Pyrimidine compound

Abstract

This invention provides novel pyrimidine compounds represented by formula [I] and their salts: [In the formula, these symbols are as defined in the specification], and they are used for the treatment, prevention and / or diagnosis of seizures or convulsive seizures (including multidrug-resistant seizures, refractory seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus), together with their medical uses.

Description

Pyrimidine compounds The present invention relates to pyrimidine compounds and salts thereof. The present invention also relates to a drug having a pyrimidine compound or a salt thereof as an active ingredient and used for treating, preventing, and / or diagnosing seizures and the like in diseases involving epileptic seizures or convulsive seizures. The prevalence of epilepsy is approximately 1% of the population. It is considered a common neurological disorder, with approximately 1 million patients in Japan, and a lifetime incidence rate of 3% to 4%. It is estimated that tens of thousands of people develop epilepsy every year. Approximately 70% of these patients can control their seizures with existing antiepileptic drugs and engage in their daily lives without problems, but the remaining 30% of epilepsy patients cannot adequately control their seizures and are worried that the seizures will occur without warning. Most existing antiepileptic drugs aim to regulate the excitation / inhibition imbalance in neural activity by suppressing excessive excitation and excessive synchronization of neuronal activity, but doses higher than the optimal dose will disrupt the balance of neuronal activity and induce motor dysfunction and epileptic seizures. PTL 1 discloses a compound having a pyrimidine in its structure for use in the treatment and the like of diseases or disorders (including epilepsy) that require a regulator of Kv3.1 and / or Kv3.2 channels. PTL 2 and 3 disclose compounds having a pyrimidine skeleton for use as kynurenine-3-monooxygenase inhibitors in the treatment of neurodegenerative disorders including epilepsy. PTL 4 discloses a uracil compound as a compound showing an antiepileptic effect. However, no compound having a structure including the 5-position carbon of a pyrimidine bonded to the 1-position nitrogen of a uracil skeleton has been disclosed or proposed in any patent literature. [Citation list] Patent literature [PTL 1]WO 2011 / 069951 [PTL 2]WO 2013 / 016488 [PTL 3]WO 2011 / 091153 [PTL 4]WO 2004 / 009559 An object of the present invention is to provide novel pyrimidine compounds or salts thereof for treating, preventing, and / or diagnosing seizures and the like in diseases involving epileptic seizures or convulsive seizures, and their medical uses. Another object of the present invention is to provide a drug having a wider treatment range compared to existing antiepileptic drugs, so that even at a dose that completely suppresses epileptic seizures, the balance of neuronal excitation / inhibition can be maintained. As a result of intensive research aimed at solving the above problems, the inventors have successfully synthesized novel pyrimidine compounds having a wide range of therapeutic effects compared with existing antiepileptic drugs. Based on these findings, the present invention has been completed. That is to say, the present invention includes the following embodiments. [1] A compound represented by formula [I] Wherein Ring A is phenyl, naphthyl or pyridyl; R 1 Is lower alkyl; R 2 Is -O-lower alkyl; R 3 Is halogen, lower alkynyl, lower alkyl optionally substituted by halogen, -O-lower alkyl optionally substituted by deuterium or halogen, -S-lower alkyl optionally substituted by halogen, phenyl, pentafluorosulfur, -CN, -O-benzyl, or -Si-mon-, di- or tri-lower alkyl, where di- or tri- may be the same or different alkyls; L is a bond, lower alkylene, -O- or -S-; Each of m or n is 0 or 1; q is 0, 1 or 2, and when q is 2, each R 3 Independently represents the same or different substituents; and Represents a single bond or a double bond), Or a salt thereof. [2] The compound or a salt thereof according to [1], wherein Ring A is phenyl, L is -O-, and n is 0. [3] The compound or a salt thereof according to [1] or [2], wherein m is 0. [4] The compound or a salt thereof according to any one of [1] to [3], wherein R 3 Is halogen, lower alkynyl, lower alkyl, or -S-lower alkyl optionally substituted by halogen. [5] The compound or a salt thereof according to any one of [1] to [4], wherein Is phenyl, mono-halophenyl, di-halophenyl, mono-lower alkynylphenyl or mono-lower alkylphenyl, or phenyl substituted by one halogen and one lower alkyl group. [6] A compound selected from the group consisting of the following compounds: Or a salt thereof. [7] A pharmaceutical composition comprising the compound or its salt according to any one of [1] to [6] as an active ingredient, and a pharmaceutically acceptable carrier or excipient. [8] A therapeutic, prophylactic and / or diagnostic agent for the onset of diseases involving epileptic seizures or convulsive seizures (including multiple drug-resistant seizures, intractable seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus), comprising the compound or its salt according to any one of [1] to [6]. [9]The therapeutic, prophylactic or diagnostic agent according to [8], wherein the seizure is selected from focal onset seizures (also known as partial seizures) with motor onset (including automatisms, atonic seizures, clonic seizures, epileptic spasms, hyperkinetic seizures, myoclonic seizures and tonic seizures) and non-motor onset (including autonomic seizures, behavior arrest seizures, cognitive seizures, emotional seizures and sensory seizures); generalized onset seizures including motor seizures (including tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures, myoclonic-tonic-clonic seizures, myoclonic-atonic seizures, atonic seizures and epileptic spasms) and non-motor onset (including typical absence seizures, atypical absence seizures, myoclonic absence seizures and eyelid myoclonic seizures); and seizures of unknown onset including motor seizures (including tonic-clonic seizures and epileptic spasms) and non-motor seizures (including behavior arrest seizures).

[10] The therapeutic, prophylactic or diagnostic agent according to [8], wherein the disease involving epileptic seizures or convulsive seizures is selected from Dravet syndrome, Lennox-Gastaut syndrome, West syndrome (epilepsia nutans), Ohtahara syndrome, Doose syndrome, Landau-Kleffner syndrome, Rasmussen syndrome, Aicardi syndrome, Panayiotopoulos syndrome, Kojewnikow syndrome, Tassinari syndrome, Geschwind syndrome, hemiconvulsion-hemiplegia-epilepsy syndrome, mesial temporal lobe epilepsy, epilepsy with structural / metabolic cause (post-stroke epilepsy, traumatic epilepsy, infectious epilepsy, epilepsy related to the blood-brain barrier, epilepsy related to brain tumors, epilepsy related to neurodegenerative diseases, epilepsy related to autoimmune disorders, etc.), and congenital malformations, congenital metabolic disorders (e.g., phenylketonuria, mitochondrial diseases, lysosomal storage disorders, Sturge-Weber syndrome, etc.) and congenital genetic abnormalities (Rett's syndrome, Angelman's syndrome, 5p syndrome, 4p syndrome, Down's syndrome, etc.), etc.

[11] A therapeutic, prophylactic and / or diagnostic pharmaceutical composition for the seizures of diseases involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, refractory seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus), comprising the compound or its salt according to any one of [1] to [6] as an active ingredient.

[12] The composition according to

[11] , wherein the seizure is selected from focal onset seizures (also known as partial epilepsy) with motor onset (including automatisms, atonic seizures, clonic seizures, epileptic spasms, hyperkinetic seizures, myoclonic seizures, and tonic seizures) and non-motor onset (including autonomic seizures, behavior arrest seizures, cognitive seizures, emotional seizures, and sensory seizures); including motor seizures (including tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures, myoclonic-tonic-clonic seizures, myoclonic-atonic seizures, atonic seizures, and epileptic spasms) and non-motor onset (including typical absence seizures, atypical absence seizures, myoclonic absence seizures, and eyelid myoclonic seizures) of generalized onset seizures; and seizures of unknown onset including motor seizures (including tonic-clonic seizures and epileptic spasms) and non-motor seizures (including behavior arrest seizures).

[13] The composition according to

[11] , wherein the disease involving epileptic seizures or convulsive seizures is selected from Dravet syndrome, Lennox-Gastaut syndrome, West syndrome (epilepsia nutans), Ohtahara syndrome, Doose syndrome, Landau-Kleffner syndrome, Rasmussen syndrome, Aicardi syndrome, Panayiotopoulos syndrome, Kojewnikow syndrome, Tassinari syndrome, Geschwind syndrome, hemiconvulsion-hemiplegia-epilepsy syndrome, mesial temporal lobe epilepsy, epilepsy with structural / metabolic cause (post-stroke epilepsy, traumatic epilepsy, infectious epilepsy, epilepsy related to the blood-brain barrier, epilepsy associated with brain tumors, epilepsy associated with neurodegenerative diseases, epilepsy associated with autoimmune disorders, etc.), and congenital malformations, congenital metabolic disorders (e.g., phenylketonuria, mitochondrial diseases, lysosomal storage disorders, Sturge-Weber syndrome, etc.) and congenital genetic abnormalities (Rett's syndrome, Angelman's syndrome, 5p syndrome, 4p syndrome, Down's syndrome, etc.), etc.

