MXPA01002976A - [1,2,4]TRIAZOLO[1,5-c]PYRIMIDINE DERIVATIVES - Google Patents

Abstract

[1,2,4]Triazolo[1,5-c]pyrimidine derivatives represented by general formula (I) or pharmacologically acceptable salts thereof which show adenosine A2A receptor antagonism, wherein R1 represents heteroaryl, etc.;R2 represents hydrogen, etc.;na and nb represent each an integer of 0 to 4;Q represents hydrogen, etc.;R6 represents hydrogen, etc.;R3 represents (i) hydroxy, (ii) hydroxy(lower alkyl), (iii) lower alkoxy, or (iv) imidazo[1,2-a]pyridyl, etc.;and R4 and R5 represent each lower alkyl or aryl, or R4 and R5 form together with the adjacent carbon atom a saturated carbon ring when R3 is any of (i) to (iii);or R4 and R5 represent each hydrogen, lower alkyl or aryl, or R4 and R5 form together with the adjacent carbon atom a saturated carbon ring when R3 is (iv).

Description

DERIVATIVES OF M, 2.41 TRIAZOL? Ri, 5-cl PI Rl MI DINA Field of the invention The present invention relates to derivatives of [1, 2,4] tpazolo [1,5-c] pyrimidine which show antagonism of A2A adenosine receptor and are useful for treating or preventing various diseases induced by hyperactivity of A2A adenosine receptors (eg, Parkinson's disease, senile dementia, or depression).

BACKGROUND OF THE INVENTION It is known that adenosine shows attenuation of neurotransmitter activity through an A2A receptor (European Journal of Pharmacology, 168: 285 (1989)). Consequently, A2A adenosine receptor antagonists are considered as remedies or preventatives for various diseases induced by hyperactivity of A2A adenosine receptors, such as a remedy for Parkinson's disease, an anti-dementia drug, a remedy for depression, and the similar. In addition, previous antagonists are expected to exhibit therapeutic and symptom-improving effects after Parkinson's disease, progressive supranuclear palsy, SI DA encephalopathy, spongiform encephalopathy, multiple sclerosis, amyotrophic lateral sclerosis, H untington's disease, atrophy Multiple system, cerebral ischemia, hyperactivity disorder, attention deficit, somnipathy, ischemic heart disease, intermittent claudication, diabetes, or the like.

On the other hand, [1, 2,4] triazolo [1,5-cyrimidine derivatives are described as compounds having diuretic activity in Japanese Published Unexamined Patent Application No. 1 3792/85, as compounds having anti-asthmatic activity in Japanese Published Unexamined Patent Application No. 56983/85, and as compounds having bronchodilator activity in Japanese Published Unexamined Patent Application No. 1 67592/84 . However, adenosine receptor antagonism of [1, 2,4] triazolo [1, 5-c] pyrimidine derivatives and their activity in the central nervous system are not known.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide derivatives of [1, 2,4] triazolo [1,5-c] pyrimidine or pharmaceutically acceptable salts thereof which have A2A adenosine receptor antagonism. and are useful for treating or preventing diseases induced by hyperactivity of an A2A adenosine receptor (eg, Parkinson's disease, dementia, depression, or the like). The present invention relates to a [1, 2, 4] triazolo [1,5-c] pyrimidine derivative represented by the formula (I): wherein R1 represents substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group; R 2 represents a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group; na and nb are the same or different, and each represents an integer from 0 to 4; Q represents a hydrogen atom or 3,4-dimethoxybenzyl; R6 represents a hydrogen atom, substituted or unsubstituted lower alkyl, halogen or hydroxy; R3 represents (i) hydroxy, (ii) hydroxy-lower alkyl, (iii) substituted or unsubstituted lower alkoxy, or (iv) a group selected from the group consisting of substituted imidazo [1,2-a] pyridyl or unsubstituted, substituted or unsubstituted imidazo [1, 2-a] pyrazinyl, substituted or unsubstituted imidazo [1, 2-a] pyrimidinyl, substituted or unsubstituted benzimidazolyl, substituted or unsubstituted benzothiazolyl, benzo-2, 1, 3-substituted or unsubstituted thiadiazolyl, substituted or unsubstituted isoxazolyl, and substituted or unsubstituted 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazinyl; and when R3 represents hydroxy, lower hydroxyalkyl, or substituted or unsubstituted lower alkoxy, R4 and R5 are the same or different, and each represents a lower alkyl substed or unsubsted or substed or unsubsted aryl, or R4 and R5 form a substed or unsubsted saturated carbocycle together with the adjacent carbon atom, and when R3 represents a group selected from the group consisting of [1, 2-a] substed or unsubsted pyridyl, substed or unsubsted or substed midozo [1, 2-a] pyrazinyl, substed or unsubsted 1, 2-a] pyrimidinyl, substed or unsubsted benzimidozolyl, substed or unsubsted benzothiazolyl, substed or unsubsted benzo-2, 1, 3-thiadiazolyl, substed or unsubsted isoxazolyl, and 3-oxo-3,4-dih-idro-2H-benzo [1,4] oxazinyl substed or unsubsted substed, R 4 and R 5 are the same or different, and each represents a hydrogen atom, substed or unsubsted lower alkyl, or substed or unsubsted aryl, or R 4 and R 5 form a substed or unsubsted saturated carbocycle together with the atom of adjacent carbon; or a pharmaceutically acceptable salt thereof. In another aspect, the present invention relates to a medicament comprising the derivative of [1, 2,4] triazolo [1,5-cjpyrimidine represented by the formula (I) or a pharmaceutically acceptable salt thereof. In still another aspect, the present invention relates to an A2A adenosine receptor antagonist or an agent for preventing or treating a disease induced by hyperactivity of an A2A adenosine receptor, comprising the derivative of [1, 2,4] triazolo [1 .5-c] pyrimidine represented by the formula (I) or a pharmaceutically acceptable salt thereof for the preparation of an agent to prevent or treat a disease induced by hyperactivity of an A2A adenosine receptor. In a further aspect, the present invention relates to a method for preventing or treating a disease induced by hyperactivity of an A2A adenosine receptor, which comprises administering an effective amount of the [1, 2,4] triazolo derivative [1.5. -cjpyrimidine represented by the formula (I) or a pharmaceutically acceptable salt thereof. In the definition of each group in the formula (I), examples of the alkyl moiety of the lower alkyl, lower alkoxy, and hydroxy-lower alkyl include linear or branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, butyl-butyl, pentyl, neopentyl, hexyl, and the like. Examples of halogen include fluorine, chlorine, bromine and iodine atoms. Examples of aryl include phenyl, naphthyl, indenyl, anthryl, and the like. Examples of the aromatic heterocyclic group include furyl, thienyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, imidezolyl, pyrimidinyl, triazinyl, indolyl, quinolyl, purinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, and the like. Examples of the saturated carbocycle include those having 3 to 8 carbon atoms, such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, and the like. Examples of the subsent on the substed lower alkyl, substed lower alkoxy, and substed saturated carbocycle include 1 to 3 subsents which with the same or different, such as hydroxy, carboxy, a saturated carbocyclic group, lower alkoxy, lower alkoxycarbonyl, aryl, aryloxy, aralkyloxy, an aromatic heterocyclic group, an aromatic heterocyclic group substed with lower alkyl, lower alkoxy substed with hydroxy, lower alkoxy substed with lower alkoxy , lower alkanoyl, lower alkanoyl substed with aryl, aroyl, formyl, halogen, trifluoromethyl, vinyl, styryl, phenylethynyl, and the like. The saturated carbocyclic group means a group formed by extracting an atom and hydrogen from the saturated carbocycle described above. Lower alkyl half of lower alkoxy, lower alkoxycarbonyl, lower alkyl substed aromatic heterocyclic group, lower alkoxy substituted with hydroxy, lower alkoxy substituted with lower alkoxy, lower alkanoyl, and lower alkanoyl substituted with aryl have the same meaning as the lower alkyl described above. The aryl and the aryl moiety of the aryloxy, aralkyloxy, lower alkanoyl substituted with aryl, and aroyl have the same meanings as the aryl described above. The aromatic heterocyclic group and the aromatic heterocyclic moiety of the lower alkyl substituted aromatic heterocyclic group have the same meaning as the above-described aromatic heterocyclic group. The alkylene moiety of aralkyloxy means a group formed by extracting a hydrogen atom from the lower alkyl described above. Halogen has the same meaning as the halogen described above. Examples of the substituted aryl substituent, substituted aromatic heterocyclic group, and group selected from the group consisting of substituted imidazo [1, 2-a] pyridyl, imidazo [1, 2] substituted chlirazinyl, substituted [1, 2-a] pyrimidinyl imidazo, substituted benzimidazolyl, substituted benzothiazolyl, substituted benzo-2, 1,3-thiadiazolyl, substituted isoxazolyl, and 3-oxo-3,4-dihydro-2H-benzo [1] , 4] -oxazinyl substituted include 1 to 3 substituents which are the same or different, such as lower alkyl, hydroxy, lower alkyl substituted with hydroxy, halogen-lower alkyl, lower alkoxy, lower alkoxycarbonyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, aryl, aryloxy, aralkyl, aralkyloxy, an aromatic heterocyclic group, halogenoaryloxy, haloalkyloxy, carboxy, carbamoyl, formyl, lower alkanoyl, aroyl, halogen, nitro, amino, cyano, trifluoromethyl, trifluoromethoxy, methylenedioxy, ethylenedioxy, and the like . The lower alkoyl and the lower alkyl moiety of the lower alkyl substituted with hydroxy, halogen-lower alkyl, lower alkoxy, lower alkoxycarbonyl, lower alkylthio, lower alkylsulfonyl, and lower alkanoyl have the same meanings as the lower alkyl described above. The aryl and the aryl moiety of the aryloxy, halogenoaryloxy, and aroyl have the same meanings as the aryl described above. The aryl moiety of aralkyl, aralkyloxy, and haloaralkyloxy has the same meaning as the aryl described above. The alkylene moiety of aralkyl, aralkyloxy, and halogenalkyloxy means a group formed by extracting a hydrogen atom from the lower alkyl described above. The halogen and the halogen moiety of the halogen-lower alkyl, halogenoaryloxy, and halogenalkyloxy have the same meanings as the halogen described above. The heterocyclic group aromatic has the same meaning as the one described above. In the following, the compound represented by the formula (I) is referred to as Compound (I). Compounds of other formula numbers are also similarly named. Among the compounds (I), a compound, wherein Q is 3,4-dimethoxybenzyl, is hereinafter referred to as Compound (IQ) which is an excellent antagonist of A2A adenosine receptor and is also useful as a synthetic intermediate. for a compound, wherein Q is a hydrogen atom, among Compounds (I). A compound, wherein Q is a hydrogen atom in the formula (I) is referred to as Compound (I H), if necessary. Preferred examples in the present invention include Compounds (I H), wherein Q is a hydrogen atom in the formula (I). Preferred examples of Compound (I H) are shown below. The compounds are preferred, wherein R 2 is a hydrogen atom, the compounds are more preferred, wherein R 2 is a hydrogen atom; and R1 is a substituted or unsubstituted aromatic heterocyclic group, and particularly preferred are compounds, where nb is 1. Also, the compounds, where R1 is furyl; and R2 is a hydrogen atom, compounds, wherein R1 is furyl; R2 and R6 are each a hydrogen atom; na and nb are each 1; R3 is hydroxy; and R 4 and R 5 are each substituted or unsubstituted lower alkyl (particularly, methyl is preferred), and compounds, wherein R 1 is furyl; R2, R4, R5 and R6 are each a hydrogen atom; na is o; nb is 1; and R3 is a group selected from the group that consists of im substituted [1, 2-a] substituted or unsubstituted pyridyl, substituted or unsubstituted 1, 2-ajpyrazinyl imidazo, substituted or unsubstituted imidazo [1,2-a] pyrimidinyl, substituted or unsubstituted benzimidazolyl, substituted benzothiazolyl or unsubstituted, substituted or unsubstituted benzo-2, 1, 3-thiadiazolyl, substituted or unsubstituted isoxazolyl, and 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazinyl substituted or unsubstituted (particularly , 5-methylisoxazol-3-yl is preferred) are preferred compounds. Examples of the pharmaceutically acceptable salts of Compound (I) include pharmaceutically acceptable metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, acid addition salts, and the like. The pharmaceutically acceptable metal salts of Compound (I) include alkali metal salts, such as sodium salts, potassium salts and the like, alkaline earth metal salts, such as magnesium salts, calcium salts, and the like. similar, aluminum salts, zinc salts and the like. The pharmaceutically acceptable ammonium salts include salts such as ammonium, tetramethylammonium and the like. The pharmaceutically acceptable organic amine addition salts include addition salts of morpholine, piperidine and the like. The pharmaceutically acceptable amino acid addition salts include addition salts of lysine, glycine, phenylalanine, and the like. The pharmaceutically acceptable acid addition salts include salts of inorganic acid, such as hydrochlorides, sulfates, phosphates, and the like, and salts of organic acid, such as acetates, maleates, fumarates, tartrates, citrates, and the similar. The production methods of Compounds (I) are explained below.

