JPH09202786A - Condensed ring pyrimidine derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new compound useful as a medicine, especially an active ingredient compound of an analgesic agent. SOLUTION: This compound is represented by formula I [R<1> is an alkyl or phenyl; R<2> is furyl, thienyl, pyridyl, naphthyl or a substituted phenyl; R<3> is H, a lower alkyl or (CO)R<2> ; X is N, CH or C-Ph; Ph is phenyl; Y and Z are each as follows: Y is CH and Z is CH, C-CN or C(CO)NH2 when X is N; Y and Z are each N when X is CH or C-Ph], e.g. 5-n-butyl-7-(3,4,5- trimethoxybenzoylamino)-1,2,4-triazole[1,5-a]pyrimidine. The compound represented by formula I is obtained by reacting a compound represented by formula II with an acid halide represented by formula III (A is a halogen) in the presence of a deacidifying agent (e.g. pyridine) in a solvent (e.g. chloroform) at ambient temperature to the refluxing temperature. The compound represented by formula I is useful as an analgestic agent for preventing postoperative pain, hemicrania, neurogenic pain, chronic pain, gout or cancerous pain and further as an antiinflammatory agent, an antimicrobial agent, a hypoglycemic agent, a hypolipidemic agent, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel fused pyrimidine derivative.

[0002]

BACKGROUND OF THE INVENTION The compound of the present invention is a novel compound which has not been described in any literature.

[0003]

An object of the present invention is to provide compounds useful as pharmaceuticals as described below.

[0004]

According to the present invention, a fused pyrimidine derivative represented by the following formula (1) is provided.

[0005]

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[In the formula, R ¹ is an alkyl group or a phenyl group, R ² is a furyl group, a thienyl group, a pyridyl group, a naphthyl group or a lower alkyl group, a lower alkoxy group, a halogen atom, a halogen-substituted lower alkyl as a substituent. Group, nitro group, phenyl lower alkoxy group, phenoxy group, lower alkylthio group, lower alkylsulfinyl group, lower alkylsulfonyl group, halogen-substituted lower alkoxy group,
Lower alkoxycarbonyl group, cyano group, phenyl group,
1 to 1 of a group selected from di-lower alkoxyphosphoryl lower alkyl group, N- (tri-lower alkoxybenzoyl) amino group, lower alkanoyloxy group and hydroxyl group.
A phenyl group which may have ^three , R ³ is a hydrogen atom, a lower alkyl group or — (CO) R ² (R ² is the same as above), X is a nitrogen atom, CH or C-Ph (Ph is A phenyl group), and Y and Z are the same when X is a nitrogen atom.
Y is CH and Z is CH, C-CN or C (CO) NH _2.
When X is CH or C-Ph, Y and Z each represent a nitrogen atom. ] The condensed pyrimidine derivative of the present invention represented by the above general formula (1) is useful as a medicine. In particular, the derivative of the present invention is an analgesic (postoperative pain, migraine, gout, chronic pain, neuropathic pain, cancer pain, etc.), anti-inflammatory agent, antibacterial agent, hypoglycemic agent, hypolipidemic agent, hypotensive agent. It is useful as an agent, an anticancer agent, etc. Among them, it is preferably used as an analgesic, and it has the characteristic that it does not show the side effects seen in conventional analgesics.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As the respective groups defined in the above general formula (1) showing the derivative of the present invention, the following respective groups can be exemplified.

That is, as the lower alkyl group, methyl,
Examples thereof include linear or branched lower alkyl groups such as ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl groups. As the alkyl group, in addition to the above lower alkyl group, heptyl,
Examples thereof include octyl, nonyl and decyl groups.

Examples of the lower alkoxy group include methoxy, ethoxy, propoxy, isopropoxy, butoxy, pentyloxy and hexyloxy groups.

The halogen atom includes a fluorine atom, a chlorine atom,
A bromine atom and an iodine atom are included.

Examples of the halogen-substituted lower alkyl group include trifluoromethyl, pentafluoroethyl, heptafluoropropyl, nonafluorobutyl, undecafluoropentyl and tridecafluorohexyl groups.

The furyl group includes 2-furyl and 3-furyl groups.

The thienyl group includes 2-thienyl and 3-thienyl groups.

The pyridyl group includes 2-pyridyl, 3-pyridyl and 4-pyridyl groups.

The naphthyl group includes 1-naphthyl and 2-naphthyl groups.

Examples of the phenyl lower alkoxy group include benzyloxy, 2-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy and 6-phenylhexyloxy groups.

Examples of the lower alkylthio group include methylthio, ethylthio, propylthio, butylthio, pentylthio and hexylthio groups.

Examples of the lower alkylsulfinyl group include methylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, pentylsulfinyl and hexylsulfinyl groups.

Examples of the lower alkylsulfonyl group include methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl and hexylsulfonyl groups.

As the halogen-substituted lower alkoxy group,
Examples thereof include trifluoromethoxy, pentafluoroethoxy, heptafluoropropoxy, nonafluorobutoxy, undecafluoropentyloxy and tridecafluorohexyloxy groups.

Examples of the lower alkoxycarbonyl group include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl groups.

Examples of the di-lower alkoxyphosphoryl lower alkyl group include dimethoxyphosphorylmethyl, diethoxyphosphorylmethyl, dipropoxyphosphorylmethyl, dibutoxyphosphorylmethyl, dipentyloxyphosphorylmethyl, dihexyloxyphosphorylmethyl, 2-
(Dimethoxyphosphoryl) ethyl, 2- (diethoxyphosphoryl) ethyl, 3- (diethoxyphosphoryl) propyl, 4- (diethoxyphosphoryl) butyl, 5- (diethoxyphosphoryl) pentyl, 6- (diethoxyphosphoryl) hexyl Examples thereof include groups.