[14] A method for treating, preventing, and / or diagnosing seizures of a disease involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, intractable seizures, acute symptomatic seizures, febrile seizures, and status epilepticus), which comprises administering to a human in need thereof an effective amount of a compound or a salt thereof according to any one of [1] to [6].

[15] The method according to

[14] , wherein the seizure is selected from focal onset seizures (also known as partial epilepsy) having motor onset (including automatisms, atonic seizures, clonic seizures, epileptic spasms, hyperkinetic seizures, myoclonic seizures, and tonic seizures) and non-motor onset (including autonomic seizures, behavior arrest seizures, cognitive seizures, emotional seizures, and sensory seizures); and focal to bilateral tonic-clonic seizures (secondary generalization of partial seizure); generalized onset seizures including motor seizures (including tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures, myoclonic-tonic-clonic seizures, myoclonic-atonic seizures, atonic seizures, and epileptic spasms) and non-motor onset (including typical absence seizures, atypical absence seizures, myoclonic absence seizures, and eyelid myoclonic seizures); and seizures of unknown onset including motor seizures (including tonic-clonic seizures and epileptic spasms) and non-motor seizures (including behavior arrest seizures).

[16] The method according to

[14] , wherein the disease involving epileptic seizures or convulsive seizures is selected from Dravet syndrome, Lennox-Gastaut syndrome, West syndrome (epilepsia nutans), Ohtahara syndrome, Doose syndrome, Landau-Kleffner syndrome, Rasmussen syndrome, Aicardi syndrome, Panayiotopoulos syndrome, Kojewnikow syndrome, Tassinari syndrome, Geschwind syndrome, hemiconvulsion-hemiplegia-epilepsy syndrome, mesial temporal lobe epilepsy, epilepsy with structural / metabolic cause (post-stroke epilepsy, traumatic epilepsy, infectious epilepsy, epilepsy related to the blood-brain barrier, epilepsy related to brain tumors, epilepsy related to neurodegenerative diseases, epilepsy related to autoimmune disorders, etc.), and congenital malformations, congenital metabolic disorders (e.g., phenylketonuria, mitochondrial diseases, lysosomal storage disorders, Sturge-Weber syndrome, etc.) and congenital genetic abnormalities (Rett's syndrome, Angelman's syndrome, 5p syndrome, 4p syndrome, Down's syndrome, etc.), etc.

[17] The compound or its salt according to any one of [1] to [6], for treating, preventing and / or diagnosing the onset of diseases involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, refractory seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus).

[18] The compound or its salt according to

[17] , wherein the seizure is selected from focal onset seizures (also known as partial epilepsy) with motor onset (including automatisms, atonic seizures, clonic seizures, epileptic spasms, hyperkinetic seizures, myoclonic seizures, and tonic seizures) and non-motor onset (including autonomic seizures, behavior arrest seizures, cognitive seizures, emotional seizures, and sensory seizures); including motor seizures (including tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures, myoclonic-tonic-clonic seizures, myoclonic-atonic seizures, atonic seizures, and epileptic spasms) and non-motor onset (including typical absence seizures, atypical absence seizures, myoclonic absence seizures, and eyelid myoclonic seizures) of generalized onset seizures; and seizures of unknown onset including motor seizures (including tonic-clonic seizures and epileptic spasms) and non-motor seizures (including behavior arrest seizures).

[19] The compound or its salt according to

[17] , wherein the disease involving epileptic seizures or convulsive seizures is selected from Dravet syndrome, Lennox-Gastaut syndrome, West syndrome (epilepsia nutans), Ohtahara syndrome, Doose syndrome, Landau-Kleffner syndrome, Rasmussen syndrome, Aicardi syndrome, Panayiotopoulos syndrome, Kojewnikow syndrome, Tassinari syndrome, Geschwind syndrome, hemiconvulsion-hemiplegia-epilepsy syndrome, mesial temporal lobe epilepsy, epilepsy with structural / metabolic cause (post-stroke epilepsy, traumatic epilepsy, infectious epilepsy, epilepsy related to the blood-brain barrier, epilepsy related to brain tumors, epilepsy related to neurodegenerative diseases, epilepsy related to autoimmune disorders, etc.), and congenital malformations, congenital metabolic disorders (e.g., phenylketonuria, mitochondrial diseases, lysosomal storage disorders, Sturge-Weber syndrome, etc.) and congenital genetic abnormalities (Rett's syndrome, Angelman's syndrome, 5p syndrome, 4p syndrome, Down's syndrome, etc.), etc.

[20] Use of the compound or its salt according to any one of [1] to [6] for the manufacture of a medicament for the treatment, prevention and / or diagnosis of seizures of a disease involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, refractory seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus).

[21] The use according to

[20] , wherein the epileptic seizure is selected from focal onset seizures (also known as partial epilepsy) with motor onset (including automatisms, atonic seizures, clonic seizures, epileptic spasms, hyperkinetic seizures, myoclonic seizures, and tonic seizures) and non-motor onset (including autonomic seizures, behavior arrest seizures, cognitive seizures, emotional seizures, and sensory seizures); including motor seizures (including tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures, myoclonic-tonic-clonic seizures, myoclonic-atonic seizures, atonic seizures, and epileptic spasms) and non-motor onset (including typical absence seizures, atypical absence seizures, myoclonic absence seizures, and eyelid myoclonic seizures); and seizures of unknown onset including motor seizures (including tonic-clonic seizures and epileptic spasms) and non-motor seizures (including behavior arrest seizures).

