) Like pyridazinone compounds; t-
Pyrazole compounds such as butyl 4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl) methyleneaminooxymethyl] benzoate (generic name: fenpyroximate); 1- (6-chloro-3-pyridylmethyl ) -N-Nitro-imidazolidin-2-ylideneamine (generic name: imidacloprid) and other nitro compounds; or dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, hydrazine compounds,
In addition, as other compounds, 2-tert-butylimino-3-isopropyl-5-phenyl-3,4,5,5
6-Tetrahydro-2H-1,3,5-thiadiazine-
4-one (generic name: bubrofedin), trans- (4
-Chlorophenyl) -N-cyclohexyl-4-methyl-2-oxothiazolidinone-3-carboxamide (generic name: hexithiazox), N-methylbis (2,4-
Xylyliminomethyl) amine (generic name: amitraz), N ′-(4-chloro-o-tolyl) -N, N-dimethylformamidine (generic name: chlordimeform),
(4-Ethoxyphenyl)-[3- (4-fluoro-3
It may be a compound such as -phenoxyphenyl) propyl] (dimethyl) silane (generic name: silafluophene). Furthermore, the compound of the present invention can be mixed or used in combination with a microbial pesticide such as a BT agent or an insect pathogenic virus agent; or an antibiotic such as avermectin or milbemycin.

The bactericide used is, for example, 2-anilino-4-methyl-6- (1-propynyl) pyrimidine (generic name: mepanipyrim), 4,6-dimethyl-N-phenyl-2-pyrimidinamine (generic name). : Pyrimesanil)
A pyrimidinamine-based compound such as 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1H-1,2,
4-triazol-1-yl) butanone (generic name: triadimefon), 1- (biphenyl-4-yloxy)-
3,3-Dimethyl-1- (1H, 1,2,4-triazol-1-yl) butan-2-ol (generic name: bitertanol), 1- [N- (4-chloro-2-trifluoromethyl) (Phenyl) -2-propoxyacetimidoyl] imidazole (generic name: triflumizole), 1-
[2- (2,4-dichlorophenyl) -4-ethyl-
1,3-dioxolan-2-ylmethyl] -1H-1,
2,4-triazole (generic name: etaconazole), 1
-[2- (2,4-Dichlorophenyl) -4-propyl-1,3-dioxolan-2-ylmethyl] -1H-
1,2,4-triazole (generic name: propiconazole), 1- [2- (2,4-dichlorophenyl) pentyl] -1H-1,2,4-triazole (generic name: penconazole), bis (4 -Fluorophenyl) (methyl) (1H-1,2,4-triazol-1-ylmethyl) silane (generic name: flusilazole), 2- (4-chlorophenyl) -2- (1H-1,2,4-triazole -1-ylmethyl) hexanenitrile (generic name: microbutanyl), (2RS, 3RS) -2- (4-chlorophenyl) -3-cyclopropyl-1- (1H-1,
2,4-triazol-1-yl) butan-2-ol (generic name: cyproconazole), (RS) -1- (4-
Chlorophenyl) -4,4-dimethyl-3- (1H-
1,2,4-triazol-1-ylmethyl) pentan-3-ol (generic name: turbuconazole), (RS)
-2- (2,4-dichlorophenyl) -1- (1H-
1,2,4-triazol-1-yl) hexane-2-
All (generic name: hexaconazole), (2RS, 5R
S) -5- (2,4-Dichlorophenyl) tetrahydro-5- (1H-1,2,4-triazol-1-ylmethyl) -2-furyl 2,2,2-trifluoroethyl ether (generic name: fur Conazol cis), N-propyl-N- [2- (2,4,6-trichlorophenoxy)
Ethyl] imidazole-1-carboxamide (generic name:
Prochloraz), 2- (4-fluorophenyl-1-)
Azole compounds such as (1H-1,2,4triazol-1-yl) -3-trimethylsilylpropan-2-ol (generic name: cimeconazole); 6-methyl-
A quinoxaline compound such as 1,3-dithiolo [4,5-b] quinoxalin-2-one (generic name: quinomethionate); a polymer of manganese ethylene bis (dithiocarbamate) (generic name: manneb), zinc ethylene Polymer of bis (dithiocarbamate) (generic name: Zineb), complex compound of zinc (zinc) and Manganese ethylene bis (dithiocarbamate) (Manneb) (generic name:
Dithiocarbamate compounds such as manzeb), dizinc bis (dimethyldithiocarbamate) ethylene bis (dithiocarbamate) (generic name: polycarbamate), zinc propylene bis (dithiocarbamate) (generic name: provineb); , 6,7-Tetrachlorophthalide (generic name: phthalide), tetrachloroisophthalonitrile (generic name: chlorothalonil), pentachloronitrobenzene (generic name: quintozene), an organochlorine compound; methyl 1- (butyl Lucarbamoyl) benzimidazol-2-ylcarbamate (generic name: benomyl), dimethyl 4,4 '-(o-phenylene) bis (3-thioallophanate) (generic name: thiophanate methyl), methylbenzimidazol-2-ylcarbamate ( common name Carbendazim) -like benzimidazole compounds; 3-chloro-N- (3-chloro-2,6-dinitro-4-α, α, α-trifluorotolyl) -5-trifluoromethyl-2-pyridinamine ( Pyridinamine-based compounds such as common name: fluazinam); Cyanoacetamide-based compounds such as 1- (2-cyano-2-methoxyiminoacetyl) -3-ethylurea (general name: Simoxanil); Methyl N- (2- Methoxyacetyl) -N- (2,6-xylyl) -DL-
Alaninate (generic name: metalaxyl), 2-methoxy-N- (2-oxo-1,3-oxazolidin-3-yl) aceto-2 ′, 6′-xylidide (generic name: oxadixyl), (±) -α -2-chloro-N- (2,6-
Xylylacetamide) -γ-butyrolactone (generic name: offlace), methyl N-phenylacetyl-N
-(2,6-xylyl) -DL-alaninate (generic name: benalaxyl), methyl N- (2-furoyl)-
Like N- (2,6-xylyl) -DL-alaninate (generic name: furaraxyl), (±) -α- [N- (3-chlorophenyl) cyclopropanecarboxamide] -γ-butyrolactone (generic name: cyprofuran) Phenylamide compounds; N-dichlorofluoromethylthio-
Sulfenic acid compounds such as N ', N'-dimethyl-N-phenylsulfamide (generic name: diclofluanide); cupric hydroxide (generic name: cupric hydroxide), kappa 8-quinolinolate Copper-based compounds such as (generic name: organic copper); Isoxazole-based compounds such as 5-methylisoxazol-3-ol (generic name: hydroxyisoxazole); Aluminum tris (ethylphosphonate) (generic name: Fosetyl aluminum), O-2,6-
Dichloro-p-tolyl-O, O-dimethylphosphorothioate (generic name: tolclofos-methyl), S-benzyl O, O-diisopropylphosphorothioate, O-
Organophosphorus compounds such as ethyl S, S-diphenylphosphorodithioate, aluminum ethylhydrogenphosphonate; N- (trichloromethylthio) cyclohex-4-ene-1,2-dicarboximide (generic name: captan), N Such as-(1,1,2,2-tetrachloroethylthio) cyclohex-4-ene-1,2-dicarboximide (generic name: captafol), N- (trichloromethylthio) phthalimide (generic name: folpet) N-halogenothioalkyl compounds; N-
(3,5-Dichlorophenyl) -1,2-dimethylcyclopropane-1,2-dicarboximide (generic name: procymidone), 3- (3,5-dichlorophenyl) -N-
Isopropyl-2,4-dioxoimidazolidine-1-
Carboxamide (generic name: iprodione), (RS)-
3- (3,5-dichlorophenyl) -5-methyl-5-
Dicarboximide-based compounds such as vinyl-1,3-oxazolidine-2,4-dione (generic name: vinclozolin); α, α, α-trifluoro-3′-isopropoxy-o-toluanilide (generic name: Flutolanil),
Benzanilide compounds such as 3'-isopropoxy-o-toluanilide (generic name: mepronil); N, N '
-Piperazine-based compounds such as [piperazine-1,4-diylbis [(trichloromethyl) methylene]] diformamide (generic name: triphorine); 2 ', 4'-dichloro-2- (3-pyridyl) acetophenone O- Pyridine compounds such as methyl oxime (generic name: pyriphenox); (±) -2,4′-dichloro-α- (pyrimidin-5-yl) benzhydryl alcohol (generic name: phenalimol), (± ) -2,4'-Difluoro-
Carbinol compounds such as α- (1H-1,2,4-triazol-1-ylmethyl) benzhydryl alcohol (generic name: flutriafol); (RS) -1-
A piperidine-based compound such as [3- (4-tert-butylphenyl) -2-methylpropyl] piperidine (generic name: phenpropidin); (±) -cis-4-
Morpholine compounds such as [3- (4-tert-butylphenyl) -2-methylpropyl] -2,6-dimethylmorpholine (generic name: phenpropimorph); triphenyltin hydroxide (generic name: Fentin hydroxide), triphenyltin acetate (generic name: fentine acetate) such as organotin compounds; 1- (4-chlorobenzyl) -1-cyclopentyl-3-phenylurea (generic name: peniculone) Urea compounds such as; (E, Z) 4- [3- (4-chlorophenyl) -3- (3,4-dimethoxyphenyl) acryloyl] morpholine (generic name: dimethomorph), cinnamic acid compounds; isopropyl 3,4-
Phenylcarbamate compounds such as diethoxycarbanilate (generic name: dietofencarb); or 3
-Cyano-4- (2,2-difluoro-1,3-benzodioxol-4-yl) pyrrole (general name: fludioxonil), 3- (2 ', 3'-dichlorophenyl)-
It may be a cyanopyrrole-based compound such as 4-cyano-pyrrole (generic name: fenpiclonyl).

The compounds of the present invention will be specifically described below with reference to Examples, Formulation Examples and Test Examples, but the present invention is not limited thereto. The mass spectrometric value is EI unless otherwise specified, and is (APCI) when the atmospheric pressure chemical ionization method is used.

[0217]

【Example】

[0218]

Example 1 N- (3-cyanobenzyl) -N- [2-
(Cyclobutylmethyl) -4-methyl-5-thiazolyl] acetamide (Compound No. 4-1) (1) 2- (Cyclobutylmethyl) -4-methylthiazole (Step A-1) 2-Cyclobutyryl-4-methyl Thiazole (321m
g, 1.77 mmol) of diethylene glycol (8.
Hydrazine monohydrate (0.662 m)
1, 13.6 mmol) and potassium carbonate (611 m
g, 4.43 mmol) and added at 190-200 ° C for 2
The mixture was heated and stirred for an hour. After cooling the reaction solution to room temperature, water (50
ml) was added, and the mixture was extracted twice with ether (50 ml).
The organic layer was washed with saturated brine (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound (295 mg).
(Yield quantitative) was obtained as an oil. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.65-2.00 (4H, m), 2.
05-2.20 (2H, m), 2.40 (3H, s), 2.60-2.82 (1H, m),
3.06 (2H, d, J = 7.7Hz), 6.70 (1H, s). (2) 2- (cyclobutylmethyl) -4-methyl-5-
Nitrothiazole (Step A-2) 2- (cyclobutylmethyl) -obtained by the method of (1) above
4-Methylthiazole (295 mg, 1.76 mmol) was stirred with concentrated sulfuric acid (2.5 ml) dropwise at 0 ° C. The reaction solution was stirred at 0 ° C for 15 minutes, and fuming nitric acid (0.95 ml, 23 mmol) was added dropwise at 0 ° C. The reaction mixture was stirred at room temperature for 2 hours, and then saturated aqueous sodium hydrogen carbonate (1
50 ml). Then, the reaction solution was made weakly alkaline (pH = 8 to 9) with saturated aqueous sodium hydrogen carbonate, and ethyl acetate (100
ml) and extracted twice. The organic layer was saturated saline (100 m
l), dried over anhydrous sodium sulfate, and concentrated,
227 mg (61% yield) of the title compound was obtained as an oil. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.70-2.03 (4H, m), 2.
08-2.28 (2H, m), 2.62-2.84 (1H, m), 2.78 (3H, s),
3.03 (2H, d, J = 7.7Hz). (3) N- [2- (cyclobutylmethyl) -4-methyl-5-thiazolyl] acetamide (step A-3) 2- (cyclobutylmethyl) -obtained by the method of (2) above.
4-Methyl-5-nitrothiazole (227 mg, 1.
Acetic anhydride (2.05 ml, 20.5 mmol) was added to a solution of 07 mmol) in acetic acid (3.6 ml), and the mixture was cooled to 0 ° C. To this solution was added zinc (546 mg, 7.49 mmol) in one portion. The reaction solution was stirred at 0 ° C. for 10 minutes and then at room temperature for another 3 hours. Zinc was filtered by rinsing sequentially with ethyl acetate (30 ml) and ethanol (30 ml), and the filtrate was stirred for 1 hour. The reaction solution was concentrated, saturated aqueous sodium hydrogen carbonate (50 ml) was added to the obtained residue, the mixture was extracted twice with ethyl acetate (50 ml), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated. , 119 mg (yield 50%) of the title compound was obtained as a gum. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.66-1.95 (4H, m), 2.
05-2.20 (2H, m), 2.20 (3H, s), 2.29 (3H, s), 2.56-
2.78 (1H, m), 2.96 (2H, d, J = 7.7Hz), 7.94 (1H, br-
s). (4) N- (3-Cyanobenzyl) -N- [2- (cyclobutylmethyl) -4-methyl-5-thiazolyl] acetamide (Compound No. 4-1, Step A-4) The method of (3) above. N- [2- (cyclobutylmethyl) -4-methyl-5-thiazolyl] acetamide (20) obtained in
To a solution of 8 mg, 0.927 mmol) in N, N-dimethylformamide (8.0 ml) was added 60% sodium hydride (40.8 mg, 1.02 mmol) at room temperature,
Stir for 10 minutes. Subsequently, 3-cyanobenzyl bromide (210 mg, 1.02 mmol) was added at room temperature, followed by stirring at room temperature for 1 hour. After completion of the reaction, water (25 ml) was added, and the mixture was extracted twice with ethyl acetate (25 ml). The organic layer was washed with saturated brine (25 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel preparative thin-layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1) to give 196 mg of the title compound of the present invention.
(Yield 62%) was obtained as a gum. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.64-1.93 (4H, m),
1.96 (3H, s), 1.97 (3H, s), 2.02-2.19 (2H, m), 2.53
-2.77 (1H, m), 2.96 (2H, d, J = 7.3 Hz), 4.67-4.92
(2H, m), 7.38-7.63 (4H, m). low MS (m / z) 339 (M ⁺ ), 326, 297, 285, 242, 181, 16
9, 116.

[0219]

Example 2 2-[(3-Cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino] -2
-Oxoethyl = acetate (Compound No. 3-23) (1) 2-[(4-methyl-2-neopentyl-5-
Thiazolyl) amino] -2-oxoethyl = acetate (steps B-1,2) N- (4-methyl-2-neopentyl-5-thiazolyl) acetamide (599m prepared according to Example 1
g, 2.82 mmol) was dissolved in a 5% hydrochloric acid ethanol-water (1: 1, 60 ml) solution, and this solution was heated under reflux for 5 hours. After cooling the reaction mixture, it was concentrated under reduced pressure to give a crude 5
-Ammonio-4-methyl-2-neopentyl-3-thiazolium = dichloride 750 mg (quantitative yield)
Was obtained as a gum.

