JPH02289518A - Adenosine antagonist - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I (R<1> and R<2> are aliphatic hydrocarbon group; R<3> is H, aliphatic hydrocarbon group or acyl; A is 2-4C bifunctional hydrocarbon chain). EXAMPLE:1-Butyl-3-propyl-1,2,3,4,6,7-hexahydro-5H-imidazo[2',1':5,1]py razolo[3,4- d]pyrimidine-2,4-dione. USE:An adenosine antagonist effective for treating and preventing cerebral apoplexy, dementia caused by trauma, etc. PREPARATION:For example, according to the reaction formula, 1mol compound shown by formula II (X is halogen; n is 1-3) is subjected to ring closure by using 1-3 mols of a base such as sodium hydride or 6-butoxypotassium to give a compound shown by formula Ia. A dose of the compound shown by formula I is about 1-50mg/kg (weight) per time and administered preferably 1-3 times daily.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to an adenosine antagonist containing a tricyclic fused pyrimidine derivative or a salt thereof.

Conventional technology Pyrazolo [3゜4-
Regarding dl pyrimidine derivatives, see JP-A-53-3169.
Pyrazolo[3,4-d]pyrimidine derivatives having brain function-improving effects are disclosed in Japanese Patent Application Laid-Open No. 63-10788. Also, 3-aminopyrazolo[3,4
Tricyclic fused pyrimidine derivatives that form a fused ring at the 2- and 3-positions of the -dl pyrimidine ring have also been synthesized. It has not been done.

On the other hand, adenosine is one of the important biological components.
It plays an important role in the expression, maintenance, and regulation of various physiological functions inside and outside cells. In other words, various physiological effects occur in most organs and tissues, including inhibition of brain function, vasodilation, decrease in cardiac function, renal vasoconstriction, inhibition of platelet aggregation, inhibition of insulin secretion, inhibition of lymphocyte function, and inhibition of renin release. , these effects are expressed through adenosine receptors that are widely distributed on the cell surface of in vivo tissues [
J, 'J1. Daly, J., Med, Ch.
em,,25. l 97 (1982), M, Wi
lliaII+s etc., Annu, Rep, Med
.

Chem, 22, 1 (1987), A, J
, Bridges et al.

Annu, Rep, Med, Chem,,23
, 41 (1988)].

Therefore, diseases caused by physiological effects due to abnormal interactions between adenosine and its receptors occur in the neuroendocrine system, cardiovascular system, and gastrointestinal system. At this time, using an adenosine antagonist that inhibits the interaction between adenosine and its receptor is considered to be useful for the treatment and prevention of these diseases [M, Williams et al.
Pharm, Bioche+++, &Behav
ior, 29, 433 (1988)]. For example, theophylline, which has an adenosine antagonistic effect, stimulates the central nervous system and heart muscle, and has a diuretic effect on the kidneys.

and relaxing effects on smooth muscle, especially bronchial smooth muscle.

It has various pharmacological effects and is widely used clinically. Now, in brain tissue, when cerebral blood circulation is impaired during hypoxia, the high-energy compound ATP is consumed and adenosine concentration increases, and adenosine acts on adenosine receptors (A I) in nerve terminals to stimulate cells. The inner cyclic AMP decreases by 211 degrees, promotes the inflow of +, and C
It is thought that this causes inhibition of the influx of ``a'', and as a result, the release of neurotransmitters in the brain such as acetylcholine, noradrenaline, dopamine, and serotonin is suppressed, resulting in abnormalities in brain function and metabolism [B, B.

Fredho1m etc.Trends in Pharm,
Sci, 9, I 30 (1988)].

Problems to be Solved by the Invention The present invention is capable of treating mental symptoms, neurological symptoms, etc., including dementia symptoms caused by stroke, head trauma, interstitial disease, etc., by improving brain function based on strong adenosine antagonism. and a novel adenosine antagonist useful for prevention.

Means for solving the problem, the present invention is a novel compound not yet described in the literature, which has the general formula [wherein R1 and R2 each represent an aliphatic hydrocarbon group,
R1 represents hydrogen, an aliphatic hydrocarbon group or an acyl group,
A represents an optionally substituted divalent hydrocarbon chain having 2 to 4 carbon atoms] or a salt thereof.

Regarding the above general formula (I), examples of the aliphatic hydrocarbon group represented by R1 or R2 include alkyl groups having about 1 to 8 carbon atoms (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, i-pentyl, hexyl, heptyl, octyl, etc.), alkenyl groups having about 2 to 8 carbon atoms (e.g., vinyl, allyl, l-propenyl, isopropenyl, 2-butenyl, 1.3-butadienyl, 2-pentenyl) , l-hexenyl, 1-hebutenyl, l-octenyl, etc.). Among these, aliphatic hydrocarbon groups having approximately 2 to 5 carbon atoms are preferred, and alkyl groups having approximately 2 to 5 carbon atoms are particularly preferred.

The aliphatic hydrocarbon group represented by R3 is, for example, an alkyl group having about 1 to 3 carbon atoms (eg, methyl).

(ethyl, propyl, i-propyl), alkenyl groups having about 2 to 3 carbon atoms (e.g., vinyl, allyl, ■-propenyl, impropenyl), and among them,
An alkyl group of about 3 is preferred.

Examples of the acyl group represented by R3 include those derived from organic acids, such as alkanoyl groups having 7 or fewer carbon atoms (e.g., acetyl, trifluoroacetyl, propionyl, butyryl, valeryl, cyclohexanecarbonyl, etc.), and aromatic groups. Carbonyl groups (e.g., optionally substituted benzoyl, etc.), alkoxycarbonyl groups whose alkyl moiety has about 1 to 4 carbon atoms (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), carbamoyl, formyl, etc. can be mentioned.

Among these, an alkanoyl group having 7 or less carbon atoms or an alkoxycarbonyl group having about 1 to 4 carbon atoms in the alkyl moiety is preferred, and acetyl, propionyl, and metquincarbonyl are particularly preferred.

The divalent hydrocarbon chain having 2 to 4 carbon atoms represented by A is alkylene (eg, ethylene, trimethylene, tetramethylene), alkenylene (eg, vinylene).

propenylene, etc.).

The hydrocarbon chain may have a substituent, and examples of the substituent include an optionally substituted aliphatic hydrocarbon group (
For example, optionally substituted amino.