[22] The use according to

[20] , wherein the disease involving epileptic seizures or convulsive seizures is selected from Dravet syndrome, Lennox-Gastaut syndrome, West syndrome (epilepsia nutans), Ohtahara syndrome, Doose syndrome, Landau-Kleffner syndrome, Rasmussen syndrome, Aicardi syndrome, Panayiotopoulos syndrome, Kojewnikow syndrome, Tassinari syndrome, Geschwind syndrome, hemiconvulsion-hemiplegia-epilepsy syndrome, mesial temporal lobe epilepsy, epilepsy with structural / metabolic cause (post-stroke epilepsy, traumatic epilepsy, infectious epilepsy, epilepsy related to the blood-brain barrier, epilepsy related to brain tumors, epilepsy related to neurodegenerative diseases, epilepsy related to autoimmune disorders, etc.), and congenital malformations, congenital metabolic disorders (e.g., phenylketonuria, mitochondrial diseases, lysosomal storage disorders, Sturge-Weber syndrome, etc.) and congenital genetic abnormalities (Rett's syndrome, Angelman's syndrome, 5p syndrome, 4p syndrome, Down's syndrome, etc.), etc. The compounds and salts thereof of the present invention are highly effective for the treatment, prevention and / or diagnosis of diseases involving epileptic seizures, convulsive seizures, etc. In addition, the compounds and salts thereof of the present invention have excellent characteristics as active ingredients in drugs, and for example, have excellent characteristics such as few side effects, tolerance, stability (storage stability, metabolic stability, etc.). In addition, compared with existing antiepileptic drugs, the compounds and salts thereof of the present invention have a wide treatment range. The phrases and terms used in this specification are explained in detail below. “Lower alkyl” may be a C 1-6 linear or branched alkyl, and specific examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, tertiary butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, 3-methylpentyl, etc. Also included are lower alkyls having 1 to 3 hydrogen atoms substituted by deuterium atoms. “Halogen” means fluorine, chlorine, bromine or iodine, and fluorine, chlorine or iodine is preferred. Fluorine or chlorine is more preferred. “Lower alkynyl” may be a C 2-6 linear or branched alkynyl, and specific examples include ethynyl, (1- or 2-) propynyl, 1-methyl-(1- or 2-) propynyl, 1-ethyl-(1- or 2-) propynyl, (1-, 2- or 3-) butynyl, (1-, 2-, 3- or 4-) pentynyl, (1-, 2-, 3-, 4- or 5-) hexynyl, etc. Examples of “lower alkyl optionally substituted by halogen” include C optionally substituted by 1 to 4 halogens 1-6 linear or branched alkyl, and specific examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertiary butyl, secondary butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, 3-methylpentyl, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 1,1,2,2-tetrafluoroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dibromohexyl, etc. Examples of “lower alkylene” include C 1-6 linear or branched alkylene, and specific examples include methylene, ethylene, 1-methylethylene, 2-methylethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, dimethylmethylene, tetramethylene, pentylene, hexamethylene, etc. Each of the groups defined in this specification may be appropriately bonded to another group via a linker (such as -O-, -CO-, -COO-, -S-, -SO-, -SO 2 -, -Si-, -O-CO-, etc.). The various substituents in the compounds represented by the general formula [I] of the present invention (hereinafter referred to as "the compounds [I] of the present invention") are explained below. Ring A of the compound [I] of the present invention is phenyl, naphthyl or pyridyl, and preferably phenyl. R in the compound [I] of the present invention 1 is lower alkyl, and preferably C 1-6 alkyl, or more preferably methyl or ethyl. R in the compound [I] of the present invention 2 is -O-lower alkyl, and preferably -O-C 1-6 alkyl, or more preferably methoxy. R in the compound [I] of the present invention 3 is halogen, lower alkynyl, lower alkyl optionally substituted by halogen, -O-lower alkyl optionally substituted by deuterium or halogen, -S-lower alkyl optionally substituted by halogen, phenyl, pentafluorosulfur, -CN, -O-benzyl or -Si-mon-, di- or tri-lower alkyl, where two or three may be the same or different alkyls, and preferably halogen, lower alkynyl, lower alkyl or trifluoromethylthio, or more preferably fluorine, chlorine, ethynyl, methyl or trifluoromethylthio, or still more preferably fluorine, ethynyl or methyl. L in the compound [I] of the present invention is a bond, lower alkylene, -O- or -S-, and preferably a bond or -O-, or more preferably -O-. n in the compound [I] of the present invention is 0 or 1, and preferably 0. m in the compound [I] of the present invention is 0 or 1, and preferably 0. q in the compound [I] of the present invention is 0, 1 or 2, and when q is 2, each R 3 independently represents the same or different substituents. Preferably, q is 1 or 2, and more preferably q is 1. In the compound [I] of the present invention is a single bond or a double bond, and preferably a single bond. In the compound [I] of the present invention, the options and preferred embodiments of the above substituents include all combinations of these forms, as long as they are consistent combinations. Preferred embodiments of the compound [I] of the present invention are given below. (1) Those in which ring A in formula [I] is phenyl and L is -O-. (2) Those in which R in formula [I] 2 is -O-lower alkyl. (3) Those in which R in formula [I] 3 is halogen, lower alkynyl, lower alkyl or -S-lower alkyl optionally substituted by halogen. The more preferred embodiments of compound [I] are given below. (1) Those in which ring A in formula [I] is phenyl, L is -O-, and n is 0. (2) Those in which R in formula [I] 2 is methoxy. (3) Those in which R in formula [I] 3 is halogen or lower alkyl. The still more preferred embodiments of compound [I] are given below. (1) Those in which L in formula [I] is -O-, m and n are each 0, and is phenyl, fluorophenyl, difluorophenyl, chlorophenyl, bromophenyl, ethynylphenyl, methylphenyl, trifluoromethylthio or methyl- and fluorine-substituted phenyl. In addition, in the present invention, compounds selected from the following group are preferred, and the group consists of: the following compounds or their salts. In this specification, options and preferred embodiments of the different features of the compounds, methods and compositions of the present invention as presented include all possible combinations of the options and preferred embodiments of such different features, provided that they are consistent combinations. The method for manufacturing compound [I] of the present invention is explained below. Compound [I] of the present invention can be manufactured based on the manufacturing methods described for the examples below. The manufacturing methods described below are examples, and the method for manufacturing compound [I] is not limited thereto. In the following reaction formulas, when carrying out alkylation reactions, hydrolysis reactions, amination reactions, esterification reactions, amidation reactions, etherification reactions, nucleophilic substitution reactions, addition reactions, oxidation reactions, reduction reactions, etc., these reactions themselves are carried out by known methods. Examples of such methods include those described in Experimental Chemistry (Fifth Edition, edited by The Chemical Society of Japan, Maruzen Co., Ltd.); Organic Functional Group Preparations, Second Edition, Academic Press, Inc., 1989; Comprehensive Organic Transformations, VCH Publishers, Inc., 1989; and P.G.M. Wuts and T.W.G. Greene, Greene's Protective Groups in Organic Synthesis (Fourth Edition, 2006), etc. Reaction Formula 1 (In the formula, all symbols are as defined above.) Compound [Ia] included in Compound [I] of the present invention can be produced by the reaction shown in Reaction Formula 1 above. Specifically, Compound [III] (acrylic acid) is added to the amino group of Compound [II] by 1,4-addition, and then the amino group of the product is converted to a urea derivative with urea, and then the urea derivative can be cyclized (intramolecular amidation) to produce Compound [Ia]. The "solvent" used in this reaction can be any solvent that is inactive in this reaction, and examples thereof include water, ethers (such as ,, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, diethylene glycol dimethyl ether or ethylene glycol dimethyl ether), halogenated hydrocarbons (such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride), aromatic hydrocarbons (such as benzene, toluene or xylene), lower alcohols (such as methanol, ethanol or isopropanol), and polar solvents (such as N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide or acetonitrile). One of these solvents can be used alone, or a mixture of two or more can be used. The "acid" used in this reaction can be, for example, an inorganic acid, an organic acid, etc. Examples of the "inorganic acid" include hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, and phosphoric acid. Examples of the "organic acid" include acetic acid, trifluoroacetic acid, oxalic acid, phthalic acid, fumaric acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, p-toluenesulfonic acid, and 10-camphorsulfonic acid. Other reaction conditions (reaction temperature, reaction time, etc.) can be appropriately selected based on known 1,4-addition reactions and amidation reactions. Reaction Scheme 2 (In the formula, X is a leaving group, L 1 is -O-, -S-, or a lower alkylene group, and the other symbols are as defined above.) The compound [Ib] included in the compound [I] of the present invention can be produced by the reaction represented by Reaction Scheme 2. Specifically, the leaving group X of the compound [V] dissociates and is replaced by the compound [IV] to produce the compound [Ib]. Examples of the "leaving group" used in the above reaction include halogen, C 1-18 alkylsulfonyl, lower alkylsulfonyloxy, arylsulfonyloxy, aralkylsulfonyloxy, perhalomethylsulfonyloxy, dihydrothio, tolylthioxy, etc. Examples of the preferred leaving group in the reaction include halogen. Examples of the above "halogen" include fluorine, chlorine, bromine, and iodine. "C 1-18 alkylsulfonyl" examples include C 1-18 linear or branched alkylsulfonyl, and specific examples include methylsulfonyl, 1-propylsulfonyl, 2-propylsulfonyl, butylsulfonyl, cyclohexylsulfonyl, dodecylsulfonyl, octadecylsulfonyl, etc. Examples of the "lower alkylsulfonyloxy" include C 1-6 linear or branched alkylsulfonyloxy, and specific examples include methylsulfonyloxy, ethylsulfonyloxy, 1-propylsulfonyloxy, 2-propylsulfonyloxy, 1-butylsulfonyloxy, 3-butylsulfonyloxy, 1-pentylsulfonyloxy, 1-hexylsulfonyloxy, etc. Examples of the "arylsulfonyloxy" include naphthalenesulfonyloxy and benzenesulfonyloxy, which may have 1 to 3 