JP2003192596A - New anticoccidial agent including organic boron compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new anticoccidial agent that includes an organic boron compound. <P>SOLUTION: The medicinal composition for mammalians except humans, the antiprotozoal agent and the anticoccidial agent of this invention include a compound represented by general formula (I), their salts or their solvates. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention belongs to the field of veterinary medicine and relates to a novel non-human veterinary pharmaceutical composition, particularly an anticoccidial agent. Specifically, the present invention relates to anticoccidial agents containing organoboron compounds.

[0002]

2. Description of the Related Art Coccidiosis is caused by protozoa (Apicompl).
coccidi, which is a subclass of exa
It is an infectious disease caused by a). Coccidial genus Eimeria tenella, Eimeria acervulina, and Eimeria necatrix mainly infect poultry, causing various symptoms such as gastrointestinal bleeding, death, or growth suppression cause. An outbreak of coccidiosis in a poultry farm, which raises poultry such as chickens and ducks for business purposes, causes extremely large losses and is often a serious problem. Therefore, there is great interest in anticoccidial agents that are effective in the prevention and treatment of coccidiosis.

Conventionally, sulfa drugs, nitrofuran agents, quinoline agents, antithiamine agents, benzamides and the like have been put into practical use as anticoccidial agents, and at present, polyether antibiotics are mainly used. Examples include salinomycin and clopidol. However,
These are not so strong in anticoccidial action, which is the main action, and have a problem in toxicity to the host. In addition, a drug-resistant strain has emerged due to long-term use of the drug, resulting in a gradual decrease in the efficacy of the drug. In consideration of such circumstances, there is a demand for the development of a new type of anticoccidial agent for poultry which is effective for resistant strains and hard to impart resistance at the same time.

Anticoccidial agents containing organoboron compounds are described in WO 00/44387. However, this organoboron compound is different from the organoboron compound which is the active ingredient in the anticoccidial agent of the present invention.

The organoboron compound of the present invention is SJ Rett
ing and J. Trotter, Can. J. Chem. 54, 3130 (1976)
And SJ Retting and J. Trotter, Acta. Cryst. B
30, 2139 (1974). However, these documents do not describe any use of the organoboron compound of the present invention. Further, WO00 / 75142 describes diphenylboron oxazolidines and a method for producing the same, and it is described that this compound exhibits antibacterial activity, but no anticoccidial action in question is described. .

[0006]

DISCLOSURE OF THE INVENTION As a result of diligent studies, the present inventors have found that the organoboron compound of the present invention has excellent anticoccidial activity and can prevent the outbreak of coccidiosis. .. Therefore, an object of the present invention is to provide a novel anticoccidial agent containing an organoboron compound.

[0007]

The present invention has the general formula (I):

[Chemical 4] [In the formula, Ar ¹ and Ar ² are each independently a cyclic group which may be substituted; G is a group represented by formulas -A- and -A-;
A group represented by CR ² R ³ — or —A—CR ⁴ R ⁵ —CR ⁶ R ⁷ — (wherein A is an oxygen atom or a sulfur atom); R
^{1 to} R ⁷ are the same or different and each is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkoxycarbonyl group, an acyl group, a halogenated lower alkyl group, a halogenated lower alkenyl group, an amide group. , Optionally substituted aralkyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy group, halogenated lower alkenyloxy group, acyloxy, optionally substituted phenyloxy, optionally substituted aralkyl Oxy, an optionally substituted amino group, an optionally substituted sulfonyl group, an optionally substituted sulfinyl group or an optionally substituted aryl group] or a salt thereof or a salt thereof. Non-human veterinary medicine containing solvates To provide a Narubutsu.

[0008] In a further aspect, the present invention provides a non-human veterinary pharmaceutical composition containing the following compounds (1) and (2), respectively: (1) General formula (II):

[Chemical 5] [In the formula, Ar ^a1 and Ar ^a2 are the same or different and each represents an optionally substituted aryl group; R ^a , R ^b1 , R a
^b2 , R ^c1 and R ^c2 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkoxycarbonyl group, an acyl group,
Halogenated lower alkyl group, halogenated lower alkenyl group, amide group, optionally substituted aralkyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy group, halogenated lower alkenyloxy group, acyloxy, substituted Optionally substituted phenyloxy, optionally substituted aralkyloxy, optionally substituted amino group, optionally substituted sulfonyl group, optionally substituted sulfinyl group or optionally substituted aryl And a salt thereof or a solvate thereof; and (2) the general formula (III):

[Chemical 6] [Wherein, X is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group or a halogenated lower alkoxy group bonded to the meta or para position; and R is , A hydrogen atom, a carboxyl group, a lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, an amide group, and an acyl group].
Or a salt thereof or a solvate thereof.

In the present specification, the "pharmaceutical composition for animals other than humans" means a drug used for diagnosing, treating or preventing diseases in animals other than humans, and as a veterinary pharmaceutical composition of the present invention. Is used for antiprotozoal agents, anticoccidial agents,
Included are all veterinary uses such as growth promoters. Examples of animals to which the veterinary pharmaceutical composition of the present invention is applicable include poultry such as chickens, geese, pheasants, turkeys and ducks, and livestock such as cattle, rabbits, sheep, goats, pigs and the like.

The antiprotozoal agent means a drug for preventing or treating the infection of protozoa including Toxoplasma, malaria and the following coccidia.

The anticoccidial agent means a drug mainly for preventing and treating infections caused by Eimeria tenella, Eimeria acervulina, Eimeria necatrix and the like. .

The organic boron compound which is the active ingredient of the pharmaceutical composition of the present invention will be described below. In the above formula, Ar
^The "optionally substituted cyclic group" represented by ¹ and Ar ² is, for example, a monocyclic or condensed polycyclic alicyclic hydrocarbon group (eg, an optionally substituted cycloalkyl group,
Optionally substituted cycloalkenyl group, optionally substituted cycloalkadienyl group, etc.), monocyclic or condensed polycyclic aromatic hydrocarbon group (eg, optionally substituted aryl group, etc.) ), A monocyclic or condensed polycyclic heterocyclic group (eg, an optionally substituted aromatic heterocyclic group, etc.), a spirocyclic hydrocarbon group or a heterocyclic group, etc. Preferably Ar ¹ and Ar ² are the same.

Examples of the above cycloalkyl group include cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl, cycloheptyl, cyclooctyl, bicyclo [2.2.1] heptyl, bicyclo [2.2.
2] octyl, bicyclo [3.2.1] octyl, bicyclo [3.2.2] nonyl, bicyclo [3.3.1] nonyl, bicyclo [4.2.1] nonyl, bicyclo [4.
3.1] Decyl, adamantyl and the like having 3 to 20 carbon atoms
And the like.

Examples of the above cycloalkenyl group are:
For example, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-
Examples thereof include cycloalkenyl groups having 4 to 20 carbon atoms such as cyclohexen-1-yl.

Examples of the above cycloalkadienyl group include, for example, 2,4-cyclopentadien-1-yl,
Examples thereof include C4-C20 cycloalkadienyl groups such as 2,4-cyclohexadiene-1-yl and 2,5-cyclohexadiene-1-yl.

Examples of the above-mentioned "aryl group" include carbon numbers such as phenyl, indenyl, naphthyl (1-naphthyl, 2-naphthyl, etc.), anthryl, phenanthryl, acenaphthylenyl, fluorenyl (9-fluorenyl, 1-fluorenyl, etc.). 6 to 20 aryl groups and the like can be mentioned.

The above-mentioned "heterocyclic group" means a heterocyclic group containing at least one heteroatom of oxygen, sulfur or nitrogen as an atom constituting the ring system, and is a monocyclic heterocyclic group or a condensed ring. A polycyclic heterocyclic group is mentioned.

Specific examples of the monocyclic heterocyclic group include, for example, isoxazolyl, isothiazolyl, imidazolyl,
1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolyl, flazanil, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3
4-thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, 1,2,3-triazolyl, 1,
2,4-triazolyl, pyranyl, pyrazinyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrrolyl, 2H-pyrrolyl, flazanyl, furyl and the like can be mentioned.

Specific examples of the fused polycyclic heterocyclic group include, for example, acridinyl, 5-azabenzo [a] anthracenyl, isoindolyl, isoquinolyl, isochromanyl,
Isobenzofuranyl, imidazo [2,1-b] thiazolyl, 4H-imidazo [4,5-d] thiazolyl, imidazo [1,2-b] [1,2,4] triazinyl, imidazo [1,2- a] pyridyl, imidazo [1,5-a] pyridyl, imidazo [1,2-b] pyridazinyl, imidazo [1,2-a] pyrimidinyl, imidazolidinyl, imidazolinyl, 1H-indazolyl, indoridinyl,
Indolyl, 4H [1,3] -oxathiolo [5,4-
b] pyrrolyl, 1H-2-oxapyrenyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, quinazolinyl, quinoxalinyl, quinolyl, chromanyl, 4H-1,3-dioxolo [4,5-b] imidazolyl, cyclopenta [ b] pyranyl, 2,3-dithia-1,5-diazaindanyl, 4H-1,3-dithianaphthalenyl, 1,4-dithianaphthalenyl, cinnonyl, thianthrenyl, thieno [2,3-b] furanyl, 2,7,9-triazaphenanthrenyl, 1,2,
4-triazolo [4,3-a] pyridazinyl, 1,2,
4-triazolo [4,3-a] pyridyl, 2,4,6-
Trithia-3a, 7a-diazaindanyl-naphthyridinyl, piperazinyl, piperidyl, pyrazolidinyl, 7
H-pyrazino [2,3-c] carbazolyl, pyrazino [2,3-d] pyridazinyl, 1H-pyrazolo [4,3
-D] oxazolyl, pyrazolo [1,5-a] pyridyl, pyrido [1 ', 2': 1,2] imidazo [4,5-
b] quinoxalinyl, 5H-pyrido [2,3-d] -o
-Oxazinyl, 4H-pyrido [2,3-c] carbazolyl, pyrrolidinyl, pyrrolinyl, 1H-pyrrolo [1,
2-b] [2] benzazepinyl, pyrrolo [1,2-
b] pyridazinyl, phenazinyl, phenathridinyl,
Phenatorolinyl, phenoxazinyl, phenoxathinyl, phenothiazinyl, phthalazinyl, pteridinyl, purinyl, 2H-furo [3,2-b] pyranyl, furo [3,4-c] cincinolinyl, 1,2-benzisoxazolyl, Benzo [h] isoquinolyl, 1,2-benzisothiazolyl, benzimidazolyl, benzoxazolyl, 4H-3,1-benzoxazinyl, 3-benzoxepinyl, benzothiazolyl, benzo [b] thienyl, 1H- Examples thereof include benzotriazolyl, benzo [b] furanyl, morpholinyl and the like.

