WO2004026841A1 - Novel 6-substituted uracil derivative and therapeutic agent for allergic disease - Google Patents

Abstract

Uracil derivative of the general formula: (I) (wherein R1 is hydrogen, substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C7-C10 aralkyl; R2 is hydrogen or C1-C6 alkyl; Ar1 is a substituted or unsubstituted aromatic carbon ring group or a substituted or unsubstituted aromatic heterocyclic group; Ar2 and Ar3 are identical with or different from each other and each represent substituted or unsubstituted phenyl or a substituted or unsubstituted single-ring aromatic heterocyclic group, or Ar2 and Ar3 may form a tricyclic carbon ring in cooperation with a divalent group capable of bonding with both of Ar2 and Ar3; X is methine (CH) or nitrogen; Y is single bond or oxygen when X is methine and is single bond when X is nitrogen; Z is hydrogen or hydroxyl when X is methine and Y single bond, and is hydrogen when X is methine and Y oxygen and when X is nitrogen (Y being single bond); and m is 2 to 6); or a pharmaceutically acceptable salt thereof; and medical use of these. A novel compound exerting not only an antihistaminic action but also an antiinflammatory action can be provided.

Description

 Novel 6-substituted peracyl derivatives and therapeutic agents for allergic diseases

 INDUSTRIAL APPLICABILITY The present invention has an excellent antiallergic action, antihistamine action, antiinflammatory action, etc., and is useful as a preventive / therapeutic agent for atopic dermatitis, allergic rhinitis, bronchial asthma, allergic conjunctivitis, chronic jujube, etc. The present invention relates to a novel peracil derivative and its pharmaceutical use. Background art

 Allergic diseases such as allergic conjunctivitis, allergic rhinitis, chronic juvenile rash, atopic dermatitis, etc. are mainly caused by type I allergies, but after chronic progress, inflammatory mainly eosinophils The cells invade the affected area and become inflammatory. Antihistamines are widely used as symptomatic treatments for these diseases. However, antihistamines are ineffective against inflammation itself and cannot be used as a curative. For this reason, treatments using steroids, which are anti-inflammatory agents, in addition to antihistamines are being performed. However, steroids have side effects such as infections, adrenal atrophy, osteoporosis, diabetes, and impaired child growth. In recent years, it has been reported that an antihistamine having an imidazopyridine structure bound thereto has an inhibitory effect on eosinophil infiltration (J. Pharmacol. Exper. Ther., 303, 1283-1290, 2002). Disclosure of the invention

Since conventional antihistamines do not have anti-inflammatory effects, there is a need for the development of new compounds that have anti-inflammatory effects in addition to anti-histamine effects and are more satisfactory in terms of safety and the like. The present inventors have conducted various intensive studies in order to solve the above-mentioned problems. (Substituted or unsubstituted) aryl-1, 4 (1H, 3H)-a novel chemical compound with a large chemical structure at the position of having a substituted piperidine-piperazine from the 6-position of the pyrimidinedione skeleton via a spacer The present inventors have found that a peracil derivative exhibits an antihistamine action and also significantly suppresses a late-onset inflammatory response, thereby completing the present invention.

 That is, the present invention includes the following inventions.

 (1) General formula (I):

(In the formula, R ¹ represents a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms or a substituted or unsubstituted aralkyl group having 7 to 10 carbon atoms, and R ² represents a hydrogen atom or a carbon atom having 1 to 6 carbon atoms. 6 represents an alkyl group, Ar ¹ represents a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group, and Ar ² and Ar ³ are the same or different, and Or an unsubstituted phenyl group or a substituted or unsubstituted monocyclic aromatic heterocyclic group, or Ar ² and Ar ³ are tricyclic together with a divalent group bonded to both Ar ² and Ar ³ X may represent a methine group (CH) or a nitrogen atom; Y represents a single bond or an oxygen atom when X is a methine group; and a single bond when X is a nitrogen atom. Z represents a hydrogen atom or a hydroxyl group when X is a methine group and Y is a single bond, and X is a methine group. When Y is an oxygen atom and X is a nitrogen atom (Y is a single bond), it represents a hydrogen atom, and m represents 2 to 6.

)

 Or a pharmaceutically acceptable salt thereof.

(2) The peracil derivative or the pharmaceutically acceptable salt thereof according to the above (1), wherein Ar ¹ in the general formula (I) is a substituted or unsubstituted aromatic carbocyclic group.

(3) — In the general formula (I), Ar ² and Ar ³ are the same or different, and Or the unsubstituted phenyl group according to the above (1) or (2), or a pharmaceutically acceptable salt thereof.

(4) In the general formula (I), Ar ² and Ar ³ are the same or different, respectively, and (i) a phenyl group which may be substituted with a halogen atom or an alkyl group having 1 to 6 carbon atoms, or (ii) A) a 5- to 8-membered monocyclic aromatic heterocyclic group containing 1 to 4 hetero P atoms selected from a nitrogen atom, a sulfur atom and an oxygen atom in addition to a carbon atom; ), Or a pharmaceutically acceptable salt thereof.

 (5) The peracil derivative or the pharmaceutically acceptable salt thereof according to any one of the above (1) to (4), wherein in the general formula (I), X is a methine group.

 (6) The peracil derivative or the pharmaceutically acceptable salt thereof according to any one of the above (1) to (4), wherein in the general formula (I), X is a nitrogen atom.

 (7) An antihistamine containing the peracil derivative or the pharmaceutically acceptable salt thereof according to any one of (1) to (6) as an active ingredient.

 (8) An antiallergic agent comprising, as an active ingredient, the peracil derivative or the pharmaceutically acceptable salt thereof according to any of (1) to (6).

 (9) Allergic conjunctivitis, allergic rhinitis, chronic junction measles, atopic dermatitis containing the peracil derivative or the pharmaceutically acceptable salt thereof according to any of the above (1) to (6) as an active ingredient. An agent for the prevention and treatment of asthma or chronic bronchitis. BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the compound of the present invention will be described in more detail.

 In the present specification, an alkyl group having 1 to 6 carbon atoms represents a linear or branched alkyl group having 1 to 6 carbon atoms, specifically, a methyl group, an ethyl group, a propyl group (1-propane group). Butyl group), isopropyl group (2-propyl group), butyl group (1-butyl group), sec-butyl group (2-butyl group), isobutyl group (2_methyl-1-propyl group), t-butyl Group (2-methyl-1-propyl group) and the like.

In the present specification, an alkoxy group having 1 to 6 carbon atoms represents a linear or branched alkoxy group having 1 to 6 carbon atoms, specifically, a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group. (2-propoxy group), butoxy group, sec-butoxy group (2-butoxy group) Xy group), isobutyloxy group (2-methyl-1-propoxy group), t-butoxy group (2-methyl-21-propoxy group) and the like.

 In the present specification, the C 2-6 oxy group represents a linear or branched C 2-6 oxy group, specifically, an acetoxy group, a propanoyloxy group, a butanoyloxy group. , 2-methyl-propanoyloxy group) and the like.

 In the present specification, an alkoxycarbonyl group having 2 to 6 carbon atoms represents a group in which a carbonyl is bonded to an oxygen atom of the alkoxy group, and specifically, a methoxycarbonyl group, an ethoxycarbel group, a propoxycarbol group, Isopropoxycarbonyl group (2-propoxycarbonyl group), butoxycarbonyl group, sec-butoxycarbol group (2-butoxycarbonyl group), isobutyloxycarbonyl group (2-methyl-1-propoxycarbol group), t -Butoxycarbyl group (2-methyl-2-propoxycarbonyl group) and the like.

 In the present specification, a carboxyalkyl group having 2 to 6 carbon atoms represents a group in which an arbitrary hydrogen atom of the alkyl group is substituted with a carboxy group, specifically, a carboxymethyl group, a 2-carboxyethyl group , 3-carboxypropyl, 2-carboxypropyl, 1-carboxy-2-propyl and the like.

 In the present specification, an alkoxycarbonylalkyl group having 3 to 6 carbon atoms represents a group in which a hydrogen atom of the above-mentioned alkyl group is substituted by an alkoxycarbonyl group having 2 to 5 carbon atoms, and specifically, methoxycarbonyl It represents a methyl group, an ethoxycarbonylmethyl group, a 2-methoxycarbonylethyl group, a 3-methoxycarbonylpropyl group, a 2-ethoxycarbonylethyl group, a 3-ethoxycarbonylpropyl group, or the like.

 In the present specification, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The halogen atom preferably represents a fluorine atom or a chlorine atom.

In the present specification, examples of the haloalkyl group having 1 to 6 carbon atoms include an alkyl group having 1 to 6 carbon atoms and substituted by 1 to 5 identical or different halogen atoms. Preferable examples include haloalkyl groups having 1 to 4 carbon atoms, and specific examples thereof include a trifluorenomethyl group, a 2,2,2-trifluoroethyl group, and a 2,2-difluoroethyl group. Is mentioned. In the present specification, examples of the aromatic carbocyclic group include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, and a biphenyl group. And a biphenyl group. In the present specification, an aralkyl group having 7 to 10 carbon atoms refers to an alkyl group having 1 to 6 carbon atoms substituted with a phenyl group, and specifically, a benzyl group, an 11-phenylethyl group, and a 2-phenylethyl group Groups (phenyl group), 1-phenylpropyl group, 2-phenylpropyl group, 2-phenyl-2-propyl group, 3-phenyl pill group and the like.

 In the present specification, the aromatic heterocyclic group includes 1 to 3 heteroatoms selected from 0 to 3 nitrogen atoms, 0 to 1 oxygen atom and 0 to 1 sulfur atom. And a monocyclic or bicyclic 5- to 10-membered aromatic heterocyclic group. Specifically, a furyl group, a phenyl group, a pyrrolyl group, an oxazolyl group, a thiazolyl group, a pyrazolyl group, an imidazolyl group, a tetrazolyl group, a pyridyl group, a pyridazier group, a pyrimidyl group, a pyrazuryl group, and a benzo [b] furyl group Benzo [b] thenyl group, indolyl group, benzoxazolyl group, benzothiazolyl group, benzoimidazolyl group, quinolyl group, isoquinolyl group, quinazolinyl group, quinoxalinyl group and the like.

In the present specification, the monocyclic aromatic heterocyclic group represents a 5- or 6-membered monocyclic aromatic heterocyclic ring, specifically, a furyl group, a phenyl group, a pyrrolyl group, an oxazolyl group. Group, thiazolyl group, pyrazolyl group, imidazolyl group, tetrazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, virazinyl group, etc. In this specification, an aromatic carbocyclic group, a phenyl group, an aromatic heterocyclic ring When a group or a monocyclic aromatic heterocyclic group is substituted, the substituent includes a halogen atom, a hydroxyl group, a cyano group, a nitro group, a nitro group, a carboxyl group, a tetrazolyl group, an alkyl group having 1 to 6 carbon atoms. A haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an alkoxy group having 2 to 6 carbon atoms, a carboxyalkyl group having 2 to 6 carbon atoms, Alkoxy force Ruponiru group or an alkoxycarbonylalkyl group having 3 to 6 carbon atoms, and the like. In the present specification, when an aralkyl group is substituted, it is substituted on the phenyl group. The substituent is the same as the substituent in the aromatic carbocyclic group or the phenyl group.

As the unsubstituted alkyl group having 1 to 6 carbon atoms represented by R ¹ , preferably, a methyl group, an ethyl group, a propyl group (1-propyl group), an isopropyl group (2-propyl group), and a butyl group (1- Butyl group), sec-butyl group (2-butyl group), isobutyl group (2-methyl-1-propyl group), t-butyl group (2-methyl-2-propyl group), the same or different substitution One or more, preferably 1 to 3 groups may be substituted.

Substituents allowed on the alkyl group having 1 to 6 carbon atoms represented by R ¹ include a fluorine atom, a halogen atom such as a chlorine atom, a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, and a carbon atom having 1 to 5 carbon atoms. And a carboxyl group and an alkoxycarbonyl group having 2 to 6 carbon atoms. Preferred examples of the substituent include a fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, an ethoxy group, an acetooxy group, a carboxyl group, a methoxycarbonyl group, and an ethoxycarboyl group.

As the substituted alkyl group having 1 to 6 carbon atoms represented by R ¹ , preferably, a trifluoromethyl group, a 2-chloroethyl group, a 2-hydroxyethyl group, a 3-hydroxypropyl group, a 2-methoxylethyl group, Examples include a 2-ethoxyethyl group, a 3-methoxypropyl group, a 2-acetoxyl group, a carboxymethyl group, a methoxycarbonylmethyl group, and an ethoxycarbonylmethyl group. As the unsubstituted aralkyl group having ¹ to 10 carbon atoms represented by R ¹ , preferably, a benzyl group, a 1-phenylethyl group, a 2-phenylethyl group (a phenyl group), an phenylpropyl group, or a 2-phenyl Examples thereof include an enylpropyl group, 2-phenyl-2-propyl group, and 3-phenylpyrrole group.

The substituted aralkyl group having 7 to 10 carbon atoms represented by R ¹ is preferably a 2-methylbenzyl group, a 3-methylbenzinole group, a 4-methyl / levenzinole group, a 4-methylphenethylenol group, or a 4-funolenobenzoyl group. Benzene group, 3-chlorobenzene group, 4-hydroxybenzyl group, 3-methoxybenzyl group, 4-methoxybenzyl group, 4-ethoxybenzyl group And 4-acetoxybenzyl group, 4-hydroxyloxybenzyl group and 4-methoxycarbonylbenzyl group.

Among these, more preferred R ^{1 includes} a hydrogen atom, a methyl group, an ethyl group, a propyl group, a butyl group, a benzyl group, and a 2-phenylethyl group, and among them, a hydrogen atom, a methyl group, and an ethyl group are preferred. Particularly preferred.

The alkyl group having 1 to 6 carbon atoms represented by R ² preferably includes a hydrogen atom, a methyl group, an ethyl group, a propyl group, and a butyl group, and among them, a hydrogen atom, a methyl group, and an ethyl group are particularly preferable. preferable.

When the aromatic carbocyclic group represented by Ar ¹ is substituted, the substituent is preferably a fluorine atom, a chlorine atom, a hydroxyl group, a propyloxyl group, a cyano group, a tetrazolyl group, a nitro group, a methyl group, or an ethyl group Methoxy group, ethoxy group, acetooxy group, methoxycarbonyl group, ethoxycarbonyl group, methoxycarbonylmethyl group, ethoxycarbonylmethyl group, carboxymethyl group, carboxamide group and the like.

As the substituted aromatic carbocyclic group represented by Ar ¹ , preferably, a 2 fluorinated phenyl group, a 3-funoleolophenylene group, a 4-phenylenophene group, a 2-phenyleneol group, or a 3-phenyleneol group Black phenol group, 4-methyl phenol group, 2-methynolephenyl group, 3-methylphenyl group, 4-methylphenyl group, 2-ethylphenol group, 3-ethylphenol group, 2,3 —Dimethinolepheninole group, 2,4-Dimethinolephenyl group, 2,5-Dimethylphenyl group, 2,6-Dimethylphenyl group, 3,4-Dimethylphenyl group, 3,5-Dimethylphenyl group, 4-methylphenyl, 2-methylnaphthyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methylphenyl Toxie fuel group 2 1-ethoxyphenyl group, 3-ethoxyphenyl group, 4-ethoxyphenyl group, 2-acetoxyphenyl group, 3-acetoxyphenyl group, 4-acetoxyphenyl group, 2-ethoxyphenol group, 2-ethoxyphenol group, (3) One-pot oleboxyphenyl group, (4) -Canolepoxyphenyl group, (2) Two-potoxymethylphenyl group, (3) -Carboxymethylphenyl group, (4) One-pot Rupoxymethylphenyl, 2-Methoxycanoleponylphenyl / 3-, 3-Methoxycarbonyl, 4-Methoxycarberphenyl, 2-Ethoxycarbenyl, 3- Ethoxycarbinolephenyl group, 4-ethoxycarbinolephenyl group, 2-methoxycarbonylmethylphenyl group, 3-methoxycarbonylmethylphenyl group, 4-methoxycarboylmethylphenyl group, 2-ethoxycarbonylmethylphenyl, 3-ethoxycarbonylmethylphenyl, 4-ethoxycarbonylmethylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-tetrazolylphenyl, 3-tetrazolylphenyl Tetrazolylphenyl, 4-tetrazolinolephenine, 2-Tropheninole, 3-Etrofenino Group, 4 one - Torofueniru group, 4-triflate Ruo Russia methyl Hue - group, may be mentioned 4 one carboxamide Hue group, and the like.

Further, as the substituent which may be present on the aromatic heterocyclic group represented by Ar ¹ , preferably, a chlorine atom, a fluorine atom, a hydroxyl group, a methyl group, a methoxy group, or an ethoxy group is mentioned. Can be.