substituents selected from the group consisting of halogen, nitro, C 1-6 linear or branched alkoxy on the benzene ring and C 1-6A straight-chain or branched-chain alkyl group. Specific examples of such "benzenesulfonyloxy groups which may have substituents" include benzenesulfonyloxy, 4-methylbenzenesulfonyloxy, 2-methylbenzenesulfonyloxy, 4-nitrobenzenesulfonyloxy, 4-methoxybenzenesulfonyloxy, 2-nitrobenzenesulfonyloxy, 3-chlorobenzenesulfonyloxy, and the like. Specific examples of "naphthalenesulfonyloxy" include α-naphthalenesulfonyloxy, β-naphthalenesulfonyloxy, and the like. Examples of "arylalkylsulfonyloxy" include naphthyl-substituted C 1-6 A straight-chain or branched-chain alkylsulfonyloxy and phenyl-substituted C 1-6 A straight-chain or branched-chain alkylsulfonyloxy having 1 to 3 substituents selected from the group consisting of halogen, nitro, C on a benzene ring 1-6 A straight-chain or branched-chain alkoxy and C 1-6 A straight-chain or branched-chain alkyl. Specific examples of such "phenyl-substituted alkylsulfonyloxy" include phenylmethylsulfonyloxy, 2-phenylethylsulfonyloxy, 4-phenylbutylsulfonyloxy, 4-tolylmethylsulfonyloxy, 2-tolylmethylsulfonyloxy, (4-nitrophenyl)methylsulfonyloxy, (4-methoxyphenyl)methylsulfonyloxy, (3-chlorophenyl)methylsulfonyloxy, and the like. Examples of "naphthyl-substituted methylsulfonyloxy" include α-naphthylmethylsulfonyloxy, β-naphthylmethylsulfonyloxy, and the like. Specific examples of the "perhaloalkylsulfonyloxy" group are trifluoromethanesulfonyloxy. Specific examples of "dihydrothio" include dimethyldihydrothio, diethyldihydrothio, dipropyldihydrothio, bis(2-cyanoethyl)dihydrothio, bis(2-nitroethyl)dihydrothio, bis(aminoethyl)dihydrothio, bis(2-methylaminoethyl)dihydrothio, bis(2-dimethylaminoethyl)dihydrothio, bis(2-hydroxyethyl)dihydrothio, bis(3-hydroxypropyl)dihydrothio, bis(2-methoxyethyl)dihydrothio, bis(2-carbamoylethyl)dihydrothio, bis(2-carboxyethyl)dihydrothio, bis(2-methoxycarbonylethyl)dihydrothio, diphenyldihydrothio, and the like. The "solvent" used in this reaction can be any solvent that is inactive in this reaction, and examples thereof include water, ethers (such as di , tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether), halogenated hydrocarbons (such as dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride), aromatic hydrocarbons (such as benzene, toluene, and xylene), lower alcohols (such as methanol, ethanol, and isopropyl alcohol), and polar solvents (such as N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide, and acetonitrile). One of these solvents can be used alone, or a mixture of two or more can be used. The "base" used in this reaction can be, for example, an inorganic base, an organic base, etc. Examples of "inorganic bases" include alkali metal hydroxides (such as sodium hydroxide and potassium hydroxide), alkaline earth metal hydroxides (such as magnesium hydroxide and calcium hydroxide), alkali metal carbonates (such as sodium carbonate and potassium carbonate), alkaline earth metal carbonates (such as magnesium carbonate and calcium carbonate), alkaline earth metal bicarbonates (such as sodium bicarbonate and potassium bicarbonate), etc. Examples of "organic bases" include trialkylamines (such as trimethylamine and triethylamine), methylpyridine, and 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene, etc. Other reaction conditions (reaction temperature, reaction time, etc.) can be appropriately determined based on known nucleophilic reactions. In each reaction of the above reaction formula, the reaction product can be used in the form of a reaction solution or as a crude product for the next reaction, but it can also be separated from the reaction mixture by conventional methods and easily purified by conventional separation techniques. Examples of conventional separation techniques include recrystallization, distillation, and chromatography. The starting material compounds, intermediate compounds, and target compounds in each of the above steps, as well as the compound [I] of the present invention itself, include geometric isomers, stereoisomers, optical isomers, and tautomers. The corresponding isomers can be separated by ordinary optical resolution methods. They can also be produced from starting material compounds with suitable optical activity. The compound [I] of the present invention can be produced by the synthesis method shown in the above reaction formula or by a similar method. Unless a specific production method is specifically described, the starting material compounds for producing the compound [I] of the present invention can be commercial compounds, or can be produced by known methods or similar methods. The starting material compounds and target compounds in each of the above steps can be used in the form of appropriate salts. Examples of such salts include salts similar to those given as examples of salts of the compound [I] of the present invention below. When the compounds or commercial products obtained in each step are free compounds, they can be converted into the target salts by known methods. When the compounds or commercial products obtained in each step are salts, they can be converted into the free form or other target salts by known methods. The compounds [I] of the present invention also include embodiments in which they are pharmaceutically acceptable salts, and in some cases, depending on the type of substituents, these compounds can also form acid addition salts or salts with bases. Examples of the "acids" herein include inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid and phosphoric acid; and organic acids such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malic acid, lactic acid, etc. Examples of the "bases" include inorganic bases such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate; organic bases such as methylamine, diethylamine, trimethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, tris(hydroxymethyl)methylamine, dicyclohexylamine, N,N'-dibenzylethylenediamine, guanidine, pyridine, methylpyridine and choline; and ammonium salts, etc. The compounds can also form salts with amino acids (such as lysine, arginine, aspartic acid, glutamic acid, etc.). The present invention also encompasses various hydrates, solvates and crystalline polymorphs of the compounds [I] and their salts. The compounds [I] of the present invention also include compounds in which one or more isotope atoms have been replaced by one or more atoms. Examples of the isotope atoms include deuterium ( 2 H), tritium ( 3 H), 13 C, 15 N, 18 O, etc. The compounds [I] of the present invention include pharmaceutically acceptable prodrugs. Examples of the substituents that can be modified to form prodrugs include reactive functional groups such as -OH, -COOH, amino groups, etc. The modifying groups of these functional groups are appropriately selected from the "substituents" in this specification. The compounds [I] of the present invention or their salts can be in the form of pharmaceutically acceptable co-crystals or co-crystalline salts. The co-crystals or co-crystalline salts herein refer to crystalline substances composed of two or more independent solids each having different physical properties (such as structure, melting point, heat of fusion, etc.) at room temperature. The co-crystals or co-crystalline salts can be appropriately prepared by well-known co-crystallization methods. The compound [I] of the present invention and its salts have excellent effects in the treatment, prevention and / or diagnosis of the onset of diseases involving epileptic seizures or convulsive seizures. The term epileptic seizure applies to any of the seizure types classified as follows: focal onset seizures (also known as partial epilepsy) with motor onset (including automatisms, atonic seizures, clonic seizures, epileptic spasms, hyperkinetic seizures, myoclonic seizures and tonic seizures) and non-motor onset (including autonomic seizures, behavior arrest seizures, cognitive seizures, emotional seizures and sensory seizures); and focal to bilateral tonic-clonic seizures (secondary generalization of partial seizure); generalized onset seizures including motor seizures (including tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures, myoclonic-tonic-clonic seizures, myoclonic-atonic seizures, atonic seizures and epileptic spasms) and non-motor onset (including typical absence seizures, atypical absence seizures, myoclonic absence seizures and eyelid myoclonic seizures); and seizures of unknown onset including motor seizures (including tonic-clonic seizures and epileptic spasms) and non-motor onset (including behavior arrest seizures). Examples of diseases involving epileptic seizures or convulsive seizures include Dravet syndrome, Lennox-Gastaut syndrome, West syndrome (epilepsia nutans), Ohtahara syndrome, Doose syndrome, Landau-Kleffner syndrome, Rasmussen syndrome, Aicardi syndrome, Panayiotopoulos syndrome, Kojewnikow syndrome, Tassinari syndrome, Geschwind syndrome, hemiconvulsion-hemiplegia-epilepsy syndrome, mesial temporal lobe epilepsy, epilepsy with structural / metabolic cause (post-stroke epilepsy, traumatic epilepsy, infectious epilepsy, epilepsy related to the blood-brain barrier, epilepsy associated with brain tumors, epilepsy associated with neurodegenerative diseases, epilepsy associated with autoimmune disorders, etc.), and congenital malformations, congenital metabolic disorders (e.g., phenylketonuria, mitochondrial diseases, lysosomal storage disorders, Sturge-Weber syndrome, etc.) as well as congenital genetic abnormalities (Rett's syndrome, Angelman's syndrome, 5p syndrome, 4p syndrome, Down's syndrome, etc.). The compound [I] or a salt thereof of the present invention is also effective for treating, preventing, and / or diagnosing multiple drug-resistant seizures, intractable seizures, acute symptomatic seizures, febrile seizures, and status epilepticus. In the present invention, multiple drug-resistant seizures and intractable seizures are defined as seizures that cannot be controlled due to the ineffectiveness or insufficient potency of one or two or more antiepileptic drugs, regardless of the type of epileptic seizure as described above. In addition, the compounds [I] of the present invention and their salts, when used as active ingredients in drugs, have excellent characteristics, and for example, have excellent characteristics such as few side effects, tolerance, stability (storage stability, metabolic stability, etc.). The group of these compounds of the present invention also has the effect of being a prophylactic and / or therapeutic agent against intractable epileptic seizures where conventional drug therapies are unsuccessful. Next, pharmaceutical preparations (hereinafter also referred to as "pharmaceutical compositions") containing the compound [I] of the present invention or