Nitro, hydroxy, alcoquine with about 1 to 4 carbon atoms,
aliphatic hydrocarbon groups which may have substituents such as alkylthio having about 1 to 4 carbon atoms), and especially alkyl groups having about 1 to 8 carbon atoms (eg, methyl).

Ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, impentyl, hexyl, isohexyl,
heptyl, octyl, etc.), optionally substituted aromatic hydrocarbon groups (e.g., ortho, meta).

Amino which may be substituted with 1 to 2 atoms at the rose position.

phenyl, which may have a substituent such as nitro, hydroxy, methoxy, methyl, etc.), halogen (e.g., F,
CQ, Br, etc.), nitro, amino, oxo, etc., and two adjacent substituents are bonded together to form a cyclic group (e.g., a cyclic aliphatic hydrocarbon group having about 5 to 8 carbon atoms). It may be formed.

The optionally substituted divalent hydrocarbon chain having 2 to 4 carbon atoms represented by A above has 2 to 4 carbon atoms.
alkylene and R2 each represent hydrogen, an optionally substituted aliphatic hydrocarbon group, an optionally substituted aromatic hydrocarbon group, or a halogen, or R1 represents a cyclic group having about 5 to 8 carbon atoms. represents an aliphatic hydrocarbon group, and n' represents an integer of 0 to 2] or a hydrocarbon chain represented by the formula −〇 (
Hydrocarbon chains represented by CH2)1 [in the formula, n represents an integer of 1 to 3] are preferred, and among them, ethylene, 7ethyl vinylene (-C-CH-), methylvinylene e (-C= CH-) and vinylene are preferred.

A compound represented by the above formula (1) [In compound (I) 1, R1 and R2 are each an aliphatic hydrocarbon group having 2 to 5 carbon atoms (especially an alkyl group having 3 to 5 carbon atoms), R
3 is hydrogen, methyl, acetyl or metquin carbonyl group (especially hydrogen), A is ethyl is hydrogen, C1
More preferred is compound (I), which is a hydrocarbon chain represented by 1 representing a lower alkyl group or an optionally substituted aromatic hydrocarbon group (among them hydrogen, methyl, and phenyl).

Examples of the salt of compound (1) include acid addition salts such as hydrochloride;
Inorganic acid salts such as hydrobromides, sulfates, nitrates, phosphates, such as acetates, tartrates, citrates.

Examples include pharmacologically acceptable salts such as organic acid salts such as fumarate and maleate.

Production method The compound of general formula (I) above can be produced, for example, by the method shown below.

Process (a) ■ a [where Rl, R! and R3 has the same meaning as above. X
represents halogen, and n represents an integer of 1 to 3. ] Process (b) b e In formula 1, Rl, R! , R3 and n have the same meanings as above.

However, R3 is not hydrogen. ] Process (C) ■ d [wherein Rl, Ri, R3 and n have the same meanings as above.

represents a lower alkyl group. ] Process (d) 1a I "In formula 1, H+, Hz, Rs and X have the same meanings as above.] Process (r) V1 1g c f In formula 1, Rl, R2 and Rs have the same meanings as above. J
Process (e) i [where Rl, R! , R3 and n have the same meanings as above. However, R3 is not hydrogen. J process (g) v h j [where RI, R! , R3, R4, RS and x have the same meanings as above. n' represents an integer from θ to 2. J The above process (a) involves carrying out a ring-closing reaction in the presence of a base, and is carried out using 1 to 3 moles of base per 1 mole of compound (It). As the base, sodium hydride, potassium t-butoxy, potassium carbonate, sodium carbonate, etc. are used, and as the solvent, the reaction is carried out in a polar aprotic solvent such as dimethylformamide, dimethylacetamide, dimethylsulfoxide, and acetonitrile. The reaction conditions are preferably about 0.5 to 30 hours at 100° C. under water cooling. When using a strong base such as sodium hydride or potassium t-butoxy, compound (II) is dissolved in the solvent;
It is preferable to add these bases little by little while cooling with water. Alternatively, a strong base such as sodium hydride is suspended in a solvent such as dimethylformamide, and compound (II) is prepared under water cooling.
The reaction can also be carried out advantageously by adding a solution of the same solvent little by little. After adding the base in this way, it is preferable to raise the reaction temperature to about room temperature and further react for 1 to 2 hours. On the other hand, when the reaction is carried out in the presence of weak bases such as potassium carbonate or sodium carbonate, the compound (
II) and these bases in dimethylformamide (DMF
It is preferable to carry out the heating reaction in a solvent such as 1θ at 50 to 130°C for about 30 hours. The reaction product obtained as described above can be easily obtained by distilling off the solvent after the reaction is completed, adding the obtained reaction product to ice water, and recrystallizing the resulting crystals from hydrous alcohols, etc. be able to. In some cases, they can also be easily obtained by conventional isolation and purification methods such as column chromatography.

Process (b) is to obtain compound (Ie) by alkylating or acylating compound (Ib), and the alkylating agent is an alkyl halide (e.g., methyl iodide,
ethyl iodide, propyl iodide, benzyl bromide, etc.), and acylating agents include acid anhydrides (e.g., acetic anhydride, propionic anhydride, butyric anhydride, etc.) and acid halides (e.g., acetyl chloride, globionyl chloride).

butyryl chloride, etc.), and in the case of alkoxycarbonylation, halogenated alkyl carbonates (eg, methyl chlorocarbonate, ethyl chlorocarbonate, etc.) are used. These reagents are used in an excess amount of about 1 to 5 moles per mole per month of the compound (Ib) and reacted in the presence of an appropriate base. Examples of the base used include potassium carbonate, sodium carbonate, triethylamine, pyridine, etc. In some cases, dimethylaminopyridine is added in a catalytic amount.Pyridine is used as a solvent.

Using dimethylformamide, dimethylacetamide, acetonitrile, dioxane, etc., under water cooling at ~100°C, 1
It is preferable to react for about 50 hours.

The alkylation is preferably carried out with about 1 to 2 moles of alkyl halide in dimethylformamide at room temperature to 50°C for a period of about 5 to 20 hours. In addition, acylation is performed with about 1 to 3 moles of acid anhydride in pyridine at about 50 to 100°C.
It is preferable to use a time window of about 20 hours. In some cases, the reaction may be carried out more advantageously by adding a catalytic amount of dimethylaminopyridine.