Production Method 1 Compound (I H) can be produced by means of Compound (I Q) by the following reaction steps.

(SAW) (where R1, R2, R3, R4, R5, R6, na and nb have the same meanings as defined above, respectively) Step 1 Compound (II) raw is commercially available (manufactured by Aldrich) or can be synthesized according to a known method (Journal of Chemical Society, 383 (1943)) or a similar method thereof. Also, Compound (11) is commercially available (manufactured by Aldrich, etc.) or can be synthesized according to a known method (New Experimental Chemistry Course, 14, Syntheses and Reactions of Organic Compounds (II), page 1221 (1977) (Maruzen)) or a similar method thereof. Compound (IV) can be obtained by reacting Compound (II) with 1 to 5 equivalents, preferably 1 to 2 equivalents of Compound (III) in a solvent inert to the reaction in the presence of 1 to 3 equivalents, preferably 2 equivalents, of a suitable base, generally at room temperature at 200 ° C, preferably at room temperature, for 10 minutes up to 48 hours. Examples of the solvent inert to the reaction include tetrahydrofuran (hereinafter referred to as "THF"), dioxane, diethylene glycol,? /, / V-dimethylformamide (hereinafter referred to as "DMF"), dimethylacetamide, dimethyl sulfoxide (in hereinafter referred to as "DMSO"), benzene, toluene, xylene, acetonitrile, ethyl acetate, pyridine, tetralin, methylene chloride, chloroform, methanol, ethanol, propanol, butanol, and the like, which may be used alone or in combination, and the preferred example are THF and DMF. Examples of the suitable base include triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] -7-undecene (hereinafter referred to as "DBU"), pyridine,? / - methylmorpholine, potassium carbonate, hydride of sodium, calcium hydride, and the like, and a preferred example is DBU.

Step 2 Raw Compound (V) is commercially available or can be synthesized according to a known method (J.

Org. Chem., 8: 338 (1943); Unexamined Patent Application Japanese Published No. 1 06375/99) or a similar method thereof. Compound (IV) can be obtained by reacting Compound (IV) with an equivalent to a large excess of Compound (V) without a solvent or in a solvent inert to the reaction in the presence of 0.1 to 3 equivalents, preferably 1.2. eq ulents, from a suitable base, generally at room temperature at 200 ° C, preferably at 1 00 to 1 50 ° C, for 1 0 minutes up to 48 hours. Examples of the solvent inert to the reaction include THF, dioxane, diethylene glycol, DMF, dimethylacetamide, DMSO, benzene, toluene, xylene, acetonitrile, ethyl acetate, pyridine, tetralin, methylene chloride, chloroform, and the like. which may be used alone or in combination, and preferred examples are DMF and THF. Examples of the suitable base include triethylamine, diisopropylethylamine, DBU, pyridine,? / - methylmorpholine, potassium carbonate, sodium hydride, calcium hydride , and the like, and preferred examples are DBU and potassium carbonate. (where R1, R2, R3, R4, R5, R6, na and nb have the same meanings as defined above, respectively) Step 3 Compound (Vl la) or Compound (Vl lb) can be obtained by treating Compound (VI) with 2 to 10 equivalents of a dehydrating-condensing agent, such as polyphosphoric acid, ethyl polyphosphate, trismethylsilyl polyphosphate, or the like, without a solvent or in a solvent inert to the reaction, generally at 1 0 to 200 ° C, preferably at 1 30 to 1 50 ° C, for 1 to 24 hours, preferably for 4 to 7 hours. The reaction for the production of the Compound (VII-a) in this step is known as the Dimroth rearrangement reaction (for example, see Journal of Medicinal Chemistry, 33: 1 321 (1990)). Examples of the solvent inert to the reaction include benzene, toluene, xylene, tetralin, phenyl ether, methylene chloride, chloroform, and the like, which are used alone or in combination, and a preferred example is xylene.

Step 4 Compound (IQ) can be obtained by reacting Compound (Vl la) or Compound (Vl lb) with 1 to 6 equivalents, preferably 3 equivalents, of 3,4-dimethoxybenzylamine (VI II) without a solvent or in solvent inert to the reaction, generally at 1 0 to 200 ° C, preferably at 1 30 to 150 ° C, for 10 minutes up to 24 hours. This step also accompanies the Dimroth rearrangement reaction described in step 3. Examples of the solvent inert to the reaction include THF, dioxane, diethylene glycol, DMF, dimethylacetamide, DMSO, benzene, toluene, xylene, acetonitrile, ethyl acetate , pyridine, tetralin, methylene chloride, chloroform, methanol, ethanol, propanol, butanol, and the like, which are used alone or in combination, and a preferred example is DMSO. or > (where R1, R2, R3, R4, R5, R6, na and nb have the same meanings as defined above, respectively) Step 5 Compound (IH) can be obtained by treating Compound (IQ) in an acidic solvent, such as hydrochloric acid, acetic acid, dichloroacetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, or the like, preferably in trifluoroacetic acid or a mixed solvent of trifluoroacetic acid and trifluoromethanesulfonic acid, generally at 1 0 to 1 00 ° C for 10 minutes up to 24 hours, or when Compound (IQ) is treated with 1 to 10 equivalents, preferably 5 equivalents, of trifluoromethanesulfonic acid or sulphonic acid in an acidic solvent, such as hydrochloric acid, acetic acid, dichloroacetic acid, trifluoroacetic acid, or the like, preferably in trifluoroacetic acid, in the presence of 1 to 10 equivalents, preferably 4 eq. equivalents, of anisole, dimethoxybenzene or trimethoxybenzene, preferably anisole, generally at -20 to 80 ° C, preferably at 1 0 to 40 ° C, for 10 minutes to 1 8 hours.

Production Method 2 As an alternative method, the Compound (I H) can also be produced by the following steps. (where R1, and R2 have the same meanings as defined above, respectively) Step 6 Compound (IX-a) or Compound (IX-b) can be obtained by treating Compound (IV) with 2 equivalents to a large excess of a dehydrating-condensing agent, such as polyphosphoric acid, ethyl polyphosphate, polyphosphate trimethylsilyl, or the like, without a solvent or in a solvent inert to the reaction, generally at 1 0 to 200 ° C, preferably at 1 30 to 160 ° C, for 1 to 1 2 hours, preferably for 3 to 6 hours . This step also accompanies the Dimroth rearrangement reaction described in step 3. Examples of the solvent inert to the reaction include toluene, xylene, tetralin, phenyl ether, methylene chloride, chloroform, hexane, and the like. which are used alone or in combination, and a preferred example is xylene.

Step 7 Compound (IX-a) can only be obtained through the rearrangement reaction of Dim roth described in step 3 when treating a mixture of Compound (IX-a) and Compound (IX-b) or Compound (IX-) b) alone in a solvent inert to the reaction in the presence of 0.5 to 3 equivalents, preferably one equivalent, of a suitable base, generally at 0 to 1 00 ° C, preferably at 10 to 40 ° C, for 5 minutes to 1 0 hours Examples of the solvent inert to the reaction include THF, dioxane, diethylene glycol, DM F, dimethylacetamide, DMSO, benzene, toluene, xylene, acetonitrile, ethyl acetate, pyridine, tetralin, methylene chloride, chloroform, methanol, ethanol, propanol, butanol, and the like, which are used alone or in combination, and the preferred examples are DMF and TH F. Examples of the suitable base include triethylamine, diisopropylethylamine , DBU, pyridine, N-methylmorpholine, potassium carbonate, potassium hydride, calcium hydride, and the like, and a preferred example is DBU.

Step 8 Compound (X) can be obtained by reacting Compound (IX-a) with 1 to 6 equivalents, prefey 3 equivalents, of 3,4-dimethoxybenzylamine (VI II) without a solvent or in a solvent inert to the reaction , generally at 0 to 200 ° C, prefey at 40 to 60 ° C, for 1 0 m inutes up to 24 hours. Examples of the solvent inert to the reaction include THF, dioxane, diethylene glycol, DMF, dimethylacetamide, DMSO, benzene, toluene, xylene, acetonitrile, ethyl acetate, pyridine, tetralin, and the like, which may be used alone or in combination , and a preferred example is TH F.

(TH) (where R1, R2, R3, R4, R5, R6, na and nb have the same meanings as defined above, respectively) Step 9 Compound (XI) can be obtained by treating Compound (X) for 10 minutes up to 24 hours in an acidic solvent, such as hydrochloric acid, acetic acid, dichloroacetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, or the like , prefey in trifluoroacetic acid or a mixed solvent of trifluoroacetic acid and trifluoromethanesulfonic acid, or by treating Compound (X) with 1 to 10 equivalents, prefey 2.5 equivalents, of trifluoromethanesulfonic acid in an acidic solvent, such as hydrochloric acid, acetic acid, dichloroacetic acid, trifluoroacetic acid, or the like, prefey in trifluoroacetic acid, in the presence of 1 equivalent to a large excess, prefey 3 to 5, of anisole, dimethoxybenzene or trimethoxybenzene, prefey anisole, generally at -20 to 1 00 ° C, prefey at 1 0 to 40 ° C, for 10 minutes to 1 8 hours.

Step 1 Compound (IH) can be obtained by reacting Compound (XI) with 1 to 10 equivalents, prefey 3 to 5 equivalents, of Compound (V) without a solvent or in a solvent inert to the reaction, optionally in the presence from 1 to 5 equivalents, prefey 1.5 equivalents, of a suitable base, generally at 1 0 to 200 ° C for 10 minutes up to 48 hours. Examples of the solvent inert to the reaction include THF, dioxane, diethylene glycol, ethoxyethanol, DMF, dimethylacetamide, dimethyl imidazolidone (DM I), DMSO, benzene, toluene, xylene, acetonitrile, ethyl acetate, pyridine, tetralin, methylene chloride. , chloroform, and the like, which are used alone or in combination, and a preferred example is DMSO. Exemplary examples of the suitable base include triethylamine, diisopropylethylamine, DBU, pyridine,? / - methylmorpholine, potassium carbonate, sodium carbonate, sodium hydride, calcium hydride, and the like, and preferred examples are potassium carbonate. and sodium carbonate.

Production method 3 As an alternative method, Compound (IH) can also be produced by the following steps. (where R1, R2, R6, and nb have the same meanings as defined above, respectively) Step 11 Compound (XIII) can be obtained by reacting Compound (XI) with Compound (Xll) in a manner similar to the method shown in Step 10.

Step 1 Compound (XV) can be obtained by reacting Compound (XI) with Compound (XIV) in a manner similar to the method shown in Step 1 0.