The substituted aromatic heterocyclic group represented by Ar ¹ is preferably a 3-methyl-2-furinole group, a 4-methyl-12-furyl group, a 5-methyl-2-furyl group, a 2-methyl-1-furyl group , 4-methyl-13-furyl, 5-methyl-13-furyl, 3-methoxy-2-furyl, 4-methoxy2-furyl, 5-methoxy-2-furyl, 2-methyl Toxyl 3-furyl, 4-methoxy 3-furyl, 5-methoxy-3-furyl, 3-chloro-2-furyl, 4-chloro-1--2-furinole, 5-chloro-1-2 -Furinole, 2-chloro-3-furinole, 4-chloro-3-furinole, 5-chloro-3, furyl, 3-fluoro-2-furyl, 4-fluoro-2-furyl, 5-furesole Mouth _ 2-furinole group, 2-furnole mouth 3-furinole group, 4-fluoro-3-furinole group, 5-Funoleo 3-Finolene, 3-Methynole-2-Chenynole, 4-Methynole-12-Cenyl, 5-Methyl-2-Cenyl, 2-Methyl-3-Cenyl, 4-Methynole3 —Chenyl group, 5-Methynole-3-Cenynole group, 3-Methoxy-12-Chenyl group, 4-Methoxy-2-Chenyl group, 5-Methoxy-12-Chenyl group, 2-Methoxy-3— Chenyl group, 4-Methoxy-3-Chenyl group, 5-Methoxy-13-Cheninole group-3-Chloro-2-Cheninole group, 4-Chloro-2-thienole group, 5- Chloro-2-Cheninole, 2-Chloro-3-Cenynole, 4-Chloro_3-Chenyl, 5-Chloro-3-Chenyl, 3-Fluoro-2-Chenyl, 4 1-Fluoro 2 _Chenole group, 5-Futhreo 1 2-Che-nore group, 2-Fnoleo _ 3 -Chenyl group, 4-Fluoro-3-Cenyl group, 5-Fluoro-3-Cenyl group , 2-methyl 3-pyridyl, 4-methyl-13-pyridyl, 5-methyl-3-pyridyl, 6-methyl-3-pyridyl, 3-methyl-2-pyridyl, 4-methyl-2-pyridyl, 5-methyl-2-pyridyl group, 6-methyl-1-pyridyl group, 2-methyl-4-pyridyl group, 3-methyl-4-pyridyl group, 5-methyl-4-pyridyl group, 6-methyl-14-pyridyl group Group, 2-methoxy-3-pyridyl group, 4-methoxy_3-pyridyl group, 5 —Methoxy-3-pyridyl group, 6-Methoxy-3-pyridyl group, 3-Methoxy-2-pyridyl group, 4-Methoxy-12-pyridyl group, 5-Methoxy-12-pyridyl group, 6 —Methoxy-2-pyridyl group, 2-Methoxy-14-pyridyl group, 3-Methoxy-14-pyridyl group, 5-Methoxy-4-pyridyl group, 6-Methoxy-14-pyridyl group, 2-ethoxy-1-pyridyl group, 4-ethoxy-3-pyridyl group, 3-ethoxy-12-pyridyl group, 4-ethoxy-12-pyridyl group, 3-ethoxy-4-pyridyl group, 2-hydroxy-13 —Pyridyl group, 4-hydroxy-13-pyridyl group, 3-hydroxy-2-pyridyl group, 3-hydroxy-4-pyridyl group, 2-chloro-3-pyridyl group, 4-chloro-3-pyridyl group, 3-— 1-pyridyl group, 4_2-pyridyl group 3-chloro-1-pyridyl group, 5-methyl-1-biradil group, 6-methyl-2-virazyl group, 5-methoxy-2-virazyl group, 6-methoxy-2-virazyl group, 5-ethoxy-1 Examples include a 2-virazyl group, a 6-ethoxy-12-virazyl group, a 5-chloro-12-virazyl group, and a 6-chloro-2-pyrazyl group.

Among the above, as more preferred Ar ¹ , a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 4-phenylolenophenyl group, a 3-chlorophenol group, and a 2,3-dimethylinophenol group , 2-methoxyphenyl group, 2-ethoxyphenyl group, 4-ethoxyphenol group, 4-methoxyphenolylphenol group, 3-cyanophenyl group, 4-cyanophenyl group, 3-phenyl group Tetrazolylphenyl group, 4-tetrazolylphenyl group, 4-port phenyl group, pyridyl group, quinolyl group, 2-methyl-3-pyridyl group, 2-methy Xy 3-pyridi / le or 2-ethoxy-13-pyridyl groups, among which phenyl, 1-naphthyl, 2,3-dimethylphenyl, and 2-methoxyphenyl are particularly preferred. , 4 isotope / repoxyphenole group, 4-methoxycanoleponinolephenine group, 3-cyanophenyl group, 4-cyanophenyl group, 3-tetrazolylphenyl group, and 4-tetrazolylphenyl group are preferred. .

The substituent which may be present on the phenyl group represented by Ar ² or Ar ³ is preferably a halogen atom such as a fluorine atom or a chlorine atom; an alkyl group such as a methyl group or an ethyl group; a hydroxyl methoxy group or an ethoxy group Alkoxy groups such as ethoxy groups; alkoxy groups such as acetyl groups; carboxyl groups; alkoxy forces such as methoxycarbon groups; rubonyl groups; cyano groups; tetrazolyl groups; nitro groups and the like; and more preferably alkyl. Groups, alkoxy groups or halogen atoms.

As the substituted phenyl group represented by Ar ² or Ar ³ , preferably, a 2-fluorophenyl group, a 3-phenyl group, a 4-phenyl group, a 2-phenyl group, 3-chloro phenyl group, 4-methyl phenyl group, 2-methyl phenyl group, 3-methylphenyl group, 4-methylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 2, 3-dimethylphenyl, 2,4-dimethylphenyl, 2,51-dimethylphenyl, 2,6-dimethyl / rephenyl, 3,4-dimethylphenyl, 3,5-dimethylinophenyl 4-, 4-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 2-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl Group, 2-ethoxyphenyl group, 3-ethoxyphenyl group, 4-ethoxyphenyl group, 2-acetoxyphenyl group, 3-acetoxyphenyl group, 4-acetoxyphenyl group, 2-force repoxyphenyl group, 3-— Carbonyloxy, 4-carboxyphenyl, 2-methoxycarbonyl, 3-methoxyphenyl, 4-methoxycarbonyl, 2-cyanophenyl, 3-cyanophenyl Nore group, 4-cyanophenyl group, 2-tetrazolylphenyl group, 3-tetrazolylphenyl group, 4-tetrazolylphenyl group, 2-ditrophenyl group, 3-nitrophenyl group, 4-nitrotrophenyl group, etc. be able to. The substituent which may be present on the monocyclic aromatic heterocyclic group represented by Ar ² or Ar ³ is preferably a halogen atom such as a chlorine atom or a fluorine atom; an alkyl group such as a methyl group An alkoxy group such as a methoxy group or an ethoxy group; and a hydroxyl group. Specific examples of the substituted monocyclic aromatic heterocyclic group represented by Ar ² or Ar ³ include, preferably, 3-methylinole 2-furinole group, 4-methylinole 1-2-furinole group, and 5-methylinole 2-furyl group. , 2-Methyl-3-furyl, 4-Methyl-13-furyl, 5-Methyl-3-furyl, 3-Methoxy-12-furyl, 4-Methoxy-2-furyl, 5-Methoxy 1- 2-furyl group, 2-methoxy 3-furyl group, 4-methoxy 3-furyl group, 5-methoxy-13-furisle group, 3-chloro-2-furinole group, 4-chloro-2-fur Linole group, 5-chloro-2-furinole group, 2-chloro-1-furinole group, 4-chloro-3-furylene group, 5-chloro-3-furinole group, 3-furinole group, 3-furinole 2-furinole group, 4 —Funoleol 2-furyl group, 5-funoleo 2-furyl group, 2-fluoro-3 _ Furyl group, 4-funoleo mouth 3-furinole group, 5-funoleo mouth 1-3-furinole group, 3-methylone-2-ene chenole group, 4-methinole 2-cheninole group, 5-methylinole 2-che 2-N-methyl group, 2-Methyl-N-yl 3-Chen-N-yl group, 4-Meth-N-N-yl 3--Che-N-N group, 5-Meth-N-I-N-3-Chen-N-O group, 3-Methoxy-12-Chenyl group, 4-M Toxi-2-enyl, 5-methoxy 2-Che7, 2-methoxy-3-Cheynole, 4-methoxy3-Cheenyl, 5-Methoxy-3-Chenyl Group, 3-chloro-1-2-phenyl, 4-chloro-2, -Chenole, 5-chloro-2-Chenole, 2-chloro-3-Ce2, le, 4-chloro-3 Cheninole group, 5-chloro-one 3-Cheninole group, 3-funoleol 2-Chenyl group, 4-fluoro-2-Chenyl group, 5- Luolow 2-Chenyl group, 2-Fluoro-3_Cher group, 4-Fluoro-3-Cher group, 5-Fluoro-3-Cenyl group, 2-Methyl-3-pyridyl group, 4-Methyl-3-pyridyl group, 5 — Methyl-3-pyridyl group, 6-methyl-3-pyridyl group, 3-methyl-2-pyridyl group, 4-methyl-2-pyridyl group, 5-methyl-12-pyridyl group, 6-methylinopyridyl group, 2 —Methyl-4-pyridyl group, 3-methyl-4-pyridyl group, 5-methyl-4-pyridyl group, 6-methyl-4-pyridyl group, 2-methoxy-3-pyridyl group Lysyl, 4-methoxy-3-pyridyl, 5-methoxy-3-pyridyl, 6-methoxy-3-pyridyl, 3-methoxy-2-pyridyl, 4-methoxy-2-pyridyl, 5-Methoxy-1-pyridyl group, 6-Methoxy-1-pyridyl group, 2-Methoxy-14-pyridyl group, 3-Methoxy-14-pyridyl group, 5-Methoxy-14-pyridyl group, 6-methoxy 4-monopyridyl group, 2-ethoxy 3-pyridyl group,

4-ethoxy-1-pyridinole group, 3-ethoxy-2-pyridinole group, 4-ethoxy-2-pyridyl group, 3-ethoxy-14-pyridyl group, 2-hydroxy-13-pyridyl group, 4-hydroxy-3-pyridyl group , 3-hydroxy-12-pyridyl, 3-hydroxy-14-pyridyl, 2-chloro-3-pyridyl, 4-chloro-3-pyridyl, 3-chloro-1-pyridinole , 4-chloro-2-pyridinole group, 3-chloro-4-pyridyl group, 5-methyl-2-virazyl group, 6-methyl-2-virazyl group,

5-methoxy-12-virazyl group, 6-methoxy-2-virazyl group, 5-ethoxy-12-viradil group, 6-ethoxy-12-virazyl group, 5-chloro-12-virazyl group,

6-chloro-1--2-virazyl group. More preferred Ar ² or Ar ³ include phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-cyanophenyl, and 3-phenyl. And pyridyl and 4-pyridyl groups. Among them, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-cyanophenyl, 3-pyridyl and 4-pyridyl are particularly preferred. preferable. When Ar ² and Ar ³ form a tricyclic carbocycle together with a divalent group bonded to both Ar ² and Ar ³ , the following formula in the formula (I):

As the structure represented by Three

And the like, and these are also preferable.

 X represents a methine group (CH) or a nitrogen atom, Y represents a single bond or an oxygen atom when X is a methine group, and represents a single bond when X is a nitrogen atom, and Z represents a methine group. And when Y is a single bond, it represents a hydrogen atom or a hydroxyl group; when X is a methine group and Y is an oxygen atom; and when X is a nitrogen atom (Y is a single bond), it represents a hydrogen atom. The following equation in (I):

The following formula is preferable as the structure represented by

In these, the following formula Four

Is particularly preferred.

 m represents 2 to 6, preferably 3 to 5, and particularly preferably 3 to 4.

 Tables 1 and 2 specifically show preferred peracyl derivatives of the present invention. In Table 1,

, I ¹ , Ar R ² , m, X, Y, Z, Ar ² and Ar ³ represent the definition of general formula (I)

9 τ

.8.llO / COOZdf / X3d 89 OOZ OAV H 0 HO 9 H 09

H 0 HO f H 69

H 0 HO ε H 89

H 0 HO z H L

HO HO s H 99

HO HO H 92

HO HO ε H

 H HO s H • id

H HO H 29

H HO ε H 19

H N 9 H OS

H N g H 6f

H N H 8

H N £ H L

H N Z H 9

H 0 HO 9 H 2f q <j H 0 HO H f

 H 0 HO ε H £ f

H 0 HO z H Zf

Hd HO HQ s H If

 HO HO H 3 Of qd HO HO ε H ^ 3 6S

 H HO s H ^ 3 8C

H HD H AS

 ^ d H HO ε H 9S

 H N 9 H se

H N s H ΐ3 ε

H N f H Ϊ3 εε

H N ε H ^ 3 zz

H M z H ΐ3 τε V Z A X z & τΗ

9 .8 .llO / fOOZdf / X3d It-8910 / tOOZ ΟΛ \ 7

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

61 Bu Ph H 2 N-H Ph Ph

62 Bu Ph H 3 N-H Ph Ph

63 Bu Ph H 4 N-H Ph Ph

64 Bu Ph H 5 N-H Ph Ph

65 Bu Ph H 6 N-H Ph Ph

66 Bu Ph H 3 CH-H Ph Ph

67 Bu Ph H 4 CH-H Ph Ph

68 Bu Ph H 5 CH-H Ph Ph

69 Bu Ph H 3 CH-0H Ph Ph

70 Bu Ph H 4 CH-0H Ph Ph

71 Bu Ph H 5 CH 1 0H Ph Ph

72 Bu Ph H 2 CH 0 H Ph Ph

73 Bu Ph H 3 CH 0 H Ph Ph

74 Bu Ph H 4 CH 0 H Ph Ph

75 Bu Ph H 5 CH 0 H Ph Ph

76 PhCH ₂ Ph H 2 N-H Ph Ph

77 PhCH ₂ Ph H 3 N-H Ph Ph

78 PhCH ₂ Ph H 4 N-H Ph Ph

79 PhCH ₂ Ph H 5 N-H Ph Ph

80 PhCH ₂ Ph H 6 N-H Ph Ph

81 PhCH ₂ Ph H 3 CH-H Ph Ph

82 PhCH ₂ Ph H 4 CH-H Ph Ph

83 PhCH ₂ Ph H 5 CH-H Ph Ph

84 PhCH ₂ Ph H 3 CH-0H Ph Ph

85 PhCH ₂ Ph H 4 CH 0H Ph Ph

86 PhCH ₂ Ph H 5 CH 0H Ph Ph

87 PhCH ₂ Ph H 2 CH 0 H Ph Ph

88 PhCH ₂ Ph H 3 CH 0 H Ph Ph

89 PhCH ₂ Ph H 4 CH 0 H Ph Ph

90 PhCH ₂ Ph H 5 CH 0 H Ph Ph 8

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

91 PhCH ₂ CH ₂ Ph H 2 N-H Ph Ph

92 PhCH ₂ CH ₂ Ph H 3 N 1 H Ph Ph

93 PhCH ₂ CH ₂ Ph H 4 N-H Ph Ph

94 PhCH ₂ CH ₂ Ph H 5 N-H Ph Ph

95 PhC¾ CH ₂ Ph H 6 N-H Ph Ph

96 PhCH ₂ CH ₂ Ph H 3 CH-H Ph Ph

97 PhCH ₂ CH ₂ Ph H 4 CH-H Ph Ph

98 PhCH ₂ CH ₂ Ph H 5 CH '-H Ph Ph

99 PhCH ₂ CH ₂ Ph H 3 CH 1 0H Ph Ph

100 PhCH ₂ C¾ Ph H 4 CH-0H Ph Ph

101 PhCH ₂ CH ₂ Ph H 5 CH 1 0H Ph Ph

102 PhCH ₂ CH ₂ Ph H 2 CH 0 H Ph Ph

103 PhCH ₂ CH ₂ Ph H 3 CH 0 H Ph Ph

104 PhCH ₂ CH ₂ Ph H 4 CH 0 H Ph Ph

105 PhCH ₂ CH ₂ Ph H 5 CH 0 H Ph Ph

106 Et0C0CH ₂ Ph H 3 N-H Ph Ph

107 Et0C0CH ₂ Ph H 4 N-H Ph Ph

108 Et0C0CH ₂ Ph H 3 CH 0 H Ph Ph

109 Me Ph Me 3 N-H Ph Ph

110 Me Ph Me 4 N One H Ph Ph

111 Me Ph Me 3 CH 0 H Ph Ph

112 Me Ph Et 3 N-H Ph Ph

113 Me Ph Et 4 N-H Ph Ph

114 Me Ph Et 3 CH 0 H Ph Ph

115 Me Ph Pr 3 N H Ph Ph

116 Me Ph Pr 4 N H Ph Ph

117 Me Ph Pr 3 CH 0 H Ph Ph

118 PhCH ₂ Ph Me 3 NH Ph Ph

119 PhCH ₂ Ph Me 4 NH Ph Ph

120 PhCH ₂ Ph Me 3 CH 0 H Ph Ph

6 I n 8 l orchid OOZdf / e :) d 89 contract OOZ OAV

 0 z

.8.ll0 / C00Zdf / X3d 89 contract 00Z OAV Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