In the alkoxycarbonylation reaction, a halogenated alkyl carbonate is added in a solvent such as dioxane in the presence of a base such as triethylamine under water cooling to about room temperature, and at room temperature to 60°C.
, it is preferable to react for about 5 to 20 hours. The product can be easily obtained as crystals by distilling off the reaction solvent and adding the resulting residue to ice water, or by using conventional isolation and purification methods.

Process (c) is a reaction to form a lactam ring in the presence of a base, and about 1 to 3 moles of base are used per 1 mole of compound (In). It is preferable to use sodium methoxide, sodium ethoxide, etc. as the base, and to use an alcoholic solvent such as methanol or ethanol as the solvent. The reaction conditions are preferably 30 minutes to 2 hours at 50°C to 50°C under water cooling. After the reaction is completed, the solvent is distilled off, the resulting residue is dissolved in water, and the product is easily obtained as crystals by neutralizing with about 1 to 2N hydrochloric acid.

70 process (d) is to obtain compound (If) by dehydrogenation reaction, in a common solvent such as dimethylformamide, dimethylacetamide, acetonitrile.

A thermal reaction is carried out at 50 to 150° C. for about 5 to 60 hours in an organic solvent such as dioxane, toluene, benzene, chloroform, or methylene chloride. At this time, benzoyl peroxide, 2
．． The reaction can be carried out in the presence of 3-dichloro-5,6-dicya-t,4-benzoquinone (DDQ), gelene dioxide, manganese dioxide, etc., or in the presence of a base such as potassium carbonate or sodium carbonate, but especially in the presence of a base such as chloroform etc. Benzoyl peroxide as an oxidizing agent in an aprotic solvent
It is preferable to use about 2 mol or so and to react under heating and reflux for about 5 to 15 hours.

Process (e) is from compound (Ila) to compound (If)
This is a method to obtain directly. The reaction conditions used at this time can be carried out in accordance with the case of process (a).

In the case of process (e), the base used may be potassium carbonate or sodium carbonate, and preferably a solvent such as dimethylformamide or dimethylacetamide. As for reaction conditions, it is more preferable to react at 80 to 120°C for about 20 to 40 hours. The products obtained in processes (d) and (e), after distilling off the reaction solvent,
It can be easily obtained as crystals by adding it to water or by using ordinary isolation and purification means such as column chromatography.

Process ([) is to subject compound (X Vl) to a ring-closing reaction in the presence of a dehydrating agent to obtain compound (Ig), and optionally acylate or alkylate it in the same manner as in process (b).
Compound (Ii) is obtained. As a dehydrating agent in the reaction from compound (XVI) to compound (Ig), dicyclohexylcarbodiimide (DCC), carbonyldiimidazole (CDI), etc., or chlorination agents such as thionyl chloride, phosphorus oxychloride, etc. may be used. I can do it. Dehydrating agent is for compound (X■)! -10 equivalent m
1. It is preferable to use methylene chloride, chloroform, benzene, etc. as a solvent and carry out the reaction at room temperature to 100° C. for about 1 to 10 hours. In particular, using 5 to 10 equivalents of thionyl chloride in a solvent such as chloroform or methylene chloride,
It is preferable to heat and reflux for about 1 to 5 hours.

Process (g) involves dehydrating compound (XV) under acidic or basic conditions to obtain target compound (Ih).
and optionally reduce compound (Ih) to obtain compound (!).
j). From compound (X V) to compound (
Examples of acids in the reaction to th) include organic and inorganic acids such as p-toluenesulfonic acid, hydrochloric acid, and sulfuric acid, and examples of bases include triethylamine.

Potassium carbonate, sodium carbonate, caustic soda, etc. are used in a catalytic amount of about 2 equivalents relative to compound (XV), and the solvent is benzene, toluene, xylene, methyl ethyl ketone, etc., at room temperature to 150°C for about 5 hours to 3 days. Make it react. In particular, using a catalytic amount of p-toluenesulfonic acid in a solvent such as benzene or toluene, and heating to reflux with lO
It is preferable to react for about 20 hours. Compound (Ih
) to compound (J), compound (Ih) is heated with hydrogen at normal pressure to about 5 atm in a usual solvent such as methanol, ethanol, chloroform, dichloromethane, benzene, acetic acid, or other organic solvent. It is preferable to coexist with a suitable catalyst under a gas flow at room temperature to 50°C for a time window of about 1 to 10 hours. Examples of the catalyst to be added include Raney nickel, palladium-attached activated carbon, platinum-attached activated carbon, platinum oxide, or rhodium catalyst.

The products obtained in processes ([) and (g) can be easily obtained as crystals by distilling off the reaction solvent and then using conventional isolation and purification means.

Among these compounds, starting compounds (n), (flI),
(XV) and (XVI) are novel compounds and can be synthesized by the following method. Chen+, Ber
,,95.

1597 (l 962) and Ann, Che+++
, 691° 142 (1966) using the compound (mV), (XI) as a starting material, which was synthesized according to the method described in Chem.

Phar+++, Bull,, 27.1328(
1978) and Chen+, Pharm, Bul
l,, 27.1965 (1978) Also published in 1978-
According to the method described in 31694 publication and 61-5082 publication, that is, processes (h), (i), (
3 obtained by the four methods shown in D and (k)
-Amino derivative (II) is prepared by preparing various alkyl civalides (e.g., l-bromo-2-chloroethane, 1-bromo-3-''lolopropane, l-bromo-4-chlorobutane, etc.) and dimethylformamide as shown in process (1). Starting compound (II) can be obtained by reacting at 50 to 120° C. for about 20 hours in the presence of potassium carbonate, sodium carbonate, etc. in an aprotic solvent such as potassium carbonate, sodium carbonate, etc. On the other hand, starting compound (1) Compound (ff) was prepared from various halogeno fatty acid alkyl esters (e.g., bromoacetic acid methyl ester) as shown in process (m).

(bromoacetic acid ethyl ester, etc.) in the presence of potassium carbonate or sodium carbonate in an aprotic solvent such as dimethylformamide at room temperature to 80°C for about 1 to 5 hours.

The starting compound (X Vl) is obtained by alkaline hydrolysis of the compound (■b) synthesized by the method shown in process (i) as shown in process (0).

Further, the raw material compound (XV) can be various haloketones (eg, bromoacetone, chloroacetone) as shown in process (n) for the above-mentioned 3-amino derivative (If).