Step 1 Compound (XI II) can be obtained by reacting Compound (XV) with 1 to 5 equivalents, prefey 1.2 equivalents, of vinyl chlorocarbonate (XVI) in a solvent inert to the reaction, generally at 0 to 1 00 ° C, prefey at 1 0 to 40 ° C, for 1 0 m inutes up to 24 hours, and then treat the reaction product in a solvent inert to the reaction containing 1 to 4 mol / l hydrogen chloride, generally at 0 to 1 00 ° C, prefey at 1 0 to 40 ° C, for 10 minutes up to 24 hours. Examples of the solvent used in the reaction with vinyl chlorocarbonate (XVI) include dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, THF, DMF, diethyl ether, and the like, which are used alone or in combination, and a preferred example is chloroform. Examples of the solvent used in the treatment with hydrogen chloride include methanol, ethanol, propanol, isopropanol, ethyl acetate, dioxane, and the like, which are used alone or in combination, and a preferred example is methanol. Also, Compound (XI I I) can be obtained from Compound (XV) by subjecting it to usual catalytic hydrogenation. reducing agent agent 2) reducer OH) (wherein R1, R2, R3, R4, R5, R6, na and nb have the same meanings as defined above, respectively, na 'represents an integer from 0 to 2, and X represents halogen having the same meaning as previously defined.) Step 14 Compound (XVI I) cousin can be synthesized according to a known method (J. Chem. Soc, Perkin Trans. I, 9: 994 (1976)) or a method similar to the same.

Compound (IH) can be obtained by reacting Compound (XIII) with 1 equivalent to a large excess, preferably 1 to 2 equivalents, of Compound (XVII) in a solvent inert to the reaction, optionally in the presence of 1 to 3 equivalents of a suitable base, generally at 0 to 150 ° C, preferably at 10 to 70 ° C, for 10 minutes up to 48 hours. Examples of the solvent inert to the reaction include pyridine, DMF, dimethylacetamide, THF, dioxane, diethyl ether, dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, methanol, ethanol, ethyl acetate, hexane, acetonitrile, and similar, which are used alone or in combination, and preferred examples are pyridine and DMF. Examples of the suitable base include triethylamine, diisopropylethylamine, DBU,? / - methylmorpholine, potassium carbonate, sodium hydride, and the like, and a preferred example is triethylamine.

Step 15 Compound (XVIII) cousin can be synthesized according to a known method (Japanese Unexamined Patent Application Laid-open No. 109791/86) or a similar method thereto. Compound (IH) can be obtained by reacting Compound (XIII) with one equivalent to a large excess, preferably 1 to 10 equivalents, of Compound (XVIII) without a solvent inert to the reaction, optionally in the presence of an equivalent to an excess large, preferably 1 to 3 equivalents, of a suitable reducing agent, generally at -78 up to 1 00 ° C, preferably at 0 up to 50 ° C, for 10 minutes up to 24 hours. Alternatively, Compound (IH) can be obtained by reacting Compound (XI II) with one equivalent to a large excess, preferably 1 to 10 equivalents, of Compound (XVIII) without a solvent or in a solvent inert to the reaction, generally at -78 to 1 99 ° C, preferably at 0 to 50 ° C, for 10 minutes up to 24 hours, followed by treatment in the presence of an equivalent to a large excess, preferably 1 to 3 equivalents, of a suitable reducing agent, generally at -78 to 1 00 ° C, preferably at 0 to 50 ° C, for 10 minutes up to 24 hours. Examples of the solvent inert to the reaction include dichloromethane, chloroform, carbon tetrachloride, dichloroethane, benzene, toluene, xylene, ether, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, acetonitrile, hexane, methanol, ethanol, water and the like. , preferably dichloroethane, dichloromethane, and ethanol, which are used alone or in combination. Examples of the suitable reducing agent include sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, and the like, and a preferred example is sodium triacetoxyborohydride. In this case, a suitable acid can optionally be added in an amount from a catalytic amount to a large excess, preferably 0.5 to 5 equivalents. Examples of the suitable acid include formic acid, acetic acid, trifluoroacetic acid, propionic acid, hydrochloric acid, and the like, and a preferred example is acetic acid.

Production Method 4 Among Compounds (I), Compound (I Ha), wherein Q is a hydrogen atom and R5 is hydroxy, can be produced from Compound (I Hb), wherein Q is a hydrogen atom and R5 is substituted or unsubstituted lower alkoxy, among Compounds (I), by the following step.

(IH-b) (IH-a) (wherein R1, R2, R3, R4, R5, R6, na and nb have the same meanings as defined above, respectively, and R5'b represents a substituted or unsubstituted lower alkoxy having the same meaning as was defined earlier) Step 1 6 Compound (I H-a) can be obtained by treating Compound (I Hb) with an equivalent to a large excess, preferably a large excess, of a suitable sulfur compound without a solvent or in a solvent inert to the reaction in the presence of a catalytic amount to a large excess, preferably 5 to 1 5 equivalents, of a suitable Lewis acid, generally at -78 to 1 00 ° C for 1 0 minutes up to 72 hours. Examples of the solvent inert to the reaction include dichloromethane, chloroform, carbon tetrachloride, dichloroethane, benzene, toluene, xylene, ether, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, ethyl acetate, hexane, acetonitrile, and the like, preferably dichloroethane, which are used alone or in combination. Examples of the suitable sulfur compound include ethanethiol, dimethyl sulfide, benzenethiol, and the like. Examples of the suitable Lewis acid include a complex of diethyl ether of boron trifluoride, aluminum trichloride, titanium tetrachloride, tin tetrachloride, and the like, and a preferred example is a boron trifluoride diethyl ether complex. . Alternatively, this step can be carried out by treating with a Lewis acid in the absence of the sulfur compound. Examples of the Lewis acid usable in the absence of the sulfur compound include boron tribromide, boron trichloride, trimethylsilyl iodide, dimethylboron bromide, and the like, and a preferred example is boron tribromide. The solvent, reaction temperature and reaction time to be used are similar to those described above. The intermediate and target compounds in the above-described production methods can be isolated and purified to be subjected to separation and purification methods generally used in synthetic organic chemistry, such as filtration, extraction, washing, drying, concentration, recrystallization, various kinds of chromatography and the like. In the case of intermediaries, they can also be applied to subsequent reactions without purification When it is desired to obtain a salt of Compound (I), in the case where Compound (I) is produced in salt form, it can be purified as it is, but in the case where it is produced in its free form, it can be dissolved or suspend in a suitable solvent, converted to a salt by adding an acid or base and then the resulting salt can be isolated and purified. In addition, Compound (I) or pharmaceutically acceptable salts thereof may exist in the form of addition products with water or various solvents, and these addition products are also included in the present invention. The specific examples of Compound (I) obtained by the present invention are shown in Table 1.

Table 1 (1) Compound No. G Q > CG? Table 1 (2) Compound No. G 2 Table 1 (3) Compound No. G Next, the pharmacological activities of Compound (I) are illustrated with reference to the Test Examples.

Test Example 1 Adenosine receptor binding activity (A2A adenosine receptor binding test) This test was carried out in a manner similar to the Bruns et al. Method. , (Molecular Pharmacology, 29: 331 (1986)). The corpus striatum of a rat was suspended in a tris (hydroxymethyl) aminomethane hydrochloride buffer (hereinafter referred to as "Tris-HCl") 50 m mol / L cooled with ice (pH 7.7) using Polytron Homogenizer (manufactured by Kinematica , Co.) The suspension was centrifuged (50,000 * g, 10 minutes), the precipitate obtained was resuspended in the same amount of 50 mmol / L of Tris-HCl buffer, and then, the suspension was centrifuged in a similar manner. The final precipitate was suspended in a regulator of 50 μmol / L of TRIS-HCl (containing 10 mmol / L of magnesium chloride and 0.02 units / mg of adenosine deaminase tissue (manufactured by Sigma Co.)) on water the regulator to the final precipitate in order to deliver a tissue concentration of 5 mg (wet weight) / m L. To 1 m L of the tissue suspension prepared in this way, 50 μL (final concentration: 4.0) was added. nmol / L) of CGS 21680 etiq with tritium. { 3H-2- [p- (2-carboxyethyl) phenethylamine] -5 '- (? / - ethylcarboxamido) adenosine: 40 Ci / mol; manufactured by New England N uclear Co. (The Journal of Pharmacology and Experimental Therapeutics, 251: 888 (1989))} and 50 μL of a test compound. The resulting mixture was allowed to stand for 1 20 minutes at 25 ° C, and then was quickly filtered by suction through a glass fiber filter (GF / C, manufactured by Whatman Co.). The fiberglass filter was immediately rinsed three times with 5 μl of a 50 μmol / L regulator of ice-cooled Tris-HCl, and transferred to a flask, a scintillator (EX-H, manufactured by Wako) was added. Puré Chemical Industries, Ltd.) to the same, and the radioactivity in the filter was determined with a liquid scintillation counter (manufactured by Packard Instrument Co.) A ratio of inhibition of each compound against the A2A receptor binding ( binding 3H-CGS 21 680) was calculated by the following equation: Proportion of inhibition (%) =. { 1 - (amount of binding in the presence of the test compound - amount of non-specific binding) / (amount of total binding - amount of non-specific binding)} * 1 00 (Note) The amount of the total binding is the amount of bound radioactivity of 3H-CGS 21 680 in the absence of the test com ponent. The amount of the non-specific binding means the amount of bound radioactivity of 3H-CGS 21 680 in the presence of 1 00 mmol / L cyclopentyladenosine (CPA, manufactured by Sigma Co.). The amount of binding in the presence of the test compound is the amount of bound radioactivity of 3H-CGS 21 680 in the presence of the compound of Test in a varied concentration. The results are shown in Table 2. Table 2 Ratio of inhibition of rat A2A receptor (%) Compound No. 1 0"e mol / L 10" 7 mol / L 1 81 42 2 84 3 93 7 81 8 84 9 89 10 87 11 88 15 92 16 88 17 90 18 96 19 95 21 90 65 22 84 23 75 24 96 25 95 26 94 27 96 From Table 2, Compounds (I) show strong antagonism of A2A adenosine receptor, and therefore, it is suggested that a drug which contains Compound (I) as the active ing network is useful for various induced diseases. by hyperactivity of an A2A adenosine receptor (eg, Parkinson's disease, senile dementia or depression).

Test Example 2 Activity in CGS-induced catalepsy 21 680 Parkinson's disease is a motor deficiency based on the degeneration of the cell mero in the nigrostriatal dopaminergic neuron. When CGS 21 680 (A2A adenosine receptor) is admired to the intracerebral ventricle, it directly inhibits the synaptic transmission of GABA in the medium-sized spiny neuron in the striatum by means of the A2A adenosine receptor. (Journal of Neuroscience, 16_: 605 (1 996)). In accordance with the above, it is considered that A2A adenosine receptor agonists positively regulate the exit of the striopalidal GABAnERGic neurons and, as a result, catalepsy is induced by the administration of CGS 21 680. This test was carried out using 10 animals per g rupe of 5-week-old male ddY mice (22 to 25 g in body weight, Japan S LC). CGS 21 680 (manufactured by RBI) was dissolved in physiological saline (manufactured by Otsuka Pharmaceutical Co., Ltd.), and 10 μg / 20μL of the solution was injected into the intracerebral ventricle of the mouse. The test compounds were used when suspended in distilled water containing 0.5% methylcellulose (hereinafter referred to as "MC") (manufactured by Otsuka Pharmaceutical Co., Ltd.). The suspension containing each of the test compounds or a solution containing no test compound (distilled water containing 0.5% MC, as a control) was determined orally (0.1 mL per 10 g of mouse body weight). minutes before injection of CGS 21680 into the intracerebral ventricle. One hour after administration of the test compound, only the forelimbs or only the hind limbs of each animal remained on a vertically installed panel made of acrylic, which was 4.5 cm high by 1.0 cm wide, to measure the symptoms of catalepsy. All the test compounds were administered orally in a dose of 10 mg / kg. Table 3 shows the judgment criteria of the catalepsy score.

Table 3 Score Duration of catalepsy The cataleptic position lasted less than 5 seconds for both the forelimbs and the hind limbs. fifteen twenty The effect was judged by the total catalepsy scores of 1 0 animals in a group (the maximum score is 50 points). When the total score was 40 points or less, the activity of the test committees was judged positive. The number of animals that showed remission of catalepsy was expressed by the number of cases in which the catalepsy score was 4 points or less in 10 cases. The rate of remission of catalepsy was expressed as the percentage reduction of the total score in the group administered with the test compound to the total score in the control group. The results are shown in Table 4.

