Abstract:
Novel 1-phenyl-1H-pyrazolo[3,4-b]pyrazine derivatives are provided which are represented by the formula: ##STR1## wherein A is (i) ##STR2## in which R 1  and R 2  are hydrogen or an alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl or amino group, or a divalent radical forming a nitrogen-containing saturated heterocyclic ring together with the nitrogen atom, (ii) ##STR3## wherein R 3  is a phenyl group which is unsubstituted or substituted by halogen or a lower alkyl, lower alokoxy, carboxyl or nitro group, and R 4  is halogen or a methyl or ethyl group, (iii)--OR 5  in which R 5  is a phenyl group which is unsubstituted or substituted by halogen or a hydroxyl, lower alkyl, lower alkoxy, amino or lower alkylamide group, or (iv)--OR 6  is an alkyl group which is unsubstituted or substituted by halogen or a phenyl, furanyl, tetrahydrofuranyl or alkylamino group. These derivatives have antitumor or antiviral activity.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a 1-phenyl-1H-pyrazolo[3,4-b]pyrazine derivative having excellent antitumor or antiviral activity, which is represented by the following formula (1): ##STR4## 
     In the above formula (1), A stands for (i) a group ##STR5## in which R 1  and R 2  stand for a hydrogen atom, a univalent group selected from an alkyl group, a substituted alkyl group, a cycloalkyl group, a substituted cycloalkyl group and an amino group or a divalent group forming a substituted or unsubstituted, nitrogen-containing saturated heterocyclic ring together with the nitrogen atom: (ii) a group ##STR6## in which R 3  stands for a phenyl group or a substituted phenyl group in which at least one hydrogen atom is substituted by a halogen atom, a lower alkyl group, a lower alkoxy group, a carboxyl group or a nitro group, and R 4  stands for a hydrogen atom, or a methyl or ethyl group; (iii) a group --OR 5  in which R 5  stands for a phenyl group or a substituted phenyl group in which at least one hydrogen atom is substituted by a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkoxy group, an amino group or a lower alkylamide group; or (iv) a group --OR 6  in which R 6  stands for an alkyl group, a cycloalkyl group or a substituted alkyl group in which at least one hydrogen atom is substituted by a halogen atom, a substituted or unsubstituted phenyl group, a furanyl group, a tetrahydrofuranyl group or an alkylamino group. 
     2. Description of the Prior Art 
     Various substances having antitumor and antiviral activities have been developed and proposed. We made researches with a view to developing a compound having an antitumor or antiviral activity and capable of being used as an antitumor or antiviral agent, and as the result, we succeeded in synthesizing noval 1-phenyl-1H-pyrazolo[3,4-b]pyrazine derivatives represented by the above formula (1) and found that these compounds have excellent antitumor and antiviral activities and are useful as an antitumor or antiviral agent. 
     SUMMARY OF THE INVENTION 
     The novel compounds of the present invention, that is, 1-phenyl-1H-pyrazol[3,4-b]pyrazine derivatives have a chemical structure represented by the following formula (1): ##STR7## wherein A stands for a group ##STR8## --OR 5  or --OR 6  and R 1  through R 6  are as defined above. 
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     When A in the formula (1) stands for a group ##STR9## as the alkyl group constituting the groups R 1  and R 2 , there can be mentioned, for example, linear alkyl groups having 1 to 10 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl and decanyl groups, and branched alkyl groups having 1 to 10 carbon atoms, such as 1-methylethyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-methylbutyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,3-dimethylbutyl, 1,2-dimethylbutyl, 2,3-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1-methylhexyl and 1-methylheptyl groups. 
     As the substituted alkyl group, there can be mentioned, for example, alkyl groups as exemplified above, in which at least one hydrogen atom is substituted by a hydroxyl group, a carboxyl group, a halogen atom, a lower alkylamino group, a phenyl group or a substituted phenyl group. As the halogen atom, there can be mentioned fluorine, chlorine and bromine, and as the alkyl group of the lower alkylamino group, there can be mentioned, for example, linear and branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, neopentyl and hexyl groups. The substituted phenyl group is a phenyl group in which at least one hydrogen atom is substituted by an appropriate substituent. As the substituent, there can be mentioned, for example, linear and branched lower alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, neopentyl and hexyl groups, halogen atoms such as fluorine, chlorine and bromine, a nitro group and a carboxyl group. 
     As the cycloalkyl group, there can be mentioned cycloalkyl groups having 5 to 8 carbon atoms, for example, cyclopentyl and cyclohexyl groups. 
     As the nitrogen-containing sautrated heterocyclic ring, there can be mentioned, for example, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl and morpholinyl groups. 