Crude 5-ammonio-4-methyl-2-neopentyl-3-thiazolium dichloride (70 mg,
0.27 mmol) at room temperature in dichloromethane (4.0 m
1) was added, followed by 2-chloro-2-oxoethyl acetate (0.058 ml, 0.54 mmol) followed by pyridine (0.087 ml, 1.08 mmol). After stirring the reaction solution at room temperature for 2.5 hours, water (25 ml) was added. After extracting twice with ethyl acetate (25 ml), the organic layer was washed with saturated brine (25 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin-layer chromatography (developing solvent:
Purification with n-hexane / ethyl acetate = 1/2) gave 40.2 mg (yield 52%) of the title compound as an oil. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.00 (9H, s), 2.23
(3H, s), 2.34 (3H, s), 2.78 (2H, s), 4.76 (2H, s),
8.08 (1H, br-s). (2) 2-[(3-cyanobenzyl) (4-methyl-
2-Neopentyl-5-thiazolyl) amino] -2-oxoethyl acetate (Compound No. 3-23, Step B
-3) 2-[(4-Methyl-2-neopentyl-5-thiazolyl) amino] -2-oxoethyl acetate (40.2 mg, 0.141 mmol) obtained in (1) was added to N, N-dimethyl. Dissolve in formamide (2.0 ml) and add to this solution 60% sodium hydride (6.
8 mg, 0.17 mmol) was added and the mixture was stirred for 10 minutes. Then at room temperature 3-cyanobenzyl bromide (33.1 m
g, 0.169 mmol) and then stirred at room temperature for 1 hour. After completion of the reaction, water (25 ml) was added, and the mixture was extracted twice with ethyl acetate (25 ml). The organic layer was washed with saturated saline (25 ml), dried over anhydrous sodium sulfate,
It was concentrated under reduced pressure. The residue was subjected to silica gel preparative thin-layer chromatography (developing solvent: n-hexane / ethyl acetate = 1 /
Purification in 1) gave 29.4 mg (52% yield) of the title compound of the invention as an oil. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (9H, s), 2.06
(3H, s), 2.18 (3H, s), 2.76 (2H, s), 4.44 (2H, s),
4.67 (1H, d, J = 13.9Hz), 4.95 (1H, d, J = 13.9Hz), 7.
39-7.64 (4H, m). low MS (m / z) 399 (M ⁺ ), 384, 343, 299, 242, 227, 12
7, 116, 101, 73, 57.

[0221]

Example 3 2-Chloro-N- (3-cyanobenzyl)
-N- (2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-12) (1) t-butyl acetyl (2-isobutyl-4-)
Methyl-5-thiazolyl) carbamate (step C-1) N- (2-isobutyl-4-methyl-5-thiazolyl)
A solution of acetamide (554 mg, 2.61 mmol) in acetonitrile (15 ml) was added at room temperature to N, N-dimethyl-N- (4-pyridyl) amine (33.0 mg, 0.
27 mmol), followed by di-t-butyl carbonate (684 m
g, 3.13 mmol) was added and the mixture was stirred for 15 hours. The reaction mixture was concentrated, water (50 ml) was added to the residue, and the mixture was extracted twice with ethyl acetate (50 ml). The organic layer was washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 3 /
Purified in 1), 556 mg of the title compound (yield 70%)
Was obtained as a gum. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (6H, d, J = 6.6H
z), 1.42 (9H, s), 1.98-2.18 (1H, m), 2.15 (3H, s),
2.57 (3H, s), 2.78 (2H, d, J = 7.0Hz). (2) t-butyl = 2-isobutyl-4-methyl-5
-Thiazolyl carbamate (Step C-2) t-Butyl acetyl (2-isobutyl-4-methyl-5-thiazolyl) carbamate (556 mg, 1.81 mmol) obtained by (1) was added to methanol (9 ．
Hydrazine monohydrate (0.448 ml, 9.05 mmol) at room temperature, and
Stir for 8 hours. The reaction mixture was concentrated under reduced pressure, water (50 ml) was added to the residue, and the mixture was extracted twice with ethyl acetate (50 ml). The organic layer was washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound 4
87 mg (yield quantitative) was obtained as a gum. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.51 (9H, s), 1.94-2.14 (1H, m), 2.27 (3H, s),
2.73 (2H, d, J = 7.0Hz), 6.40 (1H, br-s). (3) t-butyl = 3-cyanobenzyl (2-isobutyl-4-methyl-5-thiazolyl) carbamate (Step C-3) t-butyl = 2-isobutyl-4 obtained by (2).
-Methyl-5-thiazolyl carbamate (487 mg,
1.80 mmol) was dissolved in N, N-dimethylformamide (10 ml), and 60% sodium hydride (86.4 mg, 2.16 mmol) was added to this solution at room temperature, followed by stirring for 10 minutes. Then 3-cyanobenzyl bromide (423 mg, 2.16 mmol) was added at room temperature to 1.
Stir for 5 hours. After the reaction is completed, water (100 m
1) was added, and the mixture was extracted twice with ethyl acetate (100 ml). The organic layer was washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: n-hexane / ethyl acetate = 3/1) to give the title compound 600.
mg (86% yield) was obtained as a gum. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.94 (6H, d, J = 6.6H
z), 1.42 (9H, s), 1.92-2.12 (1H, m), 2.02 (3H, s),
2.70 (2H, d, J = 7.0Hz), 4.70 (2H, s), 7.38-7.61 (4
H, m). (4) 2-chloro-N- (3-cyanobenzyl) -N
-(2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-12, steps C-4 and C-
5) To t-butyl 3-cyanobenzyl (2-isobutyl-4-methyl-5-thiazolyl) carbamate (495 mg, 1.29 mmol) obtained in (3), 1.0
mol / L-hydrochloric acid ethanol solution (25.7 ml, 2
(5.7 mmol) was added at room temperature and stirred for 3 hours. After the reaction solution was concentrated under reduced pressure, dichloromethane (20 ml) and chloroacetyl chloride (0.230 ml, 2.86 mmol) were immediately added at room temperature to suspend the reaction solution. Pyridine (0.463 ml, 5.72 mmol) was added to this suspension at room temperature, and the mixture was stirred for 3 hours. Then, water (30 ml) was added to the reaction solution, and the mixture was extracted with dichloromethane (30 ml). The organic layer was washed with saturated saline (100 ml),
The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: n-hexane / ethyl acetate = 1/1) to give 304 mg (yield 59%) of the title compound of the present invention as colorless crystals (melting point: 9).
5 to 97 ° C.). ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.00 (3H, s), 1.93-2.13 (1H, m), 2.75 (2H, d,
J = 7.0Hz), 3.96 (2H, s), 4.72 (1H, d, J = 14.0Hz), 4.
93 (1H, d, J = 14.0Hz), 7.39-7.64 (4H, m). low MS (m / z) 361, 363 (M ⁺ , M + 2 ⁺ ), 319, 321, 245, 24
7, 203, 205, 162, 164, 126, 116, 101.

[0222]

Example 4 N- (3-Cyanobenzyl) -2-hydroxy-N- (4-methyl-2-neopentyl-5-thiazolyl) acetamide (Compound No. 3-12, Step D) Obtained by Example 2. 2-[(3-cyanobenzyl)
(4-Methyl-2-neopentyl-5-thiazolyl) amino] -2-oxoethyl acetate (29.4 m
g, 0.736 mmol) with methanol (2.0 ml)
And 1.0 mol / L-sodium carbonate aqueous solution (1.78 ml, 1.78 mmol) at room temperature.
Was added and stirred for 2.5 hours. After distilling off methanol, the mixture was extracted with ethyl acetate (20 ml). The organic layer was washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound of the present invention 24.5 mg.
(93% yield) was obtained as an oil. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (9H, s), 2.00
(3H, s), 2.76 (2H, s), 3.14 (1H, br-s), 3.92 (2H, b
rs), 4.44 (2H, s), 4.66-5.03 (2H, m), 7.40-7.65
(4H, m). low MS (m / z) 357 (M ⁺ ), 342, 301, 242, 185, 127, 11
6, 57.

[0223]

Example 5 N'-allyl-N- (3-cyanobenzyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-152, Step E) According to Example 3. 3-Cyanobenzyl (2-isobutyl-4-methyl-5-thiazolyl) carbamic chloride (50 mg, 0.14 mmol) prepared by the above procedure was dissolved in acetonitrile (2.5 ml) and added to allylamine (0 0.011 ml, 0.14 mmol) and triethylamine (0.020 ml, 0.14 mmol) were added, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated, water (30 ml) was added, and the mixture was extracted twice with ethyl acetate (30 ml). The organic layer was washed with saturated brine (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin-layer chromatography (developing solvent:
Purification by n-hexane / ethyl acetate = 1/1) gave 42 mg (yield 79%) of the title compound of the invention as an oil. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.93-2.14 (1H, m), 2.04 (3H, s), 2.73 (2H, d, J
= 7.3Hz), 3.84-3.91 (2H, m), 4.70 (1H, t, J = 5.9Hz),
4.79 (2H, s), 5.05-5.15 (2H, m), 5.73-5.92 (1H,
m), 7.37-7.61 (4H, m). low MS (m / z) 368 (M ⁺ ), 285, 242, 169, 116.

[0224]

Example 6 N- (3-cyanobenzyl) -N- (4-
Methyl-2-phenyl-5-thiazolyl) acetamide (Compound No. 9-1, step F) (1) (1E) -1- (4-methyl-2-phenyl-
5-thiazolyl) ethanone-oxime (step F-1) 1- (4-methyl-2-phenyl-5-thiazolyl) ethanone (5.06 g, 23.3 mmol) in ethanol (100 ml) was added with hydroxylamine hydrochloride. Salt (1.95 g, 28.0 mmol) and sodium acetate (4.59 g, 56.0 mmol) were added, and the mixture was heated under reflux for 4 hours. After cooling the reaction solution to room temperature, ethanol was distilled off under reduced pressure, water (100 ml) was added, and ethyl acetate (150
ml) and extracted twice. The organic layer was saturated saline (150 m
It was washed with l), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography (elution solvent: n
-Hexane / ethyl acetate = 4/1) to give 3.21 g (yield 59%) of the title compound as light brown crystals. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.35 (3H, s), 2.63
(3H, s), 7.39-7.46 (3H, m), 7.90-7.95 (2H, m), 8.09
(1H, s). (2) N- (4-methyl-2-phenyl-5-thiazolyl) acetamide (step F-2) (1E) -1- (4-methyl-2) obtained by (1).
-Phenyl-5-thiazolyl) ethanone-oxime (2
Polyphosphoric acid (3.0 mg to 0.8 mg, 0.86 mmol)
g) was added and the mixture was stirred at 140 ° C. for 3 hours. The reaction solution was cooled to room temperature and then neutralized with a 2.0 mol / L-sodium hydroxide aqueous solution. It was extracted twice with ethyl acetate (100 ml), the organic layer was washed with saturated brine (100 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound 20.
0 mg (quantitative yield) was obtained as light brown crystals. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.21 (3H, s), 2.39
(3H, s), 7.33-7.43 (3H, m), 7.81-7.87 (2H, m), 8.40
(1H, s). low MS (m / z) 232 (M ⁺ ), 190, 149, 121. (3) N- (3-cyanobenzyl) -N- (4-methyl-2-phenyl-5-thiazolyl) acetamide (Compound No. 9-1, step F-3) N- (obtained by (2)) 4-Methyl-2-phenyl-5-thiazolyl) acetamide (200 mg, 0.8
6 mmol) of N, N-dimethylformamide (5.0
ml), 60% sodium hydride (39 mg, 0.98 mmol) was added to this solution, and the mixture was stirred for 10 minutes. Then 3-cyanobenzyl bromide (192 m
g, 0.98 mmol) was added and stirred for 4 hours. After completion of the reaction, water (50 ml) was added to the reaction solution, and the mixture was extracted twice with ethyl acetate (50 ml). The organic layer was saturated brine (5
The extract was washed with 0 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 3/1) to give 261 mg of the title compound of the present invention (yield 85%).
Was obtained as a gum. ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.04 (3H, s), 2.07
(3H, s), 4.75-4.95 (2H, m), 7.39-7.64 (7H, m), 7.82
-7.87 (2H, m). low MS (m / z) 347 (M ⁺ ), 305, 231, 189, 121.

The following compounds were produced in the same manner as in Examples 1-6.

[0226]

Example 7 N- (3-cyanobenzyl) -N- (2-
Isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.98 (3H, s), 1.99 (3H, s), 1.91-2.15 (1H, m),
2.74 (2H, d, J = 7.0Hz), 4.67-4.93 (2H, m), 7.38-7.6
2 (4H, m). low MS (m / z) 327 (M ⁺ ), 285, 242, 169, 116.

[0227]

Example 8 N- (3-cyanobenzyl) -N- (2-
Isobutyl-4-methyl-5-thiazolyl) pentanamide (Compound No. 1-5) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.86 (3H, t, J = 7.3H
z), 0.97 (6H, d, J = 6.6Hz), 1.18-1.36 (2H, m), 1.53
-1.68 (2H, m), 1.98 (3H, s), 1.95-2.15 (1H, m), 2.
15 (2H, t, J = 7.0Hz), 2.74 (2H, d, J = 7.3Hz), 4.68
(1H, d, J = 13.6Hz), 4.93 (1H, d, J = 13.6Hz), 7.37-7.6
2 (4H, m). low MS (m / z) 369 (M ⁺ ), 354, 285, 242, 190, 169, 11
6, 101, 85, 57.

[0228]

Example 9 N- (3-cyanobenzyl) -N- (2-
Isobutyl-4-methyl-5-thiazolyl) cyclopropanecarboxamide (Compound No. 1-7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.77-0.90 (2H, m),
0.97 (6H, d, J = 6.6Hz), 1.00-1.13 (2H, m), 1.45-1.58
(1H, m), 2.02 (3H, s), 1.94-2.14 (1H, m), 2.74 (2
H, d, J = 7.3Hz), 4.75 (1H, d, J = 13.9Hz), 4.90 (1H,
d, J = 13.9Hz), 7.37-7.62 (4H, m). low MS (m / z) 353 (M ⁺ ), 285, 242, 116, 101, 69.

[0229]

Example 10 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) benzamide (Compound No. 1-19) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.89 (6H, d, J = 6.6H
z), 1.69 (3H, s), 1.85-2.06 (1H, m), 2.65 (2H, d,
J = 7.3Hz), 5.00 (2H, s), 7.18-7.48 (7H, m), 7.56-7.
63 (2H, m). low MS (m / z) 389 (M ⁺ ), 374, 265, 242, 190, 167, 14
9, 116, 105, 77.

[0230]

Example 11 N- (3-Cyanobenzyl) -2-hydroxy-N- (2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-35) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.98 (3H, s), 1.94-2.14 (1H, m), 2.75 (2H, d,
J = 7.3Hz), 3.14 (1H, br-s), 3.93 (2H, br-s), 4.65-
5.05 (2H, m), 7.40-7.66 (4H, m). low MS (m / z) 343 (M ⁺ ), 328, 301, 285, 242, 227, 19
7, 185, 169, 116, 101.

[0231]

Example 12 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-methoxyacetamide (Compound No. 1-39) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.98 (3H, s), 1.92-2.16 (1H, m), 2.75 (2H, d,
J = 7.0Hz), 3.41 (3H, s), 3.87 (2H, dd, J = 22.0,21.5H
z), 4.68-4.94 (2H, m), 7.39-7.64 (4H, m). low MS (m / z) 357 (M ⁺ ), 342, 329, 315, 285, 242, 11
6.

[0232]

Example 13 N- (3-Cyanobenzyl) -2-ethoxy-N- (2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-42) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.23 (3H, t, J = 7.0Hz), 1.97 (3H, s), 1.93-2.14
(1H, m), 2.74 (2H, d, J = 7.3Hz), 3.53 (2H, q, J = 7.0
Hz), 3.91 (2H, s), 4.73 (1H, d, J = 13.6Hz), 4.89 (1
H, d, J = 13.6Hz), 7.38-7.69 (4H, m). low MS (m / z) 371 (M ⁺ ), 356, 343, 329, 313, 285, 24
2, 116, 101.