A preferred group as the "optionally substituted cyclic group" for Ar ¹ and Ar ² is an optionally substituted aryl group, and specifically, for example, a halogen atom, a lower alkyl group, a lower group Alkenyl group, lower alkoxy group, halogenated lower alkyl group, halogenated lower alkenyl group, halogenated lower alkoxy group, aryl group,
Examples thereof include an aryl group which may be substituted with a hydroxy group, an acyl group, an amino group or the like. In addition, the number of substituents of the aryl group or the heterocyclic group in Ar ¹ and Ar ² is not limited to one, and the number thereof is not limited to one.

Hereinafter, specific examples of the case where there is one kind of substituent among the aryl groups which may be substituted will be listed. "Halogen atom" means, for example, fluorine,
Represents chlorine, bromine, etc. Therefore, examples of the aryl group substituted with a halogen atom include 2-halogenated phenyl (eg, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, etc.), 3-halogenated phenyl (eg, 3-halogenated phenyl). Fluorophenyl, 3-chlorophenyl, 3
-Bromophenyl etc.), 4-halogenated phenyl (eg,
4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, etc.), 2-halogenated naphthalen-1-yl (eg, 2-fluoronaphthalen-1-yl, 2-chloronaphthalen-1-yl, 2-bromonaphthalene) -1-yl, etc.), 3-halogenated naphthalen-1-yl (eg, 3
-Fluoronaphthalen-1-yl, 3-chloronaphthalen-1-yl, 3-bromonaphthalen-1-yl, etc.),
4-halogenated naphthalen-1-yl (eg, 4-fluoronaphthalen-1-yl, 4-chloronaphthalen-1-
Yl, 4-bromonaphthalen-1-yl, etc.), 5-halogenated naphthalen-1-yl (eg, 5-fluoronaphthalen-1-yl, 5-chloronaphthalen-1-yl, 5
-Bromonaphthalen-1-yl, etc.), 6-halogenated naphthalen-1-yl (eg, 6-fluoronaphthalene-1)
-Yl, 6-chloronaphthalen-1-yl, 6-bromonaphthalen-1-yl, etc.), 7-halogenated naphthalen-1-yl (eg, 7-fluoronaphthalen-1-yl,
7-chloronaphthalen-1-yl, 7-bromonaphthalen-1-yl, etc.), 8-halogenated naphthalen-1-yl (eg, 8-fluoronaphthalen-1-yl, 8-chloronaphthalen-1-yl, 8-Bromonaphthalene-1-
And the like), 1-halogenated naphthalen-2-yl (eg,
1-fluoronaphthalen-2-yl, 1-chloronaphthalen-2-yl, 1-bromonaphthalen-2-yl, etc.), 3-halogenated naphthalen-2-yl (eg, 3-
Fluoronaphthalen-2-yl, 3-chloronaphthalen-2-yl, 3-bromonaphthalen-2-yl, etc.), 4
-Halogenated naphthalen-2-yl (eg, 4-fluoronaphthalen-2-yl, 4-chloronaphthalen-2-yl, 4-bromonaphthalen-2-yl, etc.), 5-halogenated naphthalen-2-yl ( Example, 5-fluoronaphthalen-2-yl, 5-chloronaphthalen-2-yl, 5-
Bromonaphthalen-2-yl, etc.), 6-halogenated naphthalen-2-yl (eg, 6-fluoronaphthalene-2-yl)
Yl, 6-chloronaphthalen-2-yl, 6-bromonaphthalen-2-yl, etc.), 7-halogenated naphthalene-
2-yl (eg, 7-fluoronaphthalen-2-yl, 7
-Chloronaphthalen-2-yl, 7-bromonaphthalen-2-yl, etc.), 8-halogenated naphthalen-2-yl (eg, 8-fluoronaphthalen-2-yl, 8-chloronaphthalen-2-yl, 8 -Bromonaphthalen-2-yl, etc.), 2-halogenated inden-1-yl (eg, 2-
Fluoroinden-1-yl, 2-chloroinden-1
-Yl, 2-bromoinden-1-yl, etc.), 3-halogeninden-1-yl (eg, 3-fluoroinden-1-yl, 3-chloroinden-1-yl, 3-bromoinden-1) -Yl etc.), 4-halogenated indene-
1-yl (eg, 4-fluoroinden-1-yl, 4-
Chloroinden-1-yl, 4-bromoinden-1-
Etc.), 5-halogeninden-1-yl (eg, 5
-Fluoroinden-1-yl, 5-chloroinden-
1-yl, 5-bromoinden-1-yl, etc.), 6-halogenated inden-1-yl (eg, 6-fluoroinden-1-yl, 6-chloroinden-1-yl, 6-bromoinden-1) -Yl etc.), 7-halogenated indene-
1-yl (eg, 7-fluoroinden-1-yl, 7-
Chloroinden-1-yl, 7-bromoinden-1-
And the like), 1-halogenated inden-2-yl (eg, 1
-Fluoroinden-2-yl, 1-chloroinden-
2-yl, 1-bromoinden-2-yl, etc., 3-halogenated inden-2-yl (eg, 3-fluoroinden-2-yl, 3-chloroinden-2-yl, 3-bromoinden- 2-yl, etc.), 4-halogeninden-2-yl (eg, 4-fluoroinden-2-yl, 4
-Chloroinden-2-yl, 4-bromoindene-2
-Yl, etc.), 5-halogeninden-2-yl (eg,
5-fluoroinden-2-yl, 5-chloroinden-2-yl, 5-bromoinden-2-yl, etc.), 6-
Halogen inden-2-yl (eg, 6-fluoroinden-2-yl, 6-chloroinden-2-yl, 6-
Bromoinden-2-yl etc.), 7-halogenated inden-2-yl (eg, 7-fluoroinden-2-yl,
7-chloroinden-2-yl, 7-bromoindene-
2-yl, etc.), 7-halogenated inden-4-yl (eg, 7-fluoroinden-4-yl, 7-chloroinden-4-yl, 7-bromoinden-4-yl, etc.), 5-halogen Inden-3-yl chloride (eg, 5-fluoroinden-3-yl, 5-chloroinden-3-yl
Yl, 5-bromoinden-3-yl, etc.), 3-halogenated inden-5-yl (eg, 3-fluoroinden-
5-yl, 3-chloroinden-5-yl, 3-bromoinden-5-yl, etc.), 2-halogenated indene-6
-Yl (eg, 2-fluoroinden-6-yl, 2-chloroinden-6-yl, 2-bromoinden-6-yl, etc.), 4-halogeninden-7-yl (eg, 4-
Fluoroinden-7-yl, 4-chloroinden-7
-Yl, 4-bromoinden-7-yl, etc.), 1-halogenated inden-4-yl (eg, 1-fluoroinden-4-yl, 1-chloroinden-4-yl, 1-bromoinden-4 -Yl, etc.), 2,3-dihalogenated phenyl (eg, 2,3-difluorophenyl, 2,3-dichlorophenyl, 2,3-dibromophenyl, etc.), 2,3
-Dihalogenated naphthalen-1-yl (eg, 2,3-difluoronaphthalen-1-yl, 2,3-dichloronaphthalen-1-yl, 2,3-dibromonaphthalen-1-yl
, Etc.), 2,4-dihalogenated phenyl (eg, 2,4
-Difluorophenyl, 2,4-dichlorophenyl,
2,4-dibromophenyl, etc.), 2,6-dihalogenated phenyl (eg, 2,6-difluorophenyl, 2,6-
Dichlorophenyl, 2,6-dibromophenyl, etc.),
4,5-Dihalogenated naphthalen-1-yl (eg, 4,
5-difluoronaphthalen-1-yl, 4,5-dichloronaphthalen-1-yl, 4,5-dibromonaphthalen-1-yl, etc.), 4,6-dihalogenated naphthalene-1.
-Yl (eg, 4,6-difluoronaphthalen-1-yl, 4,6-dichloronaphthalen-1-yl, 4,6-
Dibromonaphthalen-1-yl etc.), 4,8-dihalogenated naphthalen-1-yl (eg, 4,8-difluoronaphthalen-1-yl, 4,8-dichloronaphthalene-1)
-Yl, 4,8-dibromonaphthalen-1-yl, etc.) and the like. As described above, as substitution positions, 2-, 3-, and 4- are phenyl groups and 2-, 3-, 4-, 5-, and 6-naphthalen-1-yl.
There are-, 7-, 8- and there is no particular limitation.

