JPS58180486A - 5-phenyloxy-1-phenyl-1h-pyrazolo(3,4-b)pyrazine derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula I (R is phenyl or phenyl whose one or more H are replaced with halogen, OH, lower alkyl, lower alkoxy, amino, or lower alkylamide) EXAMPLE:5-Phenyloxy-1-phenyl-1H-pyrazolo[3,4-b]pyrazine. USE:An antitumor agent. PROCESS:A 5-halogenophenyl-1-phenyl-1H-pyrazolo[3,4-b]pyrazine shown by the formula II[X is halogen, SO2-R group, NO2 group, CN group (R is alkyl, phenyl, or alkylphenyl)] is reacted with a phenol derivative shown by the formula III, to give a compound shown by the formula I .

Description

Detailed Description of the Invention (However, R is a phenyl group or a phenyl group substituted with one or more of its hydrogen atoms by a gold-halodane atom, a hydroxyl group, a lower alkyl group, a lower alkoxy group, an amine group, or a lower alkylamide group) ) Novel 5-phenyloxy-1-phenyl I represented by
The present invention relates to H-pyrazolo[3.4-b]bilanone derivatives.

Conventionally, various substances with antitumor effects have been developed.
Although there are many proposals, the present inventors have been conducting intensive research on compounds that have excellent antitumor effects and can be suitably used as antitumor agents. 3,4-b) The novel compound 5-phenyloquino 1 represented by the above formula (1) is produced by a method such as reacting with a hylanone total phenol derivative.
-Phenyl-]H-pyrazoloC3,4-1)]pyranone derivatives can be obtained, and we have discovered that these compounds have excellent antitumor effects and can be effectively used as antitumor agents, and we have developed this invention. V came up with an invention.

The present invention will be explained in more detail below.

The novel compound 5-phenyloxy-1-phenyl-I H-pyrazolo(3,4-b)bilinone derivative according to the present invention has the above-mentioned formula (1) (where R is a phenyl group or a hydrogen atom thereof). A phenyl group substituted with one or more halodane atoms such as fluorine, chlorine, bromine, or iodine, a hydroxyl group, a lower alkyl group, a lower alkoxy group, an amine group, or a lower alkylamide group. It is something.

Here, in formula (1), the lower alkyl group is:
Methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isopentyl group,
Examples include linear or branched chains having 1 to 6 carbon atoms, such as a neopentyl group.

In addition, examples of lower alkoxy groups include methoxy group, ethoxy group, noropoxy group, butoxy group, pentyloxy group,
Examples include straight or branched chains having 1 to 6 carbon atoms such as hexyloxy groups.

Furthermore, as a lower alkylamide group, an acetamide group,! Examples include linear or branched chains having 1 to 6 carbon atoms such as ropionamide group and n-butylamide group.

A specific example of the compound of the present invention having the chemical structural formula shown in formula (1) above is compound 9 shown in Table 1.

Table 1 The compound of formula (1) above is 5-...lognophenyl-1
It can be synthesized by reacting -phenyl-IH-pyrazolo(3,4-b) pyrazine or the like with a corresponding phenol derivative (see reaction formula a below).

(1) (However, X is a halogen atom, -SO2-R group, -NO2
group or -CN group. Note that R is an alkyl group,
# Also shown in group i, i alkylphenyl group. ) In addition, 5-chloro-1-phenyl-IH-pyrazolo(3,4-b]biraj/(formula (2')) in which X is a chloro atom in formula (2) is an example of the following reaction formula. As shown, 5-amino-1-phenyl-pyrazole-4-caranoic acid of formula (3) is heated to, for example, 180°C to decarburize [-, -2-enyl-virazole was synthesized and reacted with isoamyl nitrite in ethanol in the presence of dry hydrochloric acid to obtain 5-amino-4-nitrono-1-phenyl-virazole hydrochloride of formula (5). After that, 4,5-diamine-1-phenyl-pyrazole of formula (6) was synthesized by catalytic reduction using total mother carbon, and then this was catalytically reduced using Darioki/Pyrazole in water.
4,5-dihydro-1-phenyl-IH-pyrazolo(3,4-b)pyrazine-5 of formula (7)
-On? It can be obtained by synthesis and finally refluxing this with phosphorus oxychloride.

(6) (7) The compound of formula (1) has an excellent antitumor effect and suppresses the proliferation of cancerous cells, and is therefore effectively used as an antitumor agent.

(9) Hereinafter, a production example of the compound (1) of the present invention will be specifically shown.

[Production Example 1] 0.34 g (0,0085 mol) of sodium hydroxide was bathed in 5.09 (0,053 mol) of phenol, and 5-chloro-1-phenyl-I H-e' [
3,4-b) Pyranone too9 (0,o04
After reacting at 150° C. for 2 hours, the reaction mixture is dissolved in chloroform. This was washed with 10% sodium hydroxide, dried, and the solvent was distilled off. The residual gold was recrystallized from a benzene-hexane mixed solvent to give colorless needle-like crystals of 5-phenyloxy-1-phenyl-IH-pyrazolo[3,4-b]pyranone 1.20 g (yield: 92 cm).
[Production Example 2] 2.00 g (0,0115 mol) of p-promophenol and 0.5 g (0,009 mol) of potassium hydroxide
5-chloro-1-phenyl-1) 1-pyrano [3,4-b
] Pyrano 71.00ji (0,0043 mol) was added,
React at 100°C for 2 hours. The following procedure was repeated in the same manner as in Example 1, and the residue was recrystallized from hexane to obtain colorless scaly crystals of 5-(4-promophenylokino)-1-phenyl-I.
1.41 g (yield: 89%) of H-VirazoloC3,4-b) pyrazine was obtained.

[Production Examples 3 to 11] Using each phenol derivative shown in Table 2, the same operation as in Example 2 was performed, and the residue was recrystallized using the recrystallization solvent shown in Table 2. The target compound was obtained.

In addition, the shape, melting point, IR of the target compounds of Production Examples 1 to 11
All shown in Table 2.

Claims (1)

[Scope of Claims] The following formula (where R is a phenyl group, or phenyl substituted with one or more of its hydrogen atoms by a gold halide atom, a hydroxyl group, a lower alkyl group, a lower alkoxy group, an amine group, or a lower alkylamide group) 5-phenyloxy-1-phenyl-IH-
PyrazoloC3,4-b] Pyranone derivative.