3-chloro-2-butanone, phenacyl chloride, 7-enacyl bromide, 2-chlorocyclohexanone, 1-90-hexan-2-one, etc.) and a reaction accelerator in the presence of a base such as potassium carbonate, sodium carbonate, triethylamine, etc. In the presence of potassium iodide as
The raw material compound (XV) is obtained by reacting for about 4 days.

process (h) Process (i) ■ ■ [a In formula C, R' and R2 have the same meanings as above.

R6 is a lower Xa alkyl group, acyl group (acetyl, benzoyl, etc.) or C0OR' (wherein, n is in the previous C formula, and R', R'8 and X have the same meanings as above).

Same meaning as .

R7 represents a lower alkyl group.

) Indicates the group that is used.

process(") be. ] Process (1) ■ [b [In the formula, R', R2 and R3 have the same meanings as above.

just death, R3 is not hydrogen.

] ■ ■ process (k) In one set, , R'', R', X and n have the same meanings as above.

Process (m) ■ ■ [In the formula, RI, R2, R3, R@ and n have the same meanings as above.

]IV [a In formula C, Rl and R2 have the same meanings as above.

However, in Rl-RZ process (b) ■ v [where Rl, R1, R1, R4, RS and n'
has the same meaning as above. ] Process (o) ■b VI [wherein Rl, R2, R7 and n have the same meanings as above. 1 action Compound (I) has a strong antagonistic effect on adenosine receptors derived from the rat cerebral cortex, promotes the release of various neurotransmitters in the brain, increases their concentration in the brain, and activates brain function and metabolism. It is something that carries out transformation.

In other words, based on its brain function/metabolic activation effects in mammals, it is useful for the treatment and prevention of mental and neurological symptoms, including dementia symptoms caused by stroke, head trauma, or degenerative diseases (such as Alzheimer's disease). For example, amnesia, memory impairment.

It can be used to prevent and treat behavioral abnormalities such as disorientation, emotional incontinence, and decreased initiative and motivation. Also, compound (1)
has low toxicity [LD50 (oral): 500 mg/kg body weight or more (mouse)] and can be safely administered.

When compound (1) is used as an adenosine antagonist, it can be administered as it is, but generally it is mixed with an appropriate pharmacologically acceptable carrier, excipient, or diluent, and then administered with various agents. Administered as a pharmaceutical composition. Examples of dosage forms of such pharmaceutical compositions include powders and granules.

Examples include tablets, capsules, injections, suppositories, and ointments.

Examples of substances used in pharmaceutical compositions include white sugar, lactose, glucose, starch, and mannitol.

Excipients such as sorbitol, microcrystalline cellulose, talc, cyclodextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose.

Carboxymethylcellulose, glulan, methylcellulose, polyvinylpyrrolidone, gelatin.

Gum arabic, polyethylene glycol, white sugar.

Binders such as starch, starch, carboxymethylcellulose, calcium salts of carboxymethylcellulose, disintegrants such as low-substituted hydroxypropylcellulose, lubricants such as talc, magnesium stearate, hydroxypropylmethylcellulose, ethylcellulose, hydroxymethylcellulose, hydroxypropyl Methylcellulose phthalate, Eudragit [manufactured by Rohm (West Germany); methacrylic acid/acrylic acid copolymer 1, titanium oxide, pigments such as red iron oxide, sodium benzoate,
Preservatives such as sodium bisulfite, methylcellulose,
Suspending agents such as aluminum stearate, dispersing agents such as folysorbate go, Emulgel 408° Emazol 310, solvents such as water, cocoa butter, polyethylene glycol,
Examples include bases such as Lytepsol and white petrolatum, and these are appropriately selected depending on the type of formulation.

When the adenosine antagonist of the present invention is administered orally or parenterally to mammals including humans, the dosage is determined based on the target disease,
Although it varies depending on the symptoms, administration target, administration method, etc., for example, when orally administered to adult human patients exhibiting psychiatric symptoms or neurological symptoms, including dementia symptoms caused by stroke 1 head trauma or degenerative disease, the medicinal active ingredient [ Compound (I) 11
The dosage is preferably about 1 to 50 mg/kg (body weight), about 1 to 3 times a day, and about 1 to 20 mg/kg.
It is more preferable to administer about 1 to 3 kg (body weight) about 1 to 3 times a day.

Surface Layer 1 The present invention will be explained in more detail by referring to Reference Examples, Examples, Formulation Examples, and Experimental Examples below, but the present invention should not be limited to these.

Examples of abbreviations used in this specification are listed below.

Me: Methyl Hex: Hexyl Et: Ethyl Hep: Heptyl Pr: Propyl
A II: Allyl Bu: Butyl 80:
Acetyl Pen: Pentyl Ph: Phenyl S knee doublet d: Doublet L: Triplet m: Multiplet
brs: Singlet with wide convergence Reference example 1 6-(4-acetylthiosemicarbazide)-1-butyl-
3-propylpyrimidine-2,4 (lH.

3I()-dione l-Butyl-6-hydrazino-3-propylpyrimidine-2,4(lH,3H')-dione (8.0 g) in dioxane (room) was added with stirring acetyl isothiocyanate. (4.8 g) was added dropwise. After stirring at room temperature for 3 hours, the formed crystals were collected by filtration.

Recrystallization from hydroalcohol yields colorless crystals (14 g).

94%) was obtained.

Melting point! 49-152°C Elemental analysis value Cl4H2sNsOsC as S (%) H (%) N (%) Calculated value: 49.25; 6.79;
20.51 Actual value: 49.31; 6.70
; 20.48 The following compounds were synthesized in the same manner.

Reference Example 19 3-acetylamino-7-butyl-5-propylpyrazolo[3,4-d]pyrimidine-4,6 (5H.

7H)-dione 6-(4-acetylthiosemicarbazido)-1butyl-
3-propylpyrimidine-2,4 (IH.

3H)-dione (6.0 g) was dissolved in dimethylformamide (
The mixture was heated in DMFX60mj2) at 110 to +20°C for 60 hours. The residue obtained by concentrating the reaction solution contains 80%
Add methanol to dissolve and leave to cool. Recrystallize the light brown crystals from water-containing methanol to obtain colorless crystals (
4.4 g, 61%) was obtained.

Melting point +56-158°C Elemental analysis value Cl4H21Ns Os as C(
%) H (%) N (%) Calculated value: 54.71; 6.89;
22.79 Actual value: 54.63; 6.95
; 22.81 The following compounds were synthesized in the same manner as in 22.81.