Table 4 Compound Number of Score Number of animals Proportion of No. total animals that showed remission (%) used remission C at 0.5% 10 50 (control) 1 10 0 10 100 5 10 5 10 90 6 10 8 10 84 7 10 8 9 84 10 11 9 78 13 10 10 8 80 14 10 9 9 82 19 10 5 9 90 10 5 9 90 21 10 0 10 100 22 10 1 10 98 24 10 2 10 96 27 10 4 9 92 Test Example 3 Haloperidol-induced catalepsy activity Parkinson's disease is a disease based on the degeneration and cell death of the nigrostriatal dopaminergic neuron. When haloperidol (D2 dopamine antagonist) is administered, catalepsy is induced by blockade of postsynaptic D2 receptor. This haloperidol-induced catalepsy is known as a classic model in which the symptoms of Parkinson's disease are produced by the administration of the drug (European Journal of Pharmacology, 182: 327 (1990)) and the US Patent. No. 3,991,207). This test was carried out using 10 animals per group of 5-week-old male ddY mice (22 to 24 g in body weight, Japan SLC). Haloperidol (manufactured by Janssen) was suspended in 0.5% MC and administered intraperitoneally in mice at a dose of 1.0 mg / kg. Each test compound was suspended in distilled water for injection containing 0.5% MC (manufactured by Otsuka Pharmaceutical Co., Ltd.) (10 mg / kg). Also, as a drug control, 1 00 mg / kg of L-DOPA and 25 mg / kg of benserazide were used as a solution when dissolved in distilled water for injection containing 0.5% MC (manufactured by Otsuka Pharmaceutical Co., Ltd.). One hour after the intraperitoneal injection of haloperidol, the suspension containing each of the test compounds or the solution containing the control drug was administered orally (0.1 mL per 10 g of mouse body weight) and, a One hour after the administration of the test compound or the control drug, only the front limbs or only the hind limbs of the animal remained on the panel which was 4.5 cm high and 1.0 cm wide, to measure the symptoms of catalepsy. The catalepsy score was assessed by the judgment criteria shown in Table 3 above. The effect was judged by the total catalepsy scores of 10 animals in one group (the maximum score is 50 points). When the total score was 40 points or less, the activity of the test compounds was judged positive. The number of animals that showed catalepsal remission was expressed by the number of cases in which the catalepsy score was 4 points or less in 10 cases. The rate of remixing of catalepsy was expressed as the percentage reduction of the total score in the adm group in- tegrated with the test compound to the total score in the control group. The results are shown in Table 5.

Table 5 Compound Number of Score Number of animals Proportion of No. total animals that showed remission (%) used MC remission at 0.5% 10 5C (control) 1 10 0 10 100 21 10 0 10 100 Test Example 4 Reserpine-induced catalepsy activity Catalepsy induced by the administration of an antipsychotic agent such as reserpine is known as a useful symptom model of Parkinsonism (Journal of Neural Transmission, 8: 39-71 (1994)). This test was carried out using 10 animals per group of 5-week-old male ddY mice (22 to 24 g in body weight, Japan SLC). During the preliminary feeding period, they were allowed to have food and water freely in a room of animals of an ambient temperature of 23 ± 1 ° C and a humidity of 55 ± 5%. Reserpine (5 mg / kg: apoplon, Daiichi Pharmaceutical Co., Ltd., diluted with distilled water) was administered subcutaneously, and catalepsy-induced activity was observed from 18 hours after administration. Mice that showed a catalepsy score of 5 (judgment criterion in Table 3 of the Test Example 2) were selected and used in the experiment. Each test compound was suspended in distilled water for injection containing 0.5% MC (manufactured by Otsuka Pharm Aceutical Co., Ltd.). The suspension containing each of the test compounds or a solution not containing the test com ponte (distilled water for injection containing 0.5% MC (manufactured by Otsuka Pharmaceutical Co., Ltd.), was administered orally. (0. 1 m L per 1 0 g of mouse body weight) and, one hour after the administration of the test compound, only the forelimbs or only the hind limbs of each animal remained on the panel that had a size of 4.5 cm in height and 1.0 cm in width, to measure the symptoms of catalepsy.The effect was judged by total catalepsy scores of 10 animals in a group (the maximum score is 50 points). the total score was 40 points or less, the activity of the test compounds was judged positive, The number of animals that showed remission of catalepsy was expressed by the number of cases in which the catalepsal score was e 4 points or less in 1 0 cases. The rate of remission of catalepsy was expressed as the percentage reduction of the total score in the group administered with the test compound to the total score in the control group. The results are shown in Table 6.

Table 6 Compound Number of Score Number of animals Proportion of No. total animals that showed remission (%) used MC remission at 0.5% 10 50 (control) 1 10 14 8 72 5 10 12 10 76 6 10 11 9 78 7 10 23 7 54 14 10 12 8 76 19 10 19 7 62 21 10 17 7 66 22 10 13 10 74 24 10 14 9 72 Test Example 5 Activity in the Parkinson's disease model (common marmoset treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)). Parkinson's disease is a disease based on the degeneration and cell death of the nig rostriatal dopaminergic neuron. In primates, treatment with a dopamine neurotoxin of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (hereinafter referred to as "MPTP") causes selective degeneration and decrease of the dopaminergic neuron rostriatal nig and sample akinesia and rigidity of muscles or similar. These primates treated with MPTP are known as Parkinson's disease model (Proceedings of the National Academy of Science USA, 80_: 4546 (1 983)). The common marmoset belongs to the Anthropoidae, and it is known that it shows symptoms of Parkinson's disease caused by MPTP as in the case of other animals of the Anthropoidae [Neuroscience Letter, 57:37 (1988)]. This test was carried out using 4 animals per group of common male and female marmosets from 2 to 3 years of age (300 to 375 g in body weight, CLEA Japan). MPTP (manufactured by RB I) was dissolved in physiological saline for injection (manufactured by Otsuka Pharmaceutical Co., Ltd.) and administered to the common marmoset once a day for 5 days by subcutaneous injection at a dose of 2.0 mg /. kg. Six weeks or more after the administration, animals that showed chronic symptoms of Parkinson's mai were used in the test. Each test compound was used when suspended in 0.3% Tween 80 and 1% 0 sucrose solution. One hour before the administration of the test com pont, the animals to be tested were placed in an observation cage (equipped with a spontaneous locomotor count measuring device) to adapt them to the environment. The pre-motor disability prior to administration of the test compound scored, and was compared with the motor disability score after administration of the test compound. The symptoms of Parkinson's disease were observed from a window with a one-way view at intervals of 30 m inutes for 8 hours to get a score for your motor disability. The spontaneous locomotor count was measured at intervals of 30 m inutes for 1 2 hours by a computer-controlled automatic measuring device. The symptoms of Parkinson's disease were judged based on the judgment criteria of each observation element shown below, and the total points were used as the score of each animal. The relationship between the observation elements and the scores is shown in Table 7 shown below.

Table 7 The effect was judged by comparing the average symptom scores of Parkinson's disease in 4 animals per group before and after administration of the test compound (significance test: Wilcoxon Rank Sum test). The results are shown in Table 8.

Table 8 Comm. Average score before Average score to No. of the administration maximum improvement after admission 1 2.75 ± 0.25 4.75 ± 0.48 (p <0.0256) In addition to Compound 1, it was also revealed that Commands 7, 21, 22 and 24 were effective in the Parkinson's disease model treated with MPTP of common marmosets. As described above, an anti-Parkinson's activity of Compounds (I) was confirmed from Test Examples 2 through 5.

Test Example 6 Forced swimming method (measurement of immobility time) Ten animals were used per group of male ddY mice (21 to 26 g body weight, Japan SLC) as the test animal. During the preliminary feeding period, they were allowed to have food and feed freely in a room of animals of an ambient temperature of 23 ± 1 ° C and a humidity of 55 ± 5%. Animals that showed abnormal reactions in terms of spontaneous activity, myotonia, and visual ability or the like were excluded in advance. The test compound was suspended in a 0.3% Tween 80 solution and orally administered one hour before the test. In the negative control group, only 10 μL / kg of 0.3% Tween 80 were administered. The measurement of the immobility time was carried out according to the Porsolt method (Arch. Int Pharmacodyn, 229k: 32J-336 (1 977)). That is to say, a water tank of clear acrylic cylindrical (1 0 cm in diameter and 25 cm in height) was filled to 9 cm depth with water that had a temperature of 23 ± 1 ° C, and it was forced to swim to the mice for 6 minutes. When the mice were put in the water, they immediately started swimming trying to escape from the tank, but the movement gradually decreased 1 to 2 minutes after that. The measurement of the immobility time was carried out by leaving them for 2 minutes and then measuring the period of time during which they did not show the escape action (immobility time: desperation of behavior) during 4 minutes (240 minutes). sec undos) in an interval of one second. In order to reduce The effects of the daily rhythm, the test was carried out using 5 of the 1 0 animals per group in the morning, and the remaining 5 animals in the afternoon. Also, the measurement of the immobility time was carried out by observing 2 animals at the same time and by not telling the observers the differences of the group administered only with solvent and dose of the test compound. Statistical analysis of the results was carried out by means of a multiple comparison test between the control group administered with solvent and the group administered with the test com- position by means of the steel test. The results are shown in Table 9.

Table 9 Test compound. Immobility time (sec undo) MC 0.5% (control 1 80.3 ± 1 5.3 negative) 21 7.6 ± 3.2 (p <0.01) Also, a significant activity of reducing the immobility time was observed by 10 mg / kg of oral administration of Compound 1. From Example 6 of Test 6, the anti-depression activity of Compounds (I) was shown. Compound (I) or a pharmaceutically acceptable salt thereof can be administered as found, but is generally prefers to supply it as various pharmaceutical preparations. In addition, such pharmaceutical preparations are used in animals and humans. The pharmaceutical preparations of the present invention may contain Compound (I) or a pharmaceutically acceptable salt thereof as the active ingredient alone or together with other optional active ingredients for the treatment of different diseases. In addition, these pharmaceutical preparations are produced by optional methods well known in the technical field of pharmaceuticals, by mixing the active ingredient with one or more pharmaceutically acceptable carriers. It is preferred to select an administration path which is more effective in the treatment. Examples include oral administration and parenteral administration, such as intraoral, endotracheal, rectal, subcutaneous, intramuscular, intravenous, and the like. Examples of the dosage form include sprays, capsules, tablets, pills, syrups, emulsions, suppositories, injections, ointments, tapes, and the like. Liquid preparations, such as emulsions, syrups, and the like, suitable for oral administration can be produced using, for example, water; sugars, such as sucrose, sorbitol, fructose, and the like; glycols, such as polyethylene glycol, propylene glycol, and the like; oils, such as sesame oil, olive oil, soybean oil, and the like; antiseptics, such as esters of p-h idroxybenzoic acid, and the like; flavorings, such as strawberry flavor, spearmint, and the like; and else. In addition, capsules, tablets, powders, granules and the like can be produced using, for example, excipients, such as lactose, lucile g, sucrose, mannitol, and the like; disintegrants, such as sodium hydroxide, sodium alginate, and the like; lubricants, such as magnesium stearate, talc, and the like; binder materials, such as polyvinyl alcohol, hydroxypropyl cellulose, gelatin, and the like; surfactants, such as fatty acid esters, and the like; plasticizers, such as glycerol, and the like; and else. Suitable preparations for parenteral administration are preferably sterile aqueous preparations which contain an active compound which becomes isotonic in the blood of the acceptors. For example, in the case of injections, a solution for injection is prepared using a carrier comprising a salt solution, a glucose solution or a salt water mixture with a glucose solution. In that case, the injections are prepared in the form of solution, suspension or dispersion in the usual manner using a suitable auxiliary agent. Preparations for rectal administration are prepared using a carrier, such as cocoa butter, hydrogenated fat, hydrogenated carboxylic acid or the like, and are provided as suppositories. In addition, the atomizers are prepared using an active compound alone or the active compound and a carrier which does not stimulate the oral cavity and the respiratory mucous membrane of the and can facilitate the absorption of the active compound by dispersing it into fine particles. Specific examples of the carrier include lactose, glycerol and the like. Preparations, such as aerosols, dry powders and the like, can be produced depending on the properties of the active compound and the carriers to be used. In addition, these parenteral preparations can also be mixed with one or more auxiliary components selected from diluents, flavors, antiseptics, excipients, disintegrants, lubricants, binding materials, surfactants, plasticizers and the like exemplified in relation to the oral preparations. The effective amount of Compound (I) or a pharmaceutically acceptable salt thereof and the frequency of its administration vary depending on the mode of administration, the age and body weight of each patient and the properties and severity of the symptoms to be treated, but is generally preferred. administer it in a dose of from 1 to 50 mg / kg per day, by dividing the daily dose by 3 to 4 doses per day. However, these doses may vary depending on the various conditions described above.