[0233]

Example 14 N- (3-cyanobenzyl) -2-
[(Cyanomethyl) sulfanyl] -N- (2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-45) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (6H, d, J = 6.6H
z), 2.05 (3H, s), 1.95-2.15 (2H, m), 2.75 (2H, d,
J = 7.0Hz), 3.37 (2H, s), 3.59 (2H, d, J = 2.2Hz), 4.7
2 (1H, d, J = 14.3Hz), 4.85 (1H, d, J = 14.3Hz), 7.35-
7.65 (4H, m). low MS (m / z) 398 (M ⁺ ), 383, 356, 285, 242, 199, 16
9, 116, 101, 86.

[0234]

Example 15 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-phenoxyacetamide (Compound No. 1-48) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 2.04 (3H, s), 1.94-2.15 (1H, m), 2.75 (2H, d,
J = 7.3Hz), 4.49 (2H, s), 4.71 (1H, d, J = 14.3Hz), 4.
97 (1H, d, J = 14.3Hz), 6.81 (2H, d, J = 7.7Hz), 6.98
(1H, t, J = 7.3Hz), 7.27 (2H, t, J = 7.3Hz), 7.39-7.63
(4H, m). low MS (m / z) 419 (M ⁺ ), 404, 377, 298, 285, 242, 11
6, 107, 77.

[0235]

Example 16 N- (3-cyanobenzyl) -2- (3
-Fluorophenoxy) -N- (2-isobutyl-4-
Methyl-5-thiazolyl) acetamide (Compound No. 1
−59) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.95 (6H, d, J = 6.6H
z), 1.93-2.13 (1H, m), 2.03 (3H, s), 2.75 (2H, d, J
= 7.3Hz), 4.47 (2H, s), 4.71 (1H, d, J = 13.9Hz), 4.9
5 (1H, d, J = 13.9Hz), 6.48-6.73 (3H, m), 7.19 (1H,
t, J = 7.0Hz), 7.39-7.64 (4H, m). low MS (m / z) 437 (M ⁺ ), 422, 395, 321, 298, 279, 24
2, 125, 116, 101.

[0236]

Example 17 N- (3-cyanobenzyl) -2-
(2,4-Difluorophenoxy) -N- (2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-62) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.95 (6H, d, J = 6.6H
z), 1.92-2.12 (1H, m), 2.00 (3H, s), 2.74 (2H, d, J
= 7.3Hz), 4.43-4.58 (2H, m), 4.72 (1H, d, J = 13.0H
z), 4.92 (1H, d, J = 13.0Hz), 6.70-6.94 (3H, m), 7.3
8-7.63 (4H, m). low MS (m / z) 455 (M ⁺ ), 440, 413, 339, 298, 285, 24
3, 143, 116, 101.

[0237]

Example 18 N- (3-cyanobenzyl) -2- (3
-Cyanophenoxy) -N- (2-isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-
66) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 1.94-2.13 (1H, m), 2.04 (3H, s), 2.76 (2H, d, J
= 7.3Hz), 4.43-4.56 (2H, m), 4.73 (1H, d, J = 13.5H
z), 4.93 (1H, d, J = 13.5Hz), 7.01 (1H, dd, J = 2.5,
1.5Hz), 7.08 (1H, ddd, J = 8.1, 2.5, 1.5Hz), 7.29-7.
53 (5H, m), 7.62 (1H, dt, J = 7.0, 1.8Hz). low MS (m / z) 444 (M ⁺ ), 429, 402, 328, 298, 286, 24
2, 204, 174, 132, 116, 101.

[0238]

Example 19 N- (3-cyanobenzyl) -2-
[(4-Fluorophenyl) sulfanyl] -N- (2
-Isobutyl-4-methyl-5-thiazolyl) acetamide (Compound No. 1-71) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.00 (3H, s), 1.92-2.12 (1H, m), 2.73 (2H, d,
J = 7.3Hz), 3.51 (2H, s), 4.60 (1H, d, J = 14.3Hz), 4.
99 (1H, d, J = 14.3Hz), 6.95-7.06 (2H, m), 7.37-7.63
(4H, m). low MS (m / z) 453 (M ⁺ ), 438, 411, 285, 242, 141, 11
6.

[0239]

Example 20 2-[(3-Cyanobenzyl) (2-isobutyl-4-methyl-5-thiazolyl) amino] -2
-Oxoethyl = acetate (Compound No. 1-75) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 7.0H
z), 1.87-2.11 (1H, m), 2.04 (3H, s), 2.18 (3H, s),
2.74 (2H, d, J = 7.0Hz), 4.45 (3H, s), 4.69 (1H, d,
J = 13.9Hz), 4.92 (1H, d, J = 13.9Hz), 7.40-7.63 (4H,
m). low MS (m / z) 385 (M ⁺ ), 370, 343, 327, 285, 269, 24
2, 227, 186, 144, 116.

[0240]

Example 21 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-
(2-pyridinyloxy) acetamide (Compound No. 1
−89) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 1.92-2.13 (1H, m), 2.17 (3H, s), 2.74 (2H, d, J
= 7.3Hz), 4.56 (1H, d, J = 13.0Hz), 4.74 (2H, s), 5.1
1 (1H, d, J = 13.0Hz), 6.86-6.95 (2H, m), 7.38-7.65
(5H, m), 8.10 (1H, dd, J = 4.8, 2.0Hz). low MS (m / z) 420 (M ⁺ ), 405, 413, 284, 242, 136, 10
8.

[0241]

Example 22 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-
[(6-Methyl-2-pyridinyl) oxy] acetamide (Compound No. 1-91) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.94-2.14 (1H, m), 2.12 (3H, s), 2.36 (3H, s),
2.75 (2H, d, J = 7.3Hz), 4.62 (1H, d, J = 14.3Hz), 4.6
7-4.83 (2H, m), 5.04 (1H, d, J = 14.3Hz), 6.68 (1H,
d, J = 8.4Hz), 6.74 (1H, d, J = 7.3Hz), 7.38-7.63 (5H,
m). low MS (m / z) 434 (M ⁺ ), 419, 298, 285, 242, 150, 12
2, 92.

[0242]

Example 23 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-
[(5-Methyl-3-isoxazolyl) oxy] acetamide (Compound No. 1-96) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.94-2.14 (1H, m), 2.07 (3H, s), 2.33 (3H, s),
2.74 (2H, d, J = 7.0Hz), 4.66-4.76 (3H, m), 4.98 (1
H, d, J = 13.9Hz), 5.74 (1H, s), 7.39-7.63 (4H, m).

[0243]

Example 24 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-
[(5-Methyl-1,3,4-thiadiazol-2-yl) sulfanyl] acetamide (Compound No. 1-9
7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 1.94-2.13 (1H, m), 2.12 (3H, s), 2.73 (3H, s),
2.74 (2H, d, J = 7.3Hz), 3.93 (1H, d, J = 14.5Hz), 4.1
1 (1H, d, J = 14.5Hz), 4.64 (1H, d, J = 14.0Hz), 5.07
(1H, d, J = 14.0Hz), 7.39-7.62 (4H, m). low MS (m / z) 457 (M ⁺ ), 326, 285, 242, 173, 116.

[0244]

Example 25 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-
(1-Pyrazolyl) acetamide (Compound No. 1-9
8) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.03 (3H, s), 1.94-2.14 (1H, m), 2.76 (2H, d,
J = 7.3Hz), 4.69-4.92 (4H, m), 6.33 (1H, t, J = 2.2H
z), 7.39-7.64 (6H, m). low MS (m / z) 393 (M ⁺ ), 378, 284, 277, 242, 235, 16
9, 116, 101, 81.

[0245]

Example 26 2- (4-Bromo-1-pyrazolyl)-
N- (3-cyanobenzyl) -N- (2-isobutyl-
4-Methyl-5-thiazolyl) acetamide (Compound No. 1-99) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (6H, d, J = 6.6H
z), 1.95-2.15 (1H, m), 2.03 (3H, s), 2.76 (2H, d, J
= 7.3Hz), 4.63-4.90 (4H, m), 7.38-7.64 (6H, m). low MS (m / z) 471, 473 (M + 1 ⁺ , M-1 ⁺ ), 456, 458, 429,
431, 355, 357, 284, 242, 159, 161, 116.

[0246]

Example 27 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -2-
(2-oxo-1 (2H) -pyridinyl) acetamide (Compound No. 1-101) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.94-2.14 (1H, m), 2.14 (3H, s), 2.75 (2H, d, J
= 7.3Hz), 4.43 (2H, s), 4.72 (1H, d, J = 14.0Hz), 4.9
6 (1H, d, J = 14.0Hz), 6.21 (1H, t, J = 6.6Hz), 6.57
(1H, d, J = 9.2Hz), 7.21 (1H, dd, J = 7.0, 2.0Hz), 7.34
-7.62 (5H, m). low MS (m / z) 420 (M ⁺ ), 405, 285, 242, 136, 108.

[0247]

Example 28 Methyl 3-cyanobenzyl (2-isobutyl-4-methyl-5-thiazolyl) carbamate (Compound No. 1-103) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.89-2.13 (1H, m), 2.06 (3H, s), 2.78 (2H, d, J
= 7.3Hz), 3.78 (3H, s), 4.75 (2H, s), 7.40-7.63 (4
H, m). low MS (m / z) 343 (M ⁺ ), 328, 301, 227, 185, 144, 11
6.

[0248]

Example 29 t-Butyl 3-cyanobenzyl (2-
Isobutyl-4-methyl-5-thiazolyl) carbamate (Compound No. 1-107) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.89-2.13 (1H, m), 2.06 (3H, s), 2.78 (2H, d, J
= 7.3Hz), 3.78 (3H, s), 4.75 (2H, s), 7.40-7.63 (4
H, m). low MS (m / z) 343 (M ⁺ ), 328, 301, 227, 185, 144, 11
6.

[0249]

Example 30 2-Pyridyl-3-cyanobenzyl (2
-Isobutyl-4-methyl-5-thiazolyl) carbamate (Compound No. 1-118) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 1.92-2.13 (1H, m), 2.15 (3H, s), 2.73 (2H, d, J
= 7.0Hz), 4.84 (2H, br-s), 7.01-7.04 (1H, m), 7.19-
7.26 (1H, m), 7.42-7.65 (4H, m), 7.79 (1H, td, J =
9.0, 1.5Hz), 8.40 (1H, dd, J = 4.4, 1.5Hz). low MS (m / z) 406 (M ⁺ ), 391, 362, 268, 195, 153, 11
6.

[0250]

Example 31 S-methyl = 3-cyanobenzyl (2-
Isobutyl-4-methyl-5-thiazolyl) thiocarbamate (Compound No. 1-130) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.01 (3H, s), 1.95-2.15 (1H, m), 2.32 (3H, s),
2.75 (2H, d, J = 7.3Hz), 4.68-4.96 (2H, m), 7.39-7.
64 (4H, m). low MS (m / z) 359 (M ⁺ ), 344, 317, 284, 242, 201, 16
0, 116, 101, 75.

[0251]

Example 32 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-139) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 2.00 (3H, s), 1.92-2.13 (1H, m), 2.72 (2H, d,
J = 7.3Hz), 4.77 (2H, s), 4.91 (2H, br-s), 7.38-7.61
(4H, m). low MS (m / z) 328 (M ⁺ ), 313, 285, 242, 212, 170, 12
9, 116, 89.

[0252]

Example 33 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
Methylurea (Compound No. 1-140) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.95 (6H, d, J = 6.6H
z), 2.00 (3H, s), 1.93-2.13 (1H, m), 2.71 (2H, d,
J = 7.3Hz), 2.81 (3H, d, J = 4.8Hz), 4.59 (1H, q, J = 2.6
Hz), 4.77 (2H, s), 7.35-7.59 (4H, m). low MS (m / z) 342 (M ⁺ ), 285, 242, 169, 143, 116.

[0253]

Example 34 N- (3-Cyanobenzyl) -N'-ethyl-N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-141) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.10 (3H, t, J = 7.3Hz), 2.02 (3H, s), 1.93-2.13
(1H, m), 2.74 (2H, d, J = 7.3Hz), 3.28 (2H, dq, J =
7.3, 5.9Hz), 4.62 (1H, t, J = 5.5Hz), 4.78 (2H, s),
7.37-7.61 (4H, m). low MS (m / z) 356 (M ⁺ ), 285, 242, 169, 157, 127, 11
6.

[0254]

Example 35 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
Isopropylurea (Compound No. 1-142) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.10 (6H, d, J = 6.2Hz), 2.01 (3H, s), 1.94-2.14
(1H, m), 2.74 (2H, d, J = 7.3Hz), 3.91-4.09 (1H,
m), 4.35 (1H, d, J = 8.1Hz), 4.77 (2H, s), 7.37-7.59
(4H, m). low MS (m / z) 370 (M ⁺ ), 285, 242, 169, 127, 116, 10
1.

[0255]

Example 36 N′-t-butyl-N- (3-cyanobenzyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-145) ¹ H-NMR (200 MHz , CDCl ₃ ) δppm: 0.95 (6H, d, J = 6.6H
z), 1.30 (9H, s), 2.02 (3H, s), 1.93-2.13 (1H, m),
2.73 (2H, d, J = 7.3Hz), 4.47 (1H, br-s), 4.75 (2H,
s), 7.37-7.59 (4H, m). low MS (m / z) 384 (M ⁺ ), 285, 242, 169, 127, 116, 10
0.

[0256]

Example 37 N- (3-cyanobenzyl) -N'-cyclopropyl-N- (2-isobutyl-4-methyl-5)
-Thiazolyl) urea (Compound No. 1-146) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.39-0.47 (2H, m),
0.70-0.80 (2H, m), 0.97 (6H, d, J = 6.6Hz), 1.98 (3H,
s), 1.93-2.13 (1H, m), 2.58-2.70 (1H, m), 2.73 (2
H, d, J = 7.3Hz), 4.77 (2H, s), 4.78 (1H, br-s), 7.3
7-7.61 (4H, m). low MS (m / z) 368 (M ⁺ ), 285, 242, 169, 116.

[0257]

Example 38 N- (3-Cyanobenzyl) -N'-cyclobutyl-N- (2-isobutyl-4-methyl-5-
Thiazolyl) urea (Compound No. 1-147) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.60-1.80 (4H, m), 2.02 (3H, s), 1.94-2.14 (1H,
m), 2.24-2.40 (2H, m), 2.75 (2H, d, J = 7.0Hz), 4.2
1-4.41 (1H, m), 4.69 (1H, d, J = 7.7Hz), 4.76 (2H,
s), 7.36-7.60 (4H, m). low MS (m / z) 382 (M ⁺ ), 354, 285, 242, 169, 116, 10
1.

[0258]

Example 39 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
Phenylurea (Compound No. 1-148) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.99 (6H, d, J = 6.6H
z), 1.98-2.18 (1H, m), 2.10 (3H, s), 2.78 (2H, d, J
= 7.3Hz), 4.85 (2H, s), 6.51 (1H, br-s), 7.03-7.11
(1H, m), 7.25-7.47 (5H, m), 7.56-7.63 (3H, m). low MS (m / z) 404 (M ⁺ ), 285, 242, 205, 169, 127, 11
6.

[0259]

Example 40 N′-benzyl-N- (3-cyanobenzyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-149) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.94 (6H, d, J = 6.6H
z), 1.90-2.10 (1H, m), 2.00 (3H, s), 2.70 (2H, d, J
= 7.0Hz), 4.44 (2H, d, J = 5.9Hz), 4.81 (2H, s), 4.98
(1H, t, J = 5.9Hz), 7.20-7.61 (9H, m). low MS (m / z) 418 (M ⁺ ), 285, 242, 169, 127, 116, 10
1, 91.