its salt as an active ingredient are explained. The pharmaceutical preparation is obtained by formulating the compound [I] of the invention or its salt in the form of a conventional pharmaceutical preparation, and is prepared using the compound [I] of the present invention or its salt and a pharmaceutically acceptable carrier. Examples of the carrier include commonly used diluents or excipients, such as fillers, bulking agents, binders, wetting agents, disintegrants, surfactants, lubricants, etc. Depending on the therapeutic purpose, such pharmaceutical preparations can be selected from various forms, and examples thereof include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, injections (liquids, suspensions, etc.). When formulating the preparation in the form of tablets, a wide range of known carriers can be used, and examples thereof include excipients such as lactose; binders such as polyvinylpyrrolidone; disintegrants such as starch; absorption aids such as sodium lauryl sulfate; wetting agents such as glycerol and starch; adsorbents such as colloidal silica; and lubricants such as magnesium stearate, polyethylene glycol, etc. In addition, tablets can be made into tablets with ordinary coatings as needed, such as sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, double tablets or multi-layer tablets. When formulating the preparation in the form of pills, a wide range of known carriers can be used, and examples thereof include excipients such as glucose; binders such as gum arabic powder; and disintegrants such as laminarin. When formulating the preparation into a liquid, emulsion or suspension, a wide range of known diluents can be used, and examples thereof include water. It can also include ordinary solubilizers and buffers, and optionally, coloring agents, preservatives, fragrances, flavoring agents, sweeteners and other drugs. When formulating the preparation into suppositories, a wide range of known carriers can be used, and examples thereof include cocoa butter. When the preparation is an injection, the liquid, emulsion or suspension is preferably sterilized and also preferably isotonic with blood. The amount of sodium chloride sufficient to prepare an isotonic injection can be included in the injection, and other drugs, soothing agents, etc. can also be included. The amount of the compound [I] or its salt contained in the pharmaceutical preparation is not particularly limited and can be appropriately selected from a wide range. However, usually, the compound [I] or its salt of the present invention is preferably contained in an amount of 1% to 70% of the pharmaceutical preparation. The method for administering the pharmaceutical preparation of the present invention is not particularly limited and can be carried out by a method suitable for the dosage form, the age and gender of the patient, the disease state and other conditions. For example, if it is in the form of tablets, pills, liquids, suspensions, emulsions, granules or capsules, it can be administered orally. If it is an injection, it can be administered by intravenous injection alone or by mixing with a common replacement fluid (such as glucose or amino acids) and then administered by intravenous injection, or it can also be administered intramuscularly, intradermally, subcutaneously or intraperitoneally alone as needed. In the case of suppositories, it can be administered rectally. The dosage of the pharmaceutical preparation can be selected according to the administration method, the age and gender of the patient, the severity of the disease and other conditions. However, usually, it can be administered at 0.01 mg to 100 mg, or preferably 0.1 mg to 50 mg per 1 kg body weight per day in one or multiple administrations. This dosage is affected by various conditions, and in some cases, a dosage lower than the above range may be sufficient, while in other cases, a dosage higher than the above range may be required. The compound [I] or its salt of the present invention can be used in combination with various therapeutic or prophylactic agents for diseases in which the compound [I] is considered effective. Such combination use can be carried out by simultaneous administration, or by separate administration, sequential administration or administration at appropriate intervals. The preparations for simultaneous administration can be formulated alone or in combination. One embodiment of the present invention provides a pharmaceutical composition containing the compound [I] or its salt of the present invention together with a pharmaceutically acceptable carrier and / or excipient. Another embodiment provides a therapeutic, prophylactic and / or diagnostic agent for the onset of diseases involving epileptic seizures or convulsive seizures (including multiple drug-resistant seizures, intractable seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus), containing the compound [I] or its salt of the present invention together with a pharmaceutically acceptable carrier and / or excipient. Yet another embodiment provides a therapeutic, prophylactic and / or diagnostic pharmaceutical composition for the onset of diseases involving epileptic seizures or convulsive seizures (including multiple drug-resistant seizures, intractable seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus), containing the compound [I] or its salt of the present invention together with a pharmaceutically acceptable carrier and / or excipient. Yet another embodiment provides a method for treating, preventing, and / or diagnosing the onset of a disease involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, intractable seizures, acute symptomatic seizures, febrile epilepsy, and status epilepticus), which comprises administering to a human in need thereof an effective amount of the compound [I] of the present invention or a salt thereof. Yet another embodiment provides the compound [I] of the present invention or a salt thereof for treating, preventing, and / or diagnosing the onset of a disease involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, intractable seizures, acute symptomatic seizures, febrile epilepsy, and status epilepticus). Yet another embodiment provides the use of the compound [I] of the present invention or a salt thereof for manufacturing a medicament for treating, preventing, and / or diagnosing the onset of a disease involving epileptic seizures or convulsive seizures (including multi-drug resistant seizures, intractable seizures, acute symptomatic seizures, febrile epilepsy, and status epilepticus). [Examples] The present invention is further explained in detail by the following test examples, reference examples, and examples, but these do not limit the present invention, and they can be changed to the extent that they do not deviate from the scope of the present invention. The following abbreviations are used in this specification: REX: Reference example number EX: Example number STR: Structural formula (in the formula, the label "chiral" indicates the absolute configuration of the structure) RProp: Manufacturing method (the number indicates that the compound is manufactured using the corresponding raw materials in the same manner as the reference example compound with that number as the reference example number) Prop: Manufacturing method (the number indicates that the compound is manufactured using the corresponding raw materials in the same manner as the example compound with that number as the example number) Data: Physical property data (NMR1: δ (ppm) in 1 1H-NMR, in dimethyl sulfoxide-d 6 ; NMR2: in 1 1H-NMR, δ (ppm) in CDCl 3 3) Ph: Phenyl 9-BBN: 9-Borabicyclo[3.3.1]nonane CDI: 1,1'-Carbonyldiimidazole DBU: 1,8-Diazabicyclo[5.4.0]-7-undecene DIBOC: Di-tert-butyl dicarbonate WSC: 3-Ethyl-1-(3-dimethylaminopropyl)carbodiimide DEAD: Diethyl azodicarboxylate DPPA: Diphenylphosphoryl azide HOBt: 1-Hydroxybenzotriazole NCS: N-Chlorosuccinimide DCC: Dicyclohexylcarbodiimide DHP: 3,4-Dihydro-2H-pyran DMAP: 4-(Dimethylamino)pyridine ZCl: Benzyl chloroformate PPTS: Pyridinium p-toluenesulfonate MCPBA: m-Chloroperoxybenzoic acid BBr 3 : Boron tribromide n-BuLi: n-Butyllithium NaH: Sodium hydride DIPEA: Diisopropylethylamine KOtBu: Potassium tert-butoxide LDA: Lithium diisopropylamide LHMDS: Lithium hexamethyldisilazide NaOtBu: Sodium tert-butoxide DIBAL: Diisobutylaluminum hydride LAH: Lithium aluminum hydride NaBH 4 : Sodium borohydride Pd / C: Palladium on carbon AcOEt: Ethyl acetate DCE: 1,2-Dichloroethane DCM: Dichloromethane DMA: N,N-Dimethylacetamide DME: Dimethoxyethane DMF: N,N-Dimethylformamide DMSO: Dimethyl sulfoxide Et 2 O: Diethyl ether MeOH: Methanol EtOH: Ethanol Hexane: n-Hexane IPA: 2-Propanol IPE: Diisopropyl ether MeCN: Acetonitrile MEK: 2-Butanone NMP: N-Methylpyrrolidone PEG: Polyethylene glycol TEA: Triethylamine TFA: Trifluoroacetic acid THF: Tetrahydrofuran AcOH: Acetic acid HCl: Hydrochloric acid KOH: Potassium hydroxide LiOH: Lithium hydroxide NaOH: Sodium hydroxide K 3 PO 4 : Tripotassium phosphate Cs 2 CO 3 : Cesium carbonate K 2 CO 3 : Potassium carbonate KHCO 3 : Potassium hydrogen carbonate NaHCO 3 : Sodium hydrogen carbonate AcONa: Sodium acetate In the following examples, "room temperature" generally indicates from about 10 °C to about 35 °C. Unless otherwise specified, the ratios indicated for mixed solvents are volume ratios. Unless otherwise specified, percentages represent weight %. Measured by Fourier transform type NMR (using any one of Bruker AVANCE 300 (300 MHz), Bruker AVANCE 500 (500 MHz), Bruker AVANCE III 400 (400 MHz) or Bruker AVANCE III 500 (500 MHz)) 1 1H-NMR (proton nuclear magnetic resonance) spectrum. When describing basic gels for silica gel column chromatography, silica gel bonded with aminopropylsilane is used. The absolute configuration of the compound was determined by known X-ray crystal structure analysis methods (e.g., Shigeru Oba and Shigenobu Yano, "Basic Course for Chemists 12, X-ray Crystal Structure Analysis" (1st ed., 1999)), or estimated from the experimental rules of Shi asymmetric epoxidation (Waldemar Adam, Rainer T. Fell, Chantu R. Saha-Moller, and Cong-Gui Zhao: Tetrahedron: Asymmetry 1998, 9, 397-401. Yuanming Zhu, Yong Tu, Hongwu Yu, Yian Shi: Tetrahedron Lett. 1988, 29, 2437-2440). [Reference Examples] Reference Example 1 5-Nitro-2-phenoxypyrimidine Phenol (6.61 mL) and K 2 CO 3 (12.99 g) were suspended in DMF (80 mL), 2-chloro-5-nitropyrimidine (10 g) was added, and the mixture was stirred overnight at room temperature. Water was added to the reaction solution, and the resulting solid was washed with water to obtain the target compound (6.55 g). NMR2: 7.17-7.24 (2H, m), 7.31-7.39 (1H, m), 7.45-7.53 (2H, m), 9.33 (2H, s). Reference Example 2 2-Phenoxypyrimidin-5-amine 5-Nitro-2-phenoxypyrimidine (7.45 g) and 50% aqueous 10% Pd / C (3 g) were suspended in EtOH (100 mL), and stirred under a hydrogen