     These cycloalkyl and nitrogen-containing saturated heterocyclic groups may have at least one hydrogen atom thereof substituted by an appropriate substituent. As the substituent, there can be mentioned, for example, a hydroxyl group, linear and branched lower alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, neopentyl and hexyl groups, halogen atoms such as fluorine, chlorine and bromine, and a nitro group and a carboxyl group. 
     The groups R 1  and R 2  in A are preferably a hydrogen atom or a linear or branched alkyl group having 3 to 7 carbon atoms. 
     When A in the formula (1) stands for a group ##STR10## as the lower alkyl group constituting a substituent of the substituted phenyl group in R 3 , there can be mentioned, for example, linear and branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl and neopentyl groups. As the lower alkoxy group constituting a substituent of the substituted phenyl group in R 3 , there can be mentioned, for example, linear and branched alkoxy groups having 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, pentyloxy and hexyloxy groups. 
     The group R 3  in A is preferably a phenyl group which is unsubstituted or substituted by a halogen atom or an alkyl group having 1 to 4 carbon atoms. 
     When A in the formula (1) stands for a group --OR 5 , as the lower alkyl and lower alkoxy groups constituting substituents of the substituted phenyl group, there can be mentioned, for example, lower alkyl and lower alkoxy groups exemplified above with respect to R 3 . As the lower alkylamide group, there can be mentioned, for example, linear and branched alkylamide groups having 1 to 6 carbon atoms, such as acetamide, propionamide and butylamide groups. The group R 5  is preferably a phenyl group which is unsubstituted or substituted by a halogen atom or an alkyl group having 1 to 4 carbon atoms. 
     When A in the formula (1) stands for a group --OR 6 , as the alkyl, cycloalkyl and substituted alkyl groups, there can be mentioned, for example, alkyl, cycloalkyl and substituted alkyl groups exemplified above with respect to R 1  and R 2 . The group R 6  is preferably an alkyl group having 1 to 7 carbon atoms. 
     The compound of the formula (1) in which A stands for a group ##STR11## can be prepared by reacting 5-substituted-1-phenyl-1H-pyrazolo[3,4-b]pyrazine of the formula (2) with the corresponding amine or nitrogen-containing heterocyclic ring compound as expressed by the following reaction formula (a): ##STR12## wherein X stands for a halogen atom, a group --SO 2  R (R is a lower slkyl group having 1 to 6 carbon atoms, a phenyl group, a methylphenyl group or an ethylphenyl group), a group --NO 2  or a group --CN, and R 1  and R 2  are as defined above. 
     The above-mentioned reaction (a) is carried out preferably at a temperature of 200° to 250° C. for 1 to 3 hours in a sealed tube which has been flushed with nitrogen, while an excessive amount of the amine or nitrogen-containing heterocyclic ring compound is used. 
     A compound of the formula (2) in which X is a chlorine atom, that is, 5-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyrazine represented by the formula (2&#39;) given below, may be obtained, for example, according to the following reaction formula (b) by decarboxylation of 5-amino-1-phenylpyrazole-4-carboxylic acid of the formula (3) by heating at, for example, 180° C. to prepare 5-amino-1-phenylpyrazole of the formula (4), reaction of this compound with isoamyl nitrite in ethanol in the presence of dry hydrochloric acid to form 5-amino-4-nitroso-1-phenylpyrazole hydrochloride of the formula (5), catalytic reduction of this hydrochloride with palladium-carbon to prepare 4,5-diamino-1-phenylpyrazole of the formula (6), reaction of this compound with glyoxylic acid in water to prepare 4,5-dihydro-1-phenyl-1H-pyrazole[3,4-b]pyrazin-5-one of the formula (7) and refluxing of this compound with phosphorus oxychloride: ##STR13## 
     A compound of the formula (1) in which A stands for a group ##STR14## may be prepared by reacting 5-substituted-1-phenyl-1H-pyrazolo[3,4-b]pyrazine with a substituted or unsubstituted phenylamine according to the following reaction formula (a&#39;): ##STR15## wherein X stands for a halogen atom, a group --SO 2  R (R stands for a lower alkyl group having 1 to 6 carbon atoms, a phenyl group, a methylphenyl group, or an ethylphenyl group), a group --NO 2  or a group --CN, and R 3  and R 4  are as defined above. 
     The above-mentioned reaction (a&#39;) is carried out preferably at a temperature of 200° to 250° C. for 1 to 3 hours in a sealed tube which has been flushed with nitrogen, while an excessive amount of the phenylamine is used. 
     A compound of the formula (1) in which A is a group --OR 5  may be prepared by reacting a 5-substituted-1-phenyl-1H-pyrozolo[3,4b]pyrazine of the formula (2) with the corresponding phenol derivative according to the following reaction formula (a&#34;): ##STR16## wherein X stands for a halogen atom, a group --SO 2  --R&#39; (R&#39; stands for an alkyl group having 1 to 6 carbon atoms, a phenyl group, a methylphenyl group or an ethylphenyl group), a group --NO 2  or a group --CN, M is an alkali metal such as Na or K, and R 5  is as defined above. 