181 Bu Ph H 2 N-H Ph Ph (4-F)

182 Bu Ph H 3 N-H Ph Ph (4-F)

183 Bu Ph H 4 N-H Ph Ph (4-F)

184 Bu Ph H 5 N-H Ph Ph (4-F)

185 Bu Ph H 6 N-H Ph Ph (4-F)

186 Bu Ph H 3 CH-H Ph Ph (4-F)

187 Bu Ph H 4 CH-H Ph Ph (4-F)

188 Bu Ph H 5 CH-H Ph Ph (4-F)

189 Bu Ph H 3 CH-0H Ph Ph (4-F)

190 Bu Ph H 4 CH-0H Ph Ph (4-F)

191 Bu Ph H 5 CH-0H Ph Ph (4-F)

192 Bu Ph H 2 CH 0 H Ph Ph (4-F)

193 Bu Ph H 3 CH 0 H Ph Ph (4-F)

194 Bu Ph H 4 CH 0 H Ph Ph (4-F)

195 Bu Ph H 5 CH 0 H Ph Ph (4-F)

196 PhCH ₂ Ph H 2 N-H Ph Ph (4-F)

197 PhCH ₂ Ph H 3 N-H Ph Ph (4-F)

198 PhCH ₂ Ph H 4 N-H Ph Ph (4-F)

199 PhCH ₂ Ph H 5 N 1 H Ph Ph (4-F)

200 PhCH ₂ Ph H 6 N 1 H Ph Ph (4-F)

201 PhCH ₂ Ph H 3 CH-H Ph Ph (4-F)

202 PhCH ₂ Ph H 4 CH-H Ph Ph (4-F)

203 PhCH ₂ Ph H 5 CH One H Ph Ph (4-F)

204 PhCH ₂ Ph H 3 CH one 0H Ph Ph (4-F)

205 PhC¾ Ph H 4 CH 0H Ph Ph (4_F)

206 PhCH ₂ Ph H 5 CH 0H Ph Ph (4-F)

207 PhCH ₂ Ph H 2 CH 0 H Ph Ph (4-F)

208 PhCH ₂ Ph H 3 CH 0 H Ph Ph (4-F)

209 PhCH ₂ Ph H 4 CH 0 H Ph Ph (4-F)

210 PhCH ₂ Ph H CH 0 H Ph Ph (4-F)

^Five Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

211 PhCH ₂ CH ₂ Ph H 2 N-H Ph Ph (4-F)

212 PhC¾ CH ₂ Ph H 3 N-H Ph Ph (4-F)

213 PhCH ₂ CH ₂ Ph H 4 N-H Ph Ph (4-F)

214 PhCH ₂ CH ₂ Ph H 5 N-H Ph Ph (4-F)

215 PhCH ₂ CH ₂ Ph H 6 N-H Ph Ph (4-F)

216 PhCH ₂ CH ₂ Ph H 3 CH-H Ph Ph (4-F)

217 PhCH ₂ CH ₂ Ph H 4 CH-H Ph Ph (4-F)

218 PhCH ₂ CH ₂ Ph H 5 CH-H Ph Ph (4-F)

219 PhCH ₂ CH ₂ Ph H 3 CH-0H Ph Ph (4-F)

220 PhCH ₂ CH ₂ Ph H 4 CH-0H Ph Ph (4-F)

221 PhCH ₂ CH ₂ Ph H 5 CH-0H Ph Ph (4-F)

222 PhCH ₂ CH ₂ Ph H 2 CH 0 H Ph Ph (4-F)

223 PhCH ₂ CH ₂ Ph H 3 CH 0 H Ph Ph (4-F)

224 PhCH ₂ C¾ Ph H 4 CH 0 H Ph Ph (4-F)

225 PhCH ₂ CH ₂ Ph H 5 CH 0 H Ph Ph (4-F)

226 Et0C0CH ₂ Ph H 3 N-H Ph Ph

227 EtOCOCH ₂ Ph H 4 N-H Ph Ph

228 Et0C0CH ₂ Ph H 3 CH 0 H Ph Ph

229 Me Ph Me 3 N One H Ph Ph

230 Me Ph Me 4 N-H Ph Ph

231 Me Ph Me 3 CH 0 H Ph Ph

232 Me Ph Et 3 N-H Ph Ph

233 Me Ph Et 4 N-H Ph Ph

234 Me Ph Et 3 CH 0 H Ph Ph

235 Me Ph Pr 3 N H Ph Ph

236 Me Ph Pr 4 N H Ph Ph

237 Me Ph Pr 3 CH 0 H Ph Ph

238 PhCH ₂ Ph Me 3 NH Ph Ph

239 PhCH ₂ Ph Me 4 NH Ph Ph

240 PhCH ₂ Ph Me 3 CH 0 H Ph Ph

ε z

.8.llO / COOZdf / X3d 89 contract OOZ OAV H 0 HO 9 H οοε

(ID-f) Hd H 0 HO f H -id 662

(lD-) Hd H 0 HO ε H S6Z

 H 0 HO z H L6Z

(T3-^) ¾ HO HO g H 962

(ΐ.-) HO HO H 96Ζ

(ϋ-) HO HO ε H ■ id

 H HO 9 H

 (ΐθ-) H HO f H Ζ6Ζ

(TO-^) Hd H H. ε H 16Ζ

(ΙΟ-) ^ d H N 9 H 062

(ΐθ- ^) Hd H N s H 682

(ΐθ- ^) Hd H N f H 88Ζ

(ϋ-) Hd H M ε H LSZ

(ID-f) Hd H N z H 982

(ϋ-) Rd H 0 HO 9 H 98Ζ

(ϋ-) Hd H 0 HO H fSZ

(TO-) H 0 HO ε H 2SZ

(ΐ.- H 0 HO z H ZSZ

(iD-f) m HO HO 9 H 18Ζ

(13-f) Hd HO HO f H OSZ

(το-^) ¾ HO HO ε H ΐ3 6LZ

(TO- ^) H HO 9 H ΐ3 8LZ

(ΐ.- H HO f H ΐ3 LLZ

(1.-) H HO ε H 13 9LZ

(ΐ.-) ¾J H N 9 H 13 LZ

(ΐ.-) H-I M s H 13 fLZ

(τ.-) H N H £ LZ

(Τ-,) ¹ Id HN ε H ZLZ

 H N z H ILZ

ZAX UI τΗ z .8.llO / COOZdf / X3d 89 contract OOZ OAV Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

301 Bu Ph H 2 N-H Ph Ph (4-Cl)

302 Bu Ph H 3 N-H Ph Ph (4-Cl)

303 Bu Ph H 4 N 1 H Ph Ph (4-Cl)

304 Bu Ph H 5 N-H Ph Ph (4-Cl)

305 Bu Ph H 6 N-H Ph Ph (4-Cl)

306 Bu Ph H 3 CH-H Ph Ph (4-Cl)

307 Bu Ph H 4 CH-H Ph Ph (4-C1)

308 Bu Ph H 5 CH-H Ph Ph (4- CI)

309 Bu Ph H 3 CH One 0H Ph Ph (4-CI)

310 Bu Ph H 4 CH 1 0H Ph Ph (4-Cl)

311 Bu Ph H 5 CH-0H Ph Ph (4-Cl)

312 Bu Ph H 2 CH 0 H Ph Ph (4-Cl)

313 Bu Ph H 3 CH 0 H Ph Ph (4-Cl)

314 Bu Ph H 4 CH 0 H Ph Ph (4-Cl)

315 Bu Ph H 5 CH 0 H Ph Ph (4-Cl)

316 PhCH ₂ Ph H 2 N-H Ph Ph (4- CI)

317 PhCH ₂ Ph H 3 N 1 H Ph Ph (4-Cl)

318 PhCH ₂ Ph H 4 N-H Ph Ph (4-Cl)

319 PhCH ₂ Ph H 5 N-H Ph Ph (4-Cl)

320 PhCH ₂ Ph H 6 N-H Ph Ph (4-Cl)

321 PhCH ₂ Ph H 3 CH-H Ph Ph (4-Cl)

322 PhCH ₂ Ph H 4 CH-H Ph Ph (4-Cl)

323 PhC¾ Ph H 5 CH-H Ph Ph (4-Cl)

324 PhCH ₂ Ph H 3 CH 1 0H Ph Ph (4-Cl)

325 PhCH ₂ Ph H 4 CH 0H Ph Ph (4-Cl)

326 PhCH ₂ Ph H 5 CH 0H Ph Ph (4-Cl)

327 PhCH ₂ Ph H 2 CH 0 H Ph Ph (4-C1)

328 PhCH ₂ Ph H 3 CH 0 H Ph Ph (4- CI)

329 PhCH ₂ Ph H 4 CH 0 H Ph Ph (4-CI)

330 PhCH ₂ Ph H 5 CH 0 H Ph Ph (4-C1) Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

331 PhCH ₂ CH ₂ Ph H 2 N-H Ph Ph (4-Cl)

332 PhCH ₂ CH ₂ Ph H 3 N 1 H Ph Ph (4-Cl)

333 PhCH ₂ CH ₂ Ph H 4 N-H Ph Ph (4-Cl)

334 PhCH ₂ CH ₂ Ph H 5 N-H Ph Ph (4-Cl)

335 PhCH ₂ C¾ Ph H 6 N-H Ph Ph (4-Cl)

336 PhCH ₂ CH ₂ Ph H 3 CH-H Ph Ph (4-Cl)

337 PhCH ₂ CH ₂ Ph H 4 CH-H Ph Ph (4-Cl)

338 PhCH ₂ CH ₂ Ph H 5 CH 1 H Ph Ph (4-Cl)

339 PhCH ₂ CH ₂ Ph H 3 CH-0H Ph Ph (4- CI)

340 PhCH ₂ CH ₂ Ph H 4 CH-0H Ph Ph (4-Cl)

341 PhCH ₂ CH ₂ Ph H 5 CH-0H Ph Ph (4-Cl)

342 PhCH ₂ CH ₂ Ph H 2 CH 0 H Ph Ph (4-Cl)

343 PhCH ₂ CH ₂ Ph H 3 CH 0 H Ph Ph (4-CI)

344 PhCH ₂ CH ₂ Ph H 4 CH 0 H Ph Ph (4-Cl)

345 PhCH ₂ CH ₂ Ph H 5 CH 0 H Ph Ph (4-Cl)

346 EtOCOCHn Ph H 3 N-H Ph Ph

347 Et0C0CH ₂ Ph H 4 N-H Ph Ph

348 EtOCOCH ₂ Ph H 3 CH 0 H Ph Ph

349 Me Ph Me 3 N-H Ph Ph

350 Me Ph Me 4 N-H Ph Ph

351 Me Ph Me 3 CH 0 H Ph Ph

352 Me Ph Et 3 N One H Ph Ph

353 Me Ph Et 4 N-H Ph Ph

354 Me Ph Et 3 CH 0 H Ph Ph

355 Me Ph Pr 3 N H Ph Ph

356 Me Ph Pr 4 N H-Ph Ph

357 Me Ph Pr 3 CH 0 H Ph Ph

358 PhCH ₂ Ph Me 3 NH Ph Ph

359 PhCH ₂ Ph Me 4 NH Ph Ph

360 PhCH ₂ Ph Me 3 CH 0 H Ph Ph

 ι ζ

L8LU0 / £ 00Zdr / 13d 89 contract 00Ζ OAV

8 Ζ

/.8/,TTO/fOOidf/X3d 89 contract ΟΟΖ ΟΟΖ Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

421 Bu Ph H 2 N-H Ph Ph (4- Me)

422 Bu Ph H 3 N-H Ph Ph (4- Me)

423 Bu Ph H 4 N One H Ph Ph (4- Me)

424 Bu Ph H 5 N-H Ph Ph (4-Me)

425 Bu Ph H 6 N One H Ph Ph (4-Me)

426 Bu Ph H 3 CH-H Ph Ph (4-Me)

427 Bu Ph H 4 CH-H Ph Ph (4-Me)

428 Bu Ph H 5 CH-H Ph Ph (4-Me)

429 Bu Ph H 3 CH-0H Ph Ph (4-Me)

430 Bu Ph H 4 CH-0H Ph Ph (4- Me)

431 Bu Ph H 5 CH-0H Ph Ph (4-Me)

432 Bu Ph H 2 CH 0 H Ph Ph (4-Me)

433 Bu Ph H 3 CH 0 H Ph Ph (4-Me)

434 Bu Ph H 4 CH 0 H Ph Ph (4-Me)

435 Bu Ph H 5 CH 0 H Ph Ph (4-Me)

436 PhCH ₂ Ph H 2 N 1 H Ph Ph (4-Me)

437 PhCH ₂ Ph H 3 N-H Ph Ph (4-Me)

438 PhCH ₂ Ph H 4 N-H Ph Ph (4- Me)

439 PhCH ₂ Ph H 5 N-H Ph Ph (4-Me)

440 PhC¾ Ph H 6 N 1 H Ph Ph (4-Me)

441 PhCH ₂ Ph H 3 CH H Ph Ph (4-Me)

442 PhCH ₂ Ph H 4 CH-H Ph Ph (4-Me)

443 PhCH ₂ Ph H 5 CH-H Ph Ph (4-Me)

444 PhCH ₂ Ph H 3 CH-0H Ph Ph (4-Me)

445 PhCH ₂ Ph H 4 CH 0H Ph Ph (4- Me)

446 PhCH ₂ Ph H 5 CH 0H Ph Ph (4-Me)

447 PhCH ₂ Ph H 2 CH 0 H Ph Ph (4-Me)

448 PhCH ₂ Ph H 3 CH 0 H Ph Ph (4-Me)

449 PhCH ₂ Ph H 4 CH 0 H Ph Ph (4-Me)

450 PhC¾ Ph H 5 CH 0 H Ph Ph (4-Me) Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

451 PhCH ₂ CH ₂ Ph H 2 N-H Ph Ph (4-Me)

452 PhCH ₂ CH ₂ Ph H 3 N-H Ph Ph (4-Me)

453 PhCH ₂ CH ₂ Ph H 4 N-H Ph Ph (4-Me)

454 PhC¾ CH ₂ Ph H 5 N 1 H Ph Ph (4-Me)

455 PhCH ₂ CH ₂ Ph H 6 N-H Ph Ph (4-Me)

456 PhC¾ CH ₂ Ph H 3 CH One H Ph Ph (4-Me)

457 PhCH ₂ CH ₂ Ph H 4 CH One H Ph Ph (4-Me)

458 PhCH ₂ CH ₂ Ph H 5 CH _ H Ph Ph (4-Me)

459 PhCH ₂ CH ₂ Ph H 3 CH-0H Ph Ph (4-Me)

460 PhCH ₂ CH ₂ Ph H 4 CH-0H Ph Ph (4-Me)

461 PhCH ₂ CH ₂ Ph H 5 CH-0H Ph Ph (4-Me)

462 PhCH ₂ CH ₂ Ph H 2 CH 0 H Ph Ph (4-Me)

463 PhCH ₂ CH ₂ Ph H 3 CH 0 H Ph Ph (4-Me)

464 PhCH ₂ CH ₂ Ph H 4 CH 0 H Ph Ph (4-Me)

465 PhC¾ CH ₂ Ph H 5 CH 0 H Ph Ph (4-Me)

466 Et0C0CH ₂ Ph H 3 N-H Ph Ph

467 Et0C0CH ₂ Ph H 4 N-H Ph Ph

468 EtOCOCH ₂ Ph H 3 CH 0 H Ph Ph

469 Me Ph Me 3 N-H Ph Ph

470 Me Ph Me 4 N-H Ph Ph

471 Me Ph Me 3 CH 0 H Ph Ph

472 Me Ph Et 3 N-H Ph Ph

473 Me Ph Et 4 N-H Ph Ph

474 Me Ph Et 3 CH 0 H Ph Ph

475 Me Ph Pr 3 N H Ph Ph

476 Me Ph Pr 4 N H Ph Ph

477 Me Ph Pr 3 CH 0 H Ph Ph

478 PhCH ₂ Ph Me 3 NH Ph Ph

479 PhCH ₂ Ph Me 4 NH Ph Ph

480 PhCH ₂ Ph Me 3 CH 0 H Ph Ph OAV / -Π0-1

z ε .8.llO / COOZdf / X3d 89 contract OOZ OAV

ε ε n 8 n l OOZdf / e :) d 89 contract 00Z OAV H 0 H3 ε ¾OHd 009

^ d H one N ¾. 669

^ d H ― N ε Hd 869

Hd H 0 HO ε ¾ Z6S

 H N 963

^ d H one M ε • id S6S

 H 0 HO ε ΐ3 f6

 H N 13 ^ d S69

H N ε 1Η Hd 269

Hd H 0 HO ε ⁹ i 169

Hd H N f 069

 H N ε 689

H 0 HO ε H ¾ooooia 889

H N H ¾ooooia Z89

H N ε H Hd ¾ooooia 989

H 0 H3 9 H ^ d ¾. ¾. 989

Hd H 0 H3 H Hd ^ 89

 H 0 HO ε H ¾0 ¾3Hd S8S

(o-) Hd H 0 HO ζ H Hd ¾D ¾3Hd ZS9

(o-f) Hd HO H3 2 H Hd ¾0 ¾DHd 189

( ⁹ RO-^) Hd HO HO H ¾. ¾. 089

 (o-) qd Hd HO HO ε H ¾ ¾0 ¾. 6Z9

 (o-) ¾i H HO 9 H 8Z9

 H HO H ¾ ¾OHd S

 (0-) qd Hd H – HO ε H ¾. ¾. 9 9

 (o-) ^ d H ― N 9 H ¾0 ¾OHd 9Z9

 (3 —) H-N 9 H ^ d P

 (0-) qd H M f H d S S

 (0-) H N ε H Hd ¾0 ¾. ZL

 (S —) ¾J Hd H M ζ H Hd ¾3 ¾. US

₈ ^J Z people X iH ε

.8.llO / COOZdf / X3d 89 contract OOZ OAV

9 ε

L8LU0 / £ 00Zdr / 13d 89 contracts OOZ OAV

 9 ε

L8LU0 / £ 00Zdr / 13d 89 contracts OOZ OAV Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