As the N- (tri-lower alkoxybenzoyl) amino group, N- (3,4,5-trimethoxybenzoyl) amino, N- (3,4,5-triethoxybenzoyl) amino and N- (3 , 4,5-Tripropoxybenzoyl) amino, N- (2,3,4-trimethoxybenzoyl) amino, N- (2,4,5-trimethoxybenzoyl) amino group and the like can be exemplified.

As a substituent, a lower alkyl group, a lower alkoxy group, a halogen atom, a halogen-substituted lower alkyl group,
Nitro group, phenyl lower alkoxy group, phenoxy group,
Lower alkylthio group, lower alkylsulfinyl group, lower alkylsulfonyl group, halogen-substituted lower alkoxy group, lower alkoxycarbonyl group, cyano group, phenyl group, di-lower alkoxyphosphoryl lower alkyl group, N-
Examples of the phenyl group which may have 1 to 3 groups selected from the group consisting of (tri-lower alkoxybenzoyl) amino group, lower alkanoyloxy group and hydroxyl group include the following substituted phenyl groups in addition to the unsubstituted phenyl group. It can be illustrated.

2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-t-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxy Phenyl, 4-ethoxyphenyl, 4-propoxyphenyl, 4-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 2,3-dimethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4
-Dimethoxyphenyl, 3,5-dimethoxyphenyl,
2,3,4-trimethoxyphenyl, 2,3,5-trimethoxyphenyl, 2,3,6-trimethoxyphenyl, 2,4,5-trimethoxyphenyl, 2,4,6-
Trimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3,4,5-triethoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-
Chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-iodophenyl, 2,
3-dichlorophenyl, 2,4-dichlorophenyl,
2,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2,4-dichloro-5-fluorophenyl, 2
-Trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-heptafluoropropylphenyl, 4-nonafluorobutylphenyl, 4-
Undecafluoropentylphenyl, 4-tridecafluorohexylphenyl, 2,3-bis (trifluoromethyl) phenyl, 2,4-bis (trifluoromethyl)
Phenyl, 3,4-bis (trifluoromethyl) phenyl, 3,5-bis (trifluoromethyl) phenyl,
3,4,5-tris (trifluoromethyl) phenyl,
2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-benzyloxyphenyl, 3-benzyloxyphenyl, 4-benzyloxyphenyl, 4-
(2-phenylethoxy) phenyl, 4- (3-phenylpropoxy) phenyl, 4- (4-phenylbutoxy) phenyl, 4- (5-phenylpentyloxy) phenyl, 4- (6-phenylhexyloxy) phenyl, 2,4-dibenzyloxyphenyl, 3,5-dibenzyloxyphenyl, 4-benzyloxy-3,5-
Dimethoxyphenyl, 2-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, 2-methylthiophenyl, 3-methylthiophenyl, 4-methylthiophenyl, 4-ethylthiophenyl, 4-propylthiophenyl, 4-butylthiophenyl , 4-pentylthiophenyl, 4-hexylthiophenyl, 2,4-dimethylthiophenyl, 3,4-dimethylthiophenyl,
3,5-dimethylthiophenyl, 2-methylsulfinylphenyl, 3-methylsulfinylphenyl, 4-methylsulfinylphenyl, 4-ethylsulfinylphenyl, 4-propylsulfinylphenyl, 4-butylsulfinylphenyl, 4-pentylsulfinylphenyl, 4-hexylsulfinylphenyl, 2-methylsulfonylphenyl, 3-methylsulfonylphenyl, 4-methylsulfonylphenyl, 4-ethylsulfonylphenyl, 4-propylsulfonylphenyl, 4-
Butylsulfonylphenyl, 4-pentylsulfonylphenyl, 4-hexylsulfonylphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 4-pentafluoroethoxyphenyl, 4-heptafluoropropoxyphenyl , 4-nonafluorobutoxyphenyl,
4-undecafluoropentyloxyphenyl, 4-tridecafluorohexyloxyphenyl, 2-methoxycarbonylphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 4-ethoxycarbonylphenyl, 4-propoxycarbonylphenyl, 4- Butoxycarbonylphenyl, 4-pentyloxycarbonylphenyl, 4-hexyloxycarbonylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, (1,1'-biphenyl)-
4-yl, (1,1'-biphenyl) -3-yl,
(1,1'-biphenyl) -2-yl, 2- (diethoxyphosphorylmethyl) phenyl, 3- (diethoxyphosphorylmethyl) phenyl, 4- (diethoxyphosphorylmethyl) phenyl, 4- (dimethoxyphosphorylmethyl) Phenyl, 4- (dipropoxyphosphorylmethyl)
Phenyl, 4- (dibutoxyphosphorylmethyl) phenyl, 4- (dipentyloxyphosphorylmethyl) phenyl, 4- (dihexyloxyphosphorylmethyl) phenyl, 4- [2- (dimethoxyphosphoryl) ethyl] phenyl, 4- [2- (Diethoxyphosphoryl) ethyl] phenyl, 4- [N- (3,4,5-trimethoxybenzoyl) amino] phenyl, 3- [N- (3,4,5-trimethoxybenzoyl) amino] phenyl, 2 -[N-
(3,4,5-Trimethoxybenzoyl) amino] phenyl, 4- [N- (3,4,5-triethoxybenzoyl) amino] phenyl, 4- [N- (3,4,5-tripropoxybenzoyl) ) Amino] phenyl, 4- [N-
(2,3,4-Trimethoxybenzoyl) amino] phenyl, 4- [N- (2,4,6-trimethoxybenzoyl) amino] phenyl, 2-acetoxyphenyl, 3-
Acetoxyphenyl, 4-acetoxyphenyl, 4-propionyloxyphenyl, 4-butyryloxyphenyl, 4-valeryloxyphenyl, 4-pivaloyloxyphenyl, 4-hexanoyloxyphenyl, 4-heptanoyloxyphenyl, 2,3-diacetoxyphenyl, 2,4-diacetoxyphenyl, 3,4-diacetoxyphenyl, 3,5-diacetoxyphenyl, 3,
4,5-Triacetoxyphenyl, 4-acetoxy-
3,5-dimethoxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2,3-dihydroxyphenyl, 2,4-dihydroxyphenyl, 3,4-dihydroxyphenyl, 3,5
-Dihydroxyphenyl, 3,4,5-trihydroxyphenyl.