atmosphere at room temperature for 16 hours. The reaction solution was filtered through diatomaceous earth, the filtrate was concentrated, and the resulting solid was washed with IPE to obtain the target compound (4.73 g). NMR2: 3.50 (2H, brs), 7.13-7.24 (3H, m), 7.35-7.45 (2H, m), 8.07 (2H, s). Reference Example 3 2-(2-Fluorophenoxy)-5-nitropyrimidine O-Fluorophenol (6.71 mL) and K 2 CO 3 (12.99 g) was suspended in DMF (100 mL). After that, 2-chloro-5-nitropyrimidine (10 g) was added and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction solution, and the resulting solid was washed with water to obtain the target compound (13.67 g). NMR2: 7.20 - 7.38 (4H, m), 9.33 (2H, s). Reference Example 4 2-(2-Fluorophenoxy)pyrimidin-5-amine 2-(2-Fluorophenoxy)-5-nitropyrimidine (13.67 g) and 50% aqueous 10% Pd / C (3 g) were suspended in EtOH (130 mL), and stirred at room temperature for 1 hour under a hydrogen atmosphere. The reaction solution was filtered through diatomaceous earth, the filtrate was concentrated, and the resulting solid was washed with IPE to obtain the target compound (8.25 g). NMR2: 3.51 (2H, brs), 7.13 - 7.30 (4H, m), 8.05 (2H, s). Reference Example 5 2-(3-Fluorophenoxy)-5-nitropyrimidine m-Fluorophenol (5.45 mL) and K 2 CO 3 (10.40 g) was suspended in DMF (80 mL), 2-chloro-5-nitropyrimidine (8 g) was added, and the mixture was stirred at room temperature overnight. Water was added to the residue, then it was extracted with AcOEt, the organic layer was separated, washed with water and saturated brine, dried over sodium sulfate, and concentrated to obtain the target compound (8.63 g). NMR2: 6.93 - 7.12 (3H, m), 7.38 - 7.48 (1H, m), 9.34 (2H, s). Reference Example 6 2-(3-Fluorophenoxy)pyrimidin-5-amine 2-(3-Fluorophenoxy)-5-nitropyrimidine (8.65 g) and 50% aqueous 10% Pd / C (3 g) were suspended in EtOH (100 mL), and stirred at room temperature for 16 hours under a hydrogen atmosphere. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated to obtain a crude product. The crude product was purified by medium-pressure preparative liquid chromatography (DMC / AcOEt = 10:1 → 1:1), and then the resulting solid was washed with hexane to obtain the target compound (3.77 g). NMR2: 3.55 (2H, brs), 6.86 - 7.00 (3H, m), 7.30 - 7.39 (1H, m), 8.08 (2H, s). Reference Example 7 1-[2-(methylthio)pyrimidin-5-yl]pyrimidine-2,4(1H,3H)-dione A mixture of 5-bromo-2-(methylthio)pyrimidine (2.77 g), uracil (2.27 g), cuprous iodide (0.257 g), picolinic acid (0.33 g) and K 3 PO 4 (5.73 g) was suspended in DMSO (30 mL) and stirred overnight at 150 °C under a nitrogen atmosphere. An aqueous citric acid solution was added to the reaction solution, which was then extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate and concentrated to obtain the crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane: AcOEt = 10:1 → 0:1) to obtain the target compound (577 mg). NMR1: 2.56 (3H, s), 5.77 (1H, d, J = 7.9 Hz), 7.80 (1H, d, J = 7.9 Hz), 8.76 (2H, s), 11.62 (1H, brs). Reference Example 8 2-(dodecylthio)-5-nitropyrimidine Dodecyl mercaptan (24.77 mL) was dissolved in DMF (150 mL) and cooled to 0 °C. 60% NaH (4.14 g) was added and stirred for 10 minutes, and 2-chloro-5-nitropyrimidine (15 g) was added to the mixture, which was then stirred at 0 °C for 1 hour. Water was added to the reaction solution, and the resulting solid was washed with water to obtain the target compound (26.01 g). NMR2: 0.88 (3H, t, J = 7.0 Hz), 1.18 - 1.38 (16H, m), 1.38 - 1.50 (2H, m), 1.64 - 1.76 (2H, m), 3.23 (2H, t, = 7.5 Hz), 9.23 (2H, s). Reference Example 9 2-(dodecylthio)pyrimidin-5-amine 2-(Dodecylthio)-5-nitropyrimidine (26.01 g) was dissolved in EtOH (250 mL), an aqueous solution (100 mL) of ammonium chloride (25.6 g) and zinc powder (52.2 g) were added, and the mixture was stirred under reflux for 5 hours. AcOEt was added to the reaction solution and stirred overnight. After that, the reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated. Water was added to the residue, which was then extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate and concentrated to obtain the crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane:AcOEt = 4:1 → 1:1) and washed with hexane to obtain the target compound (20.17 g). NMR2: 0.88 (3H, t, J = 7.0 Hz), 1.15 - 1.40 (16H, m), 1.40 - 1.51 (2H, m), 1.62 - 1.81 (2H, m), 3.10 (2H, t, J = 7.4 Hz), 3.49 (2H, brs), 8.08 (2H, s). Reference Example 10 1-[2-(Dodecylthio)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 2-(Dodecylthio)pyrimidin-5-amine (11 g) was dissolved in toluene (100 mL), acrylic acid (3.83 mL) was added, and the mixture was stirred at 110 °C overnight. The reaction solution was concentrated, the residue was dissolved in AcOH (100 mL), urea (3.35 g) was added, and the mixture was stirred at 110 °C for 2 days. The reaction solution was concentrated and washed with an aqueous saturated sodium bicarbonate solution, and the resulting crystals were filtered out. The obtained solid was dissolved in a 10% MeOH / DCM mixed solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The obtained solid was washed with EtOH to obtain the target compound (5.67 g). NMR2: 0.88 (3H, t, J = 7.0 Hz), 1.17 - 1.38 (16H, m), 1.38 - 1.50 (2H, m), 1.68 - 1.79 (2H, m), 2.89 (2H, t, J = 6.7 Hz), 3.14 (2H, t, J = 7.4 Hz), 3.88 (2H, t, J = 6.7 Hz), 7.48 (1H, brs), 8.52 (2H, s). Reference Example 11 1-[2-(Dodecylsulfonyl)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 1-[2-(Dodecylthio)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione (7.17 g) was suspended in DCM (80 mL) and cooled. After that, aqueous 77% MCPBA (10.23 g) was added, and the mixture was stirred overnight at room temperature. Dimethyl sulfide was added to the reaction solution and stirred. After that, saturated aqueous sodium bicarbonate solution was added, and DCM was distilled off under reduced pressure. The resulting solid was washed with water to obtain the target compound (7.15 g). NMR1: 0.85 (3H, t, J = 7.1 Hz), 1.15 - 1.45 (18H, m), 1.60 - 1.73 (2H, m), 2.78 (2H, t, J = 6.6 Hz), 3.53 - 3.61 (2H, m), 4.01 (2H, t, J = 6.6 Hz), 9.08 (2H, s), 10.83 (1H, brs). Reference Example 12 1-[2-(Methylthio)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 2-(Methylthio)pyrimidin-5-amine (4.61 g) was suspended in water (25 mL), acrylic acid (4.48 mL) was added, and the resulting mixture was stirred in a nitrogen atmosphere at 70 °C for 2 days. The reaction solution was concentrated, the residue was dissolved in AcOH (25 mL), urea (2.94 g) was added, and the mixture was stirred at 90 °C for 3 days. The reaction solution was concentrated, and the residue was neutralized by adding saturated aqueous sodium bicarbonate solution and extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate and concentrated to obtain the crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane:AcOEt = 4:1 → 0:1) and washed with EtOH to obtain the target compound (478 mg). NMR2: 2.58 (3H, s), 2.90 (2H, t, J = 6.7 Hz), 3.89 (2H, t, J = 6.7 Hz), 7.61 (1H, brs), 8.54 (2H, s). Reference Example 13 1-[2-(Methylsulfonyl)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 1-[2-(Methylthio)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione (520 mg) was suspended in DCM (10 mL), aqueous 77% MCPBA (1174 mg) was added, and the mixture was stirred overnight at room temperature under a nitrogen atmosphere. Dimethyl sulfide was added to the reaction solution and stirred, and the solid was washed with DCM to obtain the target compound (449 mg). NMR1: 2.78 (2H, t, J = 6.6 Hz), 3.42 (3H, s), 4.01 (2H, t, J = 6.6 Hz), 9.08 (2H, s), 10.82 (1H, brs). Reference Example 14 Diethyl 2-(5-nitropyrimidin-2-yl)-2-phenylmalonate Diethyl phenylmalonate (21.64 mL) was suspended in a DMF (100 mL) solution and cooled in ice, 60% NaH (4.02 g) was added and stirred for 30 minutes, after which 2-chloro-5-nitropyrimidine (8.0 g) was added and stirred at 80 °C for 1 hour. Water was added to the reaction solution, which was then extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate and concentrated to obtain a crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane:AcOEt = 95:5 → 75:25) to obtain the target compound (10.04 g). NMR2: 1.29 (6H, t, J = 7.1 Hz), 4.37 (4H, q, J = 7.1 Hz), 7.31 - 7.40 (3H, m), 7.43 - 7.50 (2H, m), 9.46 (2H, s). Reference Example 15 2-Benzylpyrimidin-5-amine Diethyl 2-(5-aminopyrimidin-2-yl)-2-phenylmalonate (1.13 g) was dissolved in ethylene glycol (10 mL), 5M aqueous NaOH solution (3.43 mL) was added and stirred at 120 °C for 2 days. Aqueous citric acid solution was added to neutralize the reaction solution, which was then extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate and concentrated to obtain a crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane:AcOEt = 1:1 → 0:1) to obtain the target compound (502 mg). NMR2: 3.59 (2H, brs), 4.18 (2H, s), 7.16 - 7.24 (1H, m), 7.26 - 7.35 (4H, m), 8.14 - 8.19 (2H, m). The compounds of Reference Examples 16 to 36 were each prepared as in Reference Examples 1 and 2. The structural formulas and physicochemical data of the compounds of Reference Examples 16 to 36 are each shown in Tables 1-1 and 1-2. [Example] Example 1 1-(2-Phenoxypyrimidin-5-yl)-5,6-dihydropyrimidine-2,4(1H,3H)-dione 2-Phenoxypyrimidin-5-amine (1.00 g) and acrylic acid (1.10 mL) were dissolved in toluene (10 mL), and the mixture was stirred at 80 °C for 3 days. The reaction solution was concentrated, the residue was dissolved in AcOH (10 mL), urea (642 mg) was added, and the mixture was heated to reflux for 2 days. The reaction solution was concentrated, and the crude product was purified by medium-pressure preparative liquid chromatography (AcOEt / MeOH = 1:0 → 9:1), and the resulting solid was washed with EtOH to obtain the target compound (233 mg). NMR2: 2.90 (2H, t, J = 6.7 Hz), 3.88 (2H, t, J = 6.7 Hz), 7.17 - 7.24 (2H, m), 7.26 - 7.33 (1H, m), 7.40 - 7.49 (2H, m), 7.54 (1H, brs), 8.55 (2H, s). Example 2 1-[2-(2-Fluorophenoxy)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 2-(2-Fluorophenoxy)pyrimidin-5-amine (1.00 g) and acrylic acid (0.67 mL) were dissolved in propionitrile (10 mL), and the mixture was stirred at 110 °C for 2 days. The reaction solution was concentrated, the residue was dissolved in AcOH (10 mL), urea (585 mg) was added, and the mixture was heated to reflux overnight. The reaction solution was concentrated, and the crude product was purified by medium-pressure preparative liquid chromatography (hexane / AcOEt = 1:1 → 0:1), and the resulting solid was washed with EtOH to obtain the target compound (289 mg). NMR2: 2.90 (2H, t, J = 6.7 Hz), 3.89 (2H, t, J = 6.7 Hz), 7.12 - 7.34 (4H, m), 7.59 (1H, brs), 8.55 (2H, s). Example 3 1-[2-(3-Fluorophenoxy)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione Dissolve 2-(3-fluorophenoxy)pyrimidin-5-amine (500 mg) and acrylic acid (0.50 mL) in toluene (2.5 mL), and stir overnight