JPH0240671B2 - 11FUENIRUU1HHPIRAZORO * 3 * 44B * PIRAJINJUDOTAI - Google Patents

Description

[Detailed description of the invention]

The present invention provides the following formula (1) having excellent antitumor or antiviral effect: (However, R ₁ and R ₂ are each a hydrogen atom; an alkyl group; an alkyl group substituted with a hydroxy group, a carboxyl group, a halogen atom, an alkylamino group, a phenyl group, a nitrophenyl group, a halogenophenyl group, or an alkylphenyl group; Cycloalkyl group; cycloalkyl group substituted by an alkyl group; or amino group; or R ₁ and R ₂ are saturated heterocycles (nitrogen-containing saturated heterocycles) together with the nitrogen atom to which they are bonded, with or without an oxygen atom 1-Phenyl-1H-pyrazolo[3,4-b]pyrazine derivatives. Conventionally, various substances having antitumor and antiviral effects have been developed and proposed, and the present inventors also found that they have excellent antitumor and antiviral effects and are used as antitumor or antiviral agents. While conducting intensive research on compounds that can

[Formula] (where R ₁ and R ₂ have the above meanings) A new compound 1-phenyl-1H-pyrazolo [ 3,4-b] found that pyrazine derivatives are obtained, and that these compounds have excellent antitumor or antiviral effects and can be effectively used as antitumor or antiviral agents,
The present invention has been accomplished. The present invention will be explained in more detail below. Novel compound 1-phenyl-1H- according to the present invention
The pyrazolo[3,4-b]pyrazine derivative has the above-mentioned formula (1), i.e. (However, R ₁ and R ₂ are each a hydrogen atom; an alkyl group; an alkyl group substituted with a hydroxy group, a carboxyl group, a halogen atom, an alkylamino group, a phenyl group, a nitrophenyl group, a halogenophenyl group, or an alkylphenyl group; Cycloalkyl group; cycloalkyl group substituted by an alkyl group; or amino group; or R ₁ and R ₂ are saturated heterocycles (nitrogen-containing saturated heterocycles) together with the nitrogen atom to which they are bonded, with or without an oxygen atom (The heterocycle may be substituted with a carboxyl group.) Here, in formula (1), the alkyl group includes a straight chain alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a 1-methylethyl group, a 2-methylpropyl group, a 1- Methylpropyl group, 1,1-dimethylethyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1-dimethylpropyl group, 2,2-dimethylpropyl group, 1-methylbutyl group, 1-methylpentyl group, 2 -Methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, 1,3-dimethylbutyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 2,2-dimethylbutyl group,
Examples include branched alkyl groups such as 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1-methylhexyl group, and 1-methylheptyl group. In addition, as substituted alkyl groups, one or more hydrogen atoms of the above alkyl groups can be substituted with a hydroxy group, a carboxy group, a halogen, a lower alkylamino group,
Examples include those appropriately substituted with a phenyl group and a substituted phenyl group. In this case, examples of halogen include fluorine, chlorine, bromine, etc., and examples of the alkyl group of the lower alkylamino group include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, and isopentyl group. , a neopentyl group, a hexyl group, and other linear or branched alkyl groups having 1 to 6 carbon atoms. Furthermore, the substituted phenyl group has one or more of its hydrogen atoms replaced with a methyl group, ethyl group, propyl group, isopropyl group,
Linear or branched lower alkyl groups having 1 to 6 carbon atoms such as butyl group, isobutyl group, pentyl group, isopentyl group, neopentyl group, hexyl group, halogens such as fluorine, chlorine, bromine, nitro group, carboxyl group Examples include groups. Furthermore, examples of the cycloalkyl group include a cyclopentyl group and a cyclohexyl group. In addition, a cycloalkyl group has one of its hydrogen atoms.
or two or more of them are methyl group, ethyl group, propyl group,
It may be substituted with a linear or branched lower alkyl group having 1 to 6 carbon atoms, such as an isopropyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, a neopentyl group, a hexyl group, and the like. Furthermore, examples of the nitrogen-containing saturated heterocycle include pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl, and the like. Note that the heterocycle may be substituted with a carboxyl group. The compound of formula (1) above can be synthesized by reacting 5-halogeno-1-phenyl-1H-pyrazolo[3,4-b]pyrazine with the corresponding amine or nitrogen-containing heterocycle ( (See reaction formula a below). (However, X is a halogen atom, and R ₁ and R ₂ have the above meanings.) In addition, in formula (2), 5-
Chloro-1-phenyl-1H-pyrazolo[3,4
-b] Pyrazine (formula (2')) is produced by converting 5-amino-1-phenyl-pyrazole-4-carboxylic acid of formula (3), for example, as shown in reaction formula b below.
The 5-amino-1-phenyl-pyrazole of formula (4) was synthesized by heating to 180°C for decarboxylation, and this was reacted with isoamyl nitrite in ethanol in the presence of dry hydrochloric acid to obtain the formula (5). After obtaining 5-amino-4-nitroso-1-phenyl-pyrazole hydrochloride, it was catalytically reduced using palladium carbon to synthesize 4,5-diamino-1-phenyl-pyrazole of formula (6). Then, this was reacted with glyoxylic acid in water to obtain 4,5-dihydro-1 of formula (7).
-Phenyl-1H-pyrazolo[3,4-b]pyrazin-5-one can be synthesized and finally refluxed with phosphorus oxychloride. The compound of formula (1) has excellent antitumor or antiviral effects and suppresses the proliferation of cancerous cells or viruses, and is therefore effectively used as an antitumor or antiviral agent. Hereinafter, a production example of the compound (1) of the present invention will be specifically shown. Production Examples 1 to 27 23.1 g (0.1 mol) of 5-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyrazine and the first
After reacting with 4 moles of the amine or nitrogen-containing heterocycle shown in the table at 220°C in a sealed tube for 3 hours, it is dissolved in chloroform. This is washed with dilute hydrochloric acid and then with 10% sodium carbonate solution, dried over sodium sulfate and evaporated. The residue was recrystallized using the recrystallization solvent shown in Table 1 to obtain the target compounds shown in Table 1. The melting points and IRs of these compounds are shown in Table 2.

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Claims (1)

[Claims] 1. The following formula (However, R ₁ and R ₂ are each a hydrogen atom; an alkyl group; an alkyl group substituted with a hydroxy group, a carboxyl group, a halogen atom, an alkylamino group, a phenyl group, a nitrophenyl group, a halogenophenyl group, or an alkylphenyl group; Cycloalkyl group; cycloalkyl group substituted by an alkyl group; or amino group; or R ₁ and R ₂ together with the nitrogen atom to which they are bonded, with or without an oxygen atom, form a saturated heterocycle; 1-phenyl-1H-pyrazolo[3,
4-b] Pyrazine derivative.