Examples of the above "lower alkyl" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 1-ethylpropyl, hexyl and the like. And a straight-chain or branched alkyl group having 1 to 10 carbon atoms and the like. In the present specification, unless otherwise specified, the term "lower" has 1 to 10, preferably 1 to 8, more preferably 1 to 8 carbon atoms in an aliphatic hydrocarbon group such as an alkyl group and an alkenyl group. Indicates 1 to 6. Therefore, examples of the aryl group substituted with lower alkyl include 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,
2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-methylnaphthalen-1-yl, 3-methylnaphthalen-1-yl, 4-methylnaphthalene-1-
5-methylnaphthalen-1-yl, 6-methylnaphthalen-1-yl, 7-methylnaphthalen-1-yl, 8-methylnaphthalen-1-yl, 2,4-dimethylphenyl, 2,4,6 -Trimethylphenyl, 4,5
-Dimethylnaphthalen-1-yl, 4,6-dimethylnaphthalen-1-yl, 4,8-dimethylnaphthalene-1
-Yl, 2-methylinden-1-yl, 3-methylinden-1-yl, 4-methylinden-1-yl, 5
-Methylinden-1-yl, 6-methylinden-1
-Yl, 7-methylinden-1-yl, 1-methylinden-2-yl, 3-methylinden-2-yl, 4
-Methylinden-2-yl, 5-methylinden-2
-Yl, 6-methylinden-2-yl, 7-methylinden-2-yl, 1-methylinden-3-yl, 2
-Methylinden-3-yl, 4-methylinden-3
-Yl, 5-methylinden-3-yl, 6-methylinden-3-yl, 7-methylinden-3-yl, 1
-Methylinden-4-yl, 2-methylinden-4
-Yl, 3-methylinden-4-yl, 5-methylinden-4-yl, 6-methylinden-4-yl, 7
-Methylinden-4-yl, 1-methylinden-5
-Yl, 2-methylinden-5-yl, 3-methylinden-5-yl, 4-methylinden-5-yl, 6
-Methylinden-5-yl, 7-methylinden-5
-Yl, 1-methylinden-6-yl, 2-methylinden-6-yl, 3-methylinden-6-yl, 4
-Methylinden-6-yl, 5-methylinden-6
-Yl, 7-methylinden-6-yl, 1-methylinden-7-yl, 2-methylinden-7-yl, 3
-Methylinden-7-yl, 4-methylinden-7
-Yl, 5-methylinden-7-yl, 6-methylinden-7-yl and the like can be mentioned. As each substitution position, if it is a phenyl group, 2-, 3-, 4-
If naphthalen-1-yl, 2-, 3-, 4-, 5-
There are-, 6-, 7-, 8- and there is no particular limitation.

Examples of the above-mentioned "lower alkenyl group" include vinyl, allyl, isopropenyl, 1-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-
Butenyl, 3-butenyl, 2-ethyl-1-butenyl,
Straight-chain or branched alkenyl groups having 2 to 10 carbon atoms such as 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl and the like. Can be mentioned. Therefore, examples of the aryl group substituted with lower alkenyl include 2-vinylphenyl, 3-vinylphenyl, 4-vinylphenyl, 2-allylphenyl, 3-allylphenyl, 4-allylphenyl and 2-vinyl. Naphthalene-1-
Yl, 3-vinylnaphthalen-1-yl, 4-vinylnaphthalen-1-yl, 5-vinylnaphthalen-1-yl, 6-vinylnaphthalen-1-yl, 7-vinylnaphthalen-1-yl, 8-vinyl Naphthalen-1-yl,
2-vinylinden-1-yl, 3-vinylinden-
1-yl, 4-vinylinden-1-yl, 5-vinylinden-1-yl, 6-vinylinden-1-yl,
7-vinylinden-1-yl, 1-vinylinden-
2-yl, 3-vinylinden-2-yl, 4-vinylinden-2-yl, 5-vinylinden-2-yl,
6-vinylinden-2-yl, 7-vinylinden-
2-yl, 1-vinylinden-3-yl, 2-vinylinden-3-yl, 4-vinylinden-3-yl,
5-vinylinden-3-yl, 6-vinylinden-
3-yl, 7-vinylinden-3-yl, 1-vinylinden-4-yl, 2-vinylinden-4-yl,
3-Vinylinden-4-yl, 5-vinylinden-
4-yl, 6-vinylinden-4-yl, 7-vinylinden-4-yl, 1-vinylinden-5-yl,
2-vinylinden-5-yl, 3-vinylinden-
5-yl, 4-vinylinden-5-yl, 6-vinylinden-5-yl, 7-vinylinden-5-yl,
1-vinylinden-6-yl, 2-vinylinden-
6-yl, 3-vinylinden-6-yl, 4-vinylinden-6-yl, 5-vinylinden-6-yl,
7-vinylinden-6-yl, 1-vinylinden-
7-yl, 2-vinylinden-7-yl, 3-vinylinden-7-yl, 4-vinylinden-7-yl,
5-vinylinden-7-yl, 6-vinylinden-
Examples include, but are not limited to, 7-yl and the like.

Examples of the above "lower alkoxy group" include alkoxy groups having 1 to 10 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy and isopentoxy. To be Therefore, examples of the aryl group substituted with the above lower alkoxy group include 2-methoxyphenyl, 3-methoxyphenyl, and 4-methoxyphenyl.
Methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methoxynaphthalen-1-yl, 3-methoxynaphthalen-1-yl, 4-methoxynaphthalen-1-yl, 5-methoxynaphthalene- 1-yl, 6-methoxynaphthalene-1-
-Yl, 7-methoxynaphthalen-1-yl, 8-methoxynaphthalen-1-yl, 2,4-dimethoxyphenyl, 2,4,6-trimethoxyphenyl, 4,5-dimethoxynaphthalen-1-yl, 4, 6-dimethoxynaphthalen-1-yl, 4,8-dimethoxynaphthalene-1
-Yl, 1-methoxyinden-2-yl, 1-methoxyinden-3-yl, 1-methoxyinden-4-yl, 1-methoxyinden-5-yl, 1-methoxyinden-6-yl, 1- Methoxyinden-7-yl,
1,3-dimethoxyinden-2-yl, 1,2-dimethoxyinden-3-yl, 1,3-dimethoxyinden-4-yl, 2,3-dimethoxyinden-5-yl, 1,4-dimethoxyinden -6-yl, 1,4-
Dimethoxyinden-7-yl etc. are mentioned.

Examples of the above "halogenated lower alkyl" include fluoromethyl, chloromethyl, bromomethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1-fluoroethyl, 1-chloroethyl, 1
-Bromoethyl, trifluoromethyl, trichloromethyl, tribromomethyl, difluoromethyl, dichloromethyl, dibromomethyl, 1,2-difluoroethyl,
1,2-dichloroethyl, 1,2-dibromoethyl,
1,1-difluoroethyl, 1,1-dichloroethyl,
1,1-dibromoethyl, 2,2-difluoroethyl,
Mention may be made of halogen-substituted lower alkyl groups as defined above, such as 2,2-dichloroethyl, 2,2-dibromoethyl and the like. Therefore, examples of the aryl group substituted with a halogenated lower alkyl group include, for example, an aryl group substituted with halomethyl (eg, a phenyl group substituted with fluoromethyl, a naphthalen-1-yl substituted with fluoromethyl, Phenyl group substituted with chloromethyl, naphthalen-1-yl substituted with chloromethyl, phenyl group substituted with bromomethyl, naphthalen-1-yl substituted with bromomethyl, etc.), aryl substituted with 2-haloethyl Group (eg, phenyl group substituted with 2-fluoroethyl, naphthalen-1-yl substituted with 2-fluoroethyl, phenyl group substituted with 2-chloroethyl, naphthalene-1-substituted with 2-chloroethyl)
2-phenyl group substituted with 2-bromoethyl, 2-
Naphthalen-1-yl substituted with bromoethyl),
Aryl group substituted with 1-haloethyl (eg, phenyl group substituted with 1-fluoroethyl, naphthalen-1-yl substituted with 1-fluoroethyl, phenyl group substituted with 1-chloroethyl, 1-chloroethyl With naphthalen-1-yl, a phenyl group substituted with 1-bromoethyl, a naphthalen-1-yl substituted with 1-bromoethyl, etc., an aryl group substituted with trihalomethyl (eg, trifluoromethyl Substituted phenyl group, naphthalene-1-substituted with trifluoromethyl
Phenyl group substituted with trichloromethyl, naphthalen-1-yl substituted with trichloromethyl, phenyl group substituted with tribromomethyl, naphthalen-1-yl substituted with tribromomethyl, etc.) and the like. To be As the respective substitution positions, 2-, 3-, and 4- are phenyl groups, and 2-, 3-, 4-, 5-, 6-, 7-, and naphthalen-1-yl are phenyl groups. 8- and there is no particular limitation. If it is indenyl, for example, 1-fluoromethylinden-2-yl, 1-chloromethylinden-2-yl, 1-bromomethylinden-2-yl, 1- (2-fluoroethyl) inden-2-yl,
1- (2-chloroethyl) inden-2-yl, 1-
(2-Bromoethyl) inden-2-yl, 1- (1-
Fluoroethyl) inden-2-yl, 1- (1-chloroethyl) inden-2-yl, 1- (1-bromoethyl) inden-2-yl, 1-trifluoromethylinden-2-yl, 1-trichloromethyl Inden-2-
1-tribromomethylinden-2-yl, 1-
Fluoromethylinden-3-yl, 1-chloromethylinden-3-yl, 1-bromomethylinden-3-yl
Yl, 1- (2-fluoroethyl) inden-3-yl, 1- (2-chloroethyl) inden-3-yl, 1
-(2-Bromoethyl) inden-3-yl, 1- (1
-Fluoroethyl) inden-3-yl, 1- (1-chloroethyl) inden-3-yl, 1- (1-bromoethyl) inden-3-yl, 1-trifluoromethylinden-3-yl, 1-trichloro Methylindene-3
-Yl, 1-tribromomethylinden-3-yl, 1
-Fluoromethylinden-4-yl, 1-chloromethylinden-4-yl, 1-bromomethylinden-4
-Yl, 1- (2-fluoroethyl) inden-4-yl, 1- (2-chloroethyl) inden-4-yl, 1
-(2-Bromoethyl) inden-4-yl, 1- (1
-Fluoroethyl) inden-4-yl, 1- (1-chloroethyl) inden-4-yl, 1- (1-bromoethyl) inden-4-yl, 1-trifluoromethylinden-4-yl, 1-trichloro Methylindene-4
-Yl, 1-tribromomethylinden-4-yl, 1
-Fluoromethylinden-5-yl, 1-chloromethylinden-5-yl, 1-bromomethylinden-5
-Yl, 1- (2-fluoroethyl) inden-5-yl, 1- (2-chloroethyl) inden-5-yl, 1
-(2-Bromoethyl) inden-5-yl, 1- (1
-Fluoroethyl) inden-5-yl, 1- (1-chloroethyl) inden-5-yl, 1- (1-bromoethyl) inden-5-yl, 1-trifluoromethylinden-5-yl, 1-trichloro Methylindene-5
-Yl, 1-tribromomethylinden-5-yl, 1
-Fluoromethylinden-6-yl, 1-chloromethylinden-6-yl, 1-bromomethylinden-6
-Yl, 1- (2-fluoroethyl) inden-6-yl, 1- (2-chloroethyl) inden-6-yl, 1
-(2-Bromoethyl) inden-6-yl, 1- (1
-Fluoroethyl) inden-6-yl, 1- (1-chloroethyl) inden-6-yl, 1- (1-bromoethyl) inden-6-yl, 1-trifluoromethylinden-6-yl, 1-trichloro Methylindene-6
-Yl, 1-tribromomethylinden-6-yl, 1
-Fluoromethylinden-7-yl, 1-chloromethylinden-7-yl, 1-bromomethylinden-7
-Yl, 1- (2-fluoroethyl) inden-7-yl, 1- (2-chloroethyl) inden-7-yl, 1
-(2-Bromoethyl) inden-7-yl, 1- (1
-Fluoroethyl) inden-7-yl, 1- (1-chloroethyl) inden-7-yl, 1- (1-bromoethyl) inden-7-yl, 1-trifluoromethylinden-7-yl, 1-trichloro Methylindene-7
-Yl, 1-tribromomethylinden-7-yl and the like, but are not limited thereto.