M ANOR WAY OF CARRYING OUT THE I NVENTION The Reference Examples, Examples and Formulation Examples are shown below. In the proton nuclear magnetic resonance spectrum (1 H NMR) used in the Reference Examples and Examples, conventional symbols are used for express the multiplicity of signals, and a "br" symbol means that apparent broad signals were measured.

Reference Example 1 - (4-chloro-2-methylthiopyrimidin-6-yl) -? / '- (2-furoyl) hydrazine (Compound A) In 150 ml of DMF, 65 g (515 mmol) of hydrazide 2 were dissolved. -furoic acid and 70 ml (510 mmol) of DBU, and a solution of DMF of 4,6-dichloro-2-methylthiopyrimidine (50.0 g (256 mmol) / (100 mL) dropwise thereto at room temperature was added slowly. environment (inner temperature was controlled at 45 ° C or less) After stirring at room temperature for about 2 hours, the reaction solution was poured into ice water and the pH was adjusted to 6 to 7 with a solution of hydrochloric acid of 2 mol / L, followed by the collection of the resulting solid through filtration The collected solid was dissolved in an organic solvent (chloroform / methanol = 10/1) and, after rinsing with water, the solution was dried in sulphate of anhydrous magnesium The solvent was evaporated, and the resulting residue was triturated twice with chloroform to obtain 56.9 g of Compound A as white flocculent crystals (product: 78%). The residue obtained by concentrating the filtrate was purified by silica gel column chromatography (hexane / ethyl acetate = 6/4) to further recover Compound A in about 10% of the product. H NMR (d ppm, DMSO-d6): 10.49 (brs, 1H), 9.78 (brs, 1H), 7.95 (dd, J = 0.7, 1.7 Hz, 1H), 7.28 (dd, J = 0.7, 3.3 Hz, 1H), 6.70 (dd, J = 1.7, 3.3 Hz, 1H), 6.30 (brs, 1H), 2.50 (brs, 3H) Mass (m / z): 284, 286 (M +) IR (KBr): 3750, 1654, 1560, 1478 cm'1 Melting point: 185 ° C Reference Example 2 7-Chloro-3- (2-furyl) -5-methylthio [1, 2,4] triazolo [4,3-c] pi rimine (Compound B) In an argon atmosphere, they were suspended 225 g (1.58 mol) of diphosphorus pentaoxide in 320 mL of xylene, and 340 mL (256 g, 1.58 mol) of hexamethyldisiloxane were added thereto, followed by heating at 90 ° C for about 1.5 hours. After the content was almost dissolved, 90 g (316 mmol) of Compound A was added thereto, followed by heating at 160 ° C for another 2 hours. After completion of the reaction, the reaction solution was cooled, and frozen water was added thereto. Then, the mixture was made alkaline by adding aqueous amine under cooling (internal temperature: 5 ° C or lower), and extracted with chloroform. After evaporation of the solvent, the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1: 1) to obtain 66.1 g of Compound B as a white solid (product: 78%). 1 H NMR (d ppm, CDCl 3): 7.75 (dd, J = 0.7, 1.7 Hz, 1H), 7.74 (s, 1H), 6.97 (dd, J = 0.7, 3.3 Hz, 1H), 6.66 (dd, J = 1.7, 3.3 Hz, 1H), 2.63 (s, 3H) Mass (m / z): 266, 268 (M +) IR (KBr): 3040, 1592, 1512, 1464, 1301, 1081, 1009, 902, 897, 755 cm "1 Melting point: 122-124 ° C Reference Example 3-Chloro-2- (2-furyl) -5-methylthio [1,2,4] triazolo [1,5-c] pyridine (Compound C) In 8.5 mL of THF, 2.7 g (10 mol) of the Compound B, and 1.5 mL (10 mmol) of DBU was added thereto under ice-cooling, followed by stirring at room temperature for about 1 hour. During the period, the crystals were precipitated from the reaction solution. After completion of the reaction, the precipitated solid was rinsed with THF to obtain 2.1 g of Compound C as a white solid (product: 81%). 1 H NMR (d ppm, CDCl 3): 7.65 (dd, J = 0.7, 1.7 Hz, 1H), 7.36 (s, 1H), 7. 28 (dd, J = 0.7, 3.3 Hz, 1H), 6.60 (dd, J = 1.7, 3.3 Hz, 1H), 2.78 (s, 3H) Mass (m / z): 266, 268 (M +) IR (KBr): 3745, 1596, 1508, 1452 crn "1 Melting point: 230 ° C Reference Example 4 7-Chloro-5- (3,4-dimethoxybenzylamino) -2- (2-furyl) [1,2,4] triazolo [1,5-c] pyrimidine (Compound D) In 600 mL of THF , 50.0 g (188 mmol) of the Compound B, and 42.0 mL (280 mmol) of DBU was added thereto, followed by stirring at room temperature for approximately 30 minutes. During the period, the crystals were precipitated from the reaction solution. Then, 94 g (563 mmol) of 3,4-dimethoxybenzylamine was added thereto, followed by stirring at 60 ° C for about 2 hours. After completion of the reaction, the solvent was evaporated, the residue was diluted with chloroform and rinsed with water, and the organic layer was dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was triturated with ethyl acetate to obtain 53.2 g of Compound D as a white solid (product: 74%). The residue obtained by concentrating the part of solution present after trituration was purified by silica gel column chromatography (hexane / ethyl acetate = 7/3) to further recover Compound D in about 10% of the product. 1 H NMR (d ppm, CDCl 3): 7.60 (dd, J = 0.7, 1.7 Hz, 1H), 7.20 (dd, J = 0.7, 3.3 Hz, 1H), 6.94-6.98 (m, 3H), 6.85 (d, J = 7.9 Hz, 1H), 6.61 (brt, 1H), 6.58 (dd, J = 1.7, 3.3 Hz, 1H), 4.74 (d, J = 5.6 Hz, 2H), 3.90 (s, 3H) Mass (m / z): 385, 387 (M +) IR (KBr): 2359, 1630, 1616, 1585, 1515 cm "1 Melting point: 193 ° C Reference Example 5 5-amino-7-chloro-2- (2-furyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound E) In 260 mL of trifluoroacetic acid, 50.0 g (130 mmol) of Compound D were dissolved, and 50 g (333 mmol) of acid was added. trifluoromethanesulfonic acid and 42 mL (390 mmol) of anisole thereto, followed by stirring at room temperature for about 2 hours. After completion of the reaction, trifluoroacetic acid was evaporated under reduced pressure, and the residue was purified in ice water. The mixture was adjusted to be alkaline with a solution of 2 mol / L aqueous sodium hydroxide. The precipitated solid was rinsed with hexane and then re-pasted with chloroform to obtain 26.5 g of Compound E as a white solid (product: 83%). 1 H NMR (d ppm, CDCl 3): 7.64 (dd, J = 0.7, 1.7 Hz, 1H), 7.25 (dd, J = 0.7, 3.3 Hz, 1H), 7.04 (s, 1H), 6.60 (dd, J = 1.7, 3.3 Hz, 1H), 6.30 (brs, 2H) Mass (m / z): 235, 237 (M +) IR (KBr): 3104, 3070, 1666, 1592, 1552, 933 crn "1 Melting point: > 270 ° C Reference Example 6 5-Amino-2- (2-furyl) -7-piperazinyl [1, 2,4] triazolo [1, 5-c] piri mid i na (Compound F) In 180 ml of DMSO, they were dissolved 10.5 g (44.6 mmol) of the Compound E and 19.2 g (223 mmol) of piperazine, followed by stirring at 150 ° C for about 2 hours. After completion of the reaction, the solvent was evaporated under reduced pressure, water was added to the residue, and the mixture was extracted with chloroform. The organic layer was rinsed with water and brine, and dried over anhydrous magnesium sulfate.

After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (aqueous ammonia al 23% / methanol / chloroform = 1/10/90) and then recrystallized from ethyl acetate to obtain 9.91 g of Compound F as a white solid (product: 78%) 1H NMR (d ppm, DMSO-cie): 7.86 (dd, J = 0.7, 1.7 Hz, 1H), 7.60 (brs, 2H), 7.06 (dd, J = 0.7, 3.3 Hz, 1H), 6.68 (dd, J = 1.7, 3.3 Hz, 1H), 6.01 (s, 1H), 3.49 (t, J = 5.0 Hz, 4H), 3.40 (brs, 2H), 2.83 (t, J = 5.0 Hz, 4H) Mass (m / z): 285 (M +) IR (KBr): 1656, 1650, 1614, 1555, 1514, 1234 cm "1 Melting point: 170-172 ° C Example 1 5-Amino-2- (2-furyl) -7- (4- (2-hydroxy-2-methylpropyl) piperazine i I) [1, 2,4] triazolo [1, 5-c] pyrimidine ( Compound 1) In 7 ml of DMSO, 500 g (2.12 mmol) of Compound E were dissolved, and then 0.95 mL (6.36 mmol) of DBU and 1.50 g (9.50 mmol) of 1- (2-hydroxy-2-) were added. methylpropyl) piperazine thereto, followed by stirring at 140 ° C for about 2 hours. After the completion of the reaction, the reaction mixture was extracted by adding chloroform and water, and the organic layer was rinsed with water and brine, and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (3% methanol-chloroform) and then recrystallized from a mixed solvent of hexane-ethyl acetate to obtain 250 mg of the Compound. 1 as a white solid (product: 33%). 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3. 3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.71 (brs, 2H), 3. 55 (t, J = 5.0 Hz, 4H), 2.96 (brs, 1H), 2.73 (t, J = 5.0 Hz, 4H), 2.39 (s, 2H), 1.21 (s, 6H) Mass (m / z): 357 (M +) IR (KBr): 3853, 1678, 1608, 1558, 1471, 1331 cm "1 Melting point: 235-236 ° C Elemental analysis : as C17H23N702 Calculated (%): C = 57.13, H = 6.49, N = 27.43 Found (%): C = 57.28, H = 6.58, N = 27.48 Compounds 2 to 14 were obtained by carrying out the following Examples 2 to 14 using the corresponding piperazine derivatives in a manner similar to that of Example 1.