[0260]

Example 41 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
(1-Phenylethyl) urea (Compound No. 1-15
0) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 1.42 (3H, d, J = 7.0Hz), 2.01 (3H, s), 1.93-2.13
(1H, m), 2.74 (2H, d, J = 7.0Hz), 4.70 (1H, d, J = 14.
7Hz), 4.84 (1H, d, J = 14.7Hz), 4.86 (1H, d, J = 4.8H
z), 4.95-5.09 (1H, m), 7.19-7.60 (10H, m). low MS (m / z) 432 (M ⁺ ), 285, 242, 169, 127, 116, 10
Five.

[0261]

Example 42 N- (3-cyanobenzyl) -N'-
[Cyano (phenyl) methyl] -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1
-151) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.94 (6H, d, J = 6.6H
z), 1.96 (3H, s), 1.91-2.11 (1H, m), 2.71 (2H, d,
J = 7.0Hz), 4.76 (1H, d, J = 14.3Hz), 4.88 (1H, d, J = 1
4.3Hz), 5.17 (1H, d, J = 8.4Hz), 6.07 (1H, d, J = 8.4H
z), 7.41-7.64 (9H, m). low MS (m / z) 443 (M ⁺ ), 285, 242, 169, 132, 116, 10
1.

[0262]

Example 43 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
(2-Propinyl) urea (Compound No. 1-153) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.94-2.15 (1H, m), 2.03 (3H, s), 2.21 (1H, t, J
= 2.6Hz), 2.74 (2H, d, J = 7.0Hz), 4.04 (2H, dd, J = 5.
5, 2.6Hz), 4.79 (2H, s), 4.80 (1H, br-s), 7.37-7.6
1 (4H, m). low MS (m / z) 366 (M ⁺ ), 285, 242, 167, 116.

[0263]

Example 44 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
(2,2,2-Trifluoroethyl) urea (Compound No. 1-154) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.02 (3H, s), 1.95-2.15 (1H, m), 2.74 (2H, d,
J = 7.3Hz), 3.81-3.98 (2H, m), 4.80 (2H, br-s), 4.97
(1H, t, J = 6.6Hz), 7.39-7.62 (4H, m). low MS (m / z) 410 (M ⁺ ), 242, 211, 191, 149, 118, 10
9.

[0264]

Example 45 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
(2-Methoxyethyl) urea (Compound No. 1-15
5) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.03 (3H, s), 1.94-2.14 (1H, m), 2.73 (2H, d,
J = 7.3Hz), 3.28 (3H, s), 3.41-3.43 (4H, m), 4.78 (2
H, s), 5.00 (1H, br-s), 7.37-7.60 (4H, m). low MS (m / z) 386 (M ⁺ ), 285, 242, 169, 154, 116.

[0265]

Example 46 N- (3-cyanobenzyl) -N'-
(Cyanomethyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-156) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.01 (3H, s), 1.92-2.12 (1H, m), 2.72 (2H, d,
J = 7.0Hz), 4.16 (2H, d, J = 7.0Hz), 4.79 (2H, s), 5.3
0 (1H, t, J = 5.9Hz), 7.40-7.63 (4H, m). low MS (m / z) 367 (M ⁺ ), 352, 325, 285, 251, 242, 20
9, 196, 168, 116.

[0266]

Example 47 N- (3-cyanobenzyl) -N'-hydroxy-N- (2-isobutyl-4-methyl-5-
Thiazolyl) urea (Compound No. 1-157) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.92-2.12 (1H, m), 2.03 (3H, s), 2.73 (2H, d, J
= 7.3Hz), 4.78 (2H, s), 7.15 (1H, s), 7.38-7.63 (4
H, m). low MS (m / z) 344 (M ⁺ ), 328, 285, 242, 228, 184, 14
5, 116.

[0267]

Example 48 N '-(allyloxy) -N- (3-cyanobenzyl) -N- (2-isobutyl-4-methyl-)
5-thiazolyl) urea (Compound No. 1-158) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 2.01 (3H, s), 1.93-2.13 (1H, m), 2.73 (2H, d,
J = 7.3Hz), 4.37 (2H, d, J = 6.2Hz), 4.76 (2H, s), 5.2
6-5.36 (2H, m), 5.85-6.05 (1H, m), 7.38-7.63 (4H,
m). low MS (m / z) 384 (M ⁺ ), 328, 285, 268, 242, 185, 11
6.

[0268]

Example 49 N '-(benzyloxy) -N- (3-
Cyanobenzyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-159) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.93 (6H, d, J = 6.6H
z), 1.88-2.08 (1H, m), 1.93 (3H, s), 2.69 (2H, d, J
= 7.3Hz), 4.76 (2H, s), 4.90 (2H, s), 7.17 (1H, s),
7.31-7.63 (9H, m). low MS (m / z) 434 (M ⁺ ), 374, 285, 242, 154, 116, 9
1.

[0269]

Example 50 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -1-azetidinecarboxamide (Compound No. 1-160) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.94 (6H, d, J = 6.6H
z), 2.02 (3H, s), 1.91-2.17 (3H, m), 2.71 (2H, d,
J = 7.3Hz), 3.72 (4H, t, J = 7.7Hz), 4.72 (2H, s), 7.3
5-7.60 (4H, m). low MS (m / z) 368 (M ⁺ ), 325, 169, 116, 101, 84, 56.

[0270]

Example 51 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -1-pyrrolidinecarboxamide (Compound No. 1-161) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.94 (6H, d, J = 6.6H
z), 1.73-1.79 (4H, m), 1.97 (3H, s), 1.91-2.11 (1H,
m), 2.70 (2H, d, J = 7.0Hz), 3.09-3.16 (4H, m), 4.7
2 (2H, s), 7.33-7.59 (4H, m). low MS (m / z) 382 (M ⁺ ), 183, 116, 98, 55.

[0271]

Example 52 Methyl = (2S) -1-{[(3-cyanobenzyl) (2-isobutyl-4-methyl-5-thiazolyl) amino] carbonyl} -2-pyrrolidinecarboxylate (Compound No. 1-162) ) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.95 (6H, d, J = 6.6H
z), 1.72-2.20 (5H, m), 2.03 (3H, s), 2.71 (2H, d, J
= 7.1Hz), 2.99 (2H, t, J = 5.9Hz), 3.75 (3H, s), 4.42
-4.48 (1H, m), 4.73 (2H, s), 7.34-7.58 (4H, m). low MS (m / z) 440 (M ⁺ ), 381, 241, 156, 128, 116.

[0272]

Example 53 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) morpholinocarboxamide (Compound No. 1-164) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.94 (6H, d, J = 6.6H
z), 1.91-2.11 (1H, m), 2.02 (3H, s), 2.71 (2H, d, J
= 7.3Hz), 3.28 (4H, t, J = 4.8Hz), 3.49 (4H, t, J = 4.8H
z), 4.68 (2H, s), 7.34-7.59 (4H, m). low MS (m / z) 398 (M ⁺ ), 282, 199, 116, 114, 70.

[0273]

Example 54 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) -N'-
(3-quinolyl) urea (Compound No. 1-166) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.99 (6H, d, J = 6.6H
z), 1.96-2.16 (1H, m), 2.13 (3H, s), 2.77 (2H, d, J
= 7.3Hz), 4.89 (2H, s), 6.93 (1H, s), 7.35-7.65 (6
H, m), 7.77 (1H, dd, J = 8.1, 1.5Hz), 8.02 (1H, d, J
= 8.4Hz), 8.48-8.53 (2H, m). low MS (m / z) 455 (M ⁺ ), 285, 242, 170, 116.

[0274]

Example 55 N- (3-cyanobenzyl) -N'-
(4,5-Dihydrothiazol-2-yl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-168) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.95 (6H, d, J = 6.6H
z), 2.01 (3H, br-s), 1.91-2.11 (1H, m), 2.70 (2H,
d, J = 7.3Hz), 3.26 (2H, t, J = 7.0Hz), 3.60-3.90 (2H,
m), 4.75-5.05 (2H, m), 7.35-7.58 (4H, m). low MS (m / z) 413 (M ⁺ ), 285, 242, 129, 116.

[0275]

Example 56 N′-Acetyl-N- (3-cyanobenzyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-169) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.99 (6H, d, J = 6.6H
z), 2.02 (3H, s), 1.95-2.15 (1H, m), 2.53 (3H, s),
2.75 (2H, d, J = 7.0Hz), 4.79 (2H, br-s), 7.41 (1H,
br-s), 7.41-7.65 (4H, m). low MS (m / z) 370 (M ⁺ ), 285, 242, 171, 116, 101.

[0276]

Example 57 N′-Benzoyl-N- (3-cyanobenzyl) -N- (2-isobutyl-4-methyl-5-thiazolyl) urea (Compound No. 1-170) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.98 (6H, d, J = 6.6H
z), 1.98-2.18 (1H, m), 2.09 (3H, s), 2.79 (2H, d, J
= 7.3Hz), 4.86 (2H, br-s), 7.34-7.64 (10H, m). low MS (m / z) 432 (M ⁺ ), 354, 285, 242, 116, 105, 7
7.

[0277]

Example 58 N- (3-cyanobenzyl) -N- (2
-Isobutyl-5-thiazolyl) acetamide (Compound No. 1-171) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 6.6H
z), 1.94-2.18 (1H, m), 2.06 (3H, s), 2.79 (2H, d, J
= 7.3Hz), 4.84 (2H, s), 7.20 (1H, s), 7.38-7.61 (4
H, m). low MS (m / z) 313 (M ⁺ ), 298, 271, 256, 228, 155, 11
6.

[0278]

Example 59 N- (3-cyanobenzyl) -N- [2
-Isobutyl-4- (trifluoromethyl) -5-thiazolyl] acetamide (Compound No. 1-183) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.97 (6H, d, J = 7.0H
z), 2.05 (3H, s), 1.96-2.20 (1H, m), 2.80 (2H, d,
J = 7.3Hz), 4.30 (1H, d, J = 14.3Hz), 5.43 (1H, d, J = 1
4.3Hz), 7.40-7.67 (4H, m).

[0279]

Example 60 N- (3-cyanobenzyl) -N- (2
-Isobutyl-4-methyl-5-thiazolyl) thiourea (Compound No. 1-184) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.96 (6H, d, J = 6.6H
z), 2.00 (3H, s), 1.92-2.13 (1H, m), 2.73 (2H, d,
J = 7.0Hz), 5.30-5.52 (2H, m), 7.39-7.47 (1H, m), 7.
59-7.68 (3H, m). low MS (m / z) 344 (M ⁺ ), 310, 267, 242, 187, 158, 14
5, 116.

[0280]

Example 61 O- (2-pyridinyl) 3-cyanobenzyl (2-isobutyl-4-methyl-5-thiazolyl) thiocarbamate (Compound No. 1-187) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm : 0.95 (6H, d, J = 6.6H
z), 1.94-2.15 (1H, m), 2.14 (3H, s), 2.73 (2H, d, J
= 7.0Hz), 5.41 (2H, s), 7.00 (1H, d, J = 8.1Hz), 7.22
-7.29 (1H, m), 7.42-7.68 (4H, m), 7.63-7.84 (1H,
m), 8.37-8.47 (1H, m). low MS (m / z) 422 (M ⁺ ), 327, 284, 244, 236, 211, 16
9, 116, 78.

[0281]

Example 62 2-Pyridinyl-3-cyanobenzyl (2-isobutyl-4-methyl-5-thiazolyl) dithiocarbamate (Compound No. 1-188) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.98 (6H , d, J = 6.6H
z), 1.96-2.17 (1H, m), 2.11 (3H, s), 2.79 (2H, d, J
= 7.0Hz), 5.42-5.58 (2H, m), 7.35-7.47 (2H, m), 7.5
8-7.64 (4H, m), 7.80 (1H, td, J = 7.3, 2.0Hz), 8.71
(1H, dd, J = 4.8, 1.1Hz). low MS (m / z) 438 (M ⁺ ), 405, 355, 328, 284, 252, 16
9, 116, 78.

[0282]

Example 63 N- (3-cyanobenzyl) -N- [4
-Methyl-2- (3,3,3-trifluoro-2-methylpropyl) -5-thiazolyl] acetamide (Compound No. 2-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.15 (3H, d , J = 6.6H
z), 1.97 (3H, s), 2.00 (3H, s), 2.70-2.90 (2H, m),
3.17-3.32 (1H, m), 4.71-4.90 (2H, m), 7.38-7.64 (4
H, m). low MS (m / z) 381 (M ⁺ ), 362, 339, 242, 223, 155, 12
8, 116.

[0283]

Example 64 N- (3-cyanobenzyl) -2-hydroxy-N- [4-methyl-2- (3,3,3-trifluoro-2-methylpropyl) -5-thiazolyl] acetamide (compound No. 2-10) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.16 (3H, d, J = 6.6H
z), 1.99 (3H, s), 2.75-2.90 (2H, m), 3.18-3.32 (2
H, m), 3.91 (2H, s), 4.72-4.97 (2H, m), 7.38-7.67
(4H, m).

[0284]

Example 65 N- (3-cyanobenzyl) -N- [4
-Methyl-2- (3,3,3-trifluoro-2-methylpropyl) -5-thiazolyl] -2-methoxyacetamide (Compound No. 2-14) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.17 (3H, d, J = 6.2H
z), 1.99 (3H, s), 2.73-2.90 (2H, m), 3.18-3.32 (1
H, m), 3.41 (3H, s), 3.86 (2H, s), 4.68-4.92 (2H,
m), 7.39-7.69 (4H, m).

[0285]

Example 66 2-{(3-cyanobenzyl) [4-methyl-2- (3,3,3-trifluoro-2-methylpropyl) -5-thiazolyl] amino] -2-oxoethyl acetate ( Compound No. 2-20) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.14 (3H, d, J = 6.2H
z), 2.05 (3H, s), 2.18 (3H, s), 2.72-2.90 (2H, m),
3.17-3.32 (1H, m), 4.43 (2H, s), 4.68-4.98 (2H,
m), 7.39-7.65 (4H, m).

[0286]

Example 67 Methyl-3-cyanobenzyl [4-methyl-2- (3,3,3-trifluoro-2-methylpropyl) -5-thiazolyl] carbamate (Compound No. 2
−32) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.14 (3H, d, J = 6.2H
z), 2.03 (3H, s), 2.71-2.85 (2H, m), 3.16-3.30 (1
H, m), 3.78 (3H, s), 4.75 (2H, s), 7.39-7.63 (4H,
m).

[0287]

Example 68 N- (3-cyanobenzyl) -N- (4
-Methyl-2-neopentyl-5-thiazolyl) acetamide (Compound No. 3-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (9H, s), 1.97
(3H, s), 2.01 (3H, s), 2.75 (2H, s), 4.65, 4.95 (2
H, m), 7.37-7.62 (4H, m). low MS (m / z) 341 (M ⁺ ), 32
6, 299, 285, 242, 169, 127, 116.

[0288]

Example 69 N- (3-cyanobenzyl) -N- (4
-Methyl-2-neopentyl-5-thiazolyl) cyclopropanecarboxamide (Compound No. 3-7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.67-0.85 (2H, m),
0.99 (9H, s), 1.03-1.12 (2H, m), 1.43-1.56 (1H, m),
2.04 (3H, s), 2.76 (2H, s), 4.65 (1H, d, J = 13.5H
z), 4.92 (1H, d, J = 13.5Hz), 7.37-7.61 (4H, m). low MS (m / z) 367 (M ⁺ ), 352, 299, 242, 190, 116, 6
9.