     The above-mentioned reaction (a&#34;) is carried out preferably at a temperature of 100° to 150° C. for 1 to 3 hours in dimethylsulfoxide or an alcohol while an excessive amount of the alcoholate R 5  --OM is used. 
     A compound of the formula (1) in which A is a group --OR 6  may be prepared by reacting a 5-substituted-1-phenyl-1H-pyrazolo[3,4-b]pyrazine of the formula (2) with the corresponding alcoholate according to the following reaction formula (a&#34;&#34;): ##STR17## wherein X stands for a halogen atom, a group --SO 2  --R&#39;(R&#39; stands for an alkyl group having 1 to 6 carbon atoms, a phenyl group, a methylphenyl group or an ethylphenyl group), a group --NO 2  or a group --CN, M is an alkali metal such as Na or K and R 6  is the same as defined above. 
     The above-mentioned reaction (a&#34;&#39;) may preferably be carried out under conditions similar to those which are described hereinbefore with respect to the reaction (a&#34;). 
     Specific examples of the compound of the present invention represented by the above-mentioned formula (1) will now be described. 
     
         __________________________________________________________________________ ##STR18##Com-                                  Exam-pound                                 pleNo. R.sub.1      R.sub.2                 Name of Compound                                 No.__________________________________________________________________________1   C.sub.3 H.sub.7            H    5-propylamino-1-phenyl-1H                                 1                 pyrazolo[3,4-b]pyrazine2   C.sub.4 H.sub.9            H    5-butylamino-1-phenyl-1H                                 2                 pyrazolo[3,4-b]pyrazine3   C.sub.5 H.sub.11            H    5-pentylamino-1-phenyl-1H                                 3                 pyrazolo[3,4-b]pyrazine                                 34   C.sub.6 H.sub.13            H    5-hexylamino-1-phenyl-1H                                 4                 pyrazolo[3,4-b]pyrazine5   C.sub.10 H.sub.21            H    5-decanylamino-1-phenyl-1H                                 5                 pyrazolo[3,4-b]pyrazine6   HOC.sub.2 H.sub.4            H    5-(2-hydroxyethylamino)-1-                                 6                 phenyl-1Hpyrazolo[3,4-b]-                 pyrazine  7##STR19##   H    5-(2-hydroxypropylamino)-1- phenyl-1Hpyrazolo[3,4-b]                 - pyrazine      7  8##STR20##   H    5-(1-methylpropylamino)-1-  phenyl-1Hpyrazolo[3,4-b]                 - pyrazine      8  9##STR21##   H    5-(2-ethylhexylamino)-1- phenyl-1Hpyrazolo[3,4-b]-                 pyrazine        9  10    HOOC(CH.sub.2).sub.3            H    5-(3-carboxypropylamino)-1-                                 10                 phenyl-1Hpyrazolo[3,4-b]-                 pyrazine11  HOOC(CH.sub.2).sub.5            H    5-(5-carboxypentylamino)-1-                                 11                 phenyl-1Hpyrazolo[3,4-b]-                 pyrazine12  Cl(CH.sub.2).sub.2            H    5-(2-chloroethylamino)-1-                                 12                 phenyl-1Hpyrazolo[3,4-b]-                 pyrazine  13##STR22##   H    5-(2-N,Ndimethylamino- ethylamino)-1-phenyl-1H                 pyrazolo[3,4-b]pyrazine                                 13  14##STR23##   H    5-benzylamino-1-phenyl-1H pyrazolo[3,4-b]pyrazine                                 14  15##STR24##   H    5-(4-nitrobenzylamino)-1- phenyl-1Hpyrazolo[3,4-b]-                 yrazine         15  16##STR25##   H    5-(4-chlorobenzylamino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       16  17##STR26##   H    5-(3-methylbenzylamino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       17  18    C.sub.4 H.sub.9            C.sub.4 H.sub.9                 5-dibutylamino-1-phenyl-1H                                 18                 pyrazolo[3,4-b]pyrazine19  HO(CH.sub.2).sub.2            CH.sub.3                 5-(2-hydroxymethylamino)-1-                                 19                 phenyl-1Hpyrazolo[3,4-b]-                 pyrazine20##STR27##   CH.sub.3                 5-benzylmethylamino-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             20  21##STR28##   H    5-cyclopentylamino-1-phenyl- 1Hpyrazolo 8                 3,4-b]pyrazine  21  22##STR29##   H    5-cyclohexylamino-1-phenyl- 1Hpyrazolo[3,4-b]pyrazin                 e               22  23##STR30##   H    5-(4-methylcyclohexylamino)-1- phenyl-1Hpyrazolo[3,4                 -b]- pyrazine   23  24    NH.sub.2     H    5-hydrazino-1-phenyl-1H                                 24                 pyrazolo[3,4-b]pyrazine25##STR31##        5-piperidino-1-phenyl-1H pyrazolo[3,4-b]pyrazine                                 25  26##STR32##        5-(3-carboxypiperidion)-1-phenyl- 1Hpyrazolo[3,4-b]p                 yrazine         26  27##STR33##        5-morpholino-1-phenyl-1H pyrazolo[3,4-b]pyrazine                                 27__________________________________________________________________________ 
    
     