Examples of the above-mentioned "halogenated lower alkenyl group" include 3-fluoro-1-propenyl, 3-chloro-1-propenyl, 3-bromo-1-propenyl,
4-fluoro-2-butenyl, 4-chloro-2-butenyl, 4-bromo-2-butenyl, 1-fluoro-2-butenyl, 1-chloro-2-butenyl, 1-bromo-2-
Mention may be made of halogen-substituted lower alkenyl groups as defined above, such as butenyl. Therefore, examples of the aryl group substituted with a halogenated lower alkenyl group include an aryl group substituted with 3-halo-1-propenyl (eg, a phenyl group substituted with 3-fluoro-1-propenyl, 3 -Naphthalen-1-yl substituted with fluoro-1-propenyl, phenyl group substituted with 3-chloro-1-propenyl, naphthalen-1-yl substituted with 3-chloro-1-propenyl, 3-bromo Phenyl group substituted with -1-propenyl, naphthalen-1-yl substituted with 3-bromo-1-propenyl, etc., aryl group substituted with 4-halo-2-butenyl (eg, 4-fluoro- Phenyl group substituted with 2-butenyl, naphthalen-1-yl substituted with 4-fluoro-2-butenyl, phenyl group substituted with 4-chloro-2-butenyl Nyl group, 4-chloro-2-butenyl-substituted naphthalen-1-yl, 4-bromo-2-butenyl-substituted phenyl group, 4-bromo-2-butenyl-substituted naphthalen-1-yl Etc.), an aryl group substituted with 1-halo-2-butenyl (eg, a phenyl group substituted with 1-fluoro-2-butenyl, a naphthalen-1-yl substituted with 1-fluoro-2-butenyl, Phenyl group substituted with 1-chloro-2-butenyl, naphthalen-1-yl substituted with 1-chloro-2-butenyl, 1-bromo-
Phenyl group substituted with 2-butenyl, 1-bromo-2
-Butenyl-substituted naphthalen-1-yl etc.) and the like. As the respective substitution positions, 2-, 3-, and 4- are phenyl groups, and 2-, 3-, 4-, 5-, 6-, 7-, and naphthalen-1-yl are phenyl groups. 8-
There is no particular limitation. For indenyl, for example, 1- (3-fluoro-1-propenyl) indene-
2-yl, 1- (3-chloro-1-propenyl) inden-2-yl, 1- (3-bromo-1-propenyl) inden-2-yl, 1- (4-fluoro-2-butenyl) indene -2-yl, 1- (4-chloro-2-butenyl) inden-2-yl, 1- (4-bromo-2-butenyl) inden-2-yl, 1- (1-fluoro-2
-Butenyl) inden-2-yl, 1- (1-chloro-
2-butenyl) inden-2-yl, 1- (1-bromo-2-butenyl) inden-2-yl, 1- (3-fluoro-1-propenyl) inden-3-yl, 1- (3
-Chloro-1-propenyl) inden-3-yl, 1-
(3-bromo-1-propenyl) inden-3-yl,
1- (4-fluoro-2-butenyl) inden-3-yl, 1- (4-chloro-2-butenyl) inden-3-
Yl, 1- (4-bromo-2-butenyl) indene-3
-Yl, 1- (1-fluoro-2-butenyl) inden-3-yl, 1- (1-chloro-2-butenyl) inden-3-yl, 1- (1-bromo-2-butenyl) indene- 3-yl, 1- (3-fluoro-1-propenyl) inden-4-yl, 1- (3-chloro-1-propenyl) inden-4-yl, 1- (3-bromo-1-
Propenyl) inden-4-yl, 1- (4-fluoro-2-butenyl) inden-4-yl, 1- (4-chloro-2-butenyl) inden-4-yl, 1- (4-bromo-2 -Butenyl) inden-4-yl, 1- (1-
Fluoro-2-butenyl) inden-4-yl, 1-
(1-chloro-2-butenyl) inden-4-yl, 1
-(1-Bromo-2-butenyl) inden-4-yl,
1- (3-fluoro-1-propenyl) indene-5
Yl, 1- (3-chloro-1-propenyl) indene-
5-yl, 1- (3-bromo-1-propenyl) inden-5-yl, 1- (4-fluoro-2-butenyl) inden-5-yl, 1- (4-chloro-2-butenyl)
Inden-5-yl, 1- (4-bromo-2-butenyl) inden-5-yl, 1- (1-fluoro-2-butenyl) inden-5-yl, 1- (1-chloro-2-
Butenyl) inden-5-yl, 1- (1-bromo-2
-Butenyl) inden-5-yl, 1- (3-fluoro-1-propenyl) inden-6-yl, 1- (3-chloro-1-propenyl) inden-6-yl, 1- (3
-Bromo-1-propenyl) inden-6-yl, 1-
(4-fluoro-2-butenyl) inden-6-yl,
1- (4-chloro-2-butenyl) inden-6-yl, 1- (4-bromo-2-butenyl) inden-6-
Il, 1- (1-fluoro-2-butenyl) indene-
6-yl, 1- (1-chloro-2-butenyl) inden-6-yl, 1- (1-bromo-2-butenyl) inden-6-yl, 1- (3-fluoro-1-propenyl)
Inden-7-yl, 1- (3-chloro-1-propenyl) inden-7-yl, 1- (3-bromo-1-propenyl) inden-7-yl, 1- (4-fluoro-2)
-Butenyl) inden-7-yl, 1- (4-chloro-
2-butenyl) inden-7-yl, 1- (4-bromo-2-butenyl) inden-7-yl, 1- (1-fluoro-2-butenyl) inden-7-yl, 1- (1-
Chloro-2-butenyl) inden-7-yl, 1- (1
Examples include, but are not limited to, -bromo-2-butenyl) inden-7-yl and the like.