at 80 °C. Concentrate the reaction solution, dissolve the residue in AcOH (2.5 mL), add urea (293 mg) and heat the mixture to reflux for 2 days. Concentrate the reaction solution, and purify the crude product by medium-pressure preparative liquid chromatography (DCM / AcOEt = 4:1 → 1:1), and wash the obtained solid with IPE to obtain the target compound (63 mg). NMR2: 2.91 (2H, t, J = 6.7 Hz), 3.90 (2H, t, J = 6.7 Hz), 6.92 - 7.08 (3H, m), 7.34 - 7.48 (1H, m), 7.58 (1H, brs), 8.57 (2H, s). Example 4 1-(2-Phenoxypyrimidin-5-yl)pyrimidine-2,4(1H,3H)-dione Suspend 1-[2-(methylthio)pyrimidin-5-yl]pyrimidine-2,4(1H,3H)-dione (440 mg) in DCM (10 mL), add aqueous 77% MCPBA (1002 mg), and stir the mixture overnight at room temperature under a nitrogen atmosphere. Add dimethyl sulfide to the reaction solution, then stir and concentrate it under reduced pressure. After that, dissolve the residue in DMF (4 mL), add phenol (0.33 mL) and K 2 CO 3 (772 mg), and stir the mixture overnight at room temperature. Then stir it at 70 °C for 3 hours. Add water to the reaction solution, then extract it with AcOEt. Separate the organic layer, wash it with water and saturated brine, dry it with sodium sulfate and concentrate to obtain the crude product. Purify the crude product by medium-pressure preparative liquid chromatography (hexane / AcOEt = 1:1 → 0:1), and wash the obtained solid with IPE and recrystallize it from aqueous EtOH to obtain the target compound (270 mg). NMR2: 5.93 (1H, dd, J = 2.2 Hz, 8.0 Hz), 7.19 - 7.27 (3H, m), 7.27 - 7.35 (1H, m), 7.42 - 7.51 (2H, m), 8.46 (1H, brs), 8.59 (2H, s). Example 5 1-[2-(3-Fluorophenoxy)pyrimidin-5-yl]-3-methyl-5,6-dihydropyrimidine-2,4(1H,3H)-dione 1-[2-(3-Fluorophenoxy)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione (500 mg) and K 2 CO 3 (343 mg) were suspended in DMF (5 mL), methyl iodide (0.11 mL) was added, and the mixture was stirred at 70 °C for 1 hour. Water was added to the reaction solution, and then it was extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate, and concentrated to obtain the target compound (197 mg). NMR2: 2.94 (2H, t, J = 6.7 Hz), 3.25 (3H, s), 3.83 (2H, t, J = 6.7 Hz), 6.92 - 7.08 (3H, m), 7.35 - 7.45 (1H, m), 8.55 (2H, s). Example 6 1-[2-(3-Fluoro-2-methylphenoxy)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 1-[2-(Dodecylsulfonyl)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione (500 mg), 3-fluoro-2-methylphenol (193 mg) and K 2 CO 3 (244 mg) were suspended in DMF (7 mL), stirred at room temperature under a nitrogen atmosphere, and then stirred at 80 °C for 3 hours. Water was added to the reaction solution, and the resulting solid was washed with water to obtain the target compound (143 mg). NMR2: 2.12 (3H, d, J = 1.8 Hz), 2.90 (2H, t, J = 6.7 Hz), 3.89 (2H, t, J = 6.7 Hz), 6.93 (1H, d, J = 8.2 Hz), 6.95 - 7.03 (1H, m), 7.18 - 7.27 (1H, m), 7.61 (1H, brs), 8.55 (2H, s). Example 7 1-[2-(3-Ethylphenoxy)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 1-[2-(3-Ethynylphenoxy)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione (312 mg) was dissolved in a mixed EtOH / THF (5 / 5 mL) solution, and aqueous 10% Pd / C (108 mg) was added and stirred under a hydrogen atmosphere for 3 hours. The reaction solution was filtered through celite and washed with AcOEt, and the filtrate was concentrated to obtain the crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane:AcOEt = 1:1 → 0:1), and the resulting solid was washed with EtOH to obtain the target compound (99 mg). NMR2: 1.26 (3H, t, J = 7.6 Hz), 2.69 (2H, q, J = 7.6 Hz), 2.90 (2H, t, J = 6.7 Hz), 3.88 (2H, t, J = 6.7 Hz), 6.97 - 7.08 (2H, m), 7.09 - 7.16 (1H, m), 7.35 (1H, t, J = 7.8 Hz), 7.60 (1H, brs), 8.54 (2H, s). Example 8 1-[2-(Phenylthio)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione 1-[2-(Methylsulfonyl)pyrimidin-5-yl]-5,6-dihydropyrimidine-2,4(1H,3H)-dione (224 mg), K 2 CO 3 (172 mg) and benzenethiol (0.10 mL) were suspended in DMF (5 mL), stirred at room temperature under a nitrogen atmosphere, and then stirred at 70 °C for 10 hours. Water was added to the residue, and then it was extracted with AcOEt. The organic layer was separated, washed with water and saturated brine, dried over sodium sulfate and concentrated to obtain the crude product. The crude product was purified by medium-pressure preparative liquid chromatography (hexane:AcOEt = 1:1 → 0:1), and then washed with EtOH to obtain the target compound (47 mg). NMR2: 2.88 (2H, t, J = 6.6 Hz), 3.85 (2H, t, J = 6.6 Hz), 7.40 - 7.50 (3H, m), 7.58 (1H, brs). 7.60 - 7.68 (2H, m), 8.50 (2H, s). The compounds of Examples 9 to 56 were each prepared as in Examples 1 to 8. The structural formulas and physicochemical data of the compounds of Examples 9 to 56 are shown in Tables 2-1 to 2-6, respectively. [Test Example] The pharmacological test results of the typical compounds of the present invention are given below, and the pharmacological effects of these compounds are explained, but the present invention is not limited by these test examples. [Test Example 1] Auditory Kindling Seizure Model The animal model used in this test is a phenotypic model of partial epilepsy (including secondary generalized seizures) and generalized tonic-clonic seizures, and has high clinical predictability. This test was conducted according to the following report: De Sarro et al. (Br J Pharmacol. [British Journal of Pharmacology] February 1988; 93(2): 247-56. Anticonvulsant effects of some calcium entry blockers in DBA / 2 mice [Anticonvulsant effects of some calcium channel blockers in DBA / 2 mice], De Sarro GB, Meldrum BS, Nisticó G.). In this test example, the example compounds shown in Table 3 below were used as test compounds. The following compound (the compound of Example 5 of WO 2004 / 009559) was used as a comparative example compound, which is the most similar compound when considering the substituent positions. The test compound was suspended in 5% gum arabic / distilled water (w / v) and administered orally by force at a dose of 30 mg / kg to male and female DBA / 2 mice (Japan SLC, Inc., 3 weeks old, 8 mice per group). One hour after oral administration of the test compound, each mouse was placed in a transparent acrylic cylinder 30 cm high and 23 cm in diameter and allowed 30 seconds to acclimatize. Then, they were exposed to an auditory stimulus (12.6 kHz, 100 - 110 dB) for 1 minute or until a tonic seizure occurred. The seizure response was evaluated using the following scale: 0: no seizure, 1: running wild, 2: clonic seizure, 3: tonic seizure, and 4: respiratory arrest. The maximum response was recorded as the seizure severity score. The seizure inhibition rate for each compound-administered group was calculated according to the following formula. The results are shown in Table 3. [Test Example 2] Maximal electroshock seizure (MES) model This test was conducted to evaluate the anticonvulsant activity of the compounds. The mouse model used in this test was a phenotypic model of generalized tonic-clonic seizures and secondary generalized partial seizures. This test was conducted according to the following report: AJ Hill et al. (Br J Pharmacol. [British Journal of Pharmacology] December 2012; 167(8): 1629 - 42. Cannabidivarin is anticonvulsant in mouse and rat [Cannabidivarin is an anticonvulsant in mice and rats, Hill AJ et al.). In this test example, the compounds of Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 21, 22, 23, 24, 25, 26, 28, 30, 31, 37, 38, 40, 41, 42, 44, 45, 47, 48, 50, 52, 53, 54, and 56 were used as test compounds. The test compound was suspended in 5% gum arabic / distilled water (w / v) and orally administered to male ICR mice (Japan SLC, Inc., 5 to 6 weeks old, 8 mice per group) at a dose of 30 mg / kg by forced gavage. One hour after oral administration of the test compound, the mice were stimulated by applying an electric current (30 mA, 100 Hz, 0.2 s) through auricular electrodes using an electroshock device (UGO BASILE SRL). Then, the incidence of tonic hindlimb extension seizures was recorded. In this test, tonic hindlimb extension seizures were induced in all mice in the solvent-administered group, but the seizure inhibition ratios with Example Compounds 1, 2, 3, 5, 8, 10, 12, 13, 14, 16, 18, 22, 26, 28, 30, 31, 38, 42, 47, 48, and 54 were 75% or higher, and the inhibition rates with Example Compounds 4, 6, 9, 11, 23, 41, and 45 were 50% or higher. [Test Example 3] Subcutaneous pentylenetetrazole (scPTZ) model This test was conducted as in Test Example 2 to evaluate the anticonvulsant activity of the compounds. Different from the phenotype of Test Example 2, the animal model used in this test was a phenotypic model of generalized absence epilepsy and myoclonic seizures. In this test example, Example Compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 21, 22, 23, 24, 25, 26, 28, 30, 31, 37, 38, 40, 41, 42, 44, 45, 47, 48, 52, 53, 54, and 56 were used as test compounds. The test compound was suspended in 5% gum arabic / distilled water (w / v) and orally administered to male ICR mice (Japan SLC, Inc., 5 to 6 weeks old, 10 mice per group) at a dose of 30 mg / kg by forced gavage. One hour later, 85 mg / kg of pentylenetetrazole dissolved in saline was administered subcutaneously, and the occurrence of clonic seizures was evaluated for 30 minutes. In this test, clonic seizures were induced in all mice in the solvent-administered group, but the inhibition ratios of Example Compounds 1, 2, 3, 4, 5, 11, 13, 14, 22, 23, and 28 against clonic seizures were 75% or higher, and the inhibition rates of Example Compounds 12, 26, 41, 42, 44, and 56 were 50% or higher. [Test Example 4] Rotarod test This test was conducted to evaluate the effect of the compounds on motor coordination. In this test example, test compounds used were example compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 21, 22, 23, 24, 25, 26, 28, 30, 31, 37, 38, 40, 41, 42, 44, 45, 47, 48, 50, 52, 53, 54, and 56. Male ICR mice (Japan SLC, Inc., 5 - 6 weeks old, 8 mice per group) were trained to stay on a rotating rod (Muromachi Kikai Co., Ltd.) at a fixed speed (15 rpm) for 2 minutes. The test compound was suspended in 5% gum arabic / distilled water (w / v) and administered orally by force at a dose of 30 mg / kg. One hour after oral administration, the mice were placed on the rod again, and the speed was accelerated from 4 rpm to 40 rpm over 5 minutes, and the duration before falling off the rod was recorded for 200 seconds. The pre - fall duration of the compound - administered group was calculated as the relative value with respect to the average pre - fall duration in the solvent - administered group. In this test example, the ratio of motor dysfunction for example compounds 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 21, 22, 23, 24, 25, 26, 28, 30, 31, 37, 38, 40, 41, 42, 44, 47, 48, 50, 52, 53, 54, and 56 was 25% or less.