661 Bu Ph H 2 N 1 H Ph (4-F) Ph (4-F)

662 Bu Ph H 3 N-H Ph (4-F) Ph (4-F)

663 Bu Ph H 4 N-H Ph (4-F) Ph (4-F)

664 Bu Ph H 5 N 1 H Ph (4-F) Ph (4-F)

665 Bu Ph H 6 N-H Ph (4-F) Ph (4-F)

666 Bu Ph H 3 CH-H Ph (4-F) Ph (4-F)

667 Bu Ph H 4 CH-H Ph (4-F) Ph (4-F)

668 Bu Ph H 5 CH-H Ph (4-F) Ph (4-F)

669 Bu Ph H 3 CH-0H Ph (4-F) Ph (4-F)

670 Bu Ph H 4 CH-0H Ph (4-F) Ph (4-F)

671 Bu Ph H 5 CH-0H Ph (4-F) Ph (4-F)

672 Bu Ph H 2 CH 0 H Ph (4-F) Ph (4-F)

673 Bu Ph H 3 CH 0 H Ph (4-F) Ph (4-F)

674 Bu Ph H 4 CH 0 H Ph (4-F) Ph (4-F)

675 Bu Ph H 5 CH 0 H Ph (4-F) Ph (4-F)

676 PhCH ₂ Ph H 2 N-H Ph (4-F) Ph (4-F)

677 PhCH ₂ Ph H 3 N-H Ph (4-F) Ph (4-F)

678 PhCH ₂ Ph H 4 N-H Ph (4-F) Ph (4-F)

679 PhCH ₂ Ph H 5 N-H Ph (4-F) Ph (4-F)

680 PhCH ₂ Ph H 6 N 1 H Ph (4-F) Ph (4-F)

681 PhCH ₂ Ph H 3 CH-H Ph (4-F) Ph (4-F)

682 PhCH ₂ Ph H 4 CH-H Ph (4-F) Ph (4-F)

683 PhCH ₂ Ph H 5 CH-H Ph (4-F) Ph (4-F)

684 PhCH ₂ Ph H 3 CH-0H Ph (4-F) Ph (4-F)

685 PhCH ₂ Ph H 4 CH 0H Ph (4-F) Ph (4-F)

686 PhCH ₂ Ph H 5 CH 0H Ph (4-F) Ph (4-F)

687 PhCH ₂ Ph H 2 CH 0 H Ph (4-F) Ph (4-F)

688 PhCH ₂ Ph H 3 CH 0 H Ph (4-F) Ph (4-F)

689 PhCH ₂ Ph H 4 CH 0 H Ph (4-F) Ph (4-F)

690 PhCH ₂ Ph H 5 CH 0 H Ph (4_F) Ph (4-F) Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

691 PhCH ₂ CH ₂ Ph H 2 N-H Ph (4-F) Ph (4-F)

692 PhCH ₂ CH ₂ Ph H 3 N ― H Ph (4-F) Ph (4-F)

693 PhCH ₂ CH ₂ Ph H 4 N-H Ph (4-F) Ph (4-F)

694 PhCH ₂ CH ₂ Ph H 5 N-H Ph (4-F) Ph (4-F)

695 PhCH ₂ CH ₂ Ph H 6 N-H Ph (4-F) Ph (4-F)

696 PhCH ₂ CH ₂ Ph H 3 CH-H Ph (4-F) Ph (4-F)

697 PhCH ₂ CH ₂ Ph H 4 CH-H Ph (4-F) Ph (4-F)

698 PhCH ₂ CH ₂ Ph H 5 CH-H Ph (4-F) Ph (4-F)

699 PhCH ₂ CH ₂ Ph H 3 CH-0H Ph (4-F) Ph (4-F)

700 PhCH ₂ CH ₂ Ph H 4 CH 1 0H Ph (4-F) Ph (4-F)

701 PhCH ₂ CH ₂ Ph H 5 CH-0H Ph (4-F) Ph (4-F)

702 PhCH ₂ CH ₂ Ph H 2 CH 0 H Ph (4-F) Ph (4-F)

703 PhCH ₂ CH ₂ Ph H 3 CH 0 H Ph (4- F) Ph (4-F)

704 PhCH ₂ CH ₂ Ph H 4 CH 0 H Ph (4-F) Ph (4-F)

705 PhCH ₂ CH ₂ Ph H 5 CH 0 H Ph (4-F) Ph (4-F)

706 Et0C0CH ₂ Ph H 3 N-H Ph Ph

707 Et0C0CH ₂ Ph H 4 N-H Ph Ph

708 Et0C0CH ₂ Ph H 3 CH 0 H Ph Ph

709 Me Ph Me 3 N-H Ph Ph

710 Me Ph Me 4 N-H Ph Ph

711 Me Ph Me 3 CH 0 H Ph Ph

712 Me Ph Et 3 N One H Ph Ph

713 Me Ph Et 4 N-H Ph Ph

714 Me Ph Et 3 CH 0 H Ph Ph

715 Me Ph Pr 3 N H Ph Ph

716 Me Ph Pr 4 N H Ph Ph

717 Me Ph Pr 3 CH 0 H Ph Ph

718 PhCH ₂ Ph Me 3 NH Ph Ph

719 PhCH _z Ph Me 4 NH Ph Ph

720 PhC¾ Ph Me 3 CH 0 H Ph Ph / O u ποAV

CO

 I

One

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

751 H Ph (4-F) H 3 N-H Ph Ph

752 H Ph (4-F) H 4 N-H Ph Ph

753 H Ph (4-F) H 5 N-H Ph Ph

754 H Ph (4-F) H 3 CH-H Ph Ph

755 H Ph (4-F) H 3 CH-0H Ph Ph

756 H Ph (4-F) H 3 CH 0 H Ph Ph

757 Me Ph (4-F) H 2 N-H Ph Ph

758 Me Ph (4-F) H 3 N-H Ph Ph

759 Me Ph (4-F) H 4 N-H Ph Ph

760 Me Ph (4-F) H 5 N one H Ph Ph

761 Me Ph (4-F) H 6 N-H Ph Ph

762 Me Ph (4-F) H 3 CH-H Ph Ph

763 Me Ph (4-F) H 3 CH 1 0H Ph Ph

764 Me Ph (4-F) H 3 CH 0 H Ph Ph

765 Et Ph (4- F) H 3 N-H Ph Ph

766 Et Ph (4-F) H 3 CH-H Ph Ph

767 Et Ph (4-F) H 3 CH-0H Ph Ph

768 Et Ph (4-F) H 3 CH 0 H Ph Ph

769 Me Ph (4-F) Me 3 N-H Ph Ph

770 Me Ph (4-F) Me 3 CH 0 H Ph Ph

771 Me Ph (4-F) H 3 N-H Ph Ph (4-F)

772 Me Ph (4-F) H 3 CH 0 H Ph Ph (4-F)

773 Me Ph (4-F) H 3 N-H Ph Ph (4-Cl)

774 Me Ph (4-F) H 3 CH 0 H Ph Ph (4-Cl)

775 Me Ph (4-F) H 3 N H Ph Ph (4-Me)

776 Me Ph (4-F) H 3 CH 0 H Ph Ph (4-Me)

777 Me Ph (4-F) H 3 N H Ph Ph (4-OMe)

778 Me Ph (4-F) H 3 CH 0 H Ph Ph (4-OMe)

779 Me Ph (4-F) H 3 N H Ph (4-F) Ph (4-F)

780 Me Ph (4-F) H 3 CH 0 H Ph (4-F) Ph (4-F) Four

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

781 H Ph (4-Cl) H 3 N-H Ph Ph

782 H Ph (4-Cl) H 4 N 1 H Ph Ph

783 H Ph (4-Cl) H 5 N-H Ph Ph

784 H Ph (4-Cl) H 3 CH-H Ph Ph

785 H Ph (4-Cl) H 3 CH-0H Ph Ph

786 H Ph (4-C1) H 3 CH 0 H Ph Ph

787 Me Ph (4-Cl) H 2 N-H Ph Ph

788 Me Ph (4-Cl) H 3 N-H Ph Ph

789 Me Ph (4-CI) H 4 N-H Ph Ph

790 Me Ph (4-Cl) H 5 N-H Ph Ph

791 Me Ph (4-Cl) H 6 N-H Ph Ph

792 Me Ph (4-Cl) H 3 CH-H Ph Ph

793 Me Ph (4-Cl) H 3 CH-0H Ph Ph

794 Me Ph (4-Cl) .H 3 CH 0 H Ph Ph

795 Et Ph (4-Cl) H 3 N-H Ph Ph

796 Et Ph (4-Cl) H 3 CH-H Ph Ph

797 Et Ph (4-Cl) H 3 CH-0H Ph Ph

798 Et Ph (4-Cl) H 3 CH 0 H Ph Ph

799 Me Ph (4-Cl) Me 3 N-H Ph Ph

800 Me Ph (4-Cl) Me 3 CH 0 H Ph Ph

801 Me Ph (4-Cl) H 3 N one H Ph Ph (4-F)

802 Me Ph (4-Cl) H 3 CH 0 H Ph Ph (4-F)

803 Me Ph (4-Cl) H 3 N 1 H Ph Ph (4-Cl)

804 Me Ph (4-Cl) H 3 CH 0 H Ph Ph (4- CI)

805 Me Ph (4-Cl) H 3 N H Ph Ph (4-Me)

806 Me Ph (4-Cl) H 3 CH 0 H Ph Ph (4-Me)

807 Me Ph (4-Cl) H 3 N H Ph Ph (4-0Me)

808 Me Ph (4-Cl) H 3 CH 0 H Ph Ph (4-0Me)

809 Me Ph (4-Cl) H 3 N H Ph (4-F) Ph (4-F)

810 Me Ph (4-Cl) H 3 CH 0 H Ph (4-F) Ph (4-F) / O, 8 ποAV

Csl dimensions

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

841 H Ph (4-Me) H 3 N-H Ph Ph

842 H Ph (4-Me) H 4 N-H Ph Ph

843 H Ph (4-Me) H 5 N-H Ph Ph

844 H Ph (4-Me) H 3 CH-H Ph Ph

845 H Ph (4- Me) H 3 CH-0H Ph Ph

846 H Ph (4-Me) H 3 CH 0 H Ph Ph

847 Me Ph (4- Me) H 2 N-H Ph Ph

848 Me Ph (4-Me) H 3 N-H Ph Ph

849 Me Ph (4- Me) H 4 N-H Ph Ph

850 Me Ph (4- Me) H 5 N-H Ph Ph

851 Me Ph (4-Me) H 6 N-H Ph Ph

852 Me Ph (4- Me) H 3 CH-H Ph Ph

853 Me Ph (4- Me) H 3 CH-0H Ph Ph

854 Me Ph (4-Me) H 3 CH 0 H Ph Ph

855 Et Ph (4- Me) H 3 N-H Ph Ph

856 Et Ph (4-Me) H 3 CH one H Ph Ph

857 Et Ph (4- Me) H 3 CH-0H Ph Ph

858 Et Ph (4-Me) H 3 CH 0 H Ph Ph

859 Me Ph (4- Me) Me 3 N-H Ph Ph

860 Me Ph (4-Me) Me 3 CH 0 H Ph Ph

861 Me Ph (4-Me) H 3 N one H Ph Ph (4-F)

862 Me Ph (4- Me) H 3 CH 0 H Ph Ph (4-F)

863 Me Ph (4-Me) H 3 N one H Ph Ph (4- CI)

864 Me Ph (4-Me) H 3 CH 0 H Ph Ph (4-Cl)

865 Me Ph (4-Me) H 3 N H Ph Ph (4- Me)

866 Me Ph (4-Me) H 3 CH 0 H Ph Ph (4- Me)

867 Me Ph (4- Me) H 3 N H Ph Ph (4- OMe)

868 Me Ph (4- Me) H 3 CH 0 H Ph Ph (4-0Me)

869 Me Ph (4-Me) H 3 N H Ph (4-F) Ph (4-F)

870 Me Ph (4-Me) H 3 CH 0 H Ph (4-F) Ph (4-F) i

Dimensions

Compound R ¹ Ar ¹ R ² ra XYZ Ar ² Ar ³

901 H Ph (2-OMe) H 3 N-H Ph Ph

902 H Ph (2-OMe) H 4 N-H Ph Ph

903 H Ph (2-OMe) H 5 N-H Ph Ph

904 H Ph (2-OMe) H 3 CH-H Ph Ph

905 H Ph (2-OMe) H 3 CH 1 0H Ph Ph

906 H Ph (2-OMe) H 3 CH 0 H Ph Ph

907 Me Ph (2-OMe) H 2 N-H Ph Ph

908 Me Ph (2-OMe) H 3 N-H Ph Ph

909 Me Ph (2-OMe) H 4 N-H Ph Ph

910 Me Ph (2-OMe) H 5 N-H Ph Ph

911 Me Ph (2-OMe) H 6 N H Ph Ph

912 Me Ph (2-OMe) H 3 CH-H Ph Ph

913 Me Ph (2-OMe) H 3 CH-0H Ph Ph

914 Me Ph (2-OMe) H 3 CH 0 H Ph Ph

915 Et Ph (2-OMe) H 3 N one H Ph Ph

916 Et Ph (2-OMe) H 3 CH-H Ph Ph

917 Et Ph (2-OMe) H 3 CH-0H Ph Ph

918 Et Ph (2- OMe) H 3 CH 0 H Ph Ph

919 Me Ph (2-OMe) Me 3 N-H Ph Ph

920 Me Ph (2-OMe) Me 3 CH 0 H Ph Ph

921 Me Ph (2-OMe) H 3 N-H Ph Ph (4-F)

922 Me Ph (2-OMe) H 3 CH 0 H Ph Ph (4-F)

923 Me Ph (2-OMe) H 3 N one H Ph Ph (4-Cl)

924 Me Ph (2-OMe) H 3 CH 0 H Ph Ph (4-Cl)

925 Me Ph (2-OMe) H 3 N H Ph Ph (4-Me)

926 Me Ph (2-OMe) H 3 CH 0 H Ph Ph (4-Me)

927 Me Ph (2-OMe) H 3 N H Ph Ph (4- OMe)

928 Me Ph (2-OMe) H 3 CH 0 H Ph Ph (4- OMe)

929 Me Ph (2-OMe) H 3 N H Ph (4-F) Ph (4-F)

930 Me Ph (2-OMe) H 3 CH 0 H Ph (4-F) Ph (4-F) / O, 8 ποAV

OAV

e

Dimension

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

991 H Ph (4-CH ₂ C0 ₂ Et) H 3 N-H Ph Ph

992 H Ph (4-CH ₂ C0 ₂ Et) H 4 N-H Ph Ph

993 H Ph (4-CH ₂ C0 ₂ Et) H 5 N-H Ph Ph

994 H Ph (4-CH ₂ C0 ₂ Et) H 3 CH-H Ph Ph

995 H Ph (4-CH ₂ C0 ₂ Et) H 3 CH-0H Ph Ph

996 H Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph

997 Me Ph (4-CH ₂ C0 ₂ Et) H 2 N-H Ph Ph

998 Me Ph (4-CH ₂ C0 ₂ Et) H 3 N-H Ph Ph

999 Me Ph (4-CH ₂ C0 ₂ Et) H 4 N-H Ph Ph

1000 Me Ph (4-CH ₂ C0 ₂ Et) H 5 N-H Ph Ph

1001 Me Ph (4-CH ₂ C0 ₂ Et) H 6 N-H Ph Ph

1002 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH-H Ph Ph

1003 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 1 0H Ph Ph

1004 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph

1005 Et Ph (4-CH ₂ C0 ₂ Et) H 3 N-H Ph Ph

1006 Et Ph (4-C¾C0 ₂ Et) H 3 CH one H Ph Ph

1007 Et Ph (4-CH ₂ C0 ₂ Et) H 3 CH-0H Ph Ph

1008 Et Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph

1009 Me Ph (4-CH ₂ C0 ₂ Et) Me 3 N-H Ph Ph

1010 Me Ph (4-CH ₂ C0 ₂ Et) Me 3 CH 0 H Ph Ph

1011 Me Ph (4-CH ₂ C0 ₂ Et) H 3 N-H Ph Ph (4-F)

1012 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph (4-F)

1013 Me Ph (4-CH ₂ C0 ₂ Et) H 3 N mono H Ph Ph (4-Cl)

1014 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph (4-Cl)

1015 Me Ph (4-CH ₂ C0 ₂ Et) H 3 NH Ph Ph (4-Me)

1016 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph (4-Me)

1017 Me Ph (4-CH ₂ C0 ₂ Et) H 3 NH Ph Ph (4-0Me)

1018 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph Ph (4-OMe)

1019 Me Ph (4-CH ₂ C0 ₂ Et) H 3 NH Ph (4-F) Ph (4-F)

1020 Me Ph (4-CH ₂ C0 ₂ Et) H 3 CH 0 H Ph (4-F) Ph (4-F) Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

1021 H Ph (4-CH ₂ C0 ₂ H) H 3 N-H Ph Ph

1022 H Ph (4-CH ₂ C0 ₂ H) H 4 N 1 H Ph Ph

1023 H Ph (4-CH ₂ C0 ₂ H) H 5 N 1 H Ph Ph

1024 H Ph (4-CH ₂ C0 ₂ H) H 3 CH-H Ph Ph

1025 H Ph (4-CH ₂ C0 ₂ H) H 3 CH 1 0H Ph Ph

1026 H Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph

1027 Me Ph (4-CH ₂ C0 ₂ H) H 2 N 1 H Ph Ph

1028 Me Ph (4-CH ₂ C0 ₂ H) H 3 N-H Ph Ph

1029 Me Ph (4-CH ₂ C0 ₂ H) H 4 N 1 H Ph Ph

1030 Me Ph (4-CH ₂ C0 ₂ H) H 5 N-H Ph Ph

1031 Me Ph (4- C¾C0 ₂ H) H 6 N-H Ph Ph

1032 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH-H Ph Ph

1033 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH-0H Ph Ph

1034 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph

1035 Et Ph (4-CH ₂ C0 ₂ H) H 3 N 1 H Ph Ph

1036 Et Ph (4-CH ₂ C0 ₂ H) H 3 CH-H Ph Ph

1037 Et Ph (4-CH ₂ C0 ₂ H) H 3 CH one 0H Ph Ph

1038 Et Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph

1039 Me Ph (4-CH ₂ C0 ₂ H) Me 3 N-H Ph Ph

1040 Me Ph (4-CH ₂ C0 ₂ H) Me 3 CH 0 H Ph Ph

1041 Me Ph (4-CH ₂ C0 ₂ H) H 3 N-H Ph Ph (4-F)

1042 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph (4-F)

1043 Me Ph (4-CH ₂ C0 ₂ H) H 3 N-H Ph Ph (4-Cl)

1044 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph (4-Cl)

1045 Me Ph (4-CH ₂ C0 ₂ H) H 3 NH Ph Ph (4-Me)

1046 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph (4- Me)

1047 Me Ph (4-C¾C0 ₂ H) H 3 NH Ph Ph (4-0Me)

1048 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph Ph (4-0Me)