Among the derivatives of the present invention represented by the above general formula (1), those which are preferable as the active pharmaceutical ingredient are those in the general formula (1) in which R ¹ is an alkyl group and X is CH or C—P.
a compound of h and X is a nitrogen atom and Z is C—CN or C
More preferred are those selected from compounds that are (CO) NH ₂ , of which R ¹ is an alkyl group, especially R
^A fused pyrimidine derivative in which ¹ is an n-butyl group and R ³ is a hydrogen atom is preferable. Further, among the preferable condensed ring pyrimidine derivatives, it is preferable that R ² is a lower alkyl group as a substituent, a phenyl group or a naphthyl group having 1 to 2 halogen atoms or 3 lower alkoxy groups. .

One of the most preferred specific examples of the derivative of the present invention is 5-n-butyl-7- (3,4,5-trimethoxybenzoylamino) -1,2,4-triazolo [1,5- a] Pyrimidine can be illustrated.

The derivative of the present invention can be produced by various methods. Specific examples thereof will be described in detail below with reference to reaction process formulas.

[0029]

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[In the formula, R ¹ , R ² , X, Y and Z are the same as defined above. R ^3a is a group — (CO) R ² (R ² is the same as above),
A represents a halogen atom. In the above reaction process formula-1, the ring condensation reaction between the nitrile derivative (2) and the compound (3) is carried out in an inert solvent such as benzene, toluene, xylene, acetic acid or ethanol under the condition of room temperature to reflux temperature. It takes about 3 to 50 hours below. The ratio of both compounds used is generally approximately equimolar.

The compound (4) obtained by the above reaction is
Then, this can be converted to the compound (1a) of the present invention by reacting it with an acid halide (5). In this case, the compound (1b) may be obtained as a by-product. This reaction can be carried out in the presence of a deoxidizing agent in a suitable solvent. Here, examples of the solvent include aromatic or aliphatic hydrocarbons such as benzene, toluene, xylene, and petroleum ether, and chain or cyclic ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran (THF), and 1,4-dioxane. , Acetone, ethyl methyl ketone,
Examples thereof include ketones such as acetophenone, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane. As a deoxidizer,
Preferable examples include tertiary amines such as triethylamine, N, N-diethylaniline, N-methylmorpholine, pyridine and 4-dimethylaminopyridine, and alkali metal hydrides such as sodium hydride and potassium hydride.

The amounts of the acid halide (5) and the deoxidizing agent used with respect to the compound (4) in the above reaction are not particularly limited, but usually the acid halide is about equimolar amount and the deoxidizing agent is about equimolar amount. It is preferable that the amount is about molar excess, and the reaction is completed in about 0.5 to 20 hours under the condition of room temperature to reflux temperature. Incidentally, generally, when the amount of the acid halide used is increased, the yield of the compound (1b) tends to increase.

If the compound (1a) is reacted with the acid halide (5) again in the same manner as above, the compound (1b) can be obtained.

Here, the intermediate compound (4) in the above reaction process formula-1 can also be produced, for example, by the method shown in the following reaction process formula-2.

[0035]

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[In the formula, R ¹ , X, Y and Z are the same as defined above. E represents a lower alkyl group, and Q represents a halogen atom. The condensation reaction between the compound (6) and the compound (3) in the above reaction process formula-2 is carried out in a suitable inert solvent under temperature conditions in the range of room temperature to the boiling point of the solvent. Examples of the inert solvent used here include acetic acid, ethanol, benzene, toluene, xylene, THF and the like.
The compound (6) and the compound (3) are preferably used in an approximately equimolar amount, and the reaction is completed in about 2 to 5 hours.

The halogenation reaction of the compound (7) obtained above can be carried out using a suitable halogenating agent such as phosphorus oxychloride or phosphorus oxybromide. Since the halogenating agent also serves as a solvent, it is not necessary to use a solvent for the reaction, but other inert solvents such as benzene, toluene and xylene can also be used. Further, if necessary, N, N-dimethylaniline, N, N
-Use a deoxidizer such as diethylaniline or triethylamine.
It is also possible to add a 10-fold molar amount. The reaction is from room temperature
It is carried out under a temperature condition of about 150 ° C. for about 0.5 to 12 hours.

The halide (8) obtained by the above reaction can be converted to the compound (4) by treating it with aqueous ammonia. This treatment can be carried out by heating the compound (8) together with an excess amount of aqueous ammonia at about 100 to 150 ° C. for about 1 to 12 hours without using a solvent.