Examples of the above-mentioned "halogenated lower alkoxy group" include fluoromethoxy, chloromethoxy, bromomethoxy, 1-fluoroethoxy, 1-chloroethoxy, 1-bromoethoxy, 2-fluoroethoxy, 2
Examples include halogen-substituted lower alkoxy groups as defined above, such as -chloroethoxy and 2-bromoethoxy. Therefore, as the aryl group substituted with the halogenated lower alkoxy group, for example, an aryl group substituted with halomethoxy (eg, a phenyl group substituted with fluoromethoxy, a naphthalen-1-yl substituted with fluoromethoxy, A phenyl group substituted with chloromethoxy,
Naphthalen-1-yl substituted with chloromethoxy, phenyl group substituted with bromomethoxy, naphthalen-1-yl substituted with bromomethoxy, etc., aryl group substituted with haloethoxy (eg, 1-fluoroethoxy) Substituted phenyl group, 1-fluoroethoxy substituted naphthalen-1-yl, 1-chloroethoxy substituted phenyl group, 1-chloroethoxy substituted naphthalen-1-yl, 1-bromoethoxy Substituted phenyl group, 1-bromoethoxy substituted naphthalen-1-yl, 2-fluoroethoxy substituted phenyl group, 2-fluoroethoxy substituted naphthalen-1-yl, 2-chloroethoxy Substituted phenyl group, 2-chloroethoxy substituted naphthalene-1-
2-phenyl group substituted with 2-bromoethoxy, 2
-Bromoethoxy substituted naphthalen-1-yl etc.) and the like. As for the respective substitution positions, if it is a phenyl group, 2-, 3-, and 4- are naphthalene-
If 1-yl, 2-, 3-, 4-, 5-, 6-, 7
-, 8- and are not particularly limited. If it is indenyl, for example, 1-fluoromethoxyinden-2-yl, 1-chloromethoxyinden-2-yl, 1-bromomethoxyinden-2-yl, 1- (1-fluoroethoxy) inden-2-yl , 1- (1-chloroethoxy) inden-2-yl, 1- (1-bromoethoxy)
Inden-2-yl, 1- (2-fluoroethoxy) inden-2-yl, 1- (2-chloroethoxy) inden-2-yl, 1- (2-bromoethoxy) indene-
2-yl, 1-fluoromethoxyinden-3-yl,
1-chloromethoxyinden-3-yl, 1-bromomethoxyinden-3-yl, 1- (1-fluoroethoxy) inden-3-yl, 1- (1-chloroethoxy)
Inden-3-yl, 1- (1-bromoethoxy) inden-3-yl, 1- (2-fluoroethoxy) inden-3-yl, 1- (2-chloroethoxy) indene-
3-yl, 1- (2-bromoethoxy) indene-3-
1-fluoromethoxyinden-4-yl, 1-
Chloromethoxyinden-4-yl, 1-bromomethoxyinden-4-yl, 1- (1-fluoroethoxy)
Inden-4-yl, 1- (1-chloroethoxy) inden-4-yl, 1- (1-bromoethoxy) inden-4-yl, 1- (2-fluoroethoxy) indene-
4-yl, 1- (2-chloroethoxy) indene-4-
1- (2-bromoethoxy) inden-4-yl, 1-fluoromethoxyinden-5-yl, 1-chloromethoxyinden-5-yl, 1-bromomethoxyinden-5-yl, 1- (1 -Fluoroethoxy) inden-5-yl, 1- (1-chloroethoxy) inden-5-yl, 1- (1-bromoethoxy) indene-
5-yl, 1- (2-fluoroethoxy) indene-5
-Yl, 1- (2-chloroethoxy) inden-5-yl, 1- (2-bromoethoxy) inden-5-yl,
1-fluoromethoxyinden-6-yl, 1-chloromethoxyinden-6-yl, 1-bromomethoxyinden-6-yl, 1- (1-fluoroethoxy) inden-6-yl, 1- (1-chloro Ethoxy) indene
6-yl, 1- (1-bromoethoxy) indene-6-
1- (2-fluoroethoxy) inden-6-yl, 1- (2-chloroethoxy) inden-6-yl,
1- (2-bromoethoxy) inden-6-yl, 1-
Fluoromethoxyinden-7-yl, 1-chloromethoxyinden-7-yl, 1-bromomethoxyinden-7-yl, 1- (1-fluoroethoxy) indene-
7-yl, 1- (1-chloroethoxy) indene-7-
Yl, 1- (1-bromoethoxy) inden-7-yl, 1- (2-fluoroethoxy) inden-7-yl, 1- (2-chloroethoxy) inden-7-yl,
Examples thereof include 1- (2-bromoethoxy) inden-7-yl, but are not limited thereto.

The above "aryl group" means an aryl group as defined above, for example, phenyl, indenyl, naphthyl (1-
Naphthyl, 2-naphthyl, etc.), anthryl, phenanthryl, acenaphthylenyl, fluorenyl (9-fluorenyl, 1-fluorenyl, etc.), and other aryl groups having 6 to 20 carbon atoms. Therefore, examples of the aryl group substituted with the above aryl group include 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, 2-
(1-naphthyl) phenyl, 3- (1-naphthyl) phenyl, 4- (1-naphthyl) phenyl, 3-phenylnaphthalen-1-yl, 4-phenylnaphthalen-1-yl, 5-phenylnaphthalene-1- Yl, 6-phenylnaphthalen-1-yl, 7-phenylnaphthalene-1-
And 8-phenylnaphthalen-1-yl.

Examples of the above-mentioned aryl group substituted with a hydroxy group include 2-hydroxyphenyl, 2-hydroxynaphthalen-1-yl, 3-hydroxyphenyl, 3-hydroxynaphthalen-1-yl, 4-hydroxyphenyl, 4-hydroxynaphthalen-1-yl,
5-hydroxynaphthalen-1-yl, 6-hydroxynaphthalen-1-yl, 7-hydroxynaphthalene-1
-Yl, 8-hydroxynaphthalen-1-yl, 1-hydroxyinden-1-yl, 1-hydroxyinden-2-yl, 1-hydroxyinden-3-yl, 1-
Hydroxyinden-4-yl, 1-hydroxyinden-5-yl, 1-hydroxyinden-6-yl, 1
-Hydroxyinden-7-yl, 1,4-dihydroxyinden-1-yl, 1,5-dihydroxyinden-2-yl, 2,5-dihydroxyinden-3-yl, 1,3-dihydroxyinden-4- Ill, 1, 3
-Dihydroxyinden-5-yl, 2,4-dihydroxyinden-6-yl, 1,4-dihydroxyinden-7-yl and the like can be mentioned.

The above-mentioned "acyl group" includes an optionally substituted carboxylic acid, an optionally substituted oxycarboxylic acid, an optionally substituted sulfonic acid, an optionally substituted sulfinic acid and the like. Examples thereof include acyl groups derived from the above. Specifically, the ^{formula: R 8 CO-, R 9 OCO-} , R
¹⁰ SO ₂ −, or R ¹¹ SO − [in the formula, R ⁸ , R ⁹ , R ¹⁰
And R ¹¹ each represents an optionally substituted hydrocarbon group or a heterocyclic group]. Examples of the “hydrocarbon group” in the “optionally substituted hydrocarbon group or heterocyclic group” represented by R ⁸ , R ⁹ , R ¹⁰ and R ¹¹ include, for example, a linear or acyclic group. Examples thereof include branched aliphatic hydrocarbon groups (alkyl groups, alkenyl groups, alkynyl groups, etc.), and examples of cyclic groups include saturated or unsaturated alicyclic hydrocarbon groups (cycloalkyl groups, cycloalkenyl groups, A cycloalkadienyl group) and a monocyclic or condensed polycyclic aryl group. Specific meanings of these meanings and substituents are as described above.

Examples of the aryl group substituted with the above acyl group include 2-acetylphenyl, 2-acetylnaphthalen-1-yl, 3-acetylphenyl, 3-acetylnaphthalen-1-yl, 4-acetylphenyl, Four
-Acetylnaphthalen-1-yl, 5-acetylnaphthalen-1-yl, 6-acetylnaphthalen-1-yl,
7-acetylnaphthalen-1-yl, 8-acetylnaphthalen-1-yl, 1-acetylinden-1-yl,
1-acetylinden-2-yl, 1-acetylinden-3-yl, 1-acetylinden-4-yl, 1-
Acetylinden-5-yl, 1-acetylinden-
6-yl, 1-acetylinden-7-yl, 1-acetylinden-2-yl, 3-acetylinden-2-
Yl, 4-acetylinden-2-yl, 5-acetylinden-2-yl, 6-acetylinden-2-yl, 7-acetylinden-2-yl, 1-acetylinden-3-yl, 2-acetyl Inden-3-yl,
4-acetylinden-3-yl, 5-acetylinden-3-yl, 6-acetylinden-3-yl, 7-
Acetylinden-3-yl, 1-acetylinden-
4-yl, 2-acetylinden-4-yl, 3-acetylinden-4-yl, 5-acetylinden-4-
And 6-acetylinden-4-yl, 7-acetylinden-4-yl, and the like, but are not limited thereto.

Examples of the aryl group substituted with the above amino group include 2-aminophenyl, 2-aminonaphthalen-1-yl, 3-aminophenyl, 3-aminonaphthalen-1-yl, 4-aminophenyl, 4-aminonaphthalen-1-yl, 5-aminonaphthalen-1-yl, 6-aminonaphthalen-1-yl, 7-aminonaphthalen-1-yl, 8-aminonaphthalen-1-yl and the like can be mentioned.

A in G in the above general formula (I) is preferably an oxygen atom. In the definition of R ^{1 to} R ⁷ , “halogen atom” has the same meaning as described above. In the definition of R ^{1 to} R ⁷ ,
The “lower alkyl group” and the “lower alkenyl group” are the “lower alkyl group” as a substituent of the “optionally substituted aryl group” represented by Ar ¹ and Ar ² , respectively.
It is synonymous with "lower alkenyl group".

In the definitions of R ^{1 to} R ⁷ , preferred examples of the “lower alkoxycarbonyl group” are the lower alkoxy as defined above, for example, methoxycarbonyl,
Examples thereof include alkoxycarbonyl groups having 2 to 7 carbon atoms such as ethoxycarbonyl, propoxycarbonyl and butoxycarbonyl.

In the definition of R ^{1 to} R ⁷ , "acyl group" has the same meaning as defined above.

In the definition of R ^{1 to} R ⁷ , “halogenated lower alkyl group” and “halogenated lower alkenyl group” are the same as the “optionally substituted aryl group” represented by Ar ¹ and Ar ² , respectively. It is synonymous with "halogenated lower alkyl group" and "halogenated lower alkenyl group" as a substituent.