1049 Me Ph (4-CH ₂ C0 ₂ H) H 3 NH Ph (4-F) Ph (4-F)

1050 Me Ph (4-CH ₂ C0 ₂ H) H 3 CH 0 H Ph (4-F) Ph (4-F)

Five

Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

1081 H Ph (4-C0 ₂ Et) H 3 N one H Ph Ph

1082 H Ph (4-C0 ₂ Et) H 4 N-H Ph Ph

1083 H Ph (4-C0 ₂ Et) H 5 N 1 H Ph Ph

1084 H Ph (4-C0 ₂ Et) H 3 CH ― H Ph Ph

1085 H Ph (4-C0 ₂ Et) H 3 CH-0H Ph Ph

1086 H Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph

1087 Me Ph (4-C0 ₂ Et) H 2, N-H Ph Ph

1088 Me Ph (4-C0 ₂ Et) H 3 N-H Ph Ph

1089 Me Ph (4-C0 ₂ Et) H 4 N-H Ph Ph

1090 Me Ph (4-C0 ₂ Et) H 5 N-H Ph Ph

1091 Me Ph (4-C0 ₂ Et) H 6 N-H Ph Ph

1092 Me Ph (4-C0 ₂ Et) H 3 CH-H Ph Ph

1093 Me Ph (4-C0 ₂ Et) H 3 CH-0H Ph Ph

1094 Me Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph

1095 Et Ph (4-C0 ₂ Et) H 3 N one H Ph Ph

1096 Et Ph (4-C0 ₂ Et) H 3 CH-H Ph Ph

1097 Et Ph (4-C0 ₂ Et) H 3 CH-0H Ph Ph

1098 Et Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph

1099 Me Ph (4-C0 ₂ Et) Me 3 N-H Ph Ph

1100 Me Ph (4-C0 ₂ Et) Me 3 CH 0 H Ph Ph

1101 Me Ph (4-C0 ₂ Et) H 3 N-H Ph Ph (4-F)

1102 Me Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph (4-F)

1103 Me Ph (4-C0 ₂ Et) H 3 N 1 H Ph Ph (4-Cl)

1104 Me Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph (4-Cl)

1105 Me Ph (4- C0 ₂ Et) H 3 NH Ph Ph (4- Me)

1106 Me Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph (4- Me)

1107 Me Ph (4-C0 ₂ Et) H 3 NH Ph Ph (4-OMe)

1108 Me Ph (4-C0 ₂ Et) H 3 CH 0 H Ph Ph (4-OMe)

1109 Me Ph (4-C0 ₂ Et) H 3 NH Ph (4-F) Ph (4-F)

1110 Me Ph (4- C0 ₂ Et) H 3 CH 0 H Ph (4-F) Ph (4-F) Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

1111 H Ph (3-C0 ₂ H) H 3 N-H Ph Ph

1112 H Ph (3- C0 ₂ H) H 4 N-H Ph Ph

1113 H Ph (3-C0 ₂ H) H 5 N-H Ph Ph

1114 H Ph (3- C0 ₂ H) H 3 CH-H Ph Ph

1115 H Ph (3- C0 ₂ H) H 3 CH-0H Ph Ph

1116 H Ph (3-C0 ₂ H) H 3 CH 0 H Ph Ph

1117 Me Ph (3-C0 ₂ H) H 2 N-H Ph Ph

1118 Me Ph (3-C0 ₂ H) H 3 N-H Ph Ph

1119 Me Ph (3-C0 ₂ H) H 4 N one H Ph Ph

1120 Me Ph (3-C0 ₂ H) H 5 N-H Ph Ph

1121 Me Ph (3-C0 ₂ H) H 6 N-H Ph Ph

1122 Me Ph (3- C0 ₂ H) H 3 CH-H Ph Ph

1123 Me Ph (3-C0 ₂ H) H 3 CH-0H Ph Ph

1124 Me Ph (3-C0 ₂ H) H 3 CH 0 H Ph Ph

1125 Et Ph (3- C0 ₂ H) H 3 N-H Ph Ph

1126 Et Ph (3-C0 ₂ H) H 3 CH-H Ph Ph

1127 Et Ph (3-C0 ₂ H) H 3 CH-0H Ph Ph

1128 Et Ph (3- C0 ₂ H) H 3 CH 0 H Ph Ph

1129 Me Ph (3-C0 ₂ H) Me 3 N-H Ph Ph

1130 Me Ph (3-C0 ₂ H) Me 3 CH 0 H Ph Ph

1131 Me Ph (3-C0 ₂ H) H 3 N 1 H Ph Ph (4-F)

1132 Me Ph (3-C0 ₂ H) H 3 CH 0 H Ph Ph (4-F)

1133 Me Ph (3- C0 ₂ H) H 3 N-H Ph Ph (4-Cl)

1134 Me Ph (3-C0 ₂ H) H 3 CH 0 H Ph Ph (4-Cl)

1135 Me Ph (3- C0 ₂ H) H 3 NH Ph Ph (4- Me)

1136 Me Ph (3-C0 ₂ H) H 3 CH 0 H Ph Ph (4-Me)

1137 Me Ph (3-C0 ₂ H) H 3 NH Ph Ph (4- OMe)

1138 Me Ph (3-C0 ₂ H) H 3 CH 0 H Ph Ph (4-0Me)

1139 Me Ph (3-C0 ₂ H) H 3 NH Ph (4-F) Ph (4-F)

1140 Me Ph (3-C0 ₂ H) H 3 CH 0 H Ph (4-F) Ph (4-F) Compound R ¹ Ar ¹ m XY z Ar ² A

1141 H Ph (4-C0 ₂ H) H 3 NH Ph Ph

1142 H Ph (4-C0 ₂ H) H 4 NH Ph Ph

1143 H Ph (4-C0 ₂ H) H 5 NH Ph Ph

1144 H Ph (4-C0 ₂ H) H 3 CH H Ph Ph

1145 H Ph (4-C0 ₂ H) H 3 CH OH Ph Ph

1146 H Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph

1147 Me Ph (4-C0 ₂ H) H 2 NH Ph Ph

1148 Me Ph (4-C0 ₂ H) H 3 NH Ph Ph

1149 Me Ph (4-C0 ₂ H) H 4 N one H Ph Ph

1150 Me Ph (4-C0 ₂ H) H 5 N one H Ph Ph

1151 Me Ph (4-C0 ₂ H) H 6 NH Ph Ph

1152 Me Ph (4-C0 ₂ H) H 3 CH H Ph Ph

1153 Me Ph (4-C0 ₂ H) H 3 CH OH Ph Ph

1154 Me Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph

1155 Et Ph (4-C0 ₂ H) H 3 NH Ph Ph

1156 Et Ph (4-C0 ₂ H) H 3 CH H Ph Ph

1157 Et Ph (4-C0 ₂ H) H 3 CH OH Ph Ph

1158 Et Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph

1159 Me Ph (4-C0 ₂ H) Me 3 NH Ph Ph

1160 Me Ph (4-C0 ₂ H) Me 3 CH 0 H Ph Ph

1161 Me Ph (4-C0 ₂ H) H 3 NH Ph Ph (4-F)

1162 Me Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph (4-F)

1163 Me Ph (4-C0 ₂ H) H 3 NH Ph Ph (4-CI)

1164 Me Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph (4-Cl)

1165 Me Ph (4-C0 ₂ H) H 3 NH Ph Ph (4-Me)

1166 Me Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph (4- Me)

1167 Me Ph (4-C0 ₂ H) H 3 NH Ph Ph (4-OMe)

1168 Me Ph (4-C0 ₂ H) H 3 CH 0 H Ph Ph (4-OMe)

1169 Me Ph (4-C0 ₂ H) H 3 NH Ph (4-F) Ph (4-F)

1170 Me Ph (4-C0 ₂ H) H 3 CH 0 H Ph (4_F) Ph (4-F) cn

 丽 CO-

- Compound R ¹ Ar ¹ R ² m XYZ Ar ² Ar ³

1201 H Ph (4-C0NH ₂ ) H 3 N-H Ph Ph

1202 H Ph (4-C0NH ₂ ) H 4 N-H Ph Ph

1203 H Ph (4-C0 H ₂ ) H 5 N-H Ph Ph

1204 H Ph (4-C0 H ₂ ) H 3 CH-H Ph Ph

1205 H Ph (4-C0NH ₂ ) H 3 CH-0H Ph Ph

1206 H Ph (4-CO orchid ₂ ) H 3 CH 0 H Ph Ph

1207 Me Ph (4-C0NH ₂ ) H 2 N-H Ph Ph

1208 Me Ph (4-C0NH ₂ ) H 3 N-H Ph Ph

1209 Me Ph (4-C0 H ₂ ) H 4 N-H Ph Ph

1210 Me Ph (4-C0NH ₂ ) H 5 N-H Ph Ph

1211 Me Ph (4-C0 H ₂ ) H 6 N-H Ph Ph

1212 Me Ph (4-CO 丽₂ ) H 3 CH-H Ph Ph

1213 Me Ph (4-C0NH ₂ ) H 3 CH-0H Ph Ph

1214 Me Ph (4-C0NH ₂ ) H 3 CH 0 H Ph Ph

1215 Et Ph (4-CONH ₂ ) H 3 N-H Ph Ph

1216 Et Ph (4-CONH ₂ ) H 3 CH-H Ph Ph

1217 Et Ph (4-CONH ₂ ) H 3 CH-0H Ph Ph

1218 Et Ph (4-C0NH ₂ ) H 3 CH 0 H Ph Ph

1219 Me Ph (4-C0NH ₂ ) Me 3 N-H Ph Ph

1220 Me Ph (4-C0NH ₂ ) Me 3 CH 0 H Ph Ph

1221 Me Ph (4-C0NH ₂ ) H 3 N-H Ph Ph (4-F)

1222 Me Ph (4-C0NH ₂ ) H 3 CH 0 H Ph Ph (4-F)

1223 Me Ph (4-C0NH ₂ ) H 3 N-H Ph Ph (4-Cl)

1224 Me Ph (4-C0 H ₂ ) H 3 CH 0 H Ph Ph (4-Cl)

1225 Me Ph (4-C0 ¾) H 3 N H Ph Ph (4- Me)

1226 Me Ph (4-C0NH ₂ ) H 3 CH 0 H Ph Ph (4-Me)

1227 Me Ph (4-C0 H ₂ ) H 3 NH Ph Ph (4-0Me)

1228 Me Ph (4-C0NH ₂ ) H 3 CH 0 H Ph Ph (4- OMe)

1229 Me Ph (4-C0NH ₂ ) H 3 NH Ph (4-F) Ph (4-F)

1230 Me Ph (4-CONH ₂ ) H 3 CH 0 H Ph (4-F) Ph (4-F)

zs .8.ll0 / C00Zdf / X3d 89 contract 00Z OAV

 Halla

9 .8.llO / COOZdf / X3d 89 contract OAV

Compound R ¹ Ar ¹ R ² m XY n

1436 Me Ph (4-F) H 4 N-1

1437 Me Ph (4-F) H 3 CH 0 1

1438 Me Ph (4-F) H 3 N-2

1439 Me Ph (4-F) H 4 N-2

1440 Me Ph (4-F) H 3 CH 0 2

1441 Et Ph (4-F) H 3 N 1

1442 Et Ph (4-F) H 4 N 1

1443 Et Ph (4-F) H 3 CH 0 1

1444 Et Ph (4-F) H 3 N one 2

1445 Et Ph (4-F) H 4 N ― 2

1446 Et Ph (4-F) H 3 CH 0 2

1447 Me Ph (4-F) Me 3 N-1

1448 Me Ph (4-F) Me 4 N-1

1449 Me Ph (4-F) Me 3 CH 0 1

1450 Me Ph (4-F) Me 3 N-2

1451 Me Ph (4-F) Me 4 N-2

1452 Me Ph (4-F) Me 3 CH 0 2

1453 H Ph (2, 3-Me ₂ ) H 3 N-1

1454 H Ph (2, 3-Me ₂ ) H 4 N-1

1455 H Ph (2, 3-Me ₂ ) H 3 CH 0 1

1456 H Ph (2, 3-Me ₂ ) H 3 N-2

1457 H Ph (2, 3-Me ₂ ) H 4 N-2

1458 H Ph (2, 3-Me ₂ ) H 3 CH 0 2

1459 Me Ph (2, 3-Me ₂ ) H 3 N-1

1460 Me Ph (2, 3-Me ₂ ) H 4 N-1

1461 Me Ph (2, 3-Me ₂ ) H 3 CH 0 1

1462 Me Ph (2, 3-Me ₂ ) H 3 N 2

1463 Me Ph (2, 3-Me ₂ ) H 4 N 2

1464 Me Ph (2, 3-Me ₂ ) H 3 CH 0 2

1465 Et Ph (2, 3-Me ₂ ) H 3 N 1

1466 Et Ph (2, 3-Me ₂ ) H 4 N 1 Compound R ¹ Ar ¹ R ² ra XY n

1467 Et Ph (2, 3-Me ₂ ) H 3 CH 0 1

1468 Et Ph (2, 3-Me ₂ ) H 3 N ― 2

1469 Et Ph (2, 3-Me ₂ ) H 4 N 1 2

1470 Et Ph (2, 3-Me ₂ ) H 3 CH 0 2

1471 Me Ph (2, 3— Me ₂ ) Me 3. N one 1

1472 Me Ph (2, 3-Me ₂ ) Me 4 N ― 1

1473 Me Ph (2, 3-Me ₂ ) Me 3 CH 0 1

1474 Me Ph (2, 3-Me ₂ ) Me 3 N one 2

1475 Me Ph (2, 3-Me ₂ ) Me 4 N ― 2

1476 Me Ph (2, 3-Me ₂ ) Me 3 CH 0 2

1477 H Ph (2-OMe) H 3 N 1

1478 H Ph (2-OMe) H 4 N one 1

1479 H Ph (2-OMe) H 3 CH 0 1

1480 H Ph (2-OMe) H 3 N ― 2

1481 H Ph (2-OMe) H 4 N ― 2

1482 H Ph (2-OMe) H 3 CH 0 2

1483 Me Ph (2-OMe) H 3 N 1

1484 Me Ph (2-OMe) H 4 N ― 1

1485 Me Ph (2-OMe) H 3 CH 0 1

1486 Me Ph (2-OMe) H 3 N ― 2

1487 Me Ph (2-OMe) H 4 N ― 2

1488 Me Ph (2-OMe) H 3 CH 0 2

1489 Et Ph (2-OMe) H 3 N 1

1490 Et Ph (2-OMe) H 4 N 1

1491 Et Ph (2-OMe) H 3 CH 0 1

1492 Et Ph (2-OMe) H 3 N 2

1493 Et Ph (2-OMe) H 4 N 2

1494 Et Ph (2-OMe) H 3 CH 0 2

1495 Me Ph (2-OMe) Me 3 N 1

1496 Me Ph (2-OMe) Me 4 N 1

1497 Me Ph (2-OMe) Me 3 CH 0 1 Compound R ¹ Ar ¹ R ² m XY n

1498 Me Ph (2-0Me) Me 3 N-2

1499 Me Ph (2- OMe) Me 4 N-2

1500 Me Ph (2- OMe) Me 3 CH 0 2

1501 H Ph (4-C0 ₂ Et) H 3 N-1

1502 H Ph (4-C0 ₂ Et) H 4 N-1

1503 H Ph (4-C0 ₂ Et) H 3 CH 0 1

1504 H Ph (4-C0 ₂ Et) H 3 N-2

1505 H Ph (4-C0 ₂ Et) H 4 N-2

1506 H Ph (4- C0 ₂ Et) H 3 CH 0 2

1507 Me Ph (4-C0 ₂ Et) H 3 N-1

1508 Me Ph (4-C0 ₂ Et) H 4 N-1

1509 Me Ph (4-C0 ₂ Et) H 3 CH 0 1

1510 Me Ph (4-C0 ₂ Et) H 3 N-2

1511 Me Ph (4-C0 ₂ Et) H 4 N one 2

1512 Me Ph (4-C0 ₂ Et) H 3 CH 0 2

1513 Et Ph (4-C0 ₂ Et) H 3 N-1

1514 Et Ph (4-C0 ₂ Et) H 4 N-1

1515 Et Ph (4-C0 ₂ Et) H 3 CH 0 1

1516 Et Ph (4-C0 ₂ Et) H 3 N-2

1517 Et Ph (4-C0 ₂ Et) H 4 N-2

1518 Et Ph (4-C0 ₂ Et) H 3 CH 0 2

1519 Me Ph (4-C0 ₂ Et) Me 3 N-1

1520 Me Ph (4-C0 ₂ Et) Me 4 N one 1

1521 Me Ph (4-C0 ₂ Et) Me 3 CH 0 1

1522 Me Ph (4-C0 ₂ Et) Me 3 N one 2

1523 Me Ph (4-C0 ₂ Et) Me 4 N 2

1524 Me Ph (4-C0 ₂ Et) Me 3 CH 0 2

1525 H Ph (3-C0 ₂ H) H 3 N 1

1526 H Ph (3-C0 ₂ H) H 4 N 1

1527 H Ph (3- C0 ₂ H) H 3 CH 0 1

_{1528 H Ph (3-C0 2} H) H 3 N 2

 1610 Et Ph (4-CN) H 4 N-1

1611 Et Ph (4-CN) H 3 CH 0 1

Urashiru derivative represented by the general formula (I), _t which can be synthesized according to the following formula

(In the formula, Hal represents a halogen atom, and R ² , Ar \ Ar ² , Ar ³ , X, Y, Z and m have the same meanings as described above.)

 That is, it can be synthesized by reacting 1-aryl-16-halo 2,4 (1H, 3H) -pyrimidinedione represented by the formula (II) with an amine represented by the formula (III). The 1-aryl-16-halo 2,4 (1H, 3H) -pyrimidinedione represented by the formula (II) can be synthesized, for example, by the method described in JP-A-8-109171. The amine represented by the formula (III) can be synthesized, for example, by the method described in JP-A-11-310581.

 Since the peracyl derivative represented by the general formula (I) has a basic tertiary amino group, it can form salts with various acids. Pharmaceutically acceptable salts include hydrochloride, sulfate, acetate, succinate and the like. In addition, when the peracyl derivative has an acidic substituent, it may form a salt with various bases. In this case, the pharmaceutically acceptable salt includes a sodium salt, a potassium salt, a calcium salt, an ammonium salt and the like. These salts can be obtained by a conventional method such as recrystallization after mixing a peracil derivative with an acid or a base.