[0039]

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[In the formula, R ¹ , R ² , A, Q, X, Y and Z are the same as defined above. R ^3b represents a lower alkyl group. The compound (1c) of the present invention can be produced by the method shown in the above Reaction Scheme-3. That is, first, the compound (8) and the amine (9) are mixed in an inert solvent such as methanol or ethanol in the presence of a deoxidizing agent such as sodium hydrogencarbonate, sodium carbonate or potassium carbonate under a temperature condition of about reflux temperature. Under treatment for about 1 to 6 hours, the compound (1
Compound (1c) can be obtained by obtaining 0) and reacting this with acid halide (5).

The reaction between the compound (10) and the acid halide (5) can be carried out according to the method shown in the above reaction process formula-1.

[0042]

[Chemical 6]

[Wherein R ¹ , X, Y and Z are the same as defined above. R ^2a has a lower alkanoyloxy group as a substituent, and further has a lower alkyl group, a lower alkoxy group, a halogen atom, a halogen-substituted lower alkyl group, a nitro group, a phenyl lower alkoxy group, a phenoxy group, a halogen-substituted lower alkoxy group, cyano. A phenyl group which may have 1 or 2 groups selected from a group, a phenyl group and a lower alkanoyloxy group, R ^3c is a hydrogen atom, a lower alkyl group or a group — (CO) —R ^2a (R ^2a is the above R ^2b is a hydroxyl group at a position corresponding to the lower alkanoyloxy group in the substituted phenyl group defined by R ^2a , and R ^3d is a hydrogen atom, a lower alkyl group or a group-(C
O) -R <^2b> (R < ^{2b >} is the same as the above). The compound (1d) of the present invention can be converted to the compound (1e) of the present invention by hydrolyzing the compound. The hydrolysis reaction can be carried out by treating with an aqueous solution of sodium hydroxide or an aqueous solution of potassium hydroxide in an inert solvent such as methanol or ethanol. The reaction is generally performed at 0 ° C.
~ Complete in 10 minutes to 3 hours under room temperature conditions.

[0044]

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[In the formula, R ¹ , X, Y and Z are the same as defined above. R ^2c has a lower alkylthio group as a substituent, and further has a lower alkyl group, a lower alkoxy group, a halogen atom,
A phenyl group which may have 1 or 2 groups selected from a halogen-substituted lower alkyl group, a nitro group, a phenyl lower alkoxy group, a phenoxy group, a halogen-substituted lower alkoxy group, a cyano group, a phenyl group and a lower alkylthio group, R ^3e is a hydrogen atom, a lower alkyl group or a group- (C
O) -R ^2c (R ^2c is the same as above), R ^2d is a substituted phenyl group defined by R ^{2c in} which a position corresponding to a lower alkylthio group is a lower alkylsulfinyl group or a lower alkylsulfonyl group. , R ^3f represents a hydrogen atom, a lower alkyl group or a group — (CO) —R ^2d (R ^2d is the same as above). ] The oxidation reaction of compound (1f) is carried out using acetic acid, dichloromethane,
It is carried out using hydrogen peroxide solution, m-chloroperbenzoic acid, sodium periodate or the like as an oxidizing agent in an inert solvent such as carbon tetrachloride.

Here, when the above-mentioned oxidation reaction is limited to lower alkylsulfinyl groups, the amount of the above-mentioned oxidizing agent used is 1 to a slight excess equivalent, and the temperature is about 0 ° C. to room temperature.
The reaction may be carried out for a minute to 2 hours.

On the other hand, when the oxidation reaction is advanced to the lower alkylsulfonyl group, the amount of the oxidizing agent used is 2
~ Excess equivalent, and further add a catalyst such as sodium tungstate if necessary, and at room temperature to about reflux temperature 1
It is advisable to carry out the reaction for 5 minutes to 2 hours. The sulfonyl compound can also be produced by re-oxidizing the sulfinyl compound. In that case, the reaction conditions may be either of the above two conditions.

The derivative of the present invention can be converted into a pharmaceutically acceptable acid addition salt by subjecting the derivative of the present invention to an addition reaction with an appropriate acidic compound according to a conventional method, and the present invention also includes such an acid addition salt. The acid addition salt has the same pharmacological activity as that of the derivative of the present invention in a free form, and can be similarly used as a pharmaceutical active ingredient.

Examples of the acidic compound capable of forming the acid addition salt include inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid, and maleic acid, fumaric acid, malic acid, tartaric acid, citric acid and methanesulfonic acid. Examples thereof include organic acids such as benzene sulfonic acid.

Further, among the compounds of the present invention, those in which R ³ is a hydrogen atom can be prepared by using an alkali metal salt according to a conventional method,
For example, sodium salts, potassium salts and the like and alkaline earth metal salts, such as calcium salts, magnesium salts and the like, and other copper salts and the like, such salts are also included in the scope of the present invention, the same active pharmaceutical ingredient Can be used as

The target compound obtained by each of the above steps can be easily isolated and purified by a usual separation means. Examples of this separation means include various commonly used methods such as solvent extraction, recrystallization, column chromatography, and ion exchange chromatography.

[0052]

EXAMPLES In order to explain the present invention in more detail, production examples of starting compounds for producing the compounds of the present invention will be given as reference examples, and then production examples of the compounds of the present invention will be given as examples.

[0053]

[Reference Example 1] Production of 4-amino-8-cyano-2-phenylimidazo [1,5-a] pyrimidine Dissolve 1.9 g of 5-amino-4-cyanoimidazole and 2.6 g of benzoylacetonitrile in 5 ml of acetic acid,
The mixture was stirred at 100 ° C for 24 hours. The reaction solution was concentrated under reduced pressure, chloroform-ethyl acetate was added to the residue, and the precipitated crystals were collected by filtration, washed successively with water and ethyl acetate, and recrystallized from ethanol to give 630 mg of the desired compound (melting point: 314-
316 ° C.) was obtained.