[0289]

Example 70 N- (3-cyanobenzyl) -2-hydroxy-N- (4-methyl-2-neopentyl-5-thiazolyl) acetamide (Compound No. 3-12) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.98 (9H, s), 2.00
(3H, s), 2.75 (2H, s), 3.14 (1H, br-s), 3.92 (2H, b
rs), 4.71-5.00 (2H, m), 7.40-7.65 (4H, m). low MS
(m / z) 357 (M ⁺ ), 342, 301, 242, 185, 127, 116.

[0290]

Example 71 N- (3-Cyanobenzyl) -2-methoxy-N- (4-methyl-2-neopentyl-5-thiazolyl) acetamide (Compound No. 3-17) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.99 (9H, s), 2.00
(3H, s), 2.76 (2H, s), 3.41 (3H, s), 3.87 (2H, s),
4.69 (1H, d, J = 14.2Hz), 4.95 (1H, d, J = 14.2Hz), 7.
38-7.63 (4H, m). low MS (m / z) 371 (M ⁺ ), 356, 315, 286, 256, 242, 19
9, 116.

[0291]

Example 72 2-[(3-cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino]-
2-oxoethyl = cyclopropanecarboxylate (Compound No. 3-25) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.88-1.00 (2H, m),
0.98 (9H, s), 1.02-1.13 (2H, m), 1.68-1.82 (1H, m),
2.06 (3H, s), 2.75 (2H, s), 4.46 (2H, s), 4.66 (1
H, d, J = 14.0Hz), 4.96 (1H, d, J = 14.0Hz), 7.39-7.63
(4H, m). low MS (m / z) 425 (M ⁺ ), 410, 369, 299, 281, 253, 24
2, 149, 127, 116, 99, 69.

[0292]

Example 73 2-[(3-cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino]-
2-oxoethyl = 3-methyl-2-butenoate (Compound No. 3-28) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.98 (9H, s), 1.93
(3H, s), 2.08 (3H, s), 2.20 (3H, s), 2.76 (2H, s),
4.48 (2H, s), 4.67 (1H, d, J = 14.0Hz), 4.96 (1H, d,
J = 14.0Hz), 5.82 (1H, s), 7.39-7.63 (4H, m). low MS (m / z) 439 (M ⁺ ), 424, 383, 299, 267, 242, 14
1, 116, 83.

[0293]

Example 74 2-[(3-cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino]-
2-oxoethyl = 2- (trifluoromethyl) acrylate (Compound No. 3-30) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.99 (9H, s), 2.09
(3H, s), 2.77 (2H, s), 4.55-4.68 (2H, m), 4.69 (1H,
d, J = 13.9Hz), 4.95 (1H, d, J = 13.9Hz), 6.53-6.56
(1H, m), 6.85-6.87 (1H, m), 7.40-7.65 (4H, m). low MS (m / z) 479 (M ⁺ ), 464, 423, 307, 242, 195, 18
1, 153, 127, 123, 116, 57.

[0294]

Example 75 2-[(3-Cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino]-
2-oxoethyl chloroacetate (compound number 3-
31) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.01 (9H, s), 2.18
(3H, s), 2.91 (2H, s), 4.22 (2H, s), 4.50-4.70 (3H,
m), 4.95-5.07 (1H, m), 7.46-7.68 (4H, m). low MS (m / z) 433, 435 (M ⁺ , M + 2 ⁺ ), 418, 420, 377, 37
9, 299, 261, 263, 242, 127, 116.

[0295]

Example 76 2-[(3-cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino]-
2-oxoethyl dichloroacetate (Compound No. 3
-32) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.00 (9H, s), 2.14
(3H, s), 2.85 (2H, s), 4.50-4.70 (3H, m), 4.99 (1H,
d, J = 12.8Hz), 6.10 (1H, s), 7.42-7.65 (4H, m). low MS (m / z) 467, 469, 471 (M ⁺ , M + 2 ⁺ , M + 4 ⁺ ), 452, 4
54, 456, 411, 413, 415, 295, 297, 299, 242, 116.

[0296]

Example 77 2-[(3-cyanobenzyl) (4-methyl-2-neopentyl-5-thiazolyl) amino]-
2-oxoethyl difluoroacetate (Compound No. 3-35) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.99 (9H, s), 2.07
(3H, s), 2.77 (2H, s), 4.58-4.70 (2H, m), 4.69 (1H,
d, J = 13.9Hz), 4.94 (1H, d, J = 13.9Hz), 6.07 (1H, t,
J = 53.1Hz), 7.41-7.64 (4H, m). low MS (m / z) 435 (M ⁺ ), 420, 379, 263, 242, 195, 12
7, 116, 57.

[0297]

Example 78 Methyl-3-cyanobenzyl (4-methyl-2-neopentyl-5-thiazolyl) carbamate (Compound No. 3-42) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.98 (9H, s) , 2.03
(3H, s), 2.73 (2H, s), 3.77 (3H, s), 4.75 (2H, s),
7.38-7.63 (4H, m). low MS (m / z) 357 (M ⁺ ), 342, 301, 185, 153, 116.

[0298]

Example 79 Phenyl = 3-cyanobenzyl (4-methyl-2-neopentyl-5-thiazolyl) carbamate (Compound No. 3-47) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 0.99 (9H, s) , 2.14
(3H, s), 2.76 (2H, s), 4.83 (2H, s), 7.09 (2H, d, J
= 7.7Hz), 7.22 (1H, t, J = 7.7Hz), 7.34-7.65 (6H,
m). low MS (m / z) 419 (M ⁺ ), 404, 363, 326, 247, 153, 11
6.

[0299]

Example 80 N- (3-cyanobenzyl) -N- [2
-(Cyclobutylmethyl) -4-methyl-5-thiazolyl] -2-hydroxyacetamide (Compound No. 4-
7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.64-1.97 (4H, m),
1.96 (3H, s), 2.03-2.19 (2H, m), 2.52-2.76 (1H, m),
2.97 (2H, d, J = 7.7Hz), 3.17 (1H, br-s), 3.91 (2H,
br-s), 4.71-4.97 (2H, m), 7.40-7.66 (4H, m). low MS (m / z) 355 (M ⁺ ), 339, 327, 314, 301, 297, 26
9, 242, 209, 185, 181, 116.

[0300]

Example 81 N- (3-cyanobenzyl) -N- [2
-(Cyclobutylmethyl) -4-methyl-5-thiazolyl] -2-methoxyacetamide (Compound No. 4-1
0) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.69-1.94 (4H, m),
1.96 (3H, s), 2.04-2.20 (2H, m), 2.53-2.80 (1H, m),
2.97 (2H, d, J = 7.7Hz), 3.40 (3H, s), 3.75-3.92 (2
H, m), 4.71 (1H, d, J = 13.5Hz), 4.89 (1H, d, J = 13.5Hz)
Hz), 7.38-7.63 (4H, m). low MS (m / z) 369 (M ⁺ ), 357, 341, 328, 315, 296, 25
3, 242, 199, 130, 116, 113.

[0301]

Example 82 2-{(3-cyanobenzyl) [2-
(Cyclobutylmethyl) -4-methyl-5-thiazolyl] amino} -2-oxoethyl acetate (Compound No. 4-15) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.64-1.97 (4H, m),
2.02 (3H, s), 2.05-2.18 (2H, m), 2.18 (3H, s), 2.53
-2.76 (1H, m), 2.97 (2H, d, J = 7.7Hz), 4.43 (2H,
s), 4.69 (1H, d, J = 13.9Hz), 4.90 (1H, d, J = 13.9H)
z), 7.39-7.64 (4H, m). low MS (m / z) 397 (M ⁺ ), 356, 343, 297, 281, 269, 24
2, 227, 181, 144, 116, 101.

[0302]

Example 83 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] acetamide (Compound No. 5-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.13-1.32 (2H, m),
1.50-1.90 (6H, m), 1.98 (3H, s), 1.98 (3H, s), 2.05
-2.29 (1H, m), 2.87 (2H, d, J = 7.3 Hz), 4.68-4.90
(2H, m), 7.38-7.63 (4H, m). low MS (m / z) 353 (M ⁺ ), 311, 285, 242, 195, 169, 12
7, 119.

[0303]

Example 84 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] cyclopropanecarboxamide (Compound No. 5-
3) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.70-1.35 (6H, m),
1.45-1.90 (7H, m), 2.03 (3H, s), 2.12-2.34 (1H, m),
2.89 (2H, d, J = 7.7Hz), 4.74 (1H, d, J = 14.0Hz), 4.
89 (1H, d, J = 14.0Hz), 7.38-7.61 (4H, m). low MS (m / z) 379 (M ⁺ ), 311, 242, 195, 127, 116.

[0304]

Example 85 3-Cyanobenzyl [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl] carbamic chloride (Compound No. 5-7) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 1.13-1.32 (2H, m),
1.50-1.90 (6H, m), 1.98 (3H, s), 1.98 (3H, s), 2.05
-2.29 (1H, m), 2.87 (2H, d, J = 7.3 Hz), 4.68-4.90
(2H, m), 7.38-7.63 (4H, m). low MS (m / z) 353 (M ⁺ ), 311, 285, 242, 195, 169, 12
7, 119.

[0305]

Example 86 2-Chloro-N- (3-cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl] acetamide (Compound No. 5-
8) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.90 (6H, m), 1.99 (3H, s), 2.08-2.31 (1H, m),
2.87 (2H, d, J = 7.3Hz), 3.96 (2H, s), 4.72 (1H, d,
J = 14.0Hz), 4.91 (1H, d, J = 14.0Hz), 7.39-7.64 (4H,
m). low MS (m / z) 387, 389 (M ⁺ , M + 2 ⁺ ), 319, 321, 271, 2
73, 242, 203, 205, 185, 127, 116.

[0306]

Example 87 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] -2-hydroxyacetamide (Compound No. 5-
16) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.95 (6H, m), 1.96 (3H, s), 2.08-2.31 (1H, m),
2.87 (2H, d, J = 7.3Hz), 3.12 (1H, t, J = 4.4Hz), 3.9
2 (2H, s), 4.70-5.05 (2H, m), 7.40-7.64 (4H, m). low MS (m / z) 369 (M ⁺ ), 311, 301, 253, 242, 185, 12
7, 116.

[0307]

Example 88 2-{(3-cyanobenzyl) [2-
(Cyclopentylmethyl) -4-methyl-5-thiazolyl] amino} -2-oxoethyl = acetate (Compound No. 5-27) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.35 (2H, m),
1.46-1.89 (6H, m), 2.03 (3H, s), 2.18 (3H, s), 2.11
-2.33 (1H, m), 2.87 (2H, d, J = 7.3Hz), 4.46 (2H,
s), 4.70 (1H, d, J = 14.0Hz), 4.91 (1H, d, J = 14.0H
z), 7.44-7.63 (4H, m). low MS (m / z) 411 (M ⁺ ), 343, 311, 295, 242, 227, 11
6, 101, 73.

[0308]

Example 89 S- {2-{(3-cyanobenzyl)
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] amino} -2-oxoethyl} = ethanethioate (Compound No. 5-30) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 ( 2H, m),
1.45-1.90 (6H, m), 2.07 (3H, s), 2.10-2.32 (1H, m),
2.37 (3H, s), 2.88 (2H, d, J = 7.3Hz), 3.59 (2H,
s), 4.68 (1H, d, J = 13.9Hz), 4.96 (1H, d, J = 13.9H)
z), 7.39-7.63 (4H, m). low MS (m / z) 427 (M ⁺ ), 359, 311, 242, 127, 117, 11
6, 89.

[0309]

Example 90 Methyl-3-cyanobenzyl [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl]
Carbamate (Compound No. 5-36) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 1.12-1.35 (2H, m),
1.45-1.90 (6H, m), 2.01 (3H, s), 2.09-2.32 (1H, m),
2.85 (2H, d, J = 7.3Hz), 3.77 (3H, s), 4.74 (2H,
s), 7.37-7.60 (4H, m). low MS (m / z) 369 (M ⁺ ), 301, 253, 185, 144, 116.

[0310]

Example 91 4-Fluorophenyl = 3-cyanobenzyl [2- (cyclopentylmethyl) -4-methyl-5
-Thiazolyl] carbamate (Compound No. 5-41) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.90 (6H, m), 2.03 (3H, s), 2.12-2.34 (1H, m),
3.00 (2H, d, J = 7.7Hz), 4.83 (2H, br-s), 7.04-7.07
(4H, m), 7.40-7.70 (4H, m). low MS (m / z) 449 (M ⁺ ), 381, 338, 265, 154, 116.

[0311]

Example 92 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] urea (Compound No. 5-52) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.90 (6H, m), 2.05 (3H, s), 2.09-2.31 (1H, m),
2.86 (2H, d, J = 7.3Hz), 4.77 (2H, br-s), 4.92 (2H,
br-s), 7.38-7.61 (4H, m). low MS (m / z) 354 (M ⁺ ), 311, 286, 242, 170, 129, 12
7, 116.

[0312]

Example 93 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N'-methylurea (Compound No. 5-53) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.35 (2H, m),
1.45-1.90 (6H, m), 2.02 (3H, s), 2.09-2.32 (1H, m),
2.83 (3H, d, J = 4.4Hz), 2.86 (2H, d, J = 7.3Hz), 4.5
3-4.68 (1H, m), 4.78 (2H, s), 7.37-7.60 (4H, m). low MS (m / z) 368 (M ⁺ ), 311, 242, 195, 143, 127, 11
6.

[0313]

Example 94 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N'-ethylurea (Compound No. 5-54) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10 (3H, t, J = 7.3H
z), 1.12-1.35 (2H, m), 1.45-1.90 (6H, m), 2.02 (3H,
s), 2.10-2.32 (1H, m), 2.86 (2H, d, J = 7.3Hz), 3.2
1-3.35 (2H, m), 4.58 (1H, t, J = 5.1Hz), 4.78 (2H,
s), 7.37-7.60 (4H, m). low MS (m / z) 382 (M ⁺ ), 311, 242, 195, 127, 116.

[0314]

Example 95 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N'-isopropylurea (Compound No. 5-5
5) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10 (6H, d, J = 6.6H
z), 1.12-1.35 (2H, m), 1.45-1.90 (6H, m), 2.00 (3H,
s), 2.10-2.32 (1H, m), 2.87 (2H, d, J = 7.3Hz), 3.9
1-4.11 (1H, m), 4.35 (1H, d, J = 8.1Hz), 4.76 (2H,
s), 7.37-7.59 (4H, m). low MS (m / z) 396 (M ⁺ ), 311, 242, 195, 127, 116.

[0315]

Example 96 N'-t-butyl-N- (3-cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-
Methyl-5-thiazolyl] urea (Compound No. 5-5
8) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.35 (2H, m),
1.30 (9H, s), 1.43-1.90 (6H, m), 2.01 (3H, s), 2.10
-2.31 (1H, m), 2.86 (2H, d, J = 7.3Hz), 4.47 (1H, br
-s), 4.74 (2H, s), 7.37-7.59 (4H, m). low MS (m / z) 410 (M ⁺ ), 311, 242, 195, 127, 116.

[0316]

Example 97 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N'-cyclopropylurea (Compound No. 5-
59) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 0.39-0.47 (2H, m),
0.75 (2H, dd, J = 12.1. 7.0Hz), 1.10-1.35 (2H, m),
1.45-1.90 (6H, m), 1.97 (3H, s), 2.09-2.31 (1H,
m), 2.60-2.70 (1H, m), 2.86 (2H, d, J = 7.3Hz), 4.76
(3H, s), 7.37-7.60 (4H, m). low MS (m / z) 394 (M ⁺ ), 311, 242, 195, 127, 116.