The present invention also includes solvates such as hydrates and ethanol solvates of the peracyl derivative represented by the general formula (I) or a pharmaceutically acceptable salt. Further, in the present invention, All tautomers, all stereoisomers, such as optical isomers, of the peracyl derivative represented by the general formula (I), and crystal forms of all aspects are also included. The therapeutic drug for allergic diseases of the present invention (antihistamine, antiallergic drug, and preventive / therapeutic agent for allergic unilateral conjunctivitis, ryalgiitis rhinitis, chronic deprivation measles, atopic dermatitis, asthma or chronic bronchitis) is It can be used in various dosage forms including oral preparations such as tablets, capsules and powders, as well as injections and external preparations. For example, an ointment can be prepared by mixing a peracil derivative or a pharmaceutically acceptable salt of the present invention with an ointment base such as petrolatum. In addition, tablets are prepared by mixing the peracil derivative or the pharmaceutically acceptable salt of the present invention with excipients such as lactose and starch, lubricants such as magnesium stearate and talc, and other commonly used additives. You can also.

 The dose of the remedy for allergic diseases of the present invention is appropriately determined according to the patient's sex, age, weight, type of disease, symptoms, etc., for example, atopic dermatitis, contact dermatitis, psoriasis, etc. For skin diseases, the ointment containing 0.01 to 10% of the active ingredient can be applied to the affected area from lsi times to several times. Oral preparations such as tablets, capsules and powders can generally be administered in a single dose or in divided doses in the range of 0.01 to 100 mg / kg per day.

 Example

 Hereinafter, the present invention will be described specifically with reference to Examples, but the scope of the present invention is not limited thereto.

 (Reference Example 1) 3 _ (4-diphenylmethyl-1-piperazul) propylamine

5.0 Dissolve 5.0 g (20 mraol) of di (dipheni / lemethinole) piperazine in 150 ml of acetonitrile, 5.6 g (21 mraol) of 3-bromopropylphthalimide, 2.9 ml of triethylamine (21 mmol) ) And stirred at 80 ° C. for 2 hours. Acetonitrile was distilled off and the residue was diluted with dichloromethane. /. The mixture was partitioned with an aqueous solution of sodium hydrogen carbonate, and the organic layer was washed with a 5% aqueous solution of citric acid and a 10% aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. The dichloromethane was concentrated, the residue was dissolved in 200 ml of ethanol, 3.74 ml (59 mol) of 80% hydrazine was added, and the mixture was heated under reflux for 2 hours. Ethanol was distilled off, the residue was partitioned between 1N aqueous sodium hydroxide solution and dichloromethane, and the organic layer was washed with a 10% aqueous sodium chloride solution and dried over anhydrous sodium sulfate. Dichloromethane Was distilled off to give the title compound (5.5 g (18 mraol), two-step yield 90)

(Reference Example 2) 3- (4-bis (4-fluorophenyl) methyl-1-piperajule) propylamine

 The same procedure as in Reference Example 1 was carried out except that 1-bis (4-funorolelophenyl) methylbiperazine was used in place of 1- (dipheninolemethinole) piperazine to obtain the title compound.

 (Reference Example 3) 3- (4- ((4-Methylphenyl) phenylmethyl)-1-piladulyl) propylamine

 In the same manner as in Reference Example 1, the title compound was obtained in the same manner as in Reference Example 1 except that 1-((4-methinolepheninole) phenirmethinole) piperazine was used instead of 1- (dipheninolemethinole) piperazine.

(Reference Example 4) 3-(4- ((4-cloth fu-nore) pheninole methinole) — 1-piladul) propylamine

 The same procedure as in Reference Example 1 was carried out except that 1-((diphenolemethinole) piperazine was replaced with 1-((4-chloropheninole) phenylmethyl) piperazine to obtain the title compound.

(Reference Example 5) 3- (4-((4-Methoxyphenyl) phenylmethyl) — 1-piperazinyl) propyl / reamine

 In a similar manner to Reference Example 1, the title compound was obtained in the same manner as in Reference Example 1, except for using 11-((4-methoxyphenyl) pheninolemethinole) piperazine instead of 11- (diphenylmethyl) piperazine.

 (Reference Example 6) 3- (4-((4-fluorophenyl) pheninolemethyl) — 1-piperazinyl) propylamine

 The title compound was obtained in the same manner as in Reference Example 1 except for using 11-((4-fluorophenyl) phenylmethyl) piperazine instead of 11- (diphenylmethyl) piperazine.

 (Reference Example 7) 3- (4- (hydroxydiphenylmethyl) -11-piperidinyl) propinoleamine

1-(Dipheninolemethinole) α, α-dipheninole _ 4-pi in place of piperazine The title compound was obtained in the same manner as in Reference Example 1 using peridinylmethanol.

 (Reference Example 8) 3- (4-1 (10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5-yl) -1-piperazinyl) propylamine

 1- (10,11-dihydro-5H-dibenzo [a, d] cycloheptene-5-yl) pidazine was used instead of 1- (dipheninolemethinole) pidazine. The same procedure was performed to obtain the title compound.

 (Reference Example 9) 3- (4- (diphenylmethoxy) -1-1-piberidinyl) propylamine

 5.0 g (27 mmol) of benzhydrol was dissolved in 190 ml of toluene, 2.7 g (27 ramol) of 4-hydroxypiperidine and 5.7 g (30 raraol) of p-toluenesulfonic acid monohydrate were added, and the mixture was refluxed for 3 hours. . After cooling, the reaction solution was washed successively with a 5% aqueous sodium hydroxide solution and distilled water, and dried over anhydrous sodium sulfate. A part of the residue obtained by distilling off toluene was dissolved 1.2 g in 50 ml of acetonitrile, and 1.3 g (5.0 mmol) of 3-bromopropinolephthalimide and 697 μΐ (5.0 mmol) of triethynoleamine were added. Stir for 2 hours. After the acetonitrile was distilled off, the residue was partitioned between dichloromethane and a 5% aqueous sodium hydrogen carbonate solution, and the organic layer was washed with a 5% aqueous citric acid solution and a 10% aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. Dichloromethane was distilled off under reduced pressure, and the residue was purified by silica gel chromatography (dichloromethane: methanol = 70: 1 to 50: 1) to obtain 3- (4- (diphenylmethoxy) -11-piperidinyl) propylphthalimide. After dissolving in 50 ml of ethanol, 1.76 ml (28 mmol) of 80% hydrazine was added, and the mixture was heated under reflux for 2 hours. After the ethanol was distilled off, the residue was partitioned between a 1 N aqueous solution of sodium hydroxide and dichloromethane, and the organic layer was washed with a 10% aqueous solution of sodium chloride and then dried over sodium sulfate. Dichloromethane was distilled off under reduced pressure to obtain the title compound (1.7 g (5.2 mmol), yield of 3 steps: 19%).

 (Example 1) 6_ [3 -— [4 -— (dipheninolemethinole) -1-piperajur] propyramino] -1-methyl-1-phenylphenylacyl (Compound 17)

Dissolve 325 mg (1.1 ramol) of 3- (4- (diphenylmethyl) -11-piperazinyl) propylamine in 5 ml of dimethylsulfoxide, and add 237 mg (1.0 mmol) of Lou 1_phenylperacyl and 138 mg (1.3 mmol) of sodium carbonate were added, and the mixture was stirred at 100 ° C for 1.5 hours. After cooling, distilled water was added, extracted with ethyl acetate, and the organic layer was washed twice with distilled water. After concentration, it was redissolved in 30 ml of ethyl acetate and extracted with 1 N hydrochloric acid. The aqueous layer was adjusted to pH 11 with a 5N aqueous sodium hydroxide solution, extracted with ethyl acetate, and the organic layer was washed with a 10% aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The ethyl acetate was distilled off, and the residue was purified by silica gel column chromatography (dichloromethane: methanol = 80: 1 to 50: 1) to obtain the title compound (167 mg, 0.33 mmol, yield: 33%).

_{^ -NMR (CDC1 3, 6ppm)} : 7.15-7.56 (15H, m), 4.94 (1H, s), 4.34 (. 1H, br t, J = 5.1 Hz), 4.17 (1H, s), 3.32 (3H , S), 3.07 (2H, dt, J = 5.1 Hz, J = 6.5 Hz), 2.23-2.28 (10H, in), 1.62 (2H, tt, J = 6.5 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 510 (M + H)

 (Example 2) 6- [3- [4- (diphenylmethyl) -1-piperazul] ethylamino] -3-methyl-1-phenylperacil (Compound 16)

 The title compound was obtained in the same manner as in Example 1 except that 2- (4- (diphenylmethyl) -1-piperazyl) ethylamine was used instead of 3- (4- (diphenylmethyl) _1-piperazinyl) propylamine.

_{^ -NMR (CDC1 3, Sppm)} : 7.19-7.46 (15H, m), 5.00 (. 1H, br t, J = 4.1 Hz), 4.85 (1H, s), 4.21 (1H, s), 3.33 (3H , s), 2.97 (2H, dt, J = 4.1 Hz, J = 5.9 Hz), 2.42 (2H, t, J = 5.9 Hz), 2.20-2.30 (10H, m)

Time-of-flight mass spectrometer (TOF-Mass): 496 (M + H)

 (Example 3) 6- [3- [4- (diphenylmethyl) 1-1-piperogenole] ptynoleamino] -13-methyl-11-phenylperacyl (compound 18)

 The title compound was obtained in the same manner as in Example 1 except that 4- (4- (diphenylmethyl) -11-piperazul) butyramine was used instead of 3- (4- (diphenylmethyl) 1-1-piperazinyl) propylamine. .

^ -NMR (CDCI3, 6ppm): 7.14-7.56 (15H, m), 4.19 (1H, s), 3.70 (1H, br.t, J = 4.9 Hz), 3.23 (3H, s), 3.00 (2H, dt, J = 4.9 Hz, J = 6.5 Hz), 2.37 (8H, m), 2.26 (2H, t, J = 6.5 Hz), 1.33-1.50 (4H, ra) Time-of-flight mass spectrometer (TOF-Mass): 524 (M + H)

 (Example 4) 6- [3- [4-I- (diphenylmethoxy) -1-piperidinyl] -pyramino] -13-methyl-1-pheninoleperasinole (Compound 28)

 3- (4- (Diphenolenomethylenol) -11-piperazinole) The title compound was prepared in the same manner as in Example 1 using 3- (4- (dipheninolemethoxy) 1-1-piperidinyl) propylamine instead of propynoleamine. Got.

_{'H-NMR (CDC1 3,} δρρπι): 7.23-7.55 (15H, m), 5.47 (1H, s), 4.93 (1H, s), 4.74 (. 1H, br t, J = 4.3 Hz), 3.32 ( 4H, m), 3.09 (2H, dt, J = 4.3 Hz, J = 6.5 Hz), 2.51 (2H, m), 2.25 (2H, t, J = 6.5 Hz), 1.92 (2H, m), 1.57- 1.63 (4H, m) 1.41 (2H, m)

Time-of-flight mass spectrometer (TOF-Mass): 525 (M + H)

 (Example 5) 3-ethoxycarbonylmethyl-6- [3- [4- (diphenylmethyl) -1--1-piperazinyl] propylamino] —1-phenylperacyl (Compound 106)

 The title compound was obtained in the same manner as in Example 1, except that 6-chloro-3-ethoxyethoxycarbonylmethyl-1-phenylperacil was used instead of 6-chloro-3-methinolelate.

 ^-MR (CDCI3, δ ppm): 7.19-7.53 (14H, m), 5.30 (1H, s), 4.87 (1H, m), 4.67 (2H, s), 4.20 (2H, q, J = 7.0 Hz), 3.33 (2H, m), 2.27-2.87 (image, ra), 1.59 (2H, m), 1.26 (2H, t, J = 7.0 Hz),

Time-of-flight mass spectrometer (TOF-Mass): 582 (M + H)

 (Example 6) 6- [3- [4- (Diphenylmethyl) 1-1-piperazinyl] propylamino] —3-methyl-11- (1-naphthyl) peracyl (Compound 728)

 The title compound was obtained in the same manner as in Example 1, except that 6-chloro-3-methyl-1- (1-naphthyl) peracil was used instead of 6-chloro-3-methinolene.

^ -NMR (CDCI3, 6ppm): 7.99 (2H, m), 7.52-7.63 (10H, m), 7.37 (1H, d, J = 7.6 Hz), 7.17-7.38 (4H, m), 5.03 (1H, s), 4.42 (1H, br.t, J = 4.9 Hz), 4.09 (1H, s), 3.36 (3H, s), 3.04 (2H, m), 2.01-2.08 (10H, m), 1.53 (2H , M) ·

Time-of-flight mass spectrometer (TOF-Mass): 560 (M + H)

 (Example 7) 6- [3- [4- (diphenylmethoxy) -11-piperidinyl] propylpyramino] -13-methyl-11- (1-naphthyl) peracyl (compound 734) 6-chloro-3- Use 6-chloro-3-methyl-11- (1-naphthinole) percinole in place of methinolee 1-fue-norperazinole, and use 3 _ (4— (diphene) instead of 3- (4-1- (diphenylmethyl) _1-piperazinyl) propylamine. The title compound was obtained in the same manner as in Example 1 using dimethyl (11-piberidier) propylamine.

_{^ -NMR (CDC1 3, 6ppm)} : 7.93 (1H, d, J = 8.1 Hz), 7.84 (1H, m), 7.47-7.6

3 (5H, ra), 7.32 (10H, m), 5.42 (1H, s), 5.02 (1H, s), 4.77 (1H, brt, J = 4.9 Hz), 3.36 (3H, s), 3.21 (1H , ra), 3.05 (2H, m), 2.32 (2H, m), 2.07 (

4H, m), 1.49-1.73 (6H, m)

Time-of-flight mass spectrometer (TOF-Mass): 575 (M + H)

 (Example 8) 6- [3- [4- (Diphenylmethyl) -1-piperazul] propinoleamino] -1- (4-monofluorophenyl) -13-methylperacyl (Compound 75

8)

 The title compound was obtained in the same manner as in Example 1 except for using 6-chloro-1- (4-fluorophenyl) -13-methylperacyl in place of 6-chloro-3-methinolate.

^X HNR (CDCI3, 6ppm): 7.15-7.42 (14H, m), 4.93 (1H, s), 4.74 (1H, br.s), 4.16 (1H, s), 3.31 (3H, s), 3.19 ( 2H, m), 2.18-2.31 (lOH, m), 1.67 (2 H, m)

Time-of-flight mass spectrometer (TOF-Mass): 529 (M + H)

 (Example 9) 1- (4-chlorophenyl) -1-6- [3- (4- (diphenylmethyl) -1-piperazinyl] propylamino] -13-methylperacyl (Compound 788)

The same operation as in Example 1 was carried out using 6-chloro-1- (4-phenylphenyl) -13-methylperacyl instead of 6-chloro-3-methinolay Thus, the title compound was obtained.

丄11- employment _{R (CDC1 3, δρρπι):} 7.14-7.54 (14H, m), 4.93 (1H, s), 4.80 (. 1H, br t, J = 4.9 Hz), 4.21 (1H, s), 3.31 (3H, s), 3.08 (2H, dt, J = 4.9 Hz, J = 6.1 Hz), 2.15-2.32 (10H, ra), 1.65 (2H, tt, J = 6.1 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 545 (M + H)

 Example 10 1- (4-Bromophenyl) -6- [3- [4- (diphenylmethyl) -1-piperazul] propylamino] —3-methylperacyl (Compound 818)

 The title compound was obtained in the same manner as in Example 1 except for using 11- (4-bromophenyl) -16-methyl-3-methylperacil instead of 6-chloro-3-methyl-1-phenylperacil.

 ^ -NMR (CDClg, δρρηι): 7.14-7.71 (14H, m), 4.93 (1H, s), 4.78 (1H, br.t, J = 4.9 Hz), 4.24 (1H, s), 3.31 (3H, s), 3.08 (2H, dt, J = 4.9 Hz, J = 6.3 Hz), 2.15-2.32 (10H, m), 1.62 (2H, tt, J = 6.3 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 589 (M + H)

 (Example 1 1) 6- [3- [4- (Dipheninolemethinole) -1- (piperazul)] pyrupyramino] —3-Methyl-11 (4-methinolephenyl) peracyl (compound 848)

 The title compound was obtained in the same manner as in Example 1 except that 6-chloro-1-methyl-4- (4-methylphenyl) -peracil was used instead of 6-chloro-1-methyl-1-phenol-1. .

- thigh _{(CDC1 3, Sppm): 7.13-7.40} (14H, m), 4.92 (1H, s), 4.38 (. 1H, br t, J = 4.7 Hz), 4.15 (1H, s), 3.16 (3H, s), 3.07 (2H, dt, J = 4.7 Hz, J = 6.5 Hz), 2.42 (3H, s), 2.24-2.37 (m), 1.62 (2H, tt, J = 6.5 Hz) Mass spectrometer (TOF-Mass): 524 (M + H)

 Example 12 1- (2,3-Dimethylphenyl) -1-6- [3- [4- (diphenylmethyl) -1-1-piperazinyl] propylamino] —3-methylperacyl (Compound 878)

6—Black mouth 3—Metinore 1—Instead of Feenorelasinore 6_Chloro—11 (2,3-Dimethinorefuel) —Using 3-methyldilacil, the title compound was obtained in the same manner as in Example 1.

_{'H- MR (CDC1 3, 6} pm): 7.14-7.40 (13H, m), 4.95 (1H, s), 4.34 (. 1H, br t, J = 4.9 Hz), 4.17 (1H, s), 3.33 (3H, s), 3.07 (2H, m), 2.34 (3H, s), 2.22-2.27 (10H, ra), 2.02 (3H, s), 1.62 (2H, m),

Time-of-flight mass spectrometer (TOF-Mass): 538 (M + H)

 Example 13 1- (2,3-Dimethylphenyl) -6- [3- [4- (diphenyl-methoxy) -1-piperidinyl] propinoleamino] -3-methylperacyl (Compound 884)

 6—Black mouth 3—Methinole 1—Hue-Noredrasinole 6—Black mouth 1—

(2,3-Dimethinolephenyl) Using 3-methylperacyl, instead of 3- (4- (diphenylmethyl) -1-piperazinyl) propylamine 3- (4- (diphenylmethoxy) _1-piperidinyl) The title compound was obtained in the same manner as in Example 1 using propylamine.