In the definition of R ^{1 to} R ⁷ , the “aralkyl group” of the “optionally substituted aralkyl group” means an alkyl group substituted with an aryl group, and examples thereof include a phenylmethyl group and 1-phenyl. Ethyl group, 2-phenylethyl group,
1-phenylpropyl group, 2-phenylpropyl group, 3
-Phenylpropyl group, 1-phenylbutyl group, 2-phenylbutyl group, 3-phenylbutyl group, 4-phenylbutyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1- (1-naphthyl) ethyl group , 1- (2-naphthyl) ethyl group, 2- (1-naphthyl) ethyl group, 2-
(2-naphthyl) ethyl group, 1- (1-naphthyl) propyl group, 1- (2-naphthyl) propyl group, 2- (1-
Naphthyl) propyl group, 2- (2-naphthyl) propyl group, 3- (1-naphthyl) propyl group, 3- (2-naphthyl) propyl group, 1- (1-naphthyl) butyl group, 1
-(2-naphthyl) butyl group, 2- (1-naphthyl) butyl group, 2- (2-naphthyl) butyl group, 3- (1-naphthyl) butyl group, 3- (2-naphthyl) butyl group, 4
-(1-naphthyl) butyl group, 4- (2-naphthyl) butyl group, 2-pyridylmethyl group, 3-pyridylmethyl group, 4-pyridylmethyl group, 1- (2-pyridyl) ethyl group, 1- ( 3-pyridyl) ethyl group, 1- (4-pyridyl) ethyl group, 2- (2-pyridyl) ethyl group, 2-
(3-pyridyl) ethyl group, 2- (4-pyridyl) ethyl group, 1- (2-pyridyl) propyl group, 1- (3-pyridyl) propyl group, 1- (4-pyridyl) propyl group, 2- (2-pyridyl) propyl group, 2- (3-pyridyl) propyl group, 2- (4-pyridyl) propyl group,
3- (2-pyridyl) propyl group, 3- (3-pyridyl) propyl group, 3- (4-pyridyl) propyl group, 1
-(2-pyridyl) butyl group, 1- (3-pyridyl) butyl group, 1- (4-pyridyl) butyl group, 2- (2-pyridyl) butyl group, 2- (3-pyridyl) butyl group, 2
-(4-pyridyl) butyl group, 3- (2-pyridyl) butyl group, 3- (3-pyridyl) butyl group, 3- (4-pyridyl) butyl group, 4- (2-pyridyl) butyl group, 4
-(3-pyridyl) butyl group, 4- (4-pyridyl) butyl group, 1-furylmethyl group, 1-furylethyl group, 2
Examples include -furylethyl group, 1-furylpropyl group, 2-furylpropyl group, 3-furylpropyl group, 1-furylbutyl group, 2-furylbutyl group, 3-furylbutyl group and 4-furylbutyl group. The substituent of the “optionally substituted aralkyl group” has the same meaning as the substituent of the “optionally substituted cyclic group” represented by Ar ¹ and Ar ² . The meaning of each substituent is as described above.

In the definition of R ^{1 to} R ⁷ , "lower alkoxy group"
Is the same meaning as the "lower alkoxy group" as the substituent of the "optionally substituted aryl group" represented by Ar ¹ and Ar ² .

In the definition of R ^{1 to} R ⁷ , the meaning of “lower alkenyl” in the “lower alkenyloxy group” has the same meaning as the above “lower alkenyl group”.

In the definition of R ^{1 to} R ⁷ , “halogenated lower alkoxy group” means “halogenated lower alkoxy group” as a substituent of the “optionally substituted aryl group” represented by Ar ¹ and Ar ^2. It is synonymous with "alkoxy group".

In the definition of R ^{1 to} R ⁷ , “halogenated lower alkenyl” of “halogenated lower alkenyloxy group” has the same meaning as the above “halogenated lower alkenyl group”.

In the definition of R ^{1 to} R ⁷ , the meaning of “acyl” in “acyloxy” has the same meaning as the above “acyl group”.

In the definition of R ^{1 to} R ⁷ , the substituent of “optionally substituted phenyloxy” is the above Ar ¹ and Ar ²
It has the same meaning as the substituent of the "optionally substituted cyclic group" represented by. The meaning of each substituent is
As described above.

In the definition of R ^{1 to} R ⁷ , the meaning of “aralkyl” of “optionally substituted aralkyloxy” is as described above. The substituent of "optionally substituted aralkyloxy" has the same meaning as the substituent of the "optionally substituted cyclic group" for Ar ¹ and Ar ² . The meaning of each substituent is as described above.

In the definition of R ^{1 to} R ⁷ , the "optionally substituted amino group" is, for example, a hydroxy group,
Lower alkyl group, lower alkyl group substituted with a substituent (halogen, hydroxy group, lower alkoxy or lower alkylcarbonyl group), lower alkenyl group, lower alkoxy group, lower alkenyloxy group, lower alkylcarbonyloxy group, carboxyl group, Lower alkylcarbonyl group, lower alkoxycarbonyl group, carbamoyl group,
Lower alkylcarbamoyl group, N-dilower alkylcarbamoyl group, N-hydroxycarbamoyl group, N-hydroxy-N-lower alkylcarbamoyl group, N-phenylcarbamoyl group, N-substituted phenylcarbamoyl group,
Examples thereof include saturated or unsaturated alicyclic hydrocarbon groups, monocyclic or condensed polycyclic aryl groups, and heterocyclic groups. The meanings of “lower alkyl”, “lower alkenyl” and “lower alkoxy” in each substituent are as described above.

In the definition of R ^{1 to} R ⁷ , the "optionally substituted sulfonyl group" has, for example, a hydroxy group, a lower alkyl group or a substituent (halogen, hydroxy group, lower alkoxy or lower alkylcarbonyl). Basis)
Substituted lower alkyl group, lower alkenyl group, lower alkynyl group, lower alkoxy group, lower alkenyloxy group, lower alkylcarbonyloxy group, carboxyl group, lower alkylcarbonyl group, lower alkoxycarbonyl group, carbamoyl group, lower alkylcarbamoyl Group, N-di-lower alkylcarbamoyl group, N-hydroxycarbamoyl group, N-hydroxy-N-lower alkylcarbamoyl group, N-phenylcarbamoyl group, N-substituted phenylcarbamoyl group, cyano group, amino group, mono-lower alkylamino Group, di-lower alkylamino group, lower alkylcarbonylamino group, nitro group, saturated or unsaturated alicyclic hydrocarbon group, monocyclic or condensed polycyclic aryl group, heterocyclic group and the like. The meaning of each substituent is as described above.

In the definition of R ^{1 to} R ⁷ , the substituent of the “optionally substituted sulfinyl group” is the above Ar ¹ and Ar ²
It has the same meaning as the substituent of the "optionally substituted cyclic group" represented by. The meaning of each substituent is
As described above.

In the definition of R ^{1 to} R ⁷ , the meaning of the aryl group of the “optionally substituted aryl group” is as described above. "Aryl group which may be substituted"
Examples of the substituent include those similar to the substituents of the “optionally substituted aryl group” as the “optionally substituted cyclic group” represented by Ar ¹ and Ar ² . The meaning of each substituent is as described above.

In the general formula (II), the optionally substituted aryl group represented by Ar ^a1 and Ar ^a2 is the “optionally substituted aryl group” in Ar ¹ and Ar ² of the above general formula (I). Is equivalent to. R ^a , R ^b1 ,
Each definition in R ^b2 , R ^c1 and R ^c2 has the same meaning as R ^{1 to} R ^{7 in the} above general formula (I).

In the general formula (III), the meanings of the groups represented by X and R are the same as those defined in the above general formula (I).

The organoboron compound of the present invention may have an asymmetric carbon. Therefore, the organoboron compound of the present invention may be a specific optical isomer based on an asymmetric carbon.

The present invention also includes pharmaceutically acceptable salts of the above compounds and solvates thereof. The "salt" of the target compound of the present invention is preferably a pharmaceutically acceptable salt,
Examples thereof include salts with inorganic bases, salts with organic bases, salts with inorganic acids, salts with organic acids, and basic or acidic amino acid salts. As the salt with an inorganic base, sodium salt,
Alkali metal salts such as potassium salts, alkaline earth metal salts such as calcium salts, magnesium salts, barium salts, aluminum salts, ammonium salts and the like can be mentioned. Examples of the salt with an organic base include salts with trimethylamine, triethylamine, pyridine, picoline, ethanolamine, dietanolamine, triethanolamine, dicyclohexylamine, N, N′-dibenzylethylenediamine and the like. Examples of the salt with an inorganic acid include salts with hydrochloric acid, hydrofluoric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, perchloric acid, hydroiodic acid and the like. As salts with organic acids, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid, methanesulfonic acid , P-toluenesulfonic acid, benzenesulfonic acid and the like. Examples of the salt with a basic amino acid include salts with arginine, lysine, ornithine, and examples of the salt with an acidic amino acid include salts with aspartic acid, glutamic acid and the like.

The “solvate” of the target compound of the present invention and a salt thereof includes an organic solvent and / or a solvate with water. Hydrates are preferable, and specific examples thereof include monohydrate, dihydrate, and hexahydrate.

In the non-human veterinary pharmaceutical composition of the present invention, a compound of the general formula (I), wherein Ar ¹ and Ar ² are both optionally substituted aryl groups, salts thereof or solvates thereof. And a pharmaceutical composition for animals other than humans, which contains
Wherein Ar ¹ and Ar ² are both optionally substituted aryl groups, and G is of the formula: —O—, —O—CR ² R ³ — or —O—CR ⁴ R ⁵ —CR ⁶ R ⁷ —. A group represented by
R ^{2 to} R ⁷ are the same or different and each is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkoxycarbonyl group, an acyl group, a halogenated lower alkyl group, a halogenated lower alkenyl group, an amide group. , Optionally substituted aralkyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy group, halogenated lower alkenyloxy group, acyloxy, optionally substituted phenyloxy, optionally substituted aralkyl Oxy, optionally substituted amino group, optionally substituted sulfonyl group, optionally substituted sulfinyl group or optionally substituted aryl group) or a salt thereof or a solvent thereof Non-human veterinary drug set containing Japanese products Thing is.

Among the pharmaceutical compositions for animals other than humans, which contain the compound of the present invention, a more preferred embodiment is represented by the general formula (I
A pharmaceutical composition for animals other than humans, which comprises the compound represented by I) or a salt thereof or a solvate thereof.

Among the non-human animal pharmaceutical compositions containing the compound of the present invention, a more preferred embodiment is a human containing the compound represented by the general formula (III) or a salt thereof or a solvate thereof. It is a veterinary pharmaceutical composition to be excluded.

[0057]

BEST MODE FOR CARRYING OUT THE INVENTION The compound (I) of the present invention [that is, the compound represented by the general formula (I)]. Hereinafter, the compounds represented by other formulas may be abbreviated in the same manner. ]
Is a known document (eg, Youji Huaxue (1989), 9 (3), 226-
9, Pharmazie (1985), 40 (11), 767-71, Pharmazie (19
85), 40 (6), 387-93, Pharmazie (1985), 40 (5), 307-1
1, J. Chem. Soc. Perkin Train. 2 (1992) 527-532, Jour
nal of Organometallic Chemistry, 297 (1985) 13-19)
Can be manufactured with reference to.