[0317]

Example 98 N- (3-cyanobenzyl) -N'-cyclobutyl-N- [2- (cyclopentylmethyl) -4
-Methyl-5-thiazolyl] urea (Compound No. 5-6
0) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.32 (2H, m),
1.45-1.90 (10H, m), 2.02 (3H, s), 2.15-2.38 (3H,
m), 2.88 (2H, d, J = 7.3Hz), 4.20-4.40 (1H, m), 4.69
(1H, d, J = 8.1Hz), 4.75 (2H, s), 7.36-7.59 (4H,
m). low MS (m / z) 408 (M ⁺ ), 380, 311, 264, 242, 195, 12
7, 116.

[0318]

Example 99 N- (3-cyanobenzyl) -N- [2
-(Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N'-phenylurea (Compound No. 5-61) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.37 (2H, m),
1.43-1.90 (6H, m), 2.09 (3H, s), 2.13-2.35 (1H, m),
2.91 (2H, d, J = 7.3Hz), 4.85 (2H, s), 6.50 (1H, br
-s), 7.03-7.12 (1H, m), 7.30-7.62 (8H, m). low MS (m / z) 430 (M ⁺ ), 362, 311, 242, 205, 195, 12
7, 116.

[0319]

Example 100 N'-benzyl-N- (3-cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-
Methyl-5-thiazolyl] urea (Compound No. 5-6
2) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.85 (6H, m), 2.00 (3H, s), 2.17-2.29 (1H, m),
2.84 (2H, d, J = 7.7Hz), 4.44 (2H, d, J = 5.9Hz), 4.8
1 (2H, s), 4.94 (1H, t, J = 5.9Hz), 7.21-7.61 (9H,
m). low MS (m / z) 444 (M ⁺ ), 311, 242, 195, 127, 116, 9
1.

[0320]

Example 101 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N '-(1-phenylethyl) urea (Compound No. 5-63) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 ( 2H, m),
1.42 (3H, d, J = 7.0Hz), 1.43-1.87 (6H, m), 2.00 (3H,
s), 2.10-2.32 (1H, m), 2.86 (2H, d, J = 7.3Hz), 4.6
5-4.87 (3H, m), 4.95-5.08 (1H, m), 7.20-7.59 (9H,
m). low MS (m / z) 458 (M ⁺ ), 311, 242, 195, 127, 116, 10
Five.

[0321]

Example 102 N′-allyl-N- (3-cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl] urea (Compound No. 5-65) ¹ H-NMR ( 200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.90 (6H, m), 2.03 (3H, s), 2.10-2.32 (1H, m),
2.86 (2H, d, J = 7.7Hz), 3.84-3.91 (2H, m), 4.71 (1
H, t, J = 5.9Hz), 4.79 (2H, s), 5.05-5.15 (2H, m),
5.73-5.92 (1H, m), 7.38-7.61 (4H, m). low MS (m / z) 394 (M ⁺ ), 311, 242, 195, 169, 127, 11
6.

[0322]

Example 103 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N '-(2-propynyl) urea (Compound No. 5-66) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H , m),
1.45-1.90 (6H, m), 2.03 (3H, s), 2.10-2.33 (1H, m),
2.22 (1H, t, J = 2.4Hz), 2.87 (2H, d, J = 7.3Hz), 4.0
4 (2H, dd, J = 5.5, 2.5Hz), 4.79 (2H, s), 4.84 (1H,
t, J = 5.5Hz), 7.38-7.62 (4H, m). low MS (m / z) 392 (M ⁺ ), 324, 311, 242, 208, 195, 16
7, 127, 116.

[0323]

Example 104 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N ′-(2,2,2-trifluoroethyl) urea (Compound No. 5-67) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm : 1.15-1.35 (2H, m),
1.45-1.90 (6H, m), 2.01 (3H, s), 2.02-2.27 (3H, m),
2.83 (2H, d, J = 7.3Hz), 3.71 (4H, t, J = 7.5Hz), 4.7
2 (2H, s), 7.35-7.59 (4H, m). low MS (m / z) 394 (M ⁺ ), 326, 278, 242, 210, 169, 12
7, 116, 84.

[0324]

Example 105 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N '-(2-methoxyethyl) urea (Compound No. 5-68) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.32 ( 2H, m),
1.48-1.90 (6H, m), 2.02 (3H, s), 2.10-2.32 (1H, m),
2.86 (2H, d, J = 7.7Hz), 3.29 (3H, s), 3.41-3.43 (4
H, m), 4.78 (2H, s), 5.00 (1H, br-s), 7.37-7.60 (4
H, m). low MS (m / z) 412 (M ⁺ ), 311, 242, 195, 154, 127, 11
6.

[0325]

Example 106 N- (3-cyanobenzyl) -N'-
(Cyanomethyl) -N- [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl] urea (Compound No. 5-69) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.32 (2H, m) ,
1.48-1.90 (6H, m), 2.02 (3H, s), 2.10-2.32 (1H, m),
2.86 (2H, d, J = 7.7Hz), 3.29 (3H, s), 3.41-3.43 (4
H, m), 4.78 (2H, s), 5.00 (1H, br-s), 7.37-7.60 (4
H, m). low MS (m / z) 412 (M ⁺ ), 311, 242, 195, 154, 127, 11
6.

[0326]

Example 107 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N'-hydroxyurea (Compound No. 5-
70) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.92 (6H, m), 2.00 (3H, s), 2.08-2.31 (1H, m),
2.86 (2H, d, J = 7.3Hz), 4.77 (2H, s), 7.15 (1H,
s), 7.39-7.63 (4H, m). low MS (m / z) 370 (M ⁺ ), 354, 326, 311, 242, 210, 14
2, 127, 116.

[0327]

Example 108 N '-(allyloxy) -N- (3-
Cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl] urea (Compound No. 5-71) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m) ,
1.45-1.90 (6H, m), 2.00 (3H, s), 2.08-2.31 (1H, m),
2.86 (2H, d, J = 7.7Hz), 4.37 (2H, dd, J = 6.5,0.8H
z), 4.76 (2H, s), 5.26 (1H, s), 5.33 (1H, dd, J = 9.
2, 0.8Hz), 5.85-6.05 (1H, m), 7.28 (1H, s), 7.38-
7.62 (4H, m). low MS (m / z) 410 (M ⁺ ), 342, 311, 294, 242, 226, 18
5, 154, 127, 116.

[0328]

Example 109 N '-(benzyloxy) -N- (3
-Cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-methyl-5-thiazolyl] urea (Compound No. 5-72) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.08-1.30 (2H, m ),
1.45-1.85 (6H, m), 1.93 (3H, s), 2.05-2.28 (1H, m),
2.82 (2H, d, J = 7.3Hz), 4.75 (2H, s), 4.90 (2H,
s), 7.20 (1H, s), 7.31-7.63 (9H, m). low MS (m / z) 460 (M ⁺ ), 400, 311 242, 195, 116, 9
1.

[0329]

Example 110 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -1-azetidinecarboxamide (Compound No. 5-73) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 1.15-1.35 (2H, m),
1.45-1.90 (6H, m), 2.01 (3H, s), 2.02-2.27 (3H, m),
2.83 (2H, d, J = 7.3Hz), 3.71 (4H, t, J = 7.5Hz), 4.7
2 (2H, s), 7.35-7.59 (4H, m). low MS (m / z) 394 (M ⁺ ), 326, 278, 242, 210, 169, 12
7, 116, 84.

[0330]

Example 111 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -1-pyrrolidinecarboxamide (Compound No. 5-74) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.50-1.88 (10H, m), 1.96 (3H, s), 2.07-2.30 (1H,
m), 2.83 (2H, d, J = 7.3Hz), 3.09-3.14 (4H, m), 4.71
(2H, s), 7.34-7.59 (4H, m). low MS (m / z) 408 (M ⁺ ), 340, 311, 292, 242, 221, 18
3, 116, 98.

[0331]

Example 112 Methyl = (2S) -1-({(3-cyanobenzyl) [2- (cyclopentylmethyl) -4-
Methyl-5-thiazolyl] amino} carbonyl) -2-
Pyrrolidinecarboxylate (Compound No. 5-75) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.32 (2H, m),
1.45-2.30 (11H, m), 2.02 (3H, s), 2.84 (2H, d, J =
7.3Hz), 2.98 (2H, t, J = 6.2Hz), 3.75 (3H, s), 4.45
(1H, dd, J = 7.3, 5.5Hz), 4.72 (2H, s), 7.34-7.57 (4
H, m). low MS (m / z) 466 (M ⁺ ), 407, 350, 311, 298, 241, 22
1, 156, 154, 128, 116.

[0332]

Example 113 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -4-morpholinecarboxamide (Compound No. 5-77) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.10-1.35 (2H, m),
1.45-1.85 (6H, m), 2.01 (3H, s), 2.08-2.30 (1H, m),
2.84 (2H, d, J = 7.3Hz), 3.28 (4H, d, J = 4.8Hz), 3.5
2 (4H, d, J = 4.8Hz), 4.67 (2H, s), 7.34-7.58 (4H,
m). low MS (m / z) 424 (M ⁺ ), 356, 308, 240, 221, 199, 15
4, 116, 114, 70.

[0333]

Example 114 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N '-(3-quinolyl) urea (Compound No. 5-79) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 1.12-1.35 (2H , m),
1.45-2.00 (6H, m), 2.13 (3H, s), 2.13-2.37 (1H, m),
2.93 (2H, d, J = 7.3Hz), 4.90 (2H, s), 6.85 (1H,
s), 7.42-7.66 (5H, m), 7.79 (1H, dd, J = 8.4, 2.2H
z), 8.02 (1H, d, J = 8.1Hz), 8.54 (2H, d, J = 2.2Hz). low MS (m / z) 481 (M ⁺ ), 413, 365, 311, 297, 256, 24
2, 195, 171, 127, 116.

[0334]

Example 115 N- (3-cyanobenzyl) -N-
[2- (Cyclopentylmethyl) -4-methyl-5-thiazolyl] -N '-(4,5-dihydro-5-thiazolyl) urea (Compound No. 5-81) ¹ H-NMR (200MHz, CDCl ₃ ) δppm : 1.10-1.40 (2H, m),
1.40-1.95 (6H, m), 1.99 (3H, s), 2.05-2.28 (1H, m),
2.84 (2H, d, J = 7.7Hz), 3.09 (2H, t, J = 6.5Hz), 3.8
3 (2H, t, J = 6.5Hz), 4.83 (2H, s), 7.37-7.66 (4H,
m). low MS (m / z) 440 (M ⁺ ), 406, 372, 311, 242, 127, 11
6.

[0335]

Example 116 N'-Acetyl-N- (3-cyanobenzyl) -N- [2- (cyclopentylmethyl) -4-
Methyl-5-thiazolyl] urea (Compound No. 5-8
2) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.12-1.35 (2H, m),
1.46-1.92 (6H, m), 2.01 (3H, s), 2.10-2.33 (1H, m),
2.53 (3H, s), 2.88 (2H, d, J = 7.3Hz), 4.78 (2H, br
-s), 7.41-7.66 (4H, m). low MS (m / z) 396 (M ⁺ ), 328, 311, 242, 145, 127, 11
6.

[0336]

Example 117 N- (3-cyanobenzyl) -N-
(2,4-Dimethyl-5-thiazolyl) acetamide (Compound No. 6-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.97 (3H, s), 1.98
(3H, s), 2.62 (3H, s), 4.70-4.87 (2H, m), 7.38-7.63
(4H, m). low MS (m / z) 285 (M ⁺ ), 243, 141, 127, 116, 89, 5
9.

[0337]

Example 118 N- (3-cyanobenzyl) -N-
(2,4-Dimethyl-5-thiazolyl) -2-methylpropanamide (Compound No. 6-3) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.09 (6H, t, J = 5.7H
z), 1.98 (3H, s), 2.51-2.65 (1H, m), 2.61 (3H, s),
4.63 (1H, d, J = 13.9Hz), 4.96 (1H, d, J = 13.9Hz),
7.38-7.63 (4H, m).

[0338]

Example 119 N- (3-cyanobenzyl) -N-
(2,4-Dimethyl-5-thiazolyl) -2-methoxyacetamide (Compound No. 6-6) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.96 (3H, s), 2.62
(3H, s), 3.41 (3H, s), 3.87 (2H, dd, J = 22.0, 21.0H
z), 4.69-4.92 (2H, m), 7.39-7.64 (4H, m).

[0339]

Example 120 N- (3-cyanobenzyl) -N-
(2,4-Dimethyl-5-thiazolyl) -2-phenoxyacetamide (Compound No. 6-7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.02 (3H, s), 2.63
(3H, s), 4.49 (2H, dd, J = 22.0, 21.0Hz), 4.72 (1H,
d, J = 13.9Hz), 4.93 (1H, d, J = 13.9Hz), 6.83 (2H, d
d, J = 7.7, 1.1Hz), 6.98 (1H, td, J = 7.3, 1.1Hz), 7.2
3-7.33 (2H, m), 7.39-7.65 (4H, m).

[0340]

Example 121 2-[(3-cyanobenzyl) (2,
4-Dimethyl-5-thiazolyl) amino] -2-oxoethyl = acetate (Compound No. 6-8) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.03 (3H, s), 2.18
(3H, s), 2.62 (3H, s), 4.45 (2H, s), 4.65-4.95 (2H, s)
m), 7.40-7.65 (4H, m).

[0341]

Example 122 N- (3-cyanobenzyl) -N-
(2-Isopropyl-4-methyl-5-thiazolyl) acetamide (Compound No. 7-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.35 (6H, d, J = 7.0H
z), 1.98 (3H, s), 3.05-3.29 (1H, m), 4.72-4.85 (2
H, m), 7.38-7.62 (4H, m). low MS (m / z) 313 (M ⁺ ), 271, 256, 155, 128, 116.

[0342]

Example 123 N- (3-cyanobenzyl) -N-
(2-Isopropyl-4-methyl-5-thiazolyl)-
2-Methoxyacetamide (Compound No. 7-5) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.35 (6H, d, J = 7.0H
z), 1.96 (3H, s), 3.07-3.30 (1H, m), 3.41 (3H, s),
3.87 (2H, dd, J = 20.0, 19.0Hz), 4.73-4.89 (2H, m),
7.39-7.64 (4H, m).

[0343]

Example 124 N- (3-cyanobenzyl) -N-
(2-Isopropyl-4-methyl-5-thiazolyl)-
2-phenoxyacetamide (Compound No. 7-6) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.35 (6H, d, J = 6.6H
z), 2.02 (3H, s), 2.18 (3H, s), 3.00-3.28 (1H, m),
4.50 (2H, s), 4.75 (1H, d, J = 13.9Hz), 6.82 (2H, d
d, J = 8.8, 1.1Hz), 6.98 (1H, td, J = 7.3, 1.0Hz), 7.2
2-7.31 (2H, m), 7.37-7.65 (4H, m).

[0344]

Example 125 2-[(3-cyanobenzyl) (2-
Isopropyl-4-methyl-5-thiazolyl) amino]
2-oxoethyl acetate (Compound No. 7-7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.35 (6H, d, J = 7.0H
z), 2.03 (3H, s), 2.18 (3H, s), 3.07-3.28 (1H, m),
4.45 (2H, s), 4.72 (1H, d, J = 13.6Hz), 4.88 (1H, d,
J = 13.6Hz), 7.40-7.64 (4H, m).

[0345]

Example 126 Methyl 3-cyanobenzyl (2-isopropyl-4-methyl-5-thiazolyl) carbamate (Compound No. 7-9) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 1.33 (6H, d, J = 7.0H
z), 2.01 (3H, s), 3.05-3.27 (1H, m), 3.77 (3H, s),
4.74 (2H, s), 7.40-7.63 (4H, m).

[0346]

Example 127 N- (3-cyanobenzyl) -N-
[4-Methyl-2- (tetrahydropyran-4-ylmethyl) -5-thiazolyl] acetamide (Compound No. 8
-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.97 (3H, s), 1.97 (3
H, s), 2.01-2.25 (1H, m), 2.46-2.54 (2H, m), 2.98-
3.11 (3H, m), 3.40-3.53 (2H, s), 4.18-4.43 (3H,
m), 4.80 (2H, br-s), 7.40-7.63 (4H, m). low MS (m / z) 369 (M ⁺ ), 327, 242, 211, 143, 116.