[0054]

Reference Examples 2 to 10 In the same manner as in Reference Example 1, the following raw material compounds were produced.

(2) 4-amino-2-n-butyl-8-
Cyanoimidazo [1,5-a] pyrimidine (melting point: 25
6-258 ° C) (3) 7-amino-5-ethyl-1,2,4-triazolo [1,5-a] pyrimidine (melting point: 194-197)
Recrystallization solvent: ethanol-n-hexane) (4) 7-amino-5-n-propyl-1,2,4-triazolo [1,5-a] pyrimidine (melting point: 139-1
42 ° C, recrystallization solvent: ethanol-n-hexane) (5) 7-amino-5-n-butyl-1,2,4-triazolo [1,5-a] pyrimidine (melting point: 149-15
1 ° C, recrystallization solvent: chloroform-n-hexane) (6) 7-amino-5-n-pentyl-1,2,4-triazolo [1,5-a] pyrimidine (melting point: 178-1
81 ° C., recrystallization solvent: ethanol-n-hexane) (7) 7-amino-5-n-octyl-1,2,4-triazolo [1,5-a] pyrimidine (melting point: 148-1
50 ° C., recrystallization solvent: ethanol-n-hexane) (8) 4-amino-2-n-butyl-8-carbamoylimidazo [1,5-a] pyrimidine (9) 7-amino-5-n-butyl -2-phenyl-
1,2,4-triazolo [1,5-a] pyrimidine (melting point: 211-213 ° C., recrystallization solvent: ethanol-n-
Hexane) (10) 7-amino-5-ethyl-2-phenyl-1,
2,4-triazolo [1,5-a] pyrimidine (melting point:
224-226 ° C, recrystallization solvent: ethanol-n-hexane)

[0056]

Reference Example 11 7-amino-5-n-butyl-1,
Production of 2,4-triazolo [1,5-a] pyrimidine Step (1) 3-amino-1,2,4-triazole 34.6 g and 3
A solution of 65.0 g of -oxoheptanoic acid methyl ester in 40 ml of toluene was heated under reflux at 110 ° C for 3 hours. After cooling, toluene was distilled off under reduced pressure, and the residue was recrystallized from ethanol-n-hexane to give 5-n-butyl-7-hydroxy-1,2,4-triazolo [1,5-a] pyrimidine colorless. 63.9 g of crystals were obtained.

Step (2): 80 ml of phosphorus oxybase was added to 19.2 g of the crystal obtained in the above step (1), and the mixture was heated under reflux for 1 hour. After completion of the reaction, the mixture was concentrated under reduced pressure, the residue was poured into ice water, the mixture was neutralized with anhydrous sodium acetate, extracted with dichloromethane, and the organic layer was collected. This was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate: n-hexane = 1: 2) to give 5-n-butyl-7-chloro-1,2,4-triazolo [1,5. -A] Pyrimidine pale red oil 1
4.9 g were obtained.

8.8 g of the compound obtained in the above step and 25
% Ammonia water and 100 ml were sealed in a stainless steel closed tube and heated at 120 ° C. for 22 hours. After cooling, the precipitated crystals were collected by filtration, washed with water, and recrystallized from methanol-n-hexane to obtain 3.7 g of the target compound as colorless crystals. This was the same as the compound shown in (5) of Reference Example 5.

[0059]

Example 1 8-Cyano-2-phenyl-4- (3,
Preparation of 4,5-trimethoxybenzoylamino) imidazo [1,5-a] pyrimidine The crystals 300 obtained in Reference Example 1 in 3.0 ml of pyridine.
mg was added, and 294 mg of 3,4,5-trimethoxybenzoyl chloride was added under stirring with ice cooling. The suspension was stirred at 0 ° C. for 1 hour and then at room temperature for 10 hours. Chloroform was added to the reaction mixture, and the precipitated crystals were collected by filtration,
The crystals were washed successively with water, ethanol and chloroform to give 100 mg of crystals of the desired compound. Table 1 shows the structure and melting point of the obtained compound.

[0060]

Examples 2 to 13 In the same manner as in Example 1, the compounds shown in Table 1 were produced.

[0061]

[Table 1]

[0062]

[Table 2]

[0063]

Examples 14 to 39 The following compounds can be prepared by carrying out the same reactions as in Reference Examples and Examples using appropriate starting materials. Included in.

Example 14 4-benzoylamino-2-
n-Butyl-8-cyanoimidazo [1,5-a] pyrimidine.

Example 15: 2-n-butyl-8-cyano-4- (2-trifluoromethylbenzoylamino) imidazo [1,5-a] pyrimidine.

(Melting point: 192-195 ° C., recrystallization solvent:
Diethyl ether) Example 16 ... 2-n-butyl-8-cyano-4- (2-
Methylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 17 2-n-butyl-4- (2-
Chlorobenzoylamino) -8-cyanoimidazo [1,
5-a] pyrimidine.

(Melting point: 205 to 207 ° C., recrystallization solvent:
Ethanol-water) Example 18: 8-Cyano-2-ethyl-4- (3,4,4)
5-trimethoxybenzoylamino) imidazo [1,5
-A] pyrimidine.

Example 19 8-Cyano-2-n-octyl-4- (3,4,5-trimethoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 20: 2-n-butyl-4- (3,3
4,5-Trimethoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 21 ... 2-Ethyl-4- (3,4,
5-trimethoxybenzoylamino) imidazo [1,5
-A] pyrimidine.

Example 22 ... 2-n-octyl-4-
(3,4,5-Trimethoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 23 ... 2-n-butyl-4- (2-
Trifluoromethylbenzoylamino) imidazo [1,
5-a] pyrimidine.