It should be noted that a substituent (for example, R of the compound (I) is
^{1 to} R ⁷ ) may have undesired reactivity in the reaction of the synthetic route (eg, hydroxy group, carbonyl group, amino group, etc.), but in that case, a protective group is appropriately introduced into the substituent. After the reaction, the product may be removed by removing it.

As an example, the production of the organoboron compound of the present invention having a 5-membered ring will be described. The compound of the present invention represented by the following formula (I ′) can be produced, for example, according to the following reaction scheme 1. Reaction formula 1

[Chemical 7] In the formula, X represents a halogen atom, R ^d represents an alkyl group having 1 to 8 carbon atoms, R ′ represents a lower alkyl group, and other symbols have the same meanings as described above.

Step 1 First, the compound represented by the formula: ArMgX (b) is produced by reacting the compound (a) with magnesium in an ether solvent such as tetrahydrofuran (THF). In this reaction, the compound (a) is used in an amount of 1 equivalent or more, preferably 1.1 to 1.
3 equivalents can be used. Examples of ether solvents that can be used include tetrahydrofuran, diethyl ether, dioxane and the like. If necessary, aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.) or saturated hydrocarbons (eg, cyclohexane, hexane, etc.) can be used as a mixed solvent with an ether solvent. The reaction temperature is −20 to 150 ° C., preferably 0
~ 50 ° C. The reaction time varies depending on the compound, but is 0.
The reaction may be performed for 5 to 10 hours. The reaction product is usually obtained as a clear solution or slurry.

Step 2 The boric acid compound (B (OR ^d ) ₃ ) is reacted with the solution or slurry containing the compound (b) obtained above, and then ethanolamine (HOCH ₂ CH ₂ NH ₂ ) is further added to a suitable amount. Compound (c) is produced by reacting in a solvent. In this reaction, the borate ester can be used at 0.5 equivalents or less, preferably 0.5 to 0.4 equivalents, relative to the compound (b) obtained in the above step 1. The ethanolamine in the sequential reaction is 0.5 with respect to the compound (b).
Equivalent or more, preferably 0.5 to 0.7 equivalent can be used. Step 1 if necessary in this reaction
Solvents of ethers, aromatic hydrocarbons and saturated hydrocarbons described in 1. can be used. The reaction temperature of the compound (b) and the borate ester is -90 to 100 ° C, preferably -30 to 40 ° C, and the reaction time varies depending on the compound, but the reaction may be performed for 0.5 to 10 hours. The reaction temperature with ethanolamine in the sequential reaction is 0 to 100 ° C., preferably 30 to 80 ° C., and the reaction time is usually 0.5 to 5 hours. Compound (c) can be used in the next step as a crude product or after purification by a conventional method (eg, column chromatography, recrystallization, etc.).

Step 3 Compound (c) has the formula: HOCH ₂ CH (NH ₂ ) COOR '.
Compound (I ′) is obtained by reacting the alkyl ester of serine represented by the formula (1) in a suitable solvent. H
The compound represented by OCH ₂ CH (NH ₂ ) COOR ′ is 1 to 2 equivalents, preferably 1 to 1.5 equivalents to the compound (c).
It can be used in equivalent amounts. Solvents that can be used include
Ethers (eg, diethyl ether, tetrahydrofuran, dioxane, etc.), hydrocarbons (eg, benzene, toluene, xylene, etc.), alcohols (eg, methanol, ethanol, n-propanol, etc.), water and mixed solvents thereof, etc. Is mentioned. Reaction temperature is 0-15
It is 0 ° C., preferably 20 to 120 ° C., and the reaction time is usually 0.5 to 10 hours. The obtained desired compound (I ′) can be purified, if necessary, for example, by column chromatography, recrystallization and the like.

The organoboron compound of the present invention having a three-membered ring and a four-membered ring can also be synthesized by a known synthesis method in the same manner as the above-mentioned organoboron compound of the present invention having a five-membered ring.

When the organoboron compound of the present invention is a specific optical isomer, such a specific optical isomer can be easily obtained by a method conventionally used in this field. For example, after synthesizing the organoboron compound of the present invention as a racemate, a desired optical isomer can be isolated by, for example, a fractional crystallization method, a physical separation method such as chromatography, or a combination thereof. Alternatively, in the synthetic route of the organoboron compound of the present invention, the organoboron compound of the present invention can be synthesized as a particular optical isomer by reacting with a particular optical isomer as a reaction reagent.

The compound of the present invention can be formulated into a prophylactic agent and a therapeutic agent for poultry coccidium according to a method well known in each field. That is, the compound of the present invention, alone or together with a suitable carrier usually used for drugs of this kind, optionally with excipients, disintegrants, lubricant coatings, etc., powders, granules, solutions, It can be prepared into a suspension, a premix, a capsule, an emulsion, a tablet, or the like.

The carrier used in the preparation of the present invention is not particularly limited as long as it can be added to poultry feed or drinking water, but it is not limited to any particular species. , Corn flour,
Examples include soybeans, oil meal, ground starch, and other commercially available feeds for poultry.

When the compound of the present invention is used by adding it to feed, it is generally used in poultry feed at a concentration of at least 0.1 to 500 ppm, preferably 0.5 to 1 in terms of drug substance.
It may be added so as to have a concentration of 00 ppm. Also,
When added to drinking water and used, the concentration of the compound of the present invention in the drinking water is about half of the concentration in the above-mentioned feed, and a sufficient effect can be exhibited.

Further, the compound of the present invention can be used in combination with a known veterinary drug containing an anticoccidial agent for poultry, a parasiticidal agent, an infectious disease preventive agent or a growth promoter.

The present invention is described in more detail below with reference to Reference Examples and Examples, but these are not intended to limit the scope of the present invention. In Reference Examples and Examples, Ph
Means a phenyl group.

Reference Example 1 Ethanolamine diphenylboronic acid ester (Ph ₂ B
Synthesis of —OCH ₂ CH ₂ NH ₂ ) 83.2 g (0.53 mol) bromobenzene, magnesium 1
2.9 g (0.53 mol) and 250 tetrahydrofuran
A tetrahydrofuran solution of phenylmagnesium bromide was prepared by a conventional method using ml. Then, in a flask, 58.5 g (0.26 mol) of tributyl borate ester,
200 mL of ethyl ether was charged, the temperature was maintained at -60 ° C and the solution of phenylmagnesium bromide in tetrahydrofuran (Grignard reagent) was added dropwise. After completion of dropping, the mixture was stirred at room temperature for 10 hours and then 10% hydrochloric acid aqueous solution 1
50 mL was added and hydrolyzed to separate the organic layer. 31.1 g (0.51 mol) of ethanolamine was added to the obtained organic layer,
50 mL of ethanol was added and the mixture was stirred at room temperature for 2 hours.
The formed precipitate was collected by filtration, recrystallized from hydrous alcohol and dried to obtain 31.9 g (yield 55%) of white crystals of diphenylboronic acid ethanolamine ester.

[0071]

EXAMPLES The following Production Examples 1 to 8 relate to the compound of the present invention represented by the following formula.

[Chemical 8]

Production Example 1 Synthesis of Compound 1 (wherein Ar ¹ and Ar ² are 3-chlorophenyl, R ″ is COOCH ₃ , L-form) 3.5 g (0) of di (3-chlorophenyl) boronic acid ethanolamine ester 0.012 mol), ethyl ether 3
0 mL and 30 mL of 10% hydrochloric acid aqueous solution were charged in a funnel, shaken and mixed for about 15 minutes, then separated, the organic layer was washed once with water, and transferred to an eggplant flask. Then, 2.8 g (0.018 mol) of L-serine methyl ester hydrochloride was added to 5
What was melt | dissolved in 13.7 g (0.017 mol) of NaOH aqueous solution was added, and it stirred at room temperature for 2 hours. The generated precipitate was collected by filtration, recrystallized from hydrous alcohol and dried to obtain 2.5 g of white crystalline compound 1 (yield 59%). Melting point: 201-204 ° C.

Production Example 2 Synthesis of Compound 2 (wherein Ar ¹ and Ar ² are 4-chlorophenyl, R ″ is COOCH ₃ , L-form) 3.5 g (0) of di (4-chlorophenyl) boronic acid ethanolamine ester 0.012 mol) and L-serine methyl ester hydrochloride (2.8 g, 0.018 mol) were used in Example 1.
2.1 g of white crystalline compound 2 reacted and treated in the same manner as
(Yield 50%) was obtained. Melting point: 191-196 ° C.

Production Example 3 Synthesis of Compound 3 (wherein Ar ¹ and Ar ² are 3-trifluoromethylphenyl, R ″ is COOCH ₃ , L-form) Di (3-trifluoromethylphenyl) boronic acid ethanolamine 4.33 g (0.012 mol) of ester and L
-Serine methyl ester hydrochloride 2.8g (0.018mo
l) was reacted and treated in the same manner as in Example 1 to obtain 3.7 g of white crystalline compound 3 (yield 73.6%). Melting point: 224-226C.

Production Example 4 Synthesis of Compound 4 (wherein Ar ¹ and Ar ² are 3-chlorophenyl, R ″ is COOC ₂ H ₅ and L form) 3.5 g of di (3-chlorophenyl) boronic acid ethanolamine ester (0.012 mol) and L-serine ethyl ester hydrochloride (3.05 g, 0.018 mol) were reacted and treated in the same manner as in Example 1 to obtain white crystalline compound 4 (2.9).
g (yield 66.1%) was obtained. Melting point: 191-194 ° C.

Production Example 5 Synthesis of Compound 5 (wherein Ar ¹ and Ar ² are 4-chlorophenyl and R ″ is COOC ₂ H ₅ , L-form) 3.5 g of di (4-chlorophenyl) boronic acid ethanolamine ester (0.012 mol) and L-serine ethyl ester hydrochloride (3.05 g, 0.018 mol) were reacted and treated in the same manner as in Example 1 to give white crystalline compound 5 (3.1).
g (yield 70.6%) was obtained. Melting point: 201-203 ° C.