丄 11-NMR (CDCI3, 5ppm): 7.22-7.33 (13H, m), 5.47 (1H, s), 4.94 (1H, s),

4.59 (1H, brt, J = 4.9 Hz), 3.33 (4H, ra), 3.08 (2H, dt, J = 4.9 Hz, J =

6.2 Hz), 2.51 (2H, ra), 2.30 (3H, s), 2.23 (2H, t, J = 6.2 Hz), 2.02 (311, s) 1.93 (2H, m), 1.57--1.66 (4H, m ), 1.47 (2H, ra)

Time-of-flight mass spectrometer (T0F_Mass): 553 (M + H)

 (Example 14) 6- [3- [4- (dipheninolemethynole) -1- (piperazinyl)] pyramino] —1- (2-methoxyphenyl) —3-methylperacyl (compound

908)

 The title compound was obtained in the same manner as in Example 1 except that 6-chloro-1- (2-methoxy) -13-methylperacyl was used in place of 6-chloro-1-3-methynolethy .

 'H-NMR (CDCI3, δρρηι): 7.03-7.51 (14H, m), 4.93 (1H, s), 4.32 (1H, br.t, J = 4.9 Hz), 4.18 (1H, s), 3.80 (3H , S), 3.32 (3H, s), 3.07 (2H, m), 2.34 (3H, s), 2.22-2.28 (drawing, m), 1.62 (2H, m),

Time-of-flight mass spectrometer (TOF-Mass): 540 (M + H) (Example 15) 6- [3- [4-1- (diphenylmethoxy) -11-piperidinyl] propylamino] -11- (2-methoxyphenyl) _3-methylperacyl (Compound 914)

 Use 6-chloro-1- (2-methoxyphenyl) -13-methylperacyl instead of 6-chloro-3-methinolepercinole, and use 3- (4- (diphenylmethyl) -1-piperazinyl ) The title compound was obtained in the same manner as in Example 1 except that propylamine was replaced by 3- (4- (diphenylmethoxy) -11-piberidyl) propylamine.

_{^{X H-NMR (CDC1 3,}} Sppm):. 7.19-7.45 (13H, m), 7.06 (2H, m), 5.74 (1H, s), 4.92 (1H, s), 4.65 (1H, br t, J = 4.9 Hz), 3.80 (3H, s), 3.32-3.41 (4H, m), 3.09 (2H, s), 2.53 (2H, m), 2.24 (2H, t, J = 6.2 Hz), 1.98 (2H , M),

1.60-1.72 (4H, m), 1.49 (2H, m)

Time-of-flight mass spectrometer (TOF-Mass): 555 (M + H)

 (Example 16) 6- [3- [4- (diphenylmethyl) -1-1-piperadiel] -pyramino] —1- (4-methoxyphenyl) -13-methylperasinole (compound

938)

 The title compound was prepared in the same manner as in Example 1 except that 6-chloro-1- (4-methoxyphenol) -13-methylperacyl was used instead of 6-chloro-3-methinole-1-ol. Obtained.

^ -NMR (CDCI3, δρρηι): 7.40 (4Η, d, J = 7.4 Hz), 7.14-7.29 (11H, m), 4.91 (1H, s), 4.60 (1H, br.s), 4.16 ( 1H, s), 3.85 (1H, s), 3.32 (3H, s), 3.07 (2H, m), 2.20-2.30 (image, m), 1.64 (2H, ra)

Time-of-flight mass spectrometer (TOF-Mass): 541 (M + H)

 (Example 17) 6- [3- [4- (diphenylmethyl) -11-piperazinyl] pyramino] -13-methyl-11- (4-trifluoromethylphenyl) peracyl (compound 968)

The title compound was prepared in the same manner as in Example 1 by using 6-chloro-1-methyl-1- (4-trifluoromethyl) peracil instead of 6-chloro-1-methyl-1-phenol Obtained. _{^ -NMR (CDC1 3, 5ppm)} : 7.83 (2H, d, J = 8.4 Hz), 7.44 (2H, d, J = 8.4 H z), 7.14-7.39 (12H, ra), 4.96 (1H, s) , 4.62 (1H, br. S), 4.16 (1H, s), 3.3

2 (3H, s), 3.11 (2H, m), 2.34 (lOH, m), 1.59 (2H, m),

Time-of-flight mass spectrometer (T0F_Mass): 579 (M + H)

 (Example 18) 1- (4-ethoxycarbonylmethylphenyl) -3-ethyl

6- [3-[4-(Diphenylmethyl) 1-1-pirazur] propylamino] peracyl (Compound 1005)

 6-Chloro-1- (4-ethoxycarbonylmethylphenyl) -3- 3-ethyl-peracyl is used in place of 3-methyl- 1-pheninolecinole, and is labeled in the same manner as in Example 1. The compound was obtained.

 ^ -NMR (CDCI3, 6ppm): 7.14-7.44 (14H, m), 4.92 (1H, s), 4.24 (1H, br.t, J = 4.9 Hz), 4.10-4.18 (3H, m), 3.97 ( 2H, q, J = 7.0 Hz), 3.66 (2H, s), 3.06 (2H, dt, J = 6.5 Hz, J = 4.9 Hz), 2.23-2.31 (bandits, m), 1.65 (2H, m), 1.20-1.30 (611, m),

Time-of-flight mass spectrometer (T0F_Mass): 611 (M + H)

 (Example 19) 6- [3- [4- (Diphenylmethyl) -11-piperazinyl] p-pinoleamino] —11- (3-ethoxycanololepoylpheninole) -13-methinolesilacill (Compound 1058)

 The title compound was obtained in the same manner as in Example 1 by using 6-chloro-1- (3-ethoxycarberphenyl) -13-methylperacyl in place of 6-chloro-3-methynole-1-amine. Obtained.

-删_{R (CDC1 3, 6ppm):} 7.78 (1H, d, J = 7.8 Hz), 7.98 (1H, s), 7.14-7.6

3 (12H, m), 4.96 (1H, s), 4.56 (1H, br.t, J = 4.9 Hz), 4.37 (2H, q, J = 7.6 Hz), 4.11 (1H, s), 3.32 (3H , S), 3.09 (2H, dt, J = 4.9 Hz, J = 6.5 Hz), 2.11-2.30 (10H, m), 1.66 (2H, tt, J = 6.5 Hz), 1.35 (3H, t, J = 7.6 Hz),

Time-of-flight mass spectrometer (TOF-Mass): 583 (M + H) ''

(Example 20) 61- [3- [4- (diphenylmethyl) 1-1-piperazinyl] pyrupyramino] — 1- (4-ethoxycarbonylphenyl) —3-methylperacid (Compound 1088)

 6-Chloro-11- (4-ethoxycarbonylphenyl) -13-methyldiracil was used in place of 6-chloro-1-3-methynole-1-lacinole to obtain the title compound in the same manner as in Example 1. .

_{^ -NMR (CDC1 3, δρρηι)} :. 8.24 (2H, d, J = 8.4 Hz), 7.16-7.42 (12H, m), 4. 95 (1H, s), 4.64 (1H, br t, J = 4.9 Hz), 4.44 (2H, q, J = 7.3 Hz), 4.10 (1H, s), 3.32 (3H, s), 3.07 (2H, ra), 2.26-2.51 (lOH, m), 1.66 (211, m), 1.35 (3H, t, J = 7.3 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 583 (M + H)

 (Example 21) 6- [3- [4- (Diphenylmethoxy) -1-piperidinyl] propinoleamino] -1- (4-ethoxycarbinolerefinole) -3-methylinoreduracil (Compound 1094)

 6—Black mouth 3—Methinole 1—Fuenoleperasinole 6_Black mouth 1— (4-Ethoxycanolepodinolefe-nore)-Use 3-methylperacil, 3— (4— ( The title compound was obtained in the same manner as in Example 1 except for using 3- (4- (diphenylmethoxy) -11-piperidiel) propylamine in place of diphenylmethyl) -1-piperazinyl) propinoleamine.

 ^-MR (CDCI3, 0ppm): 8.20 (2H, d, J = 8.4 Hz), 7.23-7.32 (14H, m), 5.44 (1H, s), 4.96 (1H, s), 4.63 (1H, br.t, J = 4.6 Hz), 4.30 (2H, q, J = 7.0 Hz), 3.32 (4H, ra), 3.08 (2H, dt, J = 4.6 Hz, J = 5.9 Hz), 2.46 (2H, m), 2.25 (2H, t, J = 5.9 Hz), 1.99 (2H, m), 1.51-1.62 (8H, m), 1.33 (3H, t, J = 7.0 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 597 (M + H)

 (Example 22) 1- (3-cyanophenyl) -1-6- [3- [4- (diphenylmethyl) -1-piperazul] propinoleamino] -1-methylperacyl (Compound 1298)

The title compound was obtained in the same manner as in Example 1, except that 6-chloro-1- (3-cyanophenyl) _3-methyl-dilacil was used instead of 6-chloro-3- (methylenolene) -1-phenolazine. Was. _{^{X H-NMR (CDC1 3,}} 5ppm): 7.78 (1H, d, J = 7.8 Hz), 7.71 (2H, d, J = 7.8 H z), 7.56 (1H, m), 7.15-7.42 (10H, m ), 4.97 (1H, s), 4.68 (1H, br.t, J = 4.9 Hz), 4.19 (1H, s), 3.47 (3H, s), 3.12 (2H, dt, J = 4.9 Hz, J = 5.9 Hz), (2H, m), 2.12-2.34 (10H, ra), 1.66 (2H, tt, J = 5.9 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 537 (M + H)

 (Example 23) 1- (4-Cyanophenyl) —6 -— [3- [4- (diphenylmethyl) -1-piperazul] propylamino] —3-methinoreduracil (Compound 1328)

 The title compound was obtained in the same manner as in Example 1 except that 6-chloro-1- (4-cyanophenyl) -13-methylperacyl was used in place of 6-chloro-1-3-methylenolacinole.

 ^ -NMR (CDCI3, δρρηι): 7.85 (2Η, d, J = 8.4 Hz), 7.17-7.47 (12H, ra), 4.96 (1H, s), 4.83 (1H, br.t, J = 4.6 Hz), 4.20 (1H, s), 3.30 (3H, s), 3.10 (2H, dt, J = 4.6 Hz, J = 6.1 Hz), 2.11-2.31 (image, ra), 1.65 (2H, tt, J = 6.1 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 535 (M + H)

 Example 24 1- (4-Cyanophenyl) -6- [3- [4- (hydroxydiphenylmethyl) -1-1-piperidinyl] propylamino] -3-methylperacyl (Compound 1333)

 6—Black mouth 3—Methinole 1—Feninole

Using (4-cyanophenyl) -1-methylperacyl instead of 3- (4- (diphenyl-methyl) -1-piperazinyl) propylamine 3- (4- (hydroxydiphenylmethyl) -1-piperidinyl) propylamine And the title compound was obtained in the same manner as in Example 1.

^ -NMR (CDCI3, δρρπι): 8.03 (2H, d, J = 8.6 Hz), 7.57 (2H, d, J = 8.6 Hz), 7.09-7.51 (10H, m), 5.71 (1H, m), 5.23 (1H, s), 4.82 (1H, m), 3.08 (3H, s), 2.97 (2H, m), 2.77 (2H, m) 2.16 (2H, m), 1.80 (2H, m), 1.35- 1.53 (4H, m), 1.19 (2H, m)

Time-of-flight mass spectrometer (TOF-Mass): 550 (M + H) (Example 25) 1- (4-Cyanophenyl) -6- [3- [4- (diphenylmethoxy) -l-piperidiel] propylamino] l3-methinoredrasinole (Compound 1334)

 Use 6-chloro-1- (4-cyanophenol) instead of 6-chloro-3-methyl-1-phenylperacyl and 3- (4- (diphenylphenol) — 1 The title compound was obtained in the same manner as in Example 1 except that 3- (4- (diphenylmethoxy) _1-piperidinyl) propylamine was used instead of —piperjunole) propylamine.

_{^ -NMR (CDC1 3, δρρηι)} : 7.78 (2Η, d, J = 8.1 Hz), 7.44 (2H, d, J = 8.1 H z), 7.22-7.37 (10H, m), 5.47 (1H, s) , 4.97 (1H, s), 4.93 (1H, br.t, J = 4.6 Hz), 3.30-3.45 (4H, m), 3.08 (2H, dt, J = 4.6 Hz, J = 5.8 Hz), 2.51 ( 2H, m), 2.29 (211, t, J = 5.8 Hz), 1.92 (2H, m), 1.61-1.65 (4H, ra), 1.32 (2H, m)

Time-of-flight mass spectrometer (TOF-Mass): 550 (M + H)

 (Example 26) 1- (4-Cyanophenyl) -6- [3- [4-1 [(4-fluorophenyl) phenylmethyl] -11-piperadiel] propylamino] -13-methylperacyl (Compound 1341)

 6-Chloro-3-methinolone 1-Pheninoleurassinole 6-Chloroone 1- (4 _cyanofenerinole) 1-3-Methinoleurassinole, use 3-(4— (dihuenii) Use 3- (4-((4-fluorophenyl) phenylmethyl) -1-1-piperazinyl) propylamine instead of 1-piperazinyl) propylamine

The title compound was obtained in the same manner as in Example 1.

 ^ -NMR (CDCI3, 5ppm): 7.86 (2H, d, J = 8.6 Hz), 6.93-7.48 (11H, m), 4.96 (1H, s), 4.83 (1H, brt, J = 4.9 Hz) , 4.19 (1H, s), 3.31 (3H, s), 3.10 (2H, dt, J = 4.9 Hz, J = 6.2 Hz), 2.07-2.33 (1011, m), 1.65 (2H, tt, J =

6.2 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 553 (M + H)

(Example 27) 6- [3- [4-[(4-chlorophenyl) phenylmethinole] 1-1-pyrazul] propinoleamino "! — 1— (4-Icyanophenyl) —3-methyl Noredrasinole (Compound 1343)

 6-Chloro-3-methinole 1 1- (4-Cyanophenyl)-3-methylperacil is used in place of 1-phenylenolecinole, 3- (4-(diphenylinolemethyl) _1-piperadiel) Propylamine The title compound was obtained in the same manner as in Example 1 except that 3- (4-((4-chlorophenyl) phenylmethyl) -1-piperazul) propylamine was used instead of

_{^ -NMR (CDC1 3, 6ppm)} : 7.86 (2H, d, J = 8.6 Hz), 7.46 (2H, d, J = 8.6 H z), 7.16-7.41 (9H, m), 4.97 (1H, s) , 4.81 (1H, br.t, J = 5.1 Hz), 4.18 (1H, s), 3.31 (3H, s), 3.09 (2H, dt, J = 5.1 Hz, J = 6.2 Hz), 2.08—2.33 ( 10H, m), 1.65 (2H, tt, J = 6.2 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 570 (M + H)

 (Example 28) 1- (4-Cyanophenyl) -1-methyl-6- [3- [4-[(4-methylphenyl) phenylmethyl] -11-piperazul] propylamino] percinole (Compound 1345)

 6-Chloro 3-Methinole 1-11

3- (4- (diphenylmethyl) 1-1-piperazinyl) instead of 3- (4- (diphenylmethyl) 1-1-piperazinyl) propylamine, using 3- (4-cyanophenyl) -1-methylperacyl 3- (4-((4-methinolefeninole) phenylinolemethizole) 1 1 —Piperazinole) Using propynoleamine, the title compound was obtained in the same manner as in Example 1.

^ -NMR (CDCI3, δρρηι): 7.85 (2Η, d, J = 8.6 Hz), 7.07-7.47 (11H, ra), 4.96 (1H, s), 4.86 (1H, brt, J = 4.9 Hz) , 4.16 (1H, s), 3.30 (3H, s) 3.09 (21.1, dt, J = 4.9 Hz, J = 6.2 Hz), 2.09-2.33 (13H, m), 1.65 (2H, tt, J = 6.2 Hz) )

Time-of-flight mass spectrometer (TOF-Mass): 549 (M + H)

 (Example 29) 1- (4-Cyanophenyl) 1_6_ [3- [4-[(4-Methoxycyclophenyl) phenylmethyl] -1-piperazinyl] propinoleamino] 1-3-methylpyrazil (Compound 1347)

6-Chloro-l-methinole 1-Feninole-lacinole 6-Chloro-l-l- (4-cyanophenyl) -l-methyl-peracyl Using 3- (4-((4-methoxyphenyl) phenylmethyl) -11-piperazinyl) propylamine instead of (methyl) -1-piperazinyl) propylamine, the title compound was obtained by the same operation as in Example 1. .

_{H-NMR (CDC1 3, δρρηι} ): 7.85 (2Η, d, J = 8.6 Hz), 7.25-7.47 (9H, m), 6.8 2 (2H, d, J = 8.6 Hz), 4.96 (1H, s) , 4.86 (1H, br.t, J = 4.9 Hz), 4.15 (1H, s), 3.76 (3H, s), 3.31 (3H, s), 3.09 (2H, dt, J = 4.9 Hz, J = 5.9 Hz), 2.08-2.33 (band, m), 1.65 (2H, tt, J = 5.9 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 565 (M + H)

 (Example 30) 1- (4-Cyanophenyl) -6- [3- [4- [bis (4-fluorofluorophenylmethyl) _1-piperazi-nore] propylamino] _3-methinoleperacil (Compound 1349)

 6-Chloro-3-methino-le 1-pheno-leno-cinole 6-Chloro-l- (4-one-feno-no-re-no-le) 1-3-meth / rela-no-re-no-le, 3- (4- (di-pheno-no-re-methyl) _ The title compound was obtained in the same manner as in Example 1 except that 3- (4- (bis (4-fluorophenyl) methyl) -11-piperadiel) propylamine was used instead of 1-piperajuryl) propylamine.