Reference example 38 3-amino-7-butyl-5-propylpyrazolo[3,
4-d]Pyrimidine-4,6-(5H,7H)dione 3-acetylamino-7-butyl-5-propylpyrazolo[3,4-dlPyrimidine-4,6(5H.

7H)-dione (log) was heated to reflux for 5 hours in 80% ethanol (IOM) in which caustic soda (2 g) was dissolved. The crystals obtained by concentrating the reaction solution were mixed with water (10
0all) and made weakly acidic by adding 6N-HCQ to obtain colorless crystals (8 g, 93%).

Melting point 209-211'0 Elemental analysis value C+tH+*C as N5Ch (%)
H (%) N (%) Calculated value: 54.32; 7.22;
26.40 Actual value: 54.66; 7.20
; 26.38 The following compounds were synthesized in the same manner.

Reference example 57 3-acetylamino-8-butyl-6-broby-IH
-pyrimide[4,5-el[l, 3.41thiadiazine-5,7(6H,8H)-dione A suspension of 6-(4-acetylthio semicarbazide)-1-butyl-3-propylpyrimidine-2,4(IH,3H)-dione (3,8
A chloroform solution (20II12) of g) was placed under water cooling. After stirring for a further 3 hours at room temperature, isopropyl ether (lod) and hexane (lOW112
) was added, and the resulting crystals were collected by filtration and washed with water to obtain yellowish brown crystals (3.1 g, 82%).

Melting point 165-167°C Elemental analysis value Cl4H! l N s O, S as C (%) H (%) N (%) Calculated value: 49.54; 6.24;
20.63 Actual value: 49.49; 6.29
; 20.55 The following compounds were synthesized in the same manner as in 20.55.

Reference Example 72 3-acetylamino-7-butyl-5-propylpyrazolo[3,4 d]pyrimidine-4,6 (5H.

7H)-dione 2-acetylamino-5-butyl-7-broby-4H
-pyrimido[4,5-elN,3.4]thiadiazine-
6,8(5H,7H)-dione (2,8g) is heated at reflux in dioxane (28+d) for 1 hour. The reaction solution was concentrated to dryness, the resulting residue was dissolved in methanol, insoluble sulfur was filtered off, and a small amount of water was added to the filtrate and left to cool, yielding colorless crystals (2.3 g, 92%). Rarely.

Melting point 156-158℃ Elemental analysis value C (%) H as C0Hz+N5Oz
(%) N (%) Calculated value + 54.71; 6.89:
22.79 Actual value: 54.70; 6.93
The following compounds were synthesized in the same manner as i22.81.

Reference Example 91 6-chloro-5-cyano-1,3-diethylpyrimidine-2,4(lH,3H)-dione 1,3-diethylbarbylic acid (61g) was dissolved in phosphorus oxychloride (224d)
dimethylformamide (35t12) was added dropwise while stirring at room temperature. After dropping, reduce the reaction solution to 3.5
Refluxed for an hour. The reaction solution was concentrated under reduced pressure, and the remaining oil was added little by little to ice water. The precipitated crystals were collected by filtration, and 6
-chloro-1,3-diethyl-5-formyluracil (
64g) was obtained. Melting point: 88-89°C This product (50g)
and hydroxylamine hydrochloride (50 g) were mixed in ethanol (IQ) at room temperature for 30 minutes. Add water (
1(2) was added, the precipitate was collected by filtration, and 6-chloro-1,3
-'; Ethyluracil-5-carbaldehyde oxime (
32.5 g) was obtained. Melting point! 15-116°C Ice crystals (16 g) were dissolved in tetrahydrofuran (320 tQ), and while stirring with water cooling, phosphorus oxychloride (30 g) was added dropwise, followed by stirring at room temperature for 1 hour. The reaction solution was dried under reduced pressure and diisopropyl ether (200mff) was added to the residue.
was added, pale yellow prismatic crystals (12.4 g) of 6-chloro-5-cyano-1,3-diethylpyrimidine-2,4(lH,3H)-dione were precipitated. Melting point 92
-94°C Elemental analysis value: Cs H+ o N 302 C as CQ (%) H (%) N (%) Calculated value: 47.48, 4.43; 1
8.46 Actual value: 47.29, 4.31
; 18.35 The following compounds were synthesized in the same manner as in 18.35.

Intermediates other than these (6-chloro-5-formyl, 6
-Chloro-5-cyano form) was used in the next reaction without being purified because it was difficult to crystallize.

Reference Example 95 3-Amino-5,7-dinitylpyrazolo[3,4d]pyrimidine-4,6(5H,7H)-dione 6-chloro-
5-cyano-1,3-diethylpyrimidine-2,4(I
H,3H)-dione (5g) and hydrazine-hydrate (
2,2d) in methanol (220 mg) at room temperature.
Stir for 0 minutes. The reaction solution was dried under reduced pressure, and the residue was recrystallized from aqueous methanol to obtain colorless needle crystals (4.3 g). The following compound was obtained in the same manner with a melting point of 246,248°C.

Reference Example 99 3-amino-7-butyl-2-(2-chloroethyl)-
5-Propyl-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione 3-amino-7-butyl-5-propylpyrazolo[3,4-d]pyrimidine-4,6 (5H,7H)-dione (8 g), l-promo-2-chloroethane (3,7-) and potassium carbonate (
6,2g) in DMF (100IIL12) at 50-6
It was allowed to stir at 0° C. for 12 hours. After the reaction mixture was concentrated to dryness, the resulting residue was extracted with chloroform/water. Wash the chloroform layer with water.

The brown sills obtained by drying and concentrating are purified by flash chromatography (silica gel long, chloroform), and the obtained sills are crystallized from isoprobyl ether to give colorless needle crystals (21.5 g, 66%).
was gotten.

Melting point 118-121'C! Elemental analysis value C+aH22Ns02C12 (%
) H (%) N (%) Calculated value: 51.30; 6.76;
21.36 Actual value: 51.44; 6.79
; 21.13 The following compounds were synthesized in the same manner as in 21.13.