[0347]

Example 128 Methyl = 3-cyanobenzyl [4-methyl-2- (tetrahydropyran-4-ylmethyl)-
5-Thiazolyl] carbamate (Compound No. 8-9) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 1.40 (2H, td, J = 13.
0, 4.5Hz), 1.57-1.67 (2H, m), 1.85-2.07 (1H, m),
2.02 (3H, s), 2.78 (2H, d, J = 7.0Hz), 3.38 (2H, td,
J = 11.7, 2.2Hz), 3.77 (3H, s), 3.96 (2H, dd, J = 11.
4, 3.3Hz), 7.40-7.64 (4H, m). low MS (m / z) 385 (M ⁺ ), 342, 328, 301, 269, 237, 18
5, 116.

[0348]

Example 129 2-methoxyethyl = 3-cyanobenzyl [4-methyl-2- (tetrahydropyran-4-ylmethyl) -5-thiazolyl] carbamate (Compound No. 8-10) ¹ H-NMR (200 MHz, CDCl ₃ ) δppm: 1.40 (2H, td, J = 13.
4, 4.0Hz), 1.55-1.67 (2H, m), 1.85-2.07 (1H, m),
2.05 (3H, s), 2.78 (2H, d, J = 7.0Hz), 3.25-3.44 (5H,
m), 3.47-3.63 (2H, br-t), 3.95 (2H, dd, J = 11.7,
3.5Hz), 4.25-4.40 (2H, br-t), 4.74 (2H, s), 7.39-7.
63 (4H, m). low MS (m / z) 429 (M ⁺ ), 400, 386, 345, 313, 237, 22
9, 153, 116.

[0349]

Example 130 N- [2- (4-chlorophenyl)-
4-Methyl-5-thiazolyl) -N- (3-cyanobenzyl) acetamide (Compound No. 10-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.03 (3H, s), 2.07
(3H, s), 4.75-4.95 (2H, m), 7.40 (2H, d, J = 8.8Hz),
7.37-7.64 (4H, m), 7.77 (2H, d, J = 8.8Hz).

[0350]

Example 131 N- (3-cyanobenzyl) -N-
[4-Methyl-2- (3-pyridinyl) -5-thiazolyl] acetamide (Compound No. 11-1) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.04 (3H, s), 2.09
(3H, s), 4.86 (2H, br-s), 7.35-7.64 (5H, m), 8.15
(1H, dt, J = 8.1, 1.8Hz), 8.67 (1H, dd, J = 4.7,1.5H
z), 9.06 (1H, d, J = 1.5Hz). low MS (m / z) 348 (M ⁺ ), 306, 232, 190, 149, 122.

[0351]

Example 132 N- (3-cyanobenzyl) -2-methoxy-N- [4-methyl-2- (3-pyridinyl)-
5-thiazolyl] acetamide (Compound No. 11-5) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.08 (3H, s), 3.42
(3H, s), 3.93 (2H, s), 4.77-4.98 (2H, m), 7.36-7.65
(5H, m), 8.15 (1H, dt, J = 7.7, 1.8Hz), 8.68 (1H, d,
J = 5.1Hz), 9.06 (1H, s).

[0352]

Example 133 2-{(3cyanobenzyl) [4-methyl-2- (3-pyridinyl) -5-thiazolyl] amino} -2-oxoethylacetate (Compound No. 11
-7) ¹ H-NMR (200MHz, CDCl ₃ ) δppm: 2.15 (3H, s), 2.19
(3H, s), 4.77 (1H, d, J = 14.0Hz), 4.97 (1H, d, J = 1
4.0Hz), 7.36-7.67 (5H, m), 8.14 (1H, dt, J = 8.1, 1.
7Hz), 8.68 (1H, dd, J = 4.8, 1.8Hz), 9.06 (1H, d, J =
1.8Hz). low MS (m / z) 406 (M ⁺ ), 306, 290, 190, 122, 101.

[0353]

[Formulation Example 1] Dust formulation Compound of Example 1 (0.5 parts by mass), Hymexazole (free acid, 4 parts by mass), Carplex # 80-D
(Shionogi Pharmaceutical Co., Ltd., 5 parts by mass) and Keiwa Clay Fuhi (Keiwa Furnace Co., Ltd., 90.5 parts by mass) are mixed,
Eck sample KII-1 type (manufactured by Fuji Paudal Co., Ltd.) is pulverized to obtain a powder.

[0354]

[Formulation Example 2] Emulsion The compound of Example 2 (10 parts by mass) was dissolved in a mixed solution of xylene (40 parts by mass, manufactured by Wako Pure Chemical Industries, Ltd.) and DMSO (35 parts by mass, manufactured by Wako Pure Chemical Industries, Ltd.). , And even Par
akol KPS (Nippon Emulsifier Co., Ltd., 25 parts by mass)
Was added and mixed to obtain an emulsion.

[0355]

[Formulation Example 3] Wettable powder Compound of Example 3 (10 parts by mass), Carplex # 8
0-D (Shionogi Pharmaceutical Co., Ltd., 10 parts by mass), Gohsenol GL05 (Nippon Gosei Kagaku Co., Ltd., 2 parts by mass), Newcol 291PG (Nippon Emulsifier Co., Ltd., 0.5 parts by mass), Neogen Powder (Daiichi Kogyo Seiyaku Co., Ltd., 5 parts by mass), Radiolite # 200 (Showa Chemical Industry Co., Ltd., 10 parts by mass) and H differential (Keiwa Furnace Co., Ltd., 62.5 parts by mass) Mix well and grind with Eck Sample KII-1 type (manufactured by Fuji Paudal Co., Ltd.) to obtain a wettable powder.

[0356]

[Formulation Example 4] Granules The compound of Example 4 (2 parts by mass), sodium tripolyphosphate (manufactured by Mitsui Chemicals, Inc., 2 parts by mass), Amycol N
O. 1 (manufactured by Nitto Kagaku Co., Ltd., 1.5 parts by mass), 25 parts by mass of bentonite (manufactured by Hoshun Mining Co., Ltd.) and calcium carbonate Calhin 600 (manufactured by Adachi Lime Co., Ltd., 69.
5 parts by mass) were mixed, and the mixture was extruded and granulated using Dome Gran (Screen 0.9 mmφ manufactured by Fuji Paudal Co., Ltd.). The obtained granulated product is dried by a shelf type dryer (manufactured by Tabai Co., Ltd., PERFECT OVEN PS-222 type, 60 ° C.) and then sieved to 600 to 1180 μm to obtain granules.

[0357]

[Formulation Example 5] Paracol KPS (manufactured by Nippon Emulsifier, 20 parts by mass), xylene (manufactured by Wako Pure Chemical Industries, Ltd., 35 parts by mass), and dimethyl sulfoxide (Wako Pure Chemical Industries, Ltd.) were added to the compound of Example 11 (10 parts by mass). (Manufactured by the company, 35 parts by mass) were sequentially added, and an emulsion was obtained by stirring with a stirrer.

[0358]

[Test Example 1] Tomato epidemic control test (therapeutic effect) A plant cultivation test plant (tomato: large Fukuju) at the 3rd to 5th leaf stage was spray-inoculated with a pathogenic spore suspension and the room temperature was 20 to 22 ° C.
It was placed in the inoculation room of No. 1 to promote the onset of disease. The emulsion prepared according to Formulation Example 2 was diluted with water to prepare a spray solution containing 300 ppm of the compound of the present invention, and one day after inoculation, the spray solution was evenly applied to the test plants in the pot with a spray gun. Sprayed. The degree of illness was investigated 7 days after the inoculation. The test was performed in duplicate.

The degree of disease onset was expressed in 4 stages from 0 to 3 by visually observing the degree of disease on the test plant and judging according to the following criteria. Degree of onset 0: No onset of illness.

1: The degree of disease is less than 40% of untreated plots.

2: The degree of illness is 40% or more and less than 80%.

3: The degree of illness is 80% or more.

As a result of this test, Example 9 (Compound No. 1-
7), Example 11 (Compound No. 1-35), Example 16 (Compound No. 1-59), Example 17 (Compound No. 1-62), Example 25 (Compound No. 1-98).
No.), Example 26 (Compound No. 1-99), Example 3
2 (Compound No. 1-139), Example 63 (Compound No. 2-1), Example 64 (Compound No. 2-10),
Example 66 (Compound No. 2-20), Example 71 (Compound No. 3-17), Example 2 (Compound No. 3-23)
No.), Example 75 (Compound No. 3-31), Example 7
6 (Compound No. 3-32), Example 80 (Compound No. 4-7), Example 87 (Compound No. 5-16), Example 88 (Compound No. 5-27) and Example 92 ( The degree of disease onset was 0 for the compounds No. 5-52).

[0364]

[Test Example 2] Cucumber downy mildew control test (therapeutic effect) A pot culture test plant (cucumber: Sagamihanjiro) at the 3rd to 5th leaf stages was spray-inoculated with a pathogenic spore suspension at room temperature of 20 to 22. ℃
I put them in the vaccination room and promoted the disease. The emulsion prepared according to Formulation Example 2 was diluted with water to prepare a spray solution containing 300 ppm of the compound of the present invention, and 1 day after inoculation, the spray solution was sprayed with a spray gun to homogenize the test plants in the pot. Sprinkled on. The degree of illness was investigated 7 days after the inoculation. The test was performed in duplicate.

The degree of disease onset was expressed by four levels from 0 to 3 by visually observing the degree of disease on the test plant and judging by the same criteria as in Test Example 1.

As a result of this test, Example 9 (Compound No. 1-
7), Example 11 (Compound No. 1-35), Example 15 (Compound No. 1-48), Example 26 (Compound No. 1-99), Example 32 (Compound No. 1-139).
No.), Example 45 (Compound No. 1-155), Example 63 (Compound No. 2-1), Example 64 (Compound No. 2-10), Example 66 (Compound No. 2-20). ,
Example 69 (Compound No. 3-7), Example 71 (Compound No. 3-17), Example 2 (Compound No. 3-23)
No.), Example 79 (Compound No. 3-47) and Example 92 (Compound No. 5-52), the degree of disease onset was 0.

[0367]

INDUSTRIAL APPLICABILITY The compound of the present invention can be used as an agricultural fungicide, and is effective against various plant pathogenic fungi, particularly tomato epidemics and cucumber downy mildew, without damaging host plants. Therefore, it is an excellent fungicide for agricultural and horticultural use.

Examples of plant diseases in which the compound of the present invention exerts excellent efficacy include, for example, tomato blight (Phytophthora infe).
stans), cucumber downy mildew (Pseudoperonospora cubensi)
s), grape downy mildew (Plasmopara viticola), potato epidemic (Phytophthora infestans) and the like, but the sterilization spectrum of the compound of the present invention is not limited to these.

Continued front page    (72) Inventor, J. Tanaka             1041 Yasu, Yasu-cho, Yasu-gun, Shiga Sankyo Stock Association             In-house (72) Inventor Tohru Onishi             1041 Yasu, Yasu-cho, Yasu-gun, Shiga Sankyo Stock Association             In-house F-term (reference) 4C033 AD15 AD16 AD17                 4C063 AA01 BB01 BB03 BB08 BB09                       CC62 CC67 CC78 DD12 DD19                       DD22 DD51 DD62 EE03                 4H011 AA01 BA01 BA06 BB10 BC01                       BC03 BC07 BC18 DA02 DA15                       DA16 DC01 DC05 DC06 DD03                       DE15

Claims (17)