Example 24: 2-n-butyl-4- (2-
Methylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 25: 2-n-butyl-4- (2-
Chlorobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 26 ... 5-Methyl-7- (3,4,
5-trimethoxybenzoylamino) -1,2,4-triazolo [1,5-a] pyrimidine.

Example 27 ... 5-Phenyl-7- (3,
4,5-Trimethoxybenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 28 ... 7-Benzoylamino-5-
Phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 29: 7- (2-methylbenzoylamino) -5-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 30 7- (2-chlorobenzoylamino) -5-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 31 5-phenyl-7- (2-trifluoromethylbenzoylamino) -1,2,4-triazolo [1,5-a] pyrimidine.

Example 32 ... 5-n-butyl-7- (3,
4,5-Triethoxybenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 33: 5-n-butyl-7- (2-
Pentafluoroethylbenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 34 ... 5-n-hexyl-7-
(3,4,5-trimethoxybenzoylamino) -1,
2,4-triazolo [1,5-a] pyrimidine.

Example 35 ... 5-n-heptyl-7-
(3,4,5-trimethoxybenzoylamino) -1,
2,4-triazolo [1,5-a] pyrimidine.

Example 36 ... 5-n-nonyl-7- (3,
4,5-Trimethoxybenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 37 ... 5-n-decyl-7- (3,
4,5-Trimethoxybenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 38: 5-n-butyl-7- (2,
3,4-trimethoxybenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 39 ... 5-n-butyl-7- (2,
4,5-Trimethoxybenzoylamino) -1,2,4
-Triazolo [1,5-a] pyrimidine.

[0090]

Examples 40 and 41 2-n-Butyl-8-cyano-4- (2-methoxybenzoylamino) imidazo [1,5-a] pyrimidine and 2-n-butyl-8-cyano-4- [N , N-bis (2-methoxybenzoyl)
Production of Amino] imidazo [1,5-a] pyrimidine Using the compound obtained in Reference Example 2 and 2-methoxybenzoyl chloride, the same reaction as in Example 1 was carried out,
The crude product was recrystallized from dichloromethane-diethyl ether to give 2-n-butyl-8-cyano-4- (2-methoxybenzoylamino) imidazo [1,5-a] pyrimidine colorless crystals. Next, the recrystallization mother liquor was concentrated and the residue was recrystallized from ethyl acetate to give 2-n-butyl-8-cyano-4- [N, N-bis (2-methoxybenzoyl) amino] imidazo [1. , 5-a] Pyrimidine colorless crystals were obtained. Table 2 shows the structure and melting point of each compound obtained.

[0091]

Examples 42 to 54 In the same manner as in Example 1, the compounds shown in Table 2 were prepared.

[0092]

Example 55 Preparation of 5-n-butyl-7- (2-methylsulfinylbenzoylamino) -1,2,4-triazolo [1,5-a] pyrimidine 1.0 g of the compound obtained in Example 54 0.4 g of 30% hydrogen peroxide solution was added to a solution of 20 ml of acetic acid in (1) and the mixture was stirred at room temperature for 6 hours. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent: chloroform: ethyl acetate = 1: 2 → chloroform: methanol = 10: 1).
And further recrystallized from ethanol-n-hexane to obtain 0.76 g of colorless crystals of the target compound. The structure and melting point of the obtained compound are shown in Table 2.

[0093]

Example 56 Preparation of 5-n-butyl-7- (2-methylsulfonylbenzoylamino) -1,2,4-triazolo [1,5-a] pyrimidine 1.0 g of the compound obtained in Example 54 0.8 g of 30% hydrogen peroxide solution was added to a 20 ml solution of acetic acid of, and stirred at 80 ° C. for 2 hours. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent: chloroform: ethyl acetate = 1: 2 → chloroform: methanol = 10 :).
It was purified in 1) and recrystallized from ethanol-n-hexane to obtain 0.67 g of colorless crystals of the target compound. The structure and melting point of the obtained compound are shown in Table 2.

[0094]

Example 57 In the same manner as in Example 1, the compounds shown in Table 2 were prepared.

[0095]

Example 58 In the same manner as in Example 56, the compounds shown in Table 2 were prepared.

[0096]

Examples 59 to 74 In the same manner as in Example 1, the compounds shown in Table 2 were prepared.

[0097]

Example 75 In the same manner as in Example 55, the compounds shown in Table 2 were prepared.

[0098]

Example 76 In the same manner as in Example 1, the compounds shown in Table 2 were prepared.

[0099]

Example 77 5-n-butyl-7- (4-hydroxybenzoylamino) -1,2,4-triazolo [1,5
-A] Production of pyrimidine 1.41 g of ethanol 2 of the compound obtained in Example 76
The 0 ml suspension was cooled to 0 ° C., 5 ml of 2N sodium hydroxide aqueous solution was added thereto, and the mixture was stirred at 0 ° C. for 1 hour. After completion of the reaction, the mixture was concentrated under reduced pressure, the residue was diluted with water and washed with dichloromethane. Hydrochloric acid was added to the aqueous layer to acidify it, and the precipitated crude crystals were filtered and recrystallized from ethanol-chloroform-n-hexane to give 1.12 g of colorless crystals of the target compound.
I got The structure and melting point of the obtained compound are shown in Table 2.