Reference example 125! -7'Tyl-6-(4-ethoxycarbonylmethylthiosemicarbazide)-3-propylpyrimidine-2,4
(lH,3H)-dione l-butyl-6-hydrazino-3-propylpyrimidine-2,4(lH,3H)-dione (l1 g) in dioxane (100 sffl) was stirred with ethoxycarbonylmethylthiocyanate. (15 g) was added dropwise. After stirring at room temperature for 3 hours,
The generated crystals were collected by filtration. The crystals were washed with a small amount of dioxane to obtain colorless crystals (18.8 g, 96%). Melting point 1
14-116°C Reference Example 126 Fubutyl-3-ethoxycarponylmethylamino-5
-propylpyrazolo[3,4-d]pyrimidine-4,6
(5H,7H)-dione N-chlorosuccinimide (6.5 g) was suspended in chloroform (80d), and while stirring under water cooling, l-butyl-6-(4-ethoxycarbonylmethylthiosemicarbazide)-3- Propylpyrimidine-2,4(IH,3H
)-dione (18 g) was added portionwise. After stirring for 1 hour, hexane (200+!LI2) was added to the reaction mixture, and after stirring for a while, the precipitated crystals were filtered off. The brown silt (23 g) obtained by concentrating the filtrate was suspended in dioxane (150 ml) and heated and stirred at 100°C for 1 hour. Insoluble materials were removed by filtration, the filtrate was concentrated, and the resulting residue was crystallized from ethyl acetate/isopropyl ether to give colorless crystals (9.8 g, 67%). Melting point 147-
148°C Reference Example 127 Fubutyl-3-carboxymethylamino-5-propylpyrazolo[3,4-dlpyrimidine-4°6 (5H,
7H)-dione 7-butyl-3-ethoxy force J levonylmethylamino-
5-propylpyrazolo[3,4-dlpyrimidine-4,
5(5H,7H)-dione (2 g) was dissolved in ethanol (20
st12) and 2N-caustic soda aqueous solution (2
0d) was added, and the mixture was heated and stirred at 100°C for 1 hour. The reaction solution was concentrated to half, made weakly acidic with hydrochloric acid, and colorless crystals (1
, 74g, 95%) was obtained.

Melting point 233-234°C (decomposition) Example 1! -Butyl-3-Propyl-1.2, 3.4.6゜7-
Hexahydro-5H-imidazo [2', vinyl 5, l]
Pyrazolo[3,4-d]pyrimidine-2,4dione 3-amino-7-butyl-2-(2-chloroethyl)-
DM of 5-propyl-2H-pyrazolo[3,4d]pyrimidine-4,6(5H,7H)-dione (3°3g)
Sodium hydride (60% oil base, 1.2 g) was added little by little to the F(35d) solution while stirring under water cooling. After stirring for an additional 2 hours at room temperature, the reaction solution was concentrated to dryness. The resulting residue was added to ice water and stirred for a while to precipitate crystals. After the crystals were collected by filtration, they were recrystallized from aqueous methanol to obtain colorless crystals (2.2 g, 76%).

Melting point 170-172°C Elemental analysis value C (%) as c+4Hz+hJso□
H (%) N (%) Calculated value: 57.71, 7.26; 2
4.04 Actual value: 57.78; 7.29
;24.01'H-NMR(d,-DMSO)δ
: 0.83(31(,L).

0.90(3)1, t), 1.10-1, 8
5 (6H, m), 3.60-4.30 (8H, m)
.

7.34 (IH, br　s) The following compounds were synthesized in the same manner as in Example 1.

Example 33 5-acetyl-1,3-dibutyl-1,2,3,4゜6
．． 7-hexahydro-5H-imidazo[2', l':
5,1] pyrazolo[3,4-d]pyrimidine-
2゜4-dione 1.3-dibutyl-1,2,3,4,6,7-hexahydroimidazo [2', 1': 5,1] pyrazolo
3゜4-d] Pyrimidine-2,4-dione (1,5g
) and acetic anhydride C1.4ml! > Pyridine (20tQ)
The reaction solution was concentrated and the resulting silica was purified by flash chromatography (silica gel, chloroform) to obtain a pale yellow silica. Crystallization gave colorless crystals (1.2 g, 70%).

Melting point 120-122°C Elemental analysis value CIF526N So3 as C (%)
H (%) N (%) Calculated value: 56.19; 6.93;
19.27 Actual value: 55.94, 6.92
; 19.37'H-NMR (CDC123) δ:
0.93 (3H, t), 0.96 (3H, t),
1.15-1.95 (8H, m), 2.66 (3H, s
), 3.99 (4H, m).

4.15-4.40 (2H, m), 4.50-4.80
(2H, m) The following compound was synthesized in the same manner as in Example 33.

Example 46 1-Butyl-3-propyl-1,2,3,4-tetrahydro-5H-imidazo[2',l': 5.11 pyrazolo[3,4-dl pyrimidine-2,4-dione l- Butyl-3-propyl-1,2,3,4,6゜7-
Hexahydro-5H-imidazo[2', l': 5.11
Pyrazolo[3,4-dl pyrimidine-2°4-dione (0.6 g) and benzoyl peroxide (1.0 g) were dissolved in chloroform (50 ml) and heated under reflux for 15 hours. The reaction solution was concentrated to dryness, and the resulting residue was dissolved in chloroform and washed with an aqueous sodium carbonate solution and water. After drying the solution, the resulting residue was purified by flash chromatography (20 g of silica gel, chloroform). The obtained crystals were mixed with methylene chloride/
Recrystallized from hexane to produce colorless prismatic crystals (0°38g,
64%).

Melting point: 235-236℃ Elemental analysis value: C (%) as C+aHtsNsOz
H (%) N (%) Calculated value: 58.12, 6.62; 24.20
Actual value: 58.17; 6.61; 24
．． 281 H-NMR (dl-DMSO) δ: 0.
96 (3HX2.t).

1.11-2.00 (6H, m), 3.96 (2H, t
), 4.16(2)1. t), 6.93 (IH, d)
, 7.34 (lH, d), 12.30 (IH, br s
) The following compounds were synthesized in the same manner as in Example 46.

Example 53 1-Butyl-〇-phenyl-3-propyl-1゜2.3
．． 4-tetrahydro-5H-imidazo[2'.

Vinny 5. l] Pyrazolo[3,4-dlpyrimidine-2°4-dione 3-amino-7-butyl-5-propylpyrazolo[3,
4-dlpyrimidine-4,6(5H,7H)-dione (
1.4g), 7-enacyl chloride (1.2g), triethylamine (0.7g) and methyl ethyl ketone (40mQ)
The mixture was stirred at 60° C. for 4 days. The reaction solution was filtered and the filtrate was concentrated to dryness. The resulting residue was purified by silica gel chromatography to obtain colorless crystals (0.94 g).