Example 2 5-Amino-2- (2-furyl) -7- (4- (2-hydroxy-2-methylbutyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimid ina (Compound 2 ) Product: 54% (recrystallized from toluene-hexane, light brown needles) 1H NMR (d ppm, CDCl 3): 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3.3 Hz , 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.63 (brs, 2H), 3.55 (t, J = 5.0 Hz, 4H), 2.73 (t, J = 5.0 Hz, 4H), 2.44 (dd, J = 13.9 Hz, 1H), 2.34 (d, J = 13.9 Hz, 1H), 1.43-1.58 (m, 2H), 1.14 (s, 3H), 0.92 (t, J = 7.59 Hz, 3H) Mass (m / z): 371 (M +) IR (KBr): 3319, 3176, 2970, 2833, 1655, 1614, 1606, 1557, 1513, 1444, 1333, 1236 cm "1 Melting point: 212 ° C Elemental analysis: as C18H25N702 Calculated (%): C = 61.19, H = 6.96, N = 24.01 Found (%): C = 61.36, H = 7.06, N = 23.93 Example 3 5-Amino-2- (2-furyl) -7- (4- (2-hydroxy-2-phenylpropyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 3) Product: 34% (recrystallized from ethanol-toluene, white powder) 1 H NMR (d ppm, CDCl 3): 7.57 (dd, J = 0.7, 1.7 Hz, 1H), 7.48 (d, J = 0.7, 7. 3 Hz, 1H), 7.35 (t, J = 7.59 Hz, 1H), 7.25 (d, J = 6.6 Hz, 1H), 7.14 (dd, J = 0.7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 5.94 (s, 1H), 5.56 (brs, 2H), 4.25 (s, 1H), 3.42 (t, J = 5.0 Hz, 4H), 2.90 (d, J = 13.0 Hz, 1H), 2.68 (d, J = 13.0 Hz, 1H), 2.32-2.52 (m, 4H), 1.50 (s, 3H) Mass (m / z): 419 (M +) IR (KBr): 3333, 3176, 2361, 1664, 1647, 1603, 1560, 1442, 1417, 1334, 1225, 1007, 770 cnV1 Melting point: 267-268 ° C Elemental analysis: as C22H25N7? 2 Calculated (%): C = 62.99, H = 6.01, N = 23.37 Found (%): C = 63.04, H = 6.25 , N = 23.58 Example 4 -Amino-2- (2-furyl) -7- (4- (2-ethyl-2-hydroxybutyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 4) Product: 71% (recrystallized from toluene-hexane, light brown needles) H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3. 3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.68 (brs, 2H), 3. 54 (t, J = 5.0 Hz, 4H), 2.91 (brs, 1H), 2.71 (t, J = 5.0 Hz, 4H), 1.48 (q, J = 7.6, 4H), 0.88 (t, J = 7.6 Hz, 6H) Mass (m / z): 385 (M +) IR (KBr): 3410, 3107, 2966, 2951, 2361, 1655, 1616, 1605, 1558, 1446, 1236 cm "1 Melting point: 212-213 ° C Elemental analysis: as C19H27N702 Calculated (%): C = 59.20, H = 7.06, N = 25.44 Found (%): C = 59.52, H = 7.20, N = 25.61 Example 5 5-Amino-2- (2-furyl) -7- (4- (1-h id roxi cid or propi I met i I) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimid ina (Compound 5) Product: 48% (recrystallized from ethanol-ethyl acetate, white powder) 1 H NMR (d ppm, CDCl 3): 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd) , J = 0.7, 3. 3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.04 (s, 1H), 5.70 (brs, 2H), 3.59 (t, J = 5.0 Hz, 4H), 2.70 (t, J = 5.0 Hz, 4H), 2.55 (s, 2H), 0.86 (t, J = 6.6, 2H), 0.43 (t, J = 6.6 Hz, 2H) Mass (m / z): 355 (M +) IR (KBr): 3139, 2833, 2632, 1666, 1614, 1556, 1514, 1443, 1416 , 1331 1243, 1209, 1124, 1016, 771 cm "1 Melting point: 215-217 ° C Elemental analysis: as C17H21N7020.6H2O Calculated (%): C = 55.76, H = 6.11, N = 26.77 Found (%): C = 55.86, H = 6.13, N = 26.54 Example 6 5-Amino-2- (2-furyl) -7- (4- (2-methoxy-2-methylpropyl) piperazi nyl) [1, 2, 4] triazolo [1, 5-c] pyrimidine (Compound 6) Product: 70% (recrystallized from ethyl acetate, white powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3. 3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.01 (s, 1H), 5.78 (brs, 2H), 3. 52 (t, J = 5.0 Hz, 4H), 3.22 (s, 3H), 2.65 (t, J = 5.0 Hz, 4H), 2.36 (s, 6H), 1.20 (s, 6H) Mass (m / z): 371 (M +) IR (KBr): 3417, 3167, 2958, 2833, 2360, 1666, 1608, 1560, 1512, 1470, 1444, 1416, 1381, 1333, 1242, 1132, 1076, 1012 cm "1 Melting point: 200-201 ° C Elemental analysis: as C.8H25N7O20.2H2O Calculated (%): C = 57.92, H = 6.80, N = 26.27 Found (%): C = 57.86, H = 6.92, N = 26.24 Example 7 5-Amino-2- (2-furyl) -7- (4- (3-hydroxy-3-m ethyl bu ti I) piperazin il) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 7) Product: 59% (recrystallized from toluene-hexane, light brown powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0. 7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.87 (brs, 2H), 3.54 (t, J = 5.0 Hz, 4H), 2.68 (t, J = 5.9 Hz, 2H), 2.60 (t, J = 5.0 Hz, 4H), 1.67 (t, J = 5.9 Hz, 2H), 1.25 (s, 6H) Mass (m / z): 371 (M +) IR (KBr): 3389, 3107, 2966, 2937, 2837, 1670, 1660 , 1639, 1622, 1597, 1549, 1439, 1225 cm-1 Melting point: 194-195 ° C Elemental analysis: as C18H25N702 Calculated (%): C = 58.21, H = 6.78, N = 26.40 Found (%): C = 58.26, H = 7.00 , N = 26.49 Example 8 5-Amino-2- (2-furyl) -7- (4- (3-hydroxy-3-methylpentyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pipmidine (Compound 8 ) Product: 69% (recrystallized from ethyl acetate-toluene-hexane, brown granular crystals) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0. 7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.63 (brs, 2H), 3.56 (t, J = 5.0 Hz, 4H), 2.60- 2.71 (m, 6H), 1.51-1.71 (m, 4H), 1.18 (s, 3H), 0.91 (t, J = 7.6 Hz, 3H) Mass (m / z): 385 (M +) IR (KBr): 3417, 3139, 2972, 1660, 1606, 1564, 1516, 1479, 1443, 1416, 1338, 1223, 1122, 1020, 770 cm "1 Melting point: 196-197 ° C Elemental analysis: as Ci9H27N7? 2 Calculated (%): C = 59.20, H = 7.06, N = 25.44 Found (%): C = 59.29, H = 7.06, N = 25.05 Example 9 5-Amino-2- (2-furyl) -7- (4- (3-hydroxy-3-phenylbutyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 9) Product: 36% (recrystallized from ethyl acetate-2-propanol, white powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.48 (d, J = 7.6 Hz, 2H), 7.36 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 6.6 Hz, 1H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.63 (brs, 2H), 3.51-3.60 (m, 4H), 2.60-2.70 (m, 2H), 2.17-2.46 (m, 4H), 2.02-2.17 (m, 1H), 1.83-1.97 (m, 1H), 1.52 (s, 3H) Mass (m / z): 451 (M +) IR (KBr): 3444, 3167, 2972, 2833, 2362, 1652, 1616, 1564, 1513, 1421, 1238, 779 cm "1 Melting point: 123-124 ° C Elemental analysis: as C23H27N7021.0H2O Calculated (%): C = 61.18, H = 6.47, N = 21.71 Found (%): C = 61.20, H = 6.39, N = 21.77 Example 10 5-Amino-2- (2-furyl) -7- (4- (3-ethyl-3-hydroxypentyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 10) Product: 42% (recrystallized from ethanol-ethyl acetate, light yellow powder) 1H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0. 7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.65 (brs, 2H), 3.55 (t, J = 5.0 Hz, 4H), 2.59- 2.65 (m, 6H), 1.40-1.69 (m, 6H), 0.87 (t, J = 7.6 Hz, 6H) Mass (m / z): 399 (M +) IR (KBr): 3278, 2968, 2833, 2808, 2361, 1659, 1651, 1605, 1441, 1417, 1336, 1236, 1201 cm-1 Melting point: 183 ° C Elemental analysis: as C20H29N7O21.0H2O Calculated (%): C = 60.13, H = 7.32, N = 24.54 Found (%): C = 60.17, H = 7.49 , N = 24.63 Example 11 5-Amino-2- (2-furyl) -7- (4- (3-methoxy-3-methylbutyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] piri mid i na (Compound 11) Product: 53% (recrystallized from ethyl acetate, white powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7 , 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.77 (brs, 2H), 3.56 (t, J = 5.0 Hz, 4H), 3.20 (s, 3H), 2.54 (t, J = 5.0, 4H), 2.44 (t, J = 8.3 Hz, 2H), 1.72 (t, J = 8.3 Hz, 2H), 1.18 (s, 6H) Mass (m / z): 385 (M +) IR (KBr): 2972, 2808, 2364, 1668, 1606 , 1562, 1513, 1442, 1417, 1377, 1335, 1126, 1080, 1005, 773 cm "1 Melting point: 194-195 ° C Elemental analysis: as C19H27N702 1.0H2O Calculated (%): C = 59.20, H = 7.06, N = 25.43 Found (%): C = 59.02, H = 7.06, N = 25.10 Example 12 5-Amino-2- (2-furyl) -7- (4- (2-hydroxy-1,1-d imet i leti I) piperazine i I) [1, 2,4] triazolo [1, 5 -c] pyrimidine (Compound 12) Product: 48% (recrystallized from toluene-hexane, white needles) 1 H NMR (d ppm, CDCl 3): 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3. 3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.03 (s, 1H), 5.62 (brs, 2H), 3. 58 (brt, 4H), 3.42 (s, 2H), 2.71 (brt, 4H), 2.36 (s, 1H), 1.09 (s, 6H) Mass (m / z): 357 (M +) IR (KBr): 3444, 3167, 2972, 2833, 2362, 1663, 1616, 1560, 1514, 1444, 1230, 978, 771 cm "1 Melting point: 213-215 ° C Elemental analysis: as C17H23N7020.4H2O 0.3 toluene Calculated (%): C = 58.48, H = 6.73, N = 25.00 Found (%): C = 58.13 , H = 6.65, N = 25.05 Example 13 5-Amino-2- (2-furyl) -7- (4- (4-hydroxy-4-m eti I pen ti I) piperazin il) [1, 2,4] triazolo [1, 5-c ] pyrimidine (Compound 13) Product: 68% (recrystallized from ethyl acetate, white powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3. 3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.01 (s, 1H), 5.78 (brs, 2H), 3. 57 (t, J = 5.0 Hz, 4H), 2.59 (t, J = 5.0 Hz, 4H), 2.45 (t, J = 5.3 Hz, 2H), 1. 58-1.74 (m, 4H), 1.22 (s, 6H) Mass (m / z): 385 (M +) IR (KBr): 3417, 3153, 2958, 2819, 2364, 1647, 1610, 1560, 1514, 1444, 1417, 1381, 1335, 1236, 1126, 984, 770 cm "1 Melting point: 178 ° C Elemental analysis: as C19H27N7020.5H2O Calculated (%): C = 57.13, H = 6.49, N = 27.43 Found (%) : C = 57.28, H = 6.58, N = 27.48 Example 14 5-Amino-2- (2-furyl) -7- (4- (5-hydroxy-5-methyIhexyl) piperazinyl) [1,2,4] triazolo [1,5-c] pyrimidine (Compound 14) Product: 49% (recrystallized from ethyl acetate, white powder) 1H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.16 (dd, J = 0.7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.01 (s, 1H), 5.90 (brs, 2H), 3.55 (t, J = 5.0 Hz, 4H), 2.51 (t, J = 5.0 Hz, 4H), 2.39 (t, J = 7.6 Hz, 2H), 1.26-1.56 (m, 6H), 1.22 (s, 6H) Mass (m / z): 399 (M +) IR (KBr): 3417, 3389, 3278, 3167, 2958, 2847, 2359, 1662, 1614, 1564, 1513, 1444, 1417, 1378, 1336, 1234, 773 cm "1 Melting point: 148 ° C Elemental analysis: as C20H29N7O21.2H20 Calculated (%): C = 57.04, H = 7.51, N = 23.28 Found (%) : C = 57.07, H = 7.55, N = 23.21 Example 15 5-Amino-2- (2-furyl) -7- (4- (imidazo [1,2-a] pyridin-2-ylmethyl) piperazine I) [1, 2,4] triazolo [1, 5 -c] pyrimidine (Compound 15) In 7.5 mL of DMF, 500 g (1.75 mmol) of Compound F was dissolved, and 582 mg (3.51 mmol) of imidazo [1,2-a] pyridin-2-chloride were added. ilmetil. The solution was cooled to 0 ° C in an ice bath, and then 1-6 mL of triethylamine was added thereto, followed by stirring at room temperature overnight. After completion of the reaction, water was added to the reaction mixture and a 1.0 mol / L solution of sodium hydroxide was added thereto to adjust the solution in order to make it basic. Then, the mixture was extracted by adding chloroform, and the organic layer was rinsed with water and brine, and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (2% methanol-chloroform) and then recrystallized from ethanol to obtain 374 mg of Compound 15 as a white powder (product: 51 %) 1 H NMR (d ppm, CDCl 3): 8.07 (d, J = 6.9 Hz, 1H), 7.59 (s, 1H), 7.58- 7.54 (m, 2H), 7.18-7.12 (m, 2H), 6.76 (dd, J = 6.1, 7.4 Hz, 1H), 6.54 (dd, J = 1.7, 3.3 Hz, 1H), 6.01 (s, 1H), 5.65 (brs, 2H), 3.77 (s, 2H), 3.59 (t, J = 5.0 Hz, 4H), 2.67 (t, J = 5.0 Hz, 4H) Mass (m / z): 415 (M +) IR (KBr): 1666, 1651, 1606, 1446, 1216, 742 cm-1 Point fusion: 220-221 ° C Elemental analysis: as C21H21N90 Calculated (%): C = 60.71, H = 5.09, N = 30.34 Found (%): C = 60.70, H = 5.15, N = 30.25 Compounds 16 to 18 were obtained by carrying out Examples 16 to 18 in a manner similar to that of Example 15.