[0100]

Example 78 5-n-butyl-7- [Nn-butyl-N- (3,4,5-trimethoxybenzoyl) amino] -1,2,4-triazolo [1,5-a] Production of pyrimidine 3.16 g of the compound obtained in the step (2) of Reference Example 11,
1.10 g of n-butylamine and 1.26 g of anhydrous sodium hydrogen carbonate were added to 20 ml of ethanol, and the mixture was heated to 100 ° C.
For 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layers were collected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. This was purified by silica gel column chromatography (eluent; chloroform: ethyl acetate = 1: 2) and recrystallized from n-hexane to give 5-n-butyl-7-.
n-Butylamino-1,2,4-triazolo [1,5-
a] Pyrimidine (2.72 g) was obtained. Next, using 1.12 g of the obtained compound and 1.08 g of 3,4,5-trimethoxybenzoyl chloride, 0.52 g of colorless crystals of the target compound was obtained in the same manner as in Example 1. The structure and melting point of the obtained compound are shown in Table 2.

[0101]

[Table 3]

[0102]

[Table 4]

[0103]

[Table 5]

[0104]

[Table 6]

[0105]

[Table 7]

[0106]

[Table 8]

[0107]

[Table 9]

[0108]

[Table 10]

[0109]

Examples 79 to 141 The following compounds can be prepared by carrying out the same reactions as in Reference Examples and Examples using appropriate starting materials, and the present invention also includes each compound. .

Example 79 7- (4-benzyloxybenzoylamino) -5-n-butyl-2-phenyl-
1,2,4-triazolo [1,5-a] pyrimidine.

Example 80 7- (2-benzyloxybenzoylamino) -5-n-butyl-2-phenyl-
1,2,4-triazolo [1,5-a] pyrimidine.

Example 81 5-n-butyl-7- (2-
Phenoxybenzoylamino) -2-phenyl-1,
2,4-triazolo [1,5-a] pyrimidine.

Example 82 ... 5-n-butyl-7- (2-
Methylthiobenzoylamino) -2-phenyl-1,
2,4-triazolo [1,5-a] pyrimidine.

Example 83 5-n-butyl-7- (2-
Methylsulfinylbenzoylamino) -2-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 84 5-n-butyl-7- (2-
Methylsulfonylbenzoylamino) -2-phenyl-
1,2,4-triazolo [1,5-a] pyrimidine.

Example 85: 5-n-butyl-7- (2-
Chlorobenzoylamino) -2-phenyl-1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 86 5-n-butyl-7- (2,
4-dichloro-5-fluorobenzoylamino) -2-
Phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 87: 5-n-butyl-7- (2-
Nitrobenzoylamino) -2-phenyl-1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 88: 5-n-butyl-2-phenyl-7- (2-trifluoromethylbenzoylamino)
-1,2,4-triazolo [1,5-a] pyrimidine.

Example 89 5-n-butyl-2-phenyl-7- (4-trifluoromethoxybenzoylamino) -1,2,4-triazolo [1,5-a] pyrimidine.

Example 90 5-n-butyl-7- (4-
Methoxycarbonylbenzoylamino) -2-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 91 5-n-butyl-7- (4-
Cyanobenzoylamino) -2-phenyl-1,2,4
-Triazolo [1,5-a] pyrimidine.

Example 92 5-n-butyl-2-phenyl-7- (2-phenylbenzoylamino) -1,2,
4-Triazolo [1,5-a] pyrimidine.

Example 93: 5-n-butyl-7- (4-
Diethoxyphosphorylmethylbenzoylamino) -2-
Phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 94 5-n-butyl-2-phenyl-7- [4- (3,4,5-trimethoxybenzoylamino) benzoylamino] -1,2,4-triazolo [1,5- a] Pyrimidine.

Example 95 5-n-butyl-7- (1-
Naphthoylamino) -2-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 96 5-n-butyl-7- (2-
Furoylamino) -2-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 97 5-n-butyl-2-phenyl-7- (2-thenoylamino) -1,2,4-triazolo [1,5-a] pyrimidine.

Example 98 5-n-Butyl-7- (isonicotinoylamino) -2-phenyl-1,2,4-triazolo [1,5-a] pyrimidine.

Example 99 7- (2-acetoxybenzoylamino) -5-n-butyl-2-phenyl-1,
2,4-triazolo [1,5-a] pyrimidine.

Example 100 ... 5-n-butyl-7- (2
-Hydroxybenzoylamino) -2-phenyl-1,
2,4-triazolo [1,5-a] pyrimidine.

Example 101 2-n-butyl-4- (benzyloxybenzoylamino) -8-cyanoimidazo [1,5-a] pyrimidine.

Example 102 2-n-butyl-8-cyano-4- (2-phenoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 103 2-n-butyl-8-cyano-4- (2-methylthiobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 104 2-n-butyl-8-cyano-4- (2-methylsulfinylbenzoylamino)
Imidazo [1,5-a] pyrimidine.

Example 105 2-n-butyl-8-cyano-4- (2-methylsulfonylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 106 2-n-butyl-8-cyano-4- (4-trifluoromethoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 107 2-n-butyl-8-cyano-4- (4-methoxycarbonylbenzoylamino)
Imidazo [1,5-a] pyrimidine.

EXAMPLE 108 2-n-Butyl-8-cyano-4- (4-cyanobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 109 2-n-butyl-8-cyano-4- (2-phenylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 110 2-n-butyl-8-cyano-4- (4-diethoxyphosphorylmethylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 111 2-n-butyl-8-cyano-4- [4- (3,4,5-trimethoxybenzoylamino) benzoylamino] imidazo [1,5-a] pyrimidine.

Example 112 2-n-butyl-8-cyano-4- (2-furoylamino) imidazo [1,5-
a] Pyrimidine.

EXAMPLE 113 2-n-butyl-8-cyano-4- (2-thenoylamino) imidazo [1,5-
a] Pyrimidine.