Subsequently, the crystals were heated under reflux for 14 hours in a catalytic amount of p-toluenesulfonic acid and toluene (30 mi2).

After the reaction solution was concentrated to dryness, the resulting residue was recrystallized from aqueous alcohol to obtain colorless needles (0.79 g, 41%).

Melting point 263-265°C Elemental analysis value C (%) H (%) N (%) Calculated value: 64.15: 6.46, 1 as C2゜HzsNsOs・l/2H20
8.70 actual value, 64.05, 6.37,
18.75'HNMR (da DMSO) δ: 0
．． 91 (3H, t), 0.94 (3H, t), 1.
13-1.92 (6) f, m), 3.91 (2
H,t), 3.99 (2H.

t), 7.23-7.55 (3H, m), 7.73
-7.91 (2H, m), 8.03 (18°d),
13.10 (IH, br s) The following compound was synthesized in the same manner as in Example 53.

Example 58 6.7-dipromo1.3 dibutyl-1,2,34
-tetrahydroimidazo[2',1':5,1]pyrazolo[3,4-dlpyrimidine-2,4-dione 1,3-
Dibutyl-5H-imidazo[2',l':5゜l]pyrazolo[3,4-d]pyrimidine-2,4-dione (1,
An acetic acid solution (3-) containing bromine (0,34 precepts) was added dropwise little by little to a solution of 0 g) in acetic acid (10 mg) at room temperature. After stirring for a while at room temperature, crystals precipitated.

Colorless crystals were obtained by washing with a small amount of alcohol.

Melting point 245-250°C (decomposition) Elemental analysis values Cls H, s B r! N s O
As x, C (%) H (%) N (%) Calculated values: 39.07; 4.15;
15.19 fruit! 1j value: 39.16; 4
．． 07; 15°62'HNMR (da DM
SO) δ: 0.75-1.10 (3H, m).

1.1-1.9 (8H, m), 3.7-4.1 (4H,
m) Example 59 1-butyl-3-propyl-1,2,3,4,6°7-
Hexahydro-5H-imidazo [2', l': 5°11
Pyrazolo[3,4-dl pyrimidine-2,4,6-dorion sodium (0,31 g) in ethanol (35
-), 3-amino-7-butyl-2-ethoxycarbonylmethyl-5-propyl-2H-pyrazolo[3,4-
dlpyrimidine-4,6(5H,7H)-dione (1,
85 g) was added thereto, and the mixture was left stirring at room temperature for 30 minutes. After concentrating the reaction solution to dryness, the resulting residue was dissolved in ice water, and 1
The mixture was made weakly acidic with N-hydrochloric acid.

The precipitated crystals were collected by filtration and recrystallized from methylene chloride/ethanol to obtain colorless needle crystals (0.84 g, 52%).

Melting point 266-269°C Elemental analysis value Cl 4 H+ s N s C as O3 (%) H (%) N (%) Calculated value: 55.07; 6.27;
22.94 Actual value: 54.99, 6.23
;22.82'H-NMR(d,-DMSO)δ
: 0.88 (3H, t), 0.92 (3H, t), 1
．． 13-1.88 (6H, m), 3.81 (2H, t)
, 3.91 (2H.

t), 4.66 (2H, s), 12.34 (IH, br
s) Example 60 1-Butyl-3-propyl-1,2,3,4,5°6.
7.8-octahydrobyrimide [2', l':5.1]
Pyrazolo[3,4-d]pyrimidine-2,4-dione 3
-amino-7-butyl-2-(3-chloropropyl)-
DM of 5-propyl-2H-pyrazolo[3,4-dlpyrimidine-4,6(5H,7H)-dione (2,1 g)
Sodium hydride (60% oil, 0.7 g) was added little by little to the F(30+t12) solution while stirring under ice cooling. After further stirring at room temperature for 5 hours, the reaction solution was concentrated to dryness. The resulting residue was added to ice water and stirred for a while to precipitate crystals. The crystals were collected by filtration and recrystallized from hydroalcohol to obtain colorless crystals (0.6 g, 32%).

Melting point 147-150℃ Elemental analysis value Cr s H! C (%) H (%) N (%) Calculated value as 3 N s Oz: 59.00; 7.59;
22.93 Actual value: 59.19; 7.58
; 22.83'H-NMR (CDC12m) δ
: 0.90 (3H, t), 0.93 (3H.

t), 1.12-1, 92(6H,m), 2
-02-2.34 (2H, m), 3.42 (2H.

111), 3.87 (2H, t), 3.89 (2H, t
), 4.01 (2H, t), 5.67 (IH, br s
) Example 61 1-Butyl-5-methyl-3-propyl-1°2.3.
4.5.6,7.8-octahydropyrimide [2',l
': 5.11 pyrazolo[3,4-dlpyrimidine-2,
4-dione 7-butyl-2-(3-chloropropyl)-3methylamino-5-propyl-2H-pyrazolo[3,4-dlpyrimidine-4,6(5H,7H)-dione (2,0 g)
Sodium hydride (60% oil, 0.67 g) was added little by little to a DMF (30 m) solution under water cooling and stirring. After further stirring at room temperature for 5 hours, the reaction solution was concentrated to dryness. The resulting residue was added to ice water and stirred for a while to precipitate crystals. The crystals were collected by filtration and recrystallized from isopropyl ether to obtain colorless crystals (1.55 g, 90%).

Melting point 94-98°C Elemental analysis value Cls Ht a N s C as O2
(%) H (%) N (%) Calculated value: 60.17; 7.89;
21.93 Actual value: 60.19; 7.89
; 21.95'H-NMR (CDCQ,) δ: 0
．． 92 (3H, t), 0.93 (3H.

t), 1. lo-1,90 (6H, m), 2.15 (2
H, m), 3.23 (28, t).

3.54 (3H, s), 3-8O-4-10 (4H, m
) Example 62 1-butyl-5-methyl-3-propyl-1°2.3,
4,6,7.8.9-octahydropyrimide [5',4
':4.3]virazolo[1,5-alN,3]diazepine-2,4-dione 7-butyl-2-(4-chlorobutyl)-3-methylamino-5-propyl-2H-pyrazolo[3° 4-d1pyrimidine-4,6(5H,7H)-dione (2,0g)
Sodium hydride (60% oil, 0.65 g) was added little by little to a DMF (30 m) solution under water cooling and stirring. After stirring for an additional 5 hours at room temperature, the reaction solution was concentrated to dryness. The resulting residue was added to ice water, neutralized with IN-hydrochloric acid, and extracted with chloroform. The chloroform layer was washed with water, dried, and concentrated to dryness. The resulting silica was subjected to flash chromatography (silica gel, chloroform).
It was purified with The obtained crystals were recrystallized from isopropyl ether/hexane to give colorless crystals (1.2 g, 67%).
was gotten.