Example 16 5-Amino-2- (2-furyl) -7- (4- (imidazo [1,2-a] pyrazine-2-methylmethyl) piperazinyl [1,2,4] triazolo [1, 5 -c] piri mid i na (Compound 16) Product: 53% (recrystallized from ethanol, white powder) 1 H NMR (d ppm, CDCl 3): 9.06 (s, 1H), 8.04 (dd, J = 1.6, 4.6 Hz, 1H), 7.88 (d, J = 4.6 Hz, 1H), 7.69 (s, 1H), 7.55 (dd, J = 0.7, 1.7 Hz, 1H), 7.14 (dd, J = 0.7, 3.3 Hz, 1H ), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.65 (brs, 2H), 3.84 (s, 2H), 3.62 (t, J = 5.0 Hz, 4H), 2.68 (t, J = 5.0 Hz, 4H) Mass (m / z): 416 (M +) IR (KBr): 1666, 1606, 1234, 1213, 773 cm-1 Melting point: 242-244 ° C Elemental analysis: as C20H20N10O 1.1H20 Calculated (%): C = 55.06, H = 5.13, N = 32.11 Found (%): C = 55.22, H = 5.13, N = 31.91 Example 17 5-Amino-2- (2-furyl) -7- (4- (imidazo [1, 2-a] pyrimidin-2-ylmethyl) piperazinyl) [1, 2,4] triazolo [1,5-c ] pyrimidine (Compound 17) Product: 16% (recrystallized from ethanol, light brown powder) '1 H NMR (d ppm, DMSO-d 6): 8.92 (dd, J = 2.0, 6.6 Hz, 1H), 8.49 (dd) , J = 2.2, 4.1 Hz, 1H), 7.86 (d, J = 0.8 Hz, 1H), 7.83 (s, 1H), 7.61 (brs, 2H), 7.07-7.01 (m, 2H), 6.66 (dd, J = 0.7, 2.6 Hz, 1H), 6.02 (s, 1H), 3.70 (s, 2H), 3.54 (t, J = 7.0 Hz, 4H), 2.58 (t, J = 7.0 Hz, 4H) Mass (m / z): 416 (M +) IR (KBr): 1647, 1608, 1562, 1512, 1437, 1232, 773 cm-1 Melting point: 244-246 ° C Elemental analysis: as C20H20N10O 1.2H20 Calculated (%): C = 54.84, H = 5.15, N = 31.97 Found (%): C = 54.72, H = 4.87, N = 31.94 Example 18 5-Amino-7- (4- (benzimidazol-2-ylmethyl) piperazinyl) -2- (2-furyl) [1, 2.4 Jtpazolo [1, 5-c] pyrimidine (Compound 18) Product: 31% (recrystallized from ethanol, light brown powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.30-7.23 (m, 4H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.03 (s, 1H), 5.63 (brs, 2H), 3.90 (s, 2H), 3.60 (t, J = 5.0 Hz, 4H), 2.68 (t, J . 0 Hz, 4H) Mass (m / z): 415 (M +) IR (KBr): 1658, 1606, 1564, 1444, 1224, 999, 748 cm "1 Melting point: 284-286 ° C Elemental analysis: as C21H2lN90 Calculated (%): C = 60.71, H = 5.09, N = 30.34 Found (%): C = 60.52, H = 5.34, N = 30.07 Example 19 5-Amino-7- (4- (benzothiazol-2-ylmethyl) piperazin il) -2- (2-furi I) [1, 2, 4] tri azo I or [1, 5-c] pyrimidine (Compound 19) Compound 19 was obtained using a corresponding bromide, in place of the chloride, in a manner similar to that of Example 15. Product: 19% (recrystallized from ethanol; light brown powder ) 1 H NMR (d ppm, CDCl 3): 8.00 (d, J = 7.2 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.45 (dt, J = 1.3, 8.2 Hz, 1H), 7.39 (dd, J = 1.3, 8.2 Hz, 1H), 7.16 (dd, J = 0.7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.04 (s, 1H), 5.60 ( brs, 2H), 4.02 (s, 2H), 3.63 (t, J = . 0 Hz, 4H), 2.75 (t, J = 5.0 Hz, 4H) Mass (m / z): 432 (M +) IR (KBr): 1652, 1612, 1560, 1440, 1236, 1203 cm "1 Melting Point : 218-219 ° C Elemental analysis: as C21H20N8OS Calculated (%): C = 58.32, H = 4.66, N = 25.91 Found (%): C = 58.10, H = 4.99, N = 26.15 Example 20 5-Amino-7- (4- (benzo-2,1, 3-thiadiazol-5-ylmethyl) piperazinyl) -2- (2-furyl) [1, 2,4] triazolo [1, 5-c] ] pyrimidine (Compound 20) Compound 20 was obtained by using a corresponding methanesulfonate, in place of the chloride, in a manner similar to that of Example . Product: 70% (recrystallized from ethanol, white powder) 1H NMR (d ppm, CDCl 3): 7.99 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.59 (dd, J = 1.6, 7.6 Hz, 1H), 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.03 (s, 1H), 5.64 (brs, 2H), 3. 72 (s, 2H), 3.58 (t, J = 5.0 Hz, 4H), 2.60 (t, J = 5.0 Hz, 4H) Mass (m / z): 433 (M +) IR (KBr): 1660, 1606 , 1444, 1222, 758 cm "1 Melting point: 210-211 ° C Elemental analysis: as C20H19N9OS Calculated (%): C = 55.41, H = 4.42, N = 29.08 Found (%): C = 55.38, H = 4.47, N = 28.99 Example 21 5-Amino-2- (2-furyl) -7- (4- (5-methylisoxazol-3-ylmethyl) piperazinyl) f1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 21) In 15 mL of dichloromethane, 1.50 g was dissolved (5.26 mmol) of Compound F, and 934 mg (8.42 mmol) of 5-methylisoxazole-3-carboxaIdehyde were added, and the solution was cooled to 0 ° C in an ice bath. Then, 1.5 mL of acetic acid and 1.78 g (8.42 mmol, 1.06 eq.) Of sodium triacetoxyborohydride were added thereto, followed by stirring at room temperature overnight. After completion of the reaction, water was added to the reaction mixture and a 1.0 mol / L solution of sodium hydroxide was added thereto to adjust the solution in order to make it basic. Then, the mixture was extracted by adding chloroform, and the organic layer was rinsed with water and brine, and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (2% methanol-chloroform) and then recrystallized from ethanol to obtain 222 mg of Compound 21 as a white powder (product: 11). %) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.03 (s, 1H), 6.02 (s, 1H), 5.60 (brs, 2H), 3.61 (s, 2H), 3.56 (t, J = 5.0 Hz, 4H), 2.56 (t, J = 5.0 Hz, 4H), 2.42 (s, 3H) Mass (m / z): 380 (M +) IR (KBr): 1654, 1614, 1564, 1209 cm "1 Melting point: 222-224 ° C Elemental analysis: as C18H20N8O2 Calculated (%): C = 56.83, H = 5.30, N = 29.46 Found (%): C = 56.80, H = 5.45, N = 29.12 Example 22 5-Amino-2- (2-furyl) -7- (3-methyl-4- (5-methylisoxazol-3-ylmethyl) piperazinyl) [1, 2,4] trlazolo [1,5-c] pyrimidine (Compound 22) Compound 22 was obtained in a manner similar to that of Example 15. Product: 40% (recrystallized from ethanol, white powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 5.99 (s, 1H), 5.98 (s, 1H), 5.70 (brs , 2H), 3.98 (s, 1H), 3.92 (s, 1H), 3.89 (d, J = 14.2 Hz, 1H), 3.62 (d, J = 14.2 Hz, 1H), 3.13 (dt, J = 3.3, 10.6 Hz, 1H), 2.89-2.82 (m, 3H), 2.57-2.43 (m, 1H), 2.41 (d, J = 6.5 Hz, 3H), 1.20 (d, J = 6.3 Hz, 3H) Mass (m / z): 394 (M +) IR (KBr): 1652, 1648, 1606, 1238 cm "1 Melting point: 183-185 ° C Elemental analysis: as C19H22N802 2.0 HCl 2.1H20 Calculated (%): C = 45.17 , H = 5.63, N = 22.18 Found (%): C = 45.17, H = 5.47, N = 22.07 Compounds 23 to 25 were obtained by carrying out Examples 23 to 25 using the corresponding methanesulfonates is, in place of chloride, similar to that of Example 15 Example 23 5-Amino-2- (2-furyl) -7- (4- (1- (5-methylisoxazol-3-yl) ethyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 23) Product: 31% (recrystallized from ethanol, light brown powder) 1H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0. 7, 3.3 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.00 (s, 1H), 5.96 (s, 1H), 5.73 (brs, 2H), 3.80 (q, J = 6.9 Hz, 1H), 3.54 (t, J = 5.0 Hz, 4H), 2. 58 (t, J = 5.0 Hz, 4H), 2.41 (s, 3H), 1.43 (d, J = 6.9 Hz, 3H) Mass (m / z): 394 (M +) IR (KBr): 1666, 1604, 1444, 1227, 767 cm-1 Melting point: 106-108 ° C Example 24 5-Amino-2- (2-fupl) -7- (4- (3-methylisoxazol-4-ylmethyl) piperazinyl) [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 24) Product: 56% (recrystallized from ethanol, white powder) 1H NMR (d ppm, CDCI3): 8.23 (s, 1H), 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.62 (brs, 2H), 3.54 (t, J = 5.0 Hz, 4H), 3.38 (s, 2H), 2.51 (t, J = . 0 Hz, 4H), 2.33 (s, 3H) Mass (m / z): 380 (M +) IR (KBr): 1666, 1648, 1604, 1446, 1333, 1207, 999 cm-1 Melting point: 233- 234 ° C Elemental analysis: as C18H20N8O2 0.2H2O Calculated (%): C = 56.30, H = 5.35, N = 29.18 Found (%): C = 56.08, H = 5.37, N = 29.41 Example 25 -Am ino-2- (2-f url) -7- (4- (5-methyl-3-f-enyl-isoxazol-4-ylmethyl) -piperazinyl) [1, 2,4] -triazolo [1, 5] c] pyrimidine (Compound 25) Product: 82% (recrystallized from ethanol, white powder) 1 H NMR (d ppm, CDCl 3): 7.97-7.93 (m, 2H), 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.47-7.44 (m, 3H), 7.16 (dd, J = 0.7, 3.3 Hz, 1H), 6.56 (dd, J = 1.7, 3. 3 Hz, 1H), 6.03 (s, 1H), 5.66 (brs, 2H), 3.56 (t, J = 5.0 Hz, 4H), 3.34 (s, 2H), 2.54 (t J = 5.0 Hz, 4H), 2.47 (s, 3H) Mass (m / z): 456 (M +) IR (KBr): 1653, 1604, 1560, 1444, 1234 cm -1 Melting point: 244-246 ° C Elemental analysis: as C24H24N802 Calculated (%): C = 63.15, H = 5.30, N = 24.55 Found (%): C = 63.26, H = 5.46, N = 24.74 Compounds 26 and 27 were obtained by carrying out Examples 23 and 25 using the corresponding aldehydes in a manner similar to that of Example 21.