Production Example 6 Synthesis of Compound 6 (wherein Ar ¹ and Ar ² are 3-trifluoromethylphenyl, R ″ is COOCH ₃ , L-form) Di (3-trifluoromethylphenyl) boronic acid ethanolamine 4.33 g (0.012 mol) of ester and L
-Serine ethyl ester hydrochloride 3.05 g (0.018 m
was reacted and treated in the same manner as in Example 1 to obtain 3.1 g of white crystalline compound 6 (yield 59.6%). Melting point: 184-186 [deg.] C.

Production Example 7 Synthesis of Compound 7 (wherein Ar ¹ and Ar ² are 3-chlorophenyl and R ″ is COOCH ₃ ) 3.5 g (0.012 mol) of di (3-chlorophenyl) boronic acid ethanolamine ester And 2.8 g (0.018 mol) of DL-serine methyl ester hydrochloride were reacted and treated in the same manner as in Example 1 to obtain 2.9 of white crystalline compound 7.
g (yield 68.4%) was obtained. Melting point: 174-177 [deg.] C.

Production Example 8 Synthesis of Compound 8 (wherein Ar ¹ and Ar ² are 4-chlorophenyl and R ″ is H) 114.9 g (0.6 mo) of 4-chlorobromobenzene
l), 14.6 g (0.6 mol) of magnesium and 280 mL of tetrahydrofuran were used to prepare a tetrahydrofuran solution of 4-chlorophenylmagnesium bromide by a conventional method. Next, 67.0 g (0.29 mol) of boric acid tributyl ester and 230 mL of ethyl ether were charged into the flask, and a tetrahydrofuran solution of 4-chlorophenylmagnesium bromide (Grignard reagent) was added dropwise while maintaining cooling at -60 ° C or lower.
After completion of the dropping, the mixture was stirred at room temperature for 10 hours and then added with 170 mL of 10% hydrochloric acid aqueous solution for hydrolysis, and the organic layer was separated. 35.2 g of ethanolamine (0.
58 mol) and 60 mL of ethanol are added, and the mixture is allowed to stand at room temperature for 2
After stirring for an hour, 500 g of water was added, and the solvent was distilled off under reduced pressure. The deposited precipitate was collected by filtration, recrystallized from hydrous ethanol and dried to obtain 45.1 g (yield 52%) of white crystalline compound 8.

Test Example The test example shown below proved the anticoccidial activity of the compound of the present invention. Test Example 1 In vitro growth inhibitory activity of coccidium in cultured chicken kidney (CK) cells 1. Treatment of cells Kidneys were aseptically collected from SPF chicks by known methods, digested with trypsin, and cells were washed. After adjusting the number of cells, the cells were cultured in a CO ₂ incubator at 37 ° C. for 72 hours to obtain monolayer cells. Monolayer cells were inoculated with a test compound diluted to a predetermined concentration and artificially shelled Eimeria tenella sporozoites, and cultured at 40 ° C. for 48 hours. The cells after culture were subjected to alcohol fixation and Giemsa staining, and observed as follows. 2. Observation and judgment 1st generation schizonts that split and proliferated in chicken kidney cytoplasm
(Mature and immature) were observed under an inverted microscope, and from the number of schizonts, the growth inhibition rate of the protozoa relative to the untreated sporozoite-inoculated control group was calculated by the following formula.

[Equation 1] Growth inhibition rate (%) = 100 − [(first schizont number of drug-treated group) / first schizont number of untreated control group) × 100] The results obtained are shown in the table below. Shown in 1.

[Table 1]

The cytotoxicity (CPE) of the compound of the present invention was also observed. The observation results are shown in a 4-level evaluation of (-) to (+++). -: No difference from the untreated control group, +: Mild change, ++: Moderate change, +++: Complete cell loss (protozoa cannot be observed). The results obtained are shown in Table 2 below.

[Table 2]

Test Example 2 In Vivo Judgment of Coccidiosis Preventive / Therapeutic Effect in Chickens The efficacy of the compound of the present invention against Eimeria tenella (anticoccidial effect) was examined by continuous administration of 200 ppm feed. White leghorn chicks 3 to 7 days old
Feathers were made into one group, and the feed to which the test compound was added was administered.
On the first day of the administration, 50,000 sporulated oocysts of Eimeria tenella were infected per bird. The test compound was continuously administered for 8 days, during which the excretion of bloody stool, survival rate, and relative weight gain were observed, and autopsy was performed 7 days after infection to observe the cecal lesions, and the cecal lesion value was calculated. The criteria for this test are as follows. Relative weight gain: Weight gain of test group / weight gain of uninfected non-medicated control group × 100 (%). Excretion of bloody stool: The degree of excretion of bloody stool excreted during the test period is evaluated according to the following four grades. In the table, "d" represents the number of days after the administration of oocysts. -: No excretion of bloody stool. +: Mild excretion of bloody stool is observed. ++: Moderate bloody stool excretion is observed. +++: Severe (similar to infected untreated control) blood excretion is observed. Cecal lesion value: According to Merck's test method. Surviving chicks were autopsied 7 days after infection, and the cecal lesions of each individual were visually observed, and the lesion degree was divided into 0 to 4 (0 for no lesion, 4 for severe), and averaged. Represents a value. Judgment: A comprehensive judgment result about the activity of the test compound, which was comprehensively judged based on the above results. +: Active-: not active Table 3 shows the test results.

[Table 3] Results: With respect to Eimeria tenella, when the compound 2 and the compound 8 were administered at 200 ppm in the feed, clear clinical symptoms, relative weight gain and cecal lesion rate were observed, and the compound of the present invention has an excellent anticoccidial effect. It was confirmed.

[0083]

As is apparent from the above test examples, the compound of the present invention suppresses a decrease in relative weight gain, suppression of bloody fecal excretion, decrease of oocyst excretion and cecal lesion value in chicken chicks infected with coccidia. Shows a strong anticoccidime activity such as improvement of Further, the compound of the present invention has low toxicity as is clear from the data of dead individuals, and therefore includes chickens, turkeys, poultry such as ducks and cows,
It is useful as a prophylactic and therapeutic agent for coccidiosis in domestic animals such as pigs.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Yosuke Kawaguchi             3-1-1 Futaba-cho, Toyonaka-shi, Osaka Shiono             Within Yi Pharmaceutical Co., Ltd. (72) Inventor Hisashi Taniguchi             5-23-36, Mukonoso, Amagasaki-shi, Hyogo             Yest 5A-203 (72) Inventor Hitoshi Tabuchi             2-6-68 Nishi-Shibukawa, Kusatsu City, Shiga Prefecture F-term (reference) 4C086 AA01 AA02 DA43 MA01 MA04                       NA14 ZC64

Claims (7)

[Claims] 1. A compound represented by the general formula (I): [In the formula, Ar ¹ and Ar ² are each independently a cyclic group which may be substituted; G is a group represented by formulas -A- and -A-;
A group represented by CR ² R ³ — or —A—CR ⁴ R ⁵ —CR ⁶ R ⁷ — (wherein A is an oxygen atom or a sulfur atom); R
^{1 to} R ⁷ are the same or different and each is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkoxycarbonyl group, an acyl group, a halogenated lower alkyl group, a halogenated lower alkenyl group, an amide group. , Optionally substituted aralkyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy group, halogenated lower alkenyloxy group, acyloxy, optionally substituted phenyloxy, optionally substituted aralkyl Oxy, an optionally substituted amino group, an optionally substituted sulfonyl group, an optionally substituted sulfinyl group or an optionally substituted aryl group] or a salt thereof or a salt thereof. Non-human veterinary medicine containing solvates Narubutsu. 2. The pharmaceutical composition according to claim 1, wherein in the general formula (I), Ar ¹ and Ar ² are both optionally substituted aryl groups. 3. In the general formula (I), G is a formula: —O—, —O.
-CR ² R ³ - or ^{-O-CR 4 R 5 -CR 6} R 7 - be a group represented by; R ² to R ⁷ are the same or different and each is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl Group, lower alkenyl group, lower alkoxycarbonyl group, acyl group, halogenated lower alkyl group, halogenated lower alkenyl group, amide group, optionally substituted aralkyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower group Alkoxy group, halogenated lower alkenyloxy group, acyloxy, optionally substituted phenyloxy, optionally substituted aralkyloxy, optionally substituted amino group, optionally substituted sulfonyl group, substituted Is an optionally substituted sulfinyl group or an optionally substituted aryl group,
The pharmaceutical composition according to claim 1 or 2. 4. General formula (II): [In the formula, Ar ^a1 and Ar ^a2 are the same or different and each represents an optionally substituted aryl group; R ^a , R ^b1 , R a
^b2 , R ^c1 and R ^c2 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkoxycarbonyl group, an acyl group,
Halogenated lower alkyl group, halogenated lower alkenyl group, amide group, optionally substituted aralkyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy group, halogenated lower alkenyloxy group, acyloxy, substituted Optionally substituted phenyloxy, optionally substituted aralkyloxy, optionally substituted amino group, optionally substituted sulfonyl group, optionally substituted sulfinyl group or optionally substituted aryl The pharmaceutical composition according to claim 1, which comprises a compound represented by the formula] or a salt thereof or a solvate thereof. 5. A compound represented by the general formula (III): [Wherein, X is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group or a halogenated lower alkoxy group bonded to the meta or para position; and R is , A hydrogen atom, a carboxyl group, a lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, an amide group, and an acyl group].
The pharmaceutical composition according to claim 1, which comprises a compound represented by: or a salt thereof or a solvate thereof. 6. An antiprotozoal agent containing the compound according to claim 1. 7. An anticoccidial agent containing the compound according to claim 1.