_{^ -NMR (CDC1 3, 0ppm)} : 7.86 (2H, d, J = 8.6 Hz), 7.45 (2H, d, J = 8.6 H z), 7.38 (4H, m), 6.97 (4H, m), 4.97 (1H, s), 4.81 (1H, brt, J = 4.9 Hz), 4.19 (1H, s), 3.31 (3H, s), 3.08 (2H, dt, J = 4.9 Hz, J = 5.7 Hz), 2.0 6-2.33 (10H, m), 1.65 (2H, tt, J = 5.7 Hz)

Time-of-flight mass spectrometer (T0F_Mass): 571 (M + H)

 (Example 31) 6- [3- [4- (diphenylmethyl) -1-piperazurl] pyramino] —1- (4-nitrophenyl) -13-methylperacyl (Compound 1358)

 The title compound was obtained in the same manner as in Example 1 except that 6-chloro-3-methyl-11- (412-trophenyl) peracyl was used in place of 6-chloro-1-3-methinolene-1-lasinole. .

^ Chromatography丽_{R (CDC1 3, 6ppm):} 8.44 (2H, d, J = 8.6 Hz), 7.53 (2H, d, J = 8.6 H z), 7.16-7.40 (10H, m), 5.07 (1H, br t, J = 4.3 Hz), 4.97 (1H, s), 3.93 (1H, s), 3.13 (3H, s), 3.11 (2H, dt, J = 4.3 Hz, J = 5.9 Hz), 2.32 (2H, t, J = 5.9 Hz), 2.03 (4H, ra), 1.99 (4H, m), 1.66 (2H, tt, J = 5.9 Hz) Time-of-flight mass spectrometer (TOF-Mass): 555 (M + H)

(Example 32) 1- (4-Cyanophenyl) -6- [3- [4-1- (10,11-dihydro-5H-dibenzo [a, d] cycloheptene_5-isle) -1-piperazinyl] propylamino] — ₃ —methylperacyl (compound 1606)

 Use 6-chloro-1_ (4-cyanophenol) instead of 6-chloro-3-methyltinolecinole, and use 3- (4-1- (diphenyl-methyl) Use 3- (4- (10,11-dihydro-5H-dibenzo [a, d] cyclohexene-5-yl) -1-1-piperazinyl) propylamine instead of 1-piperazul) propylamine The title compound was obtained in the same manner as in Example 1.

_{^ - MR (CDC1 3, 6ppm} ): 7.86 (2H, d, J = 8.6Hz), 7.39 (2H, d, J = 8.6 Hz), 7.07-7.26 (8H, m), 5.91 (1H, m), 4.84 (1H, s), 4.12 (1H, m), 3.79—3.88 (2H, ra), 3.24—3.30 (7H, m), 2.65-2.87 (10H, m) 1.97 (2H, m)

Time-of-flight mass spectrometer (T0F_Mass): 560 (M + H)

 (Example 33) 1- (3-Carboxyphenyl) -6- [3- [4- (diphenylmethyl) -1-pidazur] propylamino] _3-methylperacyl (Compound 1118)

 Dissolve 400 mg (0.69 ramol) of compound 1058 in 50 ml of ethanol, add 1.4 ml of 1N aqueous sodium hydroxide solution, and stir at 50 ° C for 30 minutes. After concentrating the solvent, distilled water was added, and the solid produced by neutralizing with 1N hydrochloric acid was collected by filtration to obtain the title compound (316 mg (0.57 mmol), yield 82%).

_{^{L H- MR (DMS0 - d 6}} , δ ppm): 8.06 (1H, d, J = 7.3 Hz), 7.80 (1H, s), 7.56-7 .67 (2H, m), 7.14-7.42 (10H, m), 5.62 (1H, br.t, J = 5.7 Hz), 4.83 (1H, s), 4.22 (1H, s), 3.09 (3H, s), 2.96-3.09 (2H, m), 2.19-2.32 (10H, m), 1.54 (2H, m),

Time-of-flight mass spectrometer (TOF-Mass): 554 (M + H)

(Example 34) 1- (4-carboxymethylphenyl) -1-3-ethyl-6- [3 -[4- (Diphenylmethyl) 1-1-pidazul] propinoleamino] peracyl (Compound 1035)

 The title compound was obtained in the same manner as in Example 33, using compound 1005 instead of compound 1058.

^ -NMR (DMSO— d ₆ , δ ppm): 7.14-7.42 (14H, m), 5.42 (1H, m), 4.78 (1H, s), 4.23 (1H, s), 3.75 (2H, m), 3.60 (2H, s), 2.99 (2H, m), 2.16-2.30 (10H, m), 2.03 (2H, m), 1.05 (6H, m), 1.05 (3H, t, J = 7.3 Hz)

Time-of-flight mass spectrometer (TOF-Mass): 582 (M + H)

 (Example 35) 1- (4-Carboxyphenyl) -1-6- [3- [4- (diphenylmethyl) -11-piperazinyl] propylamino] -3-3-methinoreduracil (Compound 1148)

 The title compound was obtained in the same manner as in Example 33, except that compound 1088 was used instead of compound 1058.

_{^ -NR (DMSO- d 6, Sppm} ):. 8.07 (2H, d, J = 8.4 Hz), 7.14-7 5 (12H, ra), 5.66 (1H,, J = 5.3 Hz ra), 4.84 (1H , S), 4.22 (1H, s), 3.09 (3H, s), 3.0

1 (2H, m), 2.25-2.50 (10H, m), 1.55 (2H, ra)

Time-of-flight mass spectrometer (TOF-Mass): 554 (M + H)

 (Example 36) 1- (4-Dipoxyphenyl) -1-6- [3- [4- (diphenylmethoxy) -1-piperidinyl] propylamino] -13-methylperacyl (Compound 1154)

 The title compound was obtained in the same manner as in Example 33, using compound 1094 instead of compound 1058.

^X H-NMR (DMSO— d ₆ , δ ppm): 8.11 (2H, d, J = 8.4 Hz), 7.21-7.39 (12H, m), 5.71 (1H, ra), 5.65 (1H, s), 4.88 (1H, s), 3.12 (3H, s), 1.91—3.08 (15H, m)

Time-of-flight mass spectrometer (T0F-Mass): 569 (M + H)

(Example 37) 6- [3- [4- (diphenylmethyl) 1-1-piperazul] -pyramino] —3-methyl-11- [3- (1H-tetrazol-5-yl) phenyl] peracyl (Compound 1238) 450 mg (0.84 mmol) of compound 1298 was dissolved in 34 ml of N, N-dimethylformamide, 437 mg of sodium azide and 359 mg of ammonium chloride were added, and the mixture was stirred at 90 ° C for 8 hours. After cooling, the solvent was concentrated, distilled water was added, and the mixture was neutralized with 1N hydrochloric acid. The mixture was stirred at room temperature for 30 minutes, and the resulting solid was collected by filtration. After adding 25 ml of dichloromethane and 22 ml of hexane to the solid and stirring for 30 minutes, the solid was collected by filtration to obtain the title compound (410 mg (0.71 mmol), yield: 85%).

^-MR (DMSO— d ₆ , δ ppm): 8.12 (1H, d, J = 7.8 Hz), 7.56 (1H, br.s), 7.6 1 (2H, t, J = 7.8 Hz), 7.18-7.45 (12H, m), 5.78 (1H, br.t, J = 5.7 Hz), 4.89 (1H, s), 4.41 (1H, s), 3.46 (3H, s), 3.01-3.12 (8H, ra), 2.79 (2H, m), 2.50 (2H, ra), 1.73 (2H, m)

Time-of-flight mass spectrometer (TOF-Mass): 537 (M + H)

 (Example 38) 6- [3- [4- (Diphenylmethoxy) 1-1-piperidinyl] propylamino] —3-methyl-1- [4- (1H-tetrazol-5-yl) phenyl] perasinole (Compound 1274)

 The title compound was obtained in the same manner as in Example 37, using compound 1334 instead of compound 1298.

^ -NMR (DMS0_d ₆ , δ ppm): 8.11 (2H, d, J = 8.4 Hz), 7.26-7.33 (14H, m), 5.71 (1H, br.t, J = 5.9 Hz m), 5.65 (1H , M), 4.88 (1H, s), 3.38 (1H, ra), 3.12 (3H, s), 3.06 (4H, ra), 2.74 (4H, m), 1.91 (2H, m), 1.73 (2H, m) Time-of-flight mass spectrometer (TOF-Mass): 593 (M + l)

 (Example 39) 6- [3- [4- (diphenolemethinole) -1-1-piperazinyl] pyrpyramino] —3-methyl-11- [4- (1H-tetrazol-5-yl) phenyl ] Peracyl (Compound 1268)

 The title compound was obtained in the same manner as in Example 37, except that compound 1328 was used instead of compound 1298.

^ -NMR (DMS0-d ₆ , δ ppm): 8.14 (2H, d, J = 8.4 Hz), 7.16-7.41 (12H, m), 5.75 (2H, s), 4.87 (1H, s), 4.32 ( 1H, s), 3.11 (3H, s), 2.50-3.06 (12H, m), 1.69 (2H, m)

Time-of-flight mass spectrometer (TOF-Mass): 579 (M + H) (Example 40) 1- (3-Carboxamidophenyl) -1-6- [3- [4- (diphenylmethyl) -11-piperazul] propylamino] -13-methylperacyl (Compound 1178)

Compound 1118 300 rag (0.71 thigh ol) was suspended in N, N-dimethylformamide (20 ml), and 1-hydroxybenzotriol was 88 mg, N-ethylethyl_Ν'—3-dimethylaminopropyl carbodiimide 125 mg Was added and stirred at room temperature for 2 hours. Under ice-cooling, 254 / il of a 29% aqueous ammonia solution was added, and the mixture was stirred for 1 hour. The solvent was concentrated, extracted with dichloromethane and a 5% aqueous sodium hydrogencarbonate solution, and the organic layer was washed with a 10% aqueous sodium chloride solution and dried over anhydrous sodium sulfate. Evaporated to the resulting solid and the solvent was stirred resuspended in 30 minutes di chloromethane 15 ml, to give the target title compound can be isolated by solid (153 mg, 0.28 mmol _s yield 51).

'H-NMR (DMS0 - d 6, 6 ppm): 7.14-8.06 (16H, m), 5.76 (1H, s), 5.63 (. 1H, br t, J = 5.4 Hz), 4.84 (1H, s) , 4.21 (1H, s), 3.09 (3H, s), 3.09 (3H, s),

3.00 (2H, m), 2.17-2.30 (bandit, m), 1.53 (2H, m)

Time-of-flight mass spectrometer (T0F_Mass): 553 (M + H)

(Example 41) 1 - (4-carboxamide Hue Interview le) one 6- [3- [4- (diphenyl Enirumechiru) Ichi丄- piperazinyl] Puropiruamino] one ₃ Mechiruurashiru (Compound 1208)

 The title compound was obtained in the same manner as in Example 40, except that compound 1148 was used instead of compound 1118.

^ -NMR (DMS0-d ₆ , Sppm): 8.14 (1H, s), 8.03 (2H, d, J = 8.9 Hz), 7.56 (1 H, s) 7.13-7.43 (12H, m), 5.64 (1H , br.t, J = 5.4 Hz), 4.83 (1H, s), 4.22 (1H, s), 3.09 (3H, s), 3.00 (2H, m), 2.20-2.30 (10H, m), 1.53 (2H, m), time-of-flight mass spectrometer (TOF-Mass): 553 (M + H)

(Evaluation Example 1) Suppressive effect of OVA-induced mouse biphasic dermatitis

In order to examine the inflammation-suppressing action of the novel peracil derivative having the antihistamine action of the present invention, 0VA-induced mice biphasic skin showing both immediate-type reactions strongly involving histamine and delayed-type reactions strongly infiltrating inflammatory cells It was evaluated in a flame model. ICR male mice Then, 1 μg of ovalbumin (OVA) was intraperitoneally administered together with ₃ lmg of Al (OH) to induce sensitization. Sensitization 14: OVAlOix g was administered directly into the pinna, causing an allergic reaction. The test drug was suspended in a 0.5% CMC-Na aqueous solution and administered orally or dissolved in acetone for 1 hour before induction, and applied to the auricle. The pinna thickness was measured 1 hour and 24 hours after the induction, and the dermatitis inhibitory effect of the test compound was evaluated using the difference from the pinna thickness before the induction as an index. As a comparative example, oxatomide (0xatomide) and ketotifen fumarate (Ketot; Lfen fumarate) were used, all of which were suspended in a 0.5% CMC-Na aqueous solution and orally administered one hour before the induction. The increase in pinna thickness one hour after induction was edema due to chemical mediators such as histamine, which was defined as the immediate phase. After 24 hours, it was due to inflammatory cells such as eosinophils, which was defined as a late phase.

 As a result, as shown in Tables 3 and 4, it is found that the compound of the present invention suppresses both the immediate phase and the delayed phase. In contrast, ketotifen, a known antihistamine, strongly inhibited the immediate phase but was ineffective for the late phase.

Table 3

Compound Dose Inhibition (%)

 (mg / kg immediate phase late phase

Example 2 3 1 47 26

 10 64 49

 100 71 53

Example 2 2 30 57 47

Example 3 3 30 76 52

Oxatomide 30 27 41

Ketotifen 30 82 15

 TAK-427 3 39 18

 30 55 54

Compound Dose Inhibition (° /.)

 (rag / ear) Immediate phase Late phase

Example 2 3 0.03 27 25

 0.1 42 33

 0.3 3 55 57

 TAK-427 0.1 1 -23 24

 0.3 3 20

1 15 35 (Evaluation example 2)

In order to verify that the novel peracyl derivative of the present invention has an antihistamine action, evaluation was performed by the Magnus method using guinea pig ileum. The ileum removed from the guinea pig was washed in Tyrode solution and stored in Tyrode solution at 32 ° C with aeration. The ileum was excised to a length of about 2 cm, and one end was fixed to a fixed rod and the other end to a pressure transducer in a Magnus tube filled with Tyrode's solution, so that contraction of the ileum could be recorded. IC ₅ for each test drug to Tyrode solution at less than the Magnus tube 1. 0 mu M contraction times intestine induced when added Hi Stamine aqueous solution 100 mu L of. I asked. The test drug was added to the Tyrode solution in a volume of 5 μL two minutes before the addition of Histamine. Diphenhydramine and oxatomide were used as comparative examples.

 As shown in Table 5, it was shown that the compounds of the present invention have the same level of antihistamine activity as known antihistamines. Table 5

(Formulation Example 1) Water-soluble ointment

_T by a conventional method to create a water-soluble ointment having the following composition

Component Ointment Content per 2 _g

Compound 1328 (Example 23) 40 mg

Polyethylene glycol 400 1372 mg

Polyethylene glycol 4000 588 mg

(Formulation Example 2) Oral tablet A tablet for internal use having the following composition was prepared by a conventional method.

 Ingredient Content per tablet

Compound 1328 (Example 23) 100 mg

Lactose 353 rag

Carboxymethylcellulose calcium 30 mg

Hydroxypropinoresenolerose 7 mg

Magnesium stearate 5 mg

Crystalline cellulose 5 mg

 The invention's effect

 The peracil derivative of the present invention has both an antihistamine action and an anti-inflammatory action, and is useful as an antihistamine and / or as an antiallergic. In particular, it has a remarkable anti-inflammatory effect on allergic inflammation. The peracil derivative of the present invention suppresses itching due to histamine and also effectively suppresses allergic unilateral inflammation, so that allergic conjunctivitis, allergic rhinitis, chronic measles, atopic dermatitis, asthma or chronic bronchitis can be prevented. It is useful as a prophylactic / therapeutic agent, and is a new compound that is more satisfactory in terms of efficacy and safety than conventional anti-allergy, antihistamine, and anti-inflammatory agents.

Claims

The scope of the claims

 General formula (I)

(In the formula, R ¹ represents a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms or a substituted or unsubstituted aralkyl group having 7 to 10 carbon atoms, and R ² represents a hydrogen atom or a carbon atom having 1 to 6 carbon atoms. 6 represents an alkyl group, Ar ¹ represents a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group, and Ar ² and Ar ³ are the same or different, and Or an unsubstituted phenyl group or a substituted or unsubstituted monocyclic aromatic heterocyclic group, or Ar ² and Ar ³ are tricyclic with a divalent group bonded to both Ar ² and Ar ³ X represents a methine group (CH) or a nitrogen atom; Y represents a single bond or an oxygen atom when X is a methine group; and X represents a single bond when X is a nitrogen atom. Z represents a hydrogen atom or a hydroxyl group when X is a methine group and Y is a single bond; X is a methine group and Y When the time and X is a nitrogen atom an oxygen atom (Y represents a single bond), represents a hydrogen atom, m represents 2-6.

)

Or a pharmaceutically acceptable salt thereof.

2. The peracil derivative or the pharmaceutically acceptable salt thereof according to claim ¹ , wherein Ar ¹ in the general formula (I) is a substituted or unsubstituted aromatic carbocyclic group.

3. The peracil derivative according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein Ar ² and Ar ³ in the general formula (I) are the same or different and are each a substituted or unsubstituted phenyl group. salt.

4. In the general formula (I), Ar ² and Ar ³ are the same or different and are each (i) a phenyl group which may be substituted with a halogen atom or an alkyl group having 1 to 6 carbon atoms, or (ii) a carbon atom. Other than nitrogen atom, sulfur atom and oxygen atom 3. The peracyl derivative or a pharmaceutically acceptable salt thereof according to claim 1 or 2, which is a 5- to 8-membered monocyclic aromatic heterocyclic group containing four hetero atoms.

 5. The peracyl derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein in the general formula (I), X is a methine group.

 6. The peracyl derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein in the general formula (I), X is a nitrogen atom.

 7. An antihistamine comprising the peracil derivative according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof as an active ingredient.

 8. An antiallergic agent comprising the peracil derivative according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof as an active ingredient.

 9. Allergic conjunctivitis, allergic rhinitis, chronic juvenile measles, atopic dermatitis, asthma or the like containing the peracil derivative according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof as an active ingredient. Prevention and treatment of chronic bronchitis.