Melting point 63-65℃ Elemental analysis value CI 7 Hz t N s C as Os (%) H (%) N (%) Calculated value: 61.24; 8.16;
21.00 Actual value: 61.38, 8.12
; 21.00'H-NMR (da-DMSO) δ
: 0.93 (3H, t), 0.94 (3H, t),
1.10-2.00 (IOH, m), 3.10-3.3
0 (2H, m).

3.30 (3H, s), 3.80-4.25 (6H, m
) Example 63 1-Butyl-3-propyl-1,2,3,4,6°7-
Hexahydro-5H-imidazo [2', l': 5゜l]
Pyrazolo[3,4-dl pyrimidine-2,4,7trione 7-7'thyl-3-carboxymethylamino-propylpyrazolo[3.4-dl pyrimidine-4.

Thionyl chloride (4d) was added to a solution of 6-(5H.7H)-dione (1.0 g) in methylene chloride (25 m), and 1.
The mixture was heated under reflux for 5 hours. The reaction solution was concentrated to dryness, and the resulting crude crystals were recrystallized from methylene chloride/isopropyl ether to obtain colorless crystals (0.8 g, 85%).

Melting point 258-259℃ Elemental analysis value C (%) as C+4H+sNsCh
H (%) N (%) Calculated value: 55.07
, 6.27; 22.94 Actual value: 54.
97; 6.12; 23.00'H-N
MR(d,-DMSO)δ: 0.88(3H,t),
0.92 (3H, t), 1.13-1.88 (6H
,t), 3.81(2H,t), 3.91(2H,t
).

4.66 (2H, s), 12.34 (IH, br s)
Formulation Example When the compound (I) of the present invention is used, for example, for the treatment and prevention of dementia symptoms caused by head trauma or interstitial disease by improving brain function and activating the brain, it can be prepared, for example, by the following formulation. Can be used.

11 tablets (1) l-butyl-3-propyl-1,2,3,4゜6
．． 7-hexahydro-5H-imidazo[2', vinyl5,
1] Pyrazolo[3,4-d]pyrimidine-2,4-dione lomg(2) Lactose
35mg (3) cornstarch
150mg (4) Microcrystalline cellulose
30mg (5) Magnesium stearate 5
mg30mg (1), (2), (3) and (4) 273 and (5)
After mixing 172, it is granulated. The remaining (4) and (
5) is added to the granules and pressure molded into tablets.

2, Capsule (1) 1.3-dibutyl-1,2,3,4,6,7-hexahydro-5H-imidazo[2',l':51]pyrazolo[3,4-d]pyrimidine-2, 4 Zeon
lomg(2) lactose
100mg (3) Microcrystalline cellulose
70mg (4) Magnesium stearate
10mg190+++g After mixing 1/2 of (1), (2), (3) and (4), granulate. Add the remaining (4) to this granule,
The whole is encapsulated in a gelatin capsule.

Experimental Example 1 The adenosine antagonism membrane was prepared according to Bruns et al.
cad, sci.

77, 5547 (conducted according to the method of 1980).

That is, after the rat begins to speak, the cerebral cortex (H〇 receptor) or striatum (A receptor) is removed, and Po1yt is removed in Tris-HCl buffer (50 mM, 20 m
It was suspended using ron. Thereafter, this suspension was mixed with 48.
The pellets obtained by centrifugation at 000g for 10 minutes were further suspended and centrifuged in the same manner. The resulting sediment was suspended in 50mM Tris-HCl buffer and treated with adenosine deaminase (
20/d) and incubated at 37°C for 30 minutes. After centrifuging this suspension, the pellet was stored at -20°C.

Adenosine receptor antagonism (AI and AI) was investigated using the above properties.

1) AI receptor antagonism After melting the above compound at room temperature, it was suspended in Tris-HCl buffer, and about 0.05 μCi of 3H-cyclohexyladenosine (H-CHAX) was added to the suspension (0.9d). ,O,1m
) and the test drug (10 μQ) were added and incubated at 25°C for 60 minutes. After the reaction is completed, the reaction solution is GF/B
Filter with a filter and further add Tris-HCl buffer for 4 hours.
Washed the filter twice.

Radioactivity on the filter was measured by liquid scintillation method. The amount of non-specific binding was measured in the presence of 10-5M L-phenylisopropyladenosine.

2) A2 receptor antagonism A, according to the receptor antagonism experiment. 3H-adenosine-5'
-Ethylcarboxamide CH-NECA; about 0.1p
Experiments were conducted using Ci) as a ligand in the presence of 50 nM cyclopentyladenosine.

The amount of non-specific binding is cyclopentyladenosine lO″1M
Measured in the presence of

The results of these A1 and A2 receptor antagonisms are shown in Table 1.

(Leaving space below) Table 1 Adenosine receptor binding inhibition effect Adenosine receptor binding inhibition effect is binding inhibition Table 2 Experimental example 2 Male Jcl: ICR mouse (5 regression 2 body weight 25-30
G, Japanese Yura) was used as - group of 5 animals, and the specimen was 500 m
g/kg was suspended in 20 m/kg of 5% gum arabic solution and administered orally. The number of deaths of animals was observed one week after oral administration. The results are shown in Table 2.

[Effect of the invention] The tricyclic fused pyrimidine derivative [compound (
Since January has an antagonistic effect on adenosine receptors derived from the rat cerebral cortex, it promotes the release of various neurotransmitters in the brain, increases their concentration in the brain, and is expected to activate brain function and metabolism. It is useful as a medicament for the prevention and treatment of psychiatric and neurological symptoms, including dementia symptoms caused by stroke, head trauma, or degenerative disease.

Agent: Patent Attorney Iwa 1) Hiroshi (4 others)

Claims (1)

[Claims] (1) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^1 and R^2 each represent an aliphatic hydrocarbon group, and R^3 represents hydrogen, an aliphatic hydrocarbon group, or an acyl group. and A represents an optionally substituted divalent hydrocarbon chain having 2 to 4 carbon atoms] or a salt thereof.