[Claims] 1. A general formula [Chemical 1] [In the formula, R¹Is C which may be substituted₁~ C₆Alkyl group
(The substituent is selected from the following substituent group A), C
₂~ C₇Aliphatic acyl group, optionally substituted phenyl group (equivalent to
The substituent is selected from the following substituent group B. ), Replaced
A heterocyclic group which may be substituted (the substituent is selected from the following substituent group C
To be elected. ) Or C₁~ C₆Represents an alkylamino group, R²Is a hydrogen atom or optionally substituted C₁~ C₆Alkyl
Represents a group (the substituent is a halogen atom), R³Is a halogen atom, optionally substituted C₁~ C₆Archi
Group (the substituent is selected from the following substituent group D)
It ), C₃~ C₇A cycloalkyl group, optionally substituted
Phenyl group (the substituent is selected from the following substituent group B)
It ), Optionally substituted C₁~ C₆Alkoxy group
The substituent is C₁~ C₆It is an alkoxy group. ), Replaced
A good phenoxy group (the substituent is selected from the following substituent group B
To be elected. ), An optionally substituted heterocyclic oxy group (the position
The substituent is selected from the following substituent group C. ), Replaced
Good C₁~ C₆Alkylthio group (the substituent is cyano
Group, phenyl group or C₁~ C₆It is an alkoxy group. ),
A phenylthio group which may be substituted (the substituent is
It is selected from the substituent group B. ), Optionally substituted heterocyclethio
A group (the substituent is selected from the following substituent group C),
A cyclic amino group which may be substituted (the cyclic amino group is 1
It may be interrupted by individual oxygen atoms. The substituent is C
₁~ C₆Alkyl group and C₂~ C₇Alkoxycarbonyl group
Is selected from the group consisting of. ) Or optionally substituted amino
A group (the substituent is selected from the following substituent group E).
Represents X represents an oxygen atom or a sulfur atom, Y is C₁~ C₆Alkyl group, C₁~ C₆Alkoxy group,
Ano group, nitro group, halogen atom or C₂~ C₇Arcoki
Represents a carbonyl group, n represents an integer of 0 to 4, However, when n is 2 to 4, each Y is the same or different.
Well, Substituent group A is a halogen atom and optionally substituted C₃~
C₇Cycloalkyl group (the cycloalkyl group is one
May be interrupted by oxygen atoms of. The substituent is C₁
~ C₆Selected from the group consisting of alkyl groups and halogen atoms
Be done. ) Consisting of Substituent group B is C which may be substituted.₁~ C₆Alkyl group (this
The substituent is a halogen atom. ), C₁~ C₆Arco
Xy group, cyano group, nitro group, halogen atom, C₂~ C₇
Alkoxycarbonyl group, C₂~ C₇Alkyl carbonyl
Amino group and C ₁~ C₃Group consisting of alkylenedioxy groups
And Substituent group C is C which may be substituted.₁~ C₆Alkyl group (this
The substituent is a halogen atom. ), C₁~ C₆Arco
Xy group, cyano group, phenyl group, halogen atom, C₂~
C₇A group consisting of an alkoxycarbonyl group and an oxo group
Yes, Substituent group D includes halogen atom, hydroxyl group, C₁~ C₆Arco
Xyl group, optionally substituted C₂~ C₇Aliphatic acyloxy group
(The substituent is C₃~ C₇Cycloalkyl group, C₁~ C₆
Selected from the group consisting of alkoxy groups and halogen atoms
It ), An optionally substituted phenoxy group (the substituent is
It is selected from the above substituent group B. ), A complex that may be replaced
Ring oxy group (the substituent is selected from the above substituent group C)
It ), Optionally substituted C₁~ C₆Alkylthio group
The substituents are cyano group, phenyl group and C₁~ C₆Arcoki
Selected from the group consisting of Si groups. ), Which may be replaced
Nylthio group (the substituent is selected from the above substituent group B)
It ), An optionally substituted heterocyclic thio group (the substituent is
It is selected from the above substituent group C. ), C₂~ C₇Aliphatic reed
A ruthio group, an optionally substituted phenyl group (the substituent is
It is selected from the above substituent group B. ) And a compound that may be substituted
Elementary ring group (the substituent is selected from the above substituent group C)
It ) Consisting of Substituent group E is C which may be substituted.₁~ C₆Alkyl group (this
The substituent is a cyano group, a halogen atom, a phenyl group or
C₁~ C₆It is selected from the group consisting of alkoxy groups. ), C
₃~ C₆Alkenyl group, C₃~ C₆Alkynyl group, C₃~ C₇
Cycloalkyl group, hydroxyl group, optionally substituted C₁~ C₆A
Lucoxy group {the substituent is a phenyl group which may be substituted
(The substituent is selected from the above substituent group B).
It }, C₃~ C₆Alkenyloxy group, which may be substituted
Phenyl group (the substituent is selected from the above substituent group B)
It ), A heterocyclic group which may be substituted (the substituent is the above
It is selected from the substituent group C. ), Optionally substituted C₂~ C₇
Aliphatic acyl group (the substituent is a halogen atom
It ) And a benzoyl group which may be substituted (the substituent
Is selected from the above substituent group B. ) Consists of
It ] 5- (m-cyanobenzylamino) thio represented by
An azole derivative or a salt thereof. 2. R ¹ is a C ₁ -C ₆ alkyl group which may be substituted (the substituent is a fluorine atom, a chlorine atom, a bromine atom and an optionally substituted C ₃ -C ₆ cycloalkyl group (the said cycloalkyl group). The alkyl group may be interrupted by an oxygen atom, and the substituent is selected from the group consisting of a C ₁ -C ₄ alkyl group, a fluorine atom, a chlorine atom and a bromine atom. }, C ₂ -C ₆ aliphatic acyl group, optionally substituted phenyl group {wherein the substituent is optionally substituted C ₁ ~
A C ₄ alkyl group (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom), a C _{1 to} C ₄ alkoxy group, a cyano group, a nitro group, a fluorine atom, a chlorine atom, a bromine atom, C ₂ -C ₅ alkoxycarbonyl group, C ₂
To C ₅ alkylcarbonylamino groups and C _{1 to} C ₂ alkylenedioxy groups. }, 5 to 6-membered heterocyclic group which may be substituted {The heterocyclic ring has 1 to 3 heteroatoms which are the same or different and are selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom. The substituent is a C ₁ -C ₄ alkyl group which may be substituted (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom), a C ₁ -C ₄ alkoxy group, a cyano group, It is selected from the group consisting of a phenyl group, a fluorine atom, a chlorine atom, a bromine atom, a C ₂ -C ₅ alkoxycarbonyl group and an oxo group. } Or C ₁ -C ₄ alkylamino group, claim 1
The 5- (m-cyanobenzylamino) thiazole derivative or salt thereof according to 1. 3. R ¹ is an optionally substituted C ₁ -C ₅ alkyl group (the substituent is a fluorine atom, a chlorine atom or C ₄ -C ₆
It is selected from the group consisting of a cycloalkyl group (the cycloalkyl group may be interrupted by an oxygen atom). }, A phenyl group which may be substituted (the substituent is selected from the group consisting of a methyl group, a cyano group, a fluorine atom and a chlorine atom) or a 6-membered heterocyclic group which may be substituted (the heterocycle is 1 5 to 2 nitrogen atoms, wherein the substituent is selected from the group consisting of a methyl group, a fluorine atom and a chlorine atom.) 5. The 5- (m-cyanobenzylamino) thiazole derivative according to claim 1. Or its salt. 4. R ¹ is an optionally substituted C ₄ -C ₅ alkyl group (the said substituent is a fluorine atom) or an optionally substituted methyl group (the said substituent is C ₄ -C _5). It is a cycloalkyl group.) The 5- (m-cyanobenzylamino) thiazole derivative or salt thereof according to claim 1. 5. R ¹ is an isobutyl group, a neopentyl group,
The 5- according to claim 1, which is a 3,3,3-trifluoro-2-methylpropyl group or a cyclopentylmethyl group.
(M-Cyanobenzylamino) thiazole derivative or a salt thereof. 6. R ² is a hydrogen atom or C ₁ -which may be substituted.
5- (m-cyanobenzylamino) according to any one of claims 1 to 5, which is a C ₄ alkyl group (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom). ) A thiazole derivative or a salt thereof. Is 7. R ^2, may be substituted C ₁ -C ₂ alkyl group (said substituents are selected from the group consisting of fluorine atom and chlorine atom.) Is, any one of claims 1 to 5 5. A 5- (m-cyanobenzylamino) thiazole derivative or a salt thereof described in 1. 8. The 5- (m-cyanobenzyl) according to claim 1, wherein R ² is an optionally substituted methyl group (the substituent is a fluorine atom). Amino) thiazole derivative or a salt thereof. 9. The 5- (m-cyanobenzylamino) thiazole derivative or a salt thereof according to claim 1, wherein R ² is a methyl group. 10. R³Is a chlorine atom, C which may be substituted₁~
C_FiveAlkyl group (the substituent is selected from the following substituent group D1
To be elected. ), C₃~ C₆Cycloalkyl group, substituted
Good phenyl group (the substituent is the following substituent group B1
To be elected. ), Optionally substituted C₁~ C_FourAlkoxy group
(The substituent is C₁~ C_FourIt is an alkoxy group. ),
A phenoxy group which may be replaced (the substituent is the following substituent
Selected from group B1. ), Optionally substituted 5-6 membered complex
A ring oxy group (the heterocycle includes a nitrogen atom, a sulfur atom and an acid
Same or different 1 to 3 selected from the group consisting of elementary atoms
Has 4 heteroatoms. The substituent is the following substituent group C
Selected from 1. ), Optionally substituted C₁~ C_FourAlkyl
Thio group (the substituents are cyano group, phenyl group and C₁
~ C_FourIt is selected from the group consisting of alkoxy groups. ), Replace
A phenylthio group which may be substituted (the substituent is
Selected from group B1. ), Optionally substituted 5-6 membered complex
A ring thio group (the heterocycle is a nitrogen atom, a sulfur atom or an oxygen atom)
1-3 identical or different selected from the group consisting of atoms
It has a complex atom of. The substituent is the following substituent group C1
Chosen from. ), Optionally substituted 4- to 6-membered cyclic amino
A group (the cyclic amino group is interrupted by one oxygen atom)
You can be. The substituent is C₁~ C_FourAlkyl group and C₂
~ C_FiveSelected from the group consisting of alkoxycarbonyl groups
It ) Or an optionally substituted amino group (the substituent is
It is selected from the substituent group E1. ), And Substituent group B1 may be substituted C₁~ C_FourAlkyl group
(Does the substituent include a fluorine atom, a chlorine atom, and a bromine atom?
Selected from the group consisting of ), C₁~ C_FourAlkoxy group,
Ano group, nitro group, fluorine atom, chlorine atom, bromine atom,
C₂~ C_FiveAlkoxycarbonyl group, C₂~ C_FiveAlkyr
Rubonylamino group and C₁~ C₂Is it an alkylenedioxy group?
A group of Substituent group C1 may be substituted C₁~ C_FourAlkyl group
(Does the substituent include a fluorine atom, a chlorine atom, and a bromine atom?
Selected from the group consisting of ), C₁~ C_FourAlkoxy group,
Ano group, phenyl group, fluorine atom, chlorine atom, bromine source
Child, C₂~ C_FiveFrom an alkoxycarbonyl group and an oxo group
Is a group of Substituent group D1 is fluorine atom, chlorine atom, bromine atom, water
Acid group, C₁~ C_FourAlkoxy group, optionally substituted C₂~ C_Five
Aliphatic acyloxy group (the substituent is C₃~ C₆Cyclo
Alkyl group, C₁~ C_FourAlkoxy group, fluorine atom, chlorine
It is selected from the group consisting of atoms and bromine atoms. ), Replaced
Optionally a phenoxy group (the substituent is the above-mentioned Substituent Group B
Selected from 1. ), Optionally substituted 5- or 6-membered heterocycle
A xy group (the heterocycle is a nitrogen atom, a sulfur atom, or an oxygen source).
1-3 identical or different selected from the group consisting of offspring
It has a heteroatom. Is the substituent group C1 above?
Chosen from. ), Optionally substituted C₁~ C_FourAlkylthio
Group (the substituent is a cyano group, a phenyl group and a C group)₁~ C_Four
It is selected from the group consisting of alkoxy groups. ), Replaced
Good phenylthio group (the substituent is the above-mentioned substituent group B1
Chosen from. ), Optionally substituted 5-6 membered heterocyclic thio
A group (whether the heterocycle is a nitrogen atom, a sulfur atom or an oxygen atom)
1 to 3 same or different complex selected from the group consisting of
Have atoms. The substituent is selected from the above substituent group C1.
Be exposed. ), C₂~ C_FiveAliphatic acylthio group, substituted
A good phenyl group (the substituent is selected from the above substituent group B1)
To be elected. ) And an optionally substituted 5- or 6-membered heterocyclic group (the present
The heterocycle is composed of a nitrogen atom, a sulfur atom and an oxygen atom.
The same or different 1 to 3 heteroatoms selected from the group
Have. The substituent is selected from the above substituent group C1.
It ) Consisting of Substituent group E1 may be substituted C₁~ C_FourAlkyl group
(The substituent is a cyano group, a fluorine atom, a chlorine atom, an odor
Elementary atom, phenyl group and C₁~ C_FourConsisting of an alkoxy group
Selected from the group. ), C₃~ C_FourAlkenyl group, C₃~ C_Four
Alkynyl group, C ₃~ C_FiveCycloalkyl group, hydroxyl group, position
C that may be exchanged₁~ C_FourAlkoxy group (the substituent is
A phenyl group which may be replaced (the substituent is the above-mentioned substituent group)
Selected from B1. ). }, C₃~ C_FourAlkenyl
An oxy group, an optionally substituted phenyl group (the substituent is
It is selected from the above substituent group B1. ), Which may be replaced 4
~ 6-membered heterocyclic group (the heterocycle is a nitrogen atom, a sulfur atom and
And the same or different 1 selected from the group consisting of oxygen atoms
It has ~ 3 heteroatoms and may be fused with a benzene ring.
The substituent is selected from the above substituent group C1. ),
C that may be exchanged₂~ C_FiveAliphatic acyl group (the substituent is
Selected from the group consisting of fluorine, chlorine and bromine atoms
Be done. ) And a benzoyl group which may be substituted (the substituent
Is selected from the above substituent group B1. ) Consists of
5- (m-si) according to any one of claims 1 to 9.
Anobenzylamino) thiazole derivative or a salt thereof. 11. R ³ is an optionally substituted C ₁ -C ₄ alkyl group (the said substituent is selected from the following substituent group D2), a C ₃ -C ₅ cycloalkyl group, and may be substituted. Phenyl group (the substituent is selected from the following substituent group B2), optionally substituted C ₁ -C ₄ alkoxy group (the substituent is C ₁ -C ₂ alkoxy group), and substituted. A phenoxy group which may be substituted (the substituent is selected from the following substituent group B2), and a 6-membered heterocyclic oxy group which may be substituted (the heterocycle has 1 to 2 nitrogen atoms. Is selected from the following substituent group C2), C _{1 to} C ₄
Alkylthio group, 6-membered heterocyclic thio group (the heterocycle is 1
Has ˜2 nitrogen atoms. ) 4- to 5-membered cyclic amino group (the cyclic amino group may be interrupted by one oxygen atom) or an optionally substituted amino group (the substituent is selected from the following substituent group E2). And the substituent group B2 is a group consisting of a C _{1 to} C ₂ alkyl group, a cyano group, a fluorine atom, a chlorine atom and a bromine atom, and the substituent group C2 is a C _{1 to} C ₂ alkyl group, cyano A group consisting of a group, a fluorine atom, a chlorine atom, a bromine atom and an oxo group, wherein the substituent group D2 is a fluorine atom, a chlorine atom, a hydroxyl group, C ₁
To C ₂ alkoxy group, optionally substituted C _{2 to} C ₅ aliphatic acyloxy group (the substituent is selected from the group consisting of a fluorine atom and a chlorine atom), and optionally substituted phenoxy group (the substituent is , Selected from the above substituent group B2), and optionally substituted 5- to 6-membered heterocyclic oxy group (the heterocyclic ring is the same or different one or two selected from the group consisting of a nitrogen atom and an oxygen atom). Having a hetero atom, the substituent is selected from the above substituent group C2), an optionally substituted C ₁ -C ₂ alkylthio group (the said substituent is a cyano group), an optionally substituted phenylthio group. A group (the substituent is selected from the above substituent group B2) and a 5-membered heterocyclic thio group which may be substituted (the heterocycle is the same or different 1 selected from the group consisting of a nitrogen atom and a sulfur atom).
~ 3 heteroatoms. The substituent is selected from the above substituent group C2. And a optionally substituted 5 heterocyclic group (the heterocyclic ring has 1 to 2 nitrogen atoms. The substituent is selected from the above substituent group C2). E2 is a C ₁ -C ₄ alkyl group which may be substituted (the substituent is selected from the group consisting of a cyano group, a fluorine atom, a chlorine atom, a phenyl group and a C ₁ -C ₂ alkoxy group), C ₃ To C ₄ alkenyl group, C _{3 to} C ₄ alkynyl group, C _{3 to} C ₄ cycloalkyl group, hydroxyl group, benzyloxy group, C _{3 to} C ₄ alkenyloxy group, phenyl group, 5
6-membered Hajime Tamaki (said heterocyclic ring may have the same or different 1 to 2 heteroatoms selected from the group consisting of nitrogen atom and sulfur atom, or condensed with a benzene ring.), C ₂ ~ C ₅
The 5- (m-cyanobenzylamino) thiazole derivative or a salt thereof according to any one of claims 1 to 9, which is a group consisting of an aliphatic acyl group and a benzoyl group. 12. R ³ is an optionally substituted C ₁ -C ₂ alkyl group (the substituent is selected from the following substituent group D3), C ₃ -C ₄ cycloalkyl group, C ₁ -C. _{2 is an} alkoxy group, a pyridinyloxy group or an optionally substituted amino group (the substituent is selected from the following substituent group E3), wherein the substituent group D3 is a hydroxyl group, a methoxy group or a C ₂ -C ₄ aliphatic group. An acyloxy group, an optionally substituted phenoxy group (the said substituent is selected from the group consisting of a cyano group and a fluorine atom), an optionally substituted pyridyloxy group (the said substituent is a methyl group), cyano A group consisting of a methylthio group, an optionally substituted thiadiazolylthio group (the said substituent is a methyl group) and an optionally substituted pyrazolyl group (the said substituent is a bromine atom), Base group E3 Substituted C ₁ may -C ₂ alkyl group (said substituents are selected from the group consisting of phenyl group and methoxy group.) A group consisting of and allyl groups, in any one of claims 1 to 9 The described 5- (m-cyanobenzylamino) thiazole derivative or a salt thereof. 13. The compound according to claim 1, wherein R ³ is a methyl group, a hydroxymethyl group, a methoxymethyl group, an acetoxymethyl group, a (bromopyrazolyl) methyl group, a cyclopropyl group or an amino group. 5- (m
-Cyanobenzylamino) thiazole derivative or a salt thereof. 14. The method according to claim 1, wherein X is an oxygen atom.
5- (m-cyanobenzylamino) thiazole derivative or a salt thereof according to any one of 1. 15. The 5- (m-cyanobenzylamino) according to any one of claims 1 to 14, wherein Y is a methyl group, a fluorine atom or a chlorine atom, and n is 0 or 1.
A thiazole derivative or a salt thereof. 16. The 5- (m-cyanobenzylamino) thiazole derivative or a salt thereof according to claim 1, wherein n is 0. 17. A pesticide containing the 5- (m-cyanobenzylamino) thiazole derivative according to any one of claims 1 to 16 or a salt thereof as an active ingredient.