Example 26 5-Amino-2- (2-furyl) -7- (4- (3-oxo-3,4-dihydro-2H-benzo [1,4] oxazin-7-ylmethyl) piperazinyl [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 26) Product: 15% (recrystallized from ethanol, white powder) 1 H NMR (d ppm, CDCl 3): 8.04 (brs, 1H), 7.58 (dd) , J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7, 3.3 Hz, 1H), 7.00 (s, 1H), 6.93 (d, J = 7.9 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.01 (s, 1H), 5.62 (brs, 2H), 4.62 (s, 2H), 3.54 (t, J = 5.0 Hz, 4H), 3.47 (s, 2H), 2.53 (t, J = 5.0 Hz, 4H) Mass (m / z): 446 (M +) IR (KBr): 1606, 1230, 773, 505, 487 crrf1 Melting point: 287-288 ° C Elemental analysis: as C22H22N803 Calculated (%): C = 59.19, H = 4.97, N = 25.10 Found (%): C = 59.23, H = 5.06, N = 24.71 Example 27 5-Amino-2- (2-furyl) -7- (4- (3-oxo-3,4-dihydro-2H-benzo [1,4] oxazin-6-ylmethyl) piperazinyl [1, 2, 4] triazolo [1, 5-c] pyrimidine (Compound 27) Product: 50% (recrystallized from ethanol, light brown powder) 1 H NMR (d ppm, DMSO-d 6): 10.67 (brs, 1H), 7.87 (t, J = 0.8 Hz, 1H), 7.61 (brs, 2H), 7.06 (d.J = 3.6 Hz, 1H), 6.90-6.87 (m, 3H), 6.67 (dd, J = 0.7, 2.6 Hz , 1H), 6.01 (s, 1H), 4.55 (s, 2H), 3.51 (t, J = 7.0 Hz, 4H), 3.41 (s, 2H), 2.42 (t, J = 7.0 Hz, 4H) Mass ( m / z): 446 (M +) IR (KBr): 1677, 1645, 1606, 1564, 1197, 773 crn "1 Melting point: 284-285 ° C Elemental analysis: as C22H22N803 Calculated (%): C = 59.19 , H = 4.97, N = 25.10 Found (%): C = 59.01, H = 5.28, N = 25.11 Example 28 5-Amino-2- (2-furyl) -7- (4- (1- methoxycyclic propyl I methyl) piperazine I [1, 2,4] triazolo [1, 5-c] pyrimidine (Compound 28) Compound 28 was obtained using a corresponding piperazine derivative similarly to that of Example 1. Product: 59% (recrystallized from ethanol-ethyl acetate, white powder) 1 H NMR (d ppm, CDCl 3): 7.58 (dd, J = 0.7, 1.7 Hz, 1H), 7.15 (dd, J = 0.7, 1. 7 Hz, 1H), 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.02 (s, 1H), 5.83 (brs, 2H), 3. 58 (t, J = 5.0 Hz, 4H), 3.34 (s, 3H), 2.65 (t, J = 5.0 Hz, 4H), 2.55 (s, 2H), 0.83 (dd, J = 5.0, 6.6 Hz, 2H), 0.48 (dd, J = 5.0, 6.6 Hz, 2H) Mass (m / z): 370 (M +) IR (KBr): 3458, 3115 , 2835, 1655, 1608, 1556, 1514, 1470, 1443, 1417, 1331, 1230, 1205, 1117, 1063, 1012, 984, 906, 885, 771 cm "1 Melting point: 201-202 ° C Elemental analysis: as C18H23N7020.3 H20 Calculated (%): C = 57.68, H = 6.34, N = 26.16 Found (%): C = 55.61, H = 6.24, N = 26.09 Formulation Example 1: Tablets Tablets having the following composition are prepared in the usual manner. Compound 1 10 mg Lactose 30 mg Potato starch 15 mg Polyvinyl alcohol 1.5 mg Magnesium stearate 0.5 mg Formulation Example 2: Capsules Capsules having the following composition are prepared in the usual manner. Compound 2 1 0 mg Lactose 1 00 mg Magnesium stearate 2.5 mg These components are mixed and packaged in gelatin capsules.

Formulation Example 3: Injections Injections with the following composition are prepared in the usual way. Compound 1 5 2 mg Purified soybean oil 200 mg Purified yolk lecithin 24 mg Glycerol for injection 50 mg Distilled water for injection 1.72 ml DUSTRIAL APPLICABILITY The present invention provides novel triazolopyrimidine derivatives or pharmaceutically acceptable salts thereof, which have A2A adenosine receptor antagonism and are useful for treating or preventing various diseases induced by hyperactivity of an A2A adenosine receptor (eg, Parkinson's disease, senile dementia or depression).

Claims (9)

REVIVAL NAME IS

1 . A [1, 2, 4] triazolo [1, 5-c] pyrimidine derivative represented by the formula (I): wherein R1 represents substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group; R 2 represents a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group; na and nb are the same or different, and each represents an integer from 0 to 4; Q represents a hydrogen atom or 3,4-dimethoxybenzyl; R6 represents a hydrogen atom, substituted or unsubstituted lower alkyl, halogen or hydroxy; R3 represents (i) hydroxy, (ii) hydroxy-lower alkyl, (iii) substituted or unsubstituted lower alkoxy, or (iv) a group selected from the group consisting of substituted imidazo [1,2-a] pyridyl or unsubstituted, substituted or unsubstituted imidazo [1, 2-a] pyrazinyl, substituted or unsubstituted imidazo [1, 2-a] pyrimidinyl, substituted or unsubstituted benzimidazolyl, substituted or unsubstituted benzothiazolyl, benzo-2, 1, 3-thiadiazolyl substituted or unsubstituted, isoxazolyl substituted or unsubstituted, and substituted or unsubstituted 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazinyl; and when R3 represents hydroxy, lower hydroxyalkyl, or substituted or unsubstituted lower alkoxy, R4 and R5 are the same or different, and each represents a substituted or unsubstituted lower alkyl or substituted or unsubstituted aryl, or R4 and R5 form a substituted or unsubstituted saturated carbocycle together with the adjacent carbon atom, and when R3 represents a group selected from the group consisting of substituted or unsubstituted imidazo [1, 2-a] pyridyl, imidazo [1, 2-a] ] substituted or unsubstituted pyrazinyl, substituted or unsubstituted midazo [1, 2-a] pyrimidinyl, substituted or unsubstituted benzimidazolyl, substituted or unsubstituted benzothiazolyl, substituted or unsubstituted benzo-2, 1, 3-thiadiazolyl, isoxazolyl substituted or unsubstituted, and 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazinyl substituted or unsubstituted, R4 and R5 are the same or different, and each represents a hydrogen atom, lower alkyl replaced or not substituted or substituted or unsubstituted aryl, or R4 and R5 form a substituted or unsubstituted saturated carbocycle together with the adjacent carbon atom; or a pharmaceutically acceptable salt thereof.

2. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 1, characterized in that R3 is hydroxy, hydroxy-lower alkyl, or substituted or unsubstituted lower alkoxy, or a pharmaceutically acceptable salt thereof.

3. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 1, characterized in that R3 is a group selected from from the group consisting of substituted or unsubstituted midazo [1, 2-a] pyridyl, substituted or unsubstituted imidazo [1, 2-a] pyrazinyl, substituted or unsubstituted midozo [1, 2-a] pyrimidinyl , substituted or unsubstituted benzimidazolyl, substituted or unsubstituted benzothiazolyl, substituted or unsubstituted benzo-2, 1, 3-thiadiazolyl, substituted or unsubstituted isoxazolyl, and 3-oxo-3,4-dihydro-2H-benzo [1, 4] substituted or unsubstituted oxazinyl, or a pharmaceutically acceptable salt thereof.

4. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to any one of claims 1 to 3, characterized in that Q is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

5. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 4, characterized in that R2 is a hydrogen atom, or 15 a pharmaceutically acceptable salt thereof.

6. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 5, characterized in that R1 is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof.

7. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 5, characterized in that R1 is furyl, or a pharmaceutically acceptable salt thereof.

8. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 7, characterized in that R6 is a hydrogen atom, na 25 and nb are each 1; R3 is hydroxy; and R4 and R5 are each alkyou substituted or unsubstituted lower, or a pharmaceutically acceptable salt thereof.

9. The [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to claim 8, characterized in that R4 and R5 are each methyl, or 5 a pharmaceutically acceptable salt thereof. 1. The derivative of [1, 2, 4] triazolo [1, 5-c] pyrimidine according to claim 7, characterized in that R6 is a hydrogen atom, na is 0; nb is 1; R3 is a group selected from the group consisting of substituted or unsubstituted imidazo [1, 2-a] pyridyl, 10 substituted or unsubstituted imidazo [1, 2-a] pyrazinyl, substituted or unsubstituted, substituted or unsubstituted benzimidazolyl imidazo [1, 2-a] pyrimidinyl, substituted or unsubstituted benzothiazolyl, benzo-2, 1, 3-thiadiazolyl substituted or unsubstituted, substituted or unsubstituted isoxazolyl, and 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazinyl substituted or not 15 replaced; or a pharmaceutically acceptable salt thereof. eleven . The [1, 2, 4] triazolo [1, 5-c] pyrimidine derivative according to claim 10, characterized in that R3 is 5-methylisoxazol-3-yl, or a pharmaceutically acceptable salt thereof. 12. A medicament characterized in that it comprises the derivative of [1, 2,4] triazolo [1, 5-c] pyrimidine according to any of claims 1 to 11, or a pharmaceutically acceptable salt thereof. 1 3. An A2A adenosine receptor antagonist characterized in that it comprises the [1, 2,4] triazolo [1, 5, 25 c] pyrimidine derivative according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof. 14. An agent for preventing or treating a disease induced by hyperactivity of an A2A adenosine receptor, characterized in that it comprises the [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to any of claims 1 to 1 1 or a pharmaceutically acceptable salt thereof. 15. The use of the [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to any of claims 1 to 11 or a pharmaceutically acceptable salt thereof characterized for the preparation of an agent to prevent or treat a disease induced by hyperactivity of an A2A adenosine receptor. 16. A method for preventing or treating a disease induced by hyperactivity of an A2A adenosine receptor, characterized in that it comprises administering an effective amount of the [1, 2,4] triazolo [1, 5-c] pyrimidine derivative according to any of the claims 1 to 11, or a pharmaceutically acceptable salt thereof. ARY The present invention relates to [1, 2, 4] triazolo [1, 5-c] pyrimidine derivatives represented by the formula (I): wherein R1 represents substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group; R 2 represents a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, or the like; na and nb are the same or different, and each represents an integer from 0 to 4; Q represents a hydrogen atom or 3,4-dimethoxybenzyl; R6 represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like; R3 represents (i) hydroxy, (ii) hydroxy-lower alkyl, (iii) substituted or unsubstituted lower alkoxy, or (iv) a group selected from the group consisting of substituted midazo [1, 2-a] pyridyl or unsubstituted, substituted or unsubstituted midozo [1, 2-a] pyrazinyl, unsubstituted or substituted or substituted or unsubstituted imidazo [1, 2-a] pyrim, substituted or unsubstituted benzim idazolyl, and the like; and when R3 represents hydroxy, hydroxy-lower alkyl, or substituted or unsubstituted lower alkoxy, R4 and R5 are the same or different, and each represents a substituted or unsubstituted lower alkyl or substituted or unsubstituted aryl, or R4 and R5 they form a r *** * • 86 substituted or unsubstituted saturated carbocycle together with the adjacent carbon atom, and when R3 represents a group selected from the group consisting of substituted or unsubstituted imidazo [1, 2-a] pyridyl, substituted or unsubstituted imidazo [1, 2-a] pyrazinyl, im idazo [1, 2 a] substituted or unsubstituted pyrimidinyl, substituted or unsubstituted benzimidazolyl, and the like, R4 and R5 are the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like, or R4 and R5 form a substituted or unsubstituted saturated carbocycle together with the carbon atom 10 adjacent; or pharmaceutically acceptable salts thereof. fifteen