Example 114 2-n-butyl-8-cyano-4- (isonicotinoylamino) imidazo [1,5
-A] pyrimidine.

Example 115 4- (2-acetoxybenzoylamino) -2-n-butyl-8-cyanoimidazo [1,5-a] pyrimidine.

Example 116 2-n-butyl-8-cyano-4- (2-hydroxybenzoylamino) imidazo [1,5-a] pyrimidine.

EXAMPLE 117 2-n-butyl-4- (2
-Benzyloxybenzoylamino) -8-carbamoylimidazo [1,5-a] pyrimidine.

Example 118: 2-n-butyl-8-carbamoyl-4- (2-phenoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 119 2-n-butyl-8-carbamoyl-4- (2-chlorobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 120 2-n-butyl-8-carbamoyl-4- (2,4-dichlorobenzoylamino)
Imidazo [1,5-a] pyrimidine.

Example 121 2-n-butyl-8-carbamoyl-4- (2-nitrobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 122 2-n-butyl-8-carbamoyl-4- (2-trifluoromethylbenzoylamino) -imidazo [1,5-a] pyrimidine.

Example 123 2-n-butyl-8-carbamoyl-4- (2-methylthiobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 124 2-n-butyl-8-carbamoyl-4- (2-methylsulfinylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 125 2-n-butyl-8-carbamoyl-4- (2-methylsulfonylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 126 2-n-butyl-8-carbamoyl-4- (4-trifluoromethoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 127 2-n-butyl-8-carbamoyl-4- (4-methoxycarbonylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 128 2-n-butyl-8-carbamoyl-4- (4-cyanobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 129 2-n-butyl-8-carbamoyl-4- (2-phenylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 130 2-n-butyl-8-carbamoyl-4- (4-diethoxyphosphorylmethylbenzoylamino) imidazo [1,5-a] pyrimidine.

Example 131 2-n-butyl-8-carbamoyl-4- [4- (3,4,5-trimethoxybenzoylamino) benzoylamino] imidazo [1,5-
a] Pyrimidine.

Example 132 2-n-butyl-8-carbamoyl-4- (1-naphthoylamino) imidazo [1,5-a] pyrimidine.

Example 133 2-n-butyl-8-carbamoyl-4- (2-furoylamino) imidazo [1,
5-a] pyrimidine.

Example 134 2-n-butyl-8-carbamoyl-4- (2-thenoylamino) imidazo [1,
5-a] pyrimidine.

Example 135 2-n-butyl-8-carbamoyl-4- (isonicotinoylamino) imidazo [1,5-a] pyrimidine.

Example 136 4- (2-acetoxybenzoylamino) -2-n-butyl-8-carbamoylimidazo [1,5-a] pyrimidine.

Example 137 2-n-butyl-8-carbamoyl-4- (2-hydroxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 138 2-n-butyl-8-carbamoyl-4- (2-methoxybenzoylamino) imidazo [1,5-a] pyrimidine.

Example 139 ... 2-n-butyl-4- (4
-T-Butylbenzoylamino) -8-carbamoylimidazo [1,5-a] pyrimidine.

EXAMPLE 140 2-n-Butyl-8-carbamoyl-4- (2-bromobenzoylamino) imidazo [1,5-a] pyrimidine.

Example 141 2-n-butyl-8-carbamoyl-4- [N, N-bis (2-methoxybenzoyl) amino] imidazo [1,5-a] pyrimidine.

Claims (6)

[Claims] 1. A compound of the general formula [Wherein R ¹ is an alkyl group or a phenyl group, R ² is a furyl group, a thienyl group, a pyridyl group, a naphthyl group or a lower alkyl group as a substituent, a lower alkoxy group, a halogen atom, a halogen-substituted lower alkyl group, a nitro group. Group, phenyl lower alkoxy group, phenoxy group, lower alkylthio group, lower alkylsulfinyl group, lower alkylsulfonyl group, halogen-substituted lower alkoxy group, lower alkoxycarbonyl group, cyano group, phenyl group, di-lower alkoxyphosphoryl lower alkyl group, N A phenyl group which may have 1 to 3 groups selected from a-(tri-lower alkoxybenzoyl) amino group, a lower alkanoyloxy group and a hydroxyl group, R ³ is a hydrogen atom, a lower alkyl group or-(CO) R ² (R ² is the same), X is a nitrogen atom, CH or -Ph (Ph is phenyl group), Y and Z, when X is a nitrogen atom, Y is Z in CH is CH, a C-CN or C (CO) NH _2, X is CH or C-Ph In the case of, Y and Z each represent a nitrogen atom. ] The condensed-ring pyrimidine derivative represented by these. 2. A compound of the general formula as claimed in claim 1, wherein R ¹ is an alkyl group and X is CH or C—Ph, and X is a nitrogen atom and Z is C—CN or C (CO) NH ₂ . The condensed pyrimidine derivative according to claim 1, which is selected from certain compounds. 3. The fused pyrimidine derivative according to claim 2, wherein R ¹ is an alkyl group. 4. The fused pyrimidine derivative according to claim 3, wherein R ¹ is an n-butyl group and R ³ is a hydrogen atom. 5. The condensed pyrimidine derivative according to claim 4, wherein R ² is a phenyl group or a naphthyl group having a lower alkyl group as a substituent, 1 to 2 halogen atoms or 3 lower alkoxy groups. 6. The condensed product according to claim 5, which is 5-n-butyl-7- (3,4,5-trimethoxybenzoylamino) -1,2,4-triazolo [1,5-a] pyrimidine. Ring pyrimidine derivatives.