Industrial Applicability

Claims

1. A pharmaceutical composition comprising a compound represented by formula [I]:

1. Wherein the ring A is phenyl, naphthyl, or pyridyl; R1 is a lower alkyl group; R2 is -O-lower alkyl group; R3 is halogen, lower alkynyl, lower alkyl group substituted with halogen as appropriate, -O-lower alkyl group substituted with deuterium or halogen as appropriate, -S-lower alkyl group substituted with halogen as appropriate, phenyl, pentafluorosulfur, -CN, -O-benzyl, or -Si-mono-, di-, or tri-lower alkyl group, wherein di or tri can be the same or different alkyl groups; L is a bond, lower alkyl group, -O- or -S-; each of m or n is 0 or 1; q is 0, 1, or 2, and when q is 2, each R3 independently represents the same or different substituents; and represents a single or double bond), or a salt thereof as an active ingredient, a pharmaceutical agent relating to the treatment or prevention of diseases involving seizures or convulsions, and a pharmaceutically acceptable carrier or excipient.

2. The pharmaceutical composition as described in claim 1, wherein the cyclic A-type phenyl group, the L-type -O- group, and the n-type 0- group.

3. The pharmaceutical composition as described in claim 1 or 2, wherein m is 0.

4. The pharmaceutical composition as described in claim 1 or 2, wherein R3 is a halogen, a lower alkynyl group, a lower alkyl group, or a -S-lower alkyl group substituted with halogen as appropriate.

5. The pharmaceutical composition as described in claim 1 or 2, wherein 5. A phenyl group, a monohalogenated phenyl group, a dihalogenated phenyl group, a mono-lower alkynyl phenyl group or a mono-lower alkyl phenyl group, or a phenyl group substituted with one halogen and one lower alkyl group.

6. A pharmaceutical composition comprising a compound selected from the group consisting of an active ingredient, a medicament for the treatment or prevention of diseases involving epileptic seizures or convulsive episodes, and a pharmaceutically acceptable carrier or excipient, wherein, This group consists of the following compounds:

6. Or its salt.

7. A therapeutic, preventive, and / or diagnostic pharmaceutical composition for the treatment of seizures or convulsive seizures (including multidrug-resistant seizures, refractory seizures, acute symptomatic seizures, febrile epilepsy, and status epilepticus), comprising a compound or salt thereof as an active ingredient, and an agent for the treatment or prevention of seizures or convulsive seizures.

8. Use of a pharmaceutical composition described in any one of claims 1 to 6 of the patent application for the manufacture of a medicament for the treatment, prevention and / or diagnosis of seizures involving epileptic seizures or convulsive seizures (including multidrug-resistant seizures, refractory seizures, acute symptomatic seizures, febrile epilepsy and status epilepticus).