         __________________________________________________________________________ ##STR34##Compound                              ExampleNo.   R.sub.3     R.sub.4                 Name of Compound                                 No.__________________________________________________________________________28  ##STR35##  H   5-anilino-1-phenyl-1Hpyraz- olo[3,4-b]pyrazine                                 28  29  ##STR36##  CH.sub.3                 5-Nmethylanilino-1-phenyl- 1Hpyrazolo[3,4-b]pyrazine                                 29  30  ##STR37##  H   5-(2-toluidino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazine                                 30  31  ##STR38##  H   5-(3-toluidino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazine                                 31  32  ##STR39##  H   5-(4-toluidino)-1-phenyl-  1Hpyrazolo[3,4-b]pyrazine                                 --  33  ##STR40##  H   5-(2-anisidino)-1-phenyl-  1Hpyrazolo[3,4-b]pyrazine                                 34  34  ##STR41##  H   5-(3-anisidino)-1-phenyl  1Hpyrazolo[3,4-b]pyrazine                                 --  35  ##STR42##  H   5-(4-anisidino)-1-phenyl-  1Hpyrazolo[3,4-b]pyrazine                                 --  36  ##STR43##  H   5-(2-phenetidino)-1-phenyl- 1Hpyrazolo                 [3,4-b]pyrazine --  37  ##STR44##  H   5-(3-phenetidino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazin                 e               --  38  ##STR45##  H   5-(4-phenetidino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazin                 e               35  39  ##STR46##  H   5-(2-chloroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  40  ##STR47##  H   5-(3-chloroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  41  ##STR48##  H   5-(4-chloroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             36  42  ##STR49##  H   5-(2-fluoroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  43  ##STR50##  H   5-(3-fluoroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  44  ##STR51##  H   5-(4-fluoroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             37  45  ##STR52##  H   5-(2-bromoanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  46  ##STR53##  H   5-(3-bromoanilino)-1-phenyl- 1Hpyrazolo[                 3,4-b]pyrazine  --  47  ##STR54##  H   5-(4-bromoanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  48  ##STR55##  H   5-(2-nitroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  49  ##STR56##  H   5-(3-nitroanilino)-1-phenyl- 1Hpyrazolo[                 3,4-b]pyrazine  38  50  ##STR57##  H   5-(4-nitroanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  51  ##STR58##  H   5-(2-ethylanilino)-1-phenyl- 1Hpytrazolo[3,4-b]pyraz                 ine             --  52  ##STR59##  H   5-(3-ethylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  53  ##STR60##  H   5-(4-ethylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  54  ##STR61##  H   5-(2-propylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  55  ##STR62##  H   5-(3-propylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  56  ##STR63##  H   5-(4-propylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                 ine             --  57  ##STR64##  H   5-(2-butylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              &#39;58  ##STR65##  H   5-(3-butylanilino)-1-phenyl- 1Hpyrazolo[                 3,4-b]pyrazine  33  59  ##STR66##  H   5-(4-butylanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                 ne              --  60  ##STR67##  H   5-(2-carboxyanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyra                 zine            --  61  ##STR68##  H   5-(3-carboxyanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyra                 zine            --  62  ##STR69##  H   5-(4-carboxyanilino)-1-phenyl- 1Hpyrazolo[3,4-b]pyra                 zine            --  63  ##STR70##  H   5-(2,3-dimethylanilino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       33  64  ##STR71##  H   5-(2,4-dimethylanilino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       --  65  ##STR72##  H   5-(2,5-dimethylanilino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       --  66  ##STR73##  H   5-(2,6-dimethylanilino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       --  67  ##STR74##  H   5-(3,4-dimethylanilino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       --  68  ##STR75##  H   5-(3,5-dimethylanilino)-1- phenyl-1Hpyrazolo[3,4-b]-                  pyrazine       --__________________________________________________________________________ 
    
     
         __________________________________________________________________________(3) A = OR.sub.5Compound                                 ExampleNo.   R.sub.5        Name of Compound    No.__________________________________________________________________________69  ##STR76##     5-phenoxy-1-phenyl-1Hpyrazolo- [3,4-b]pyrazine                                   39  70  ##STR77##     5-(4-methylphenoxy)-1-phenyl-  1Hpyrazolo[3,4-b]pyraz                ine                40  71  ##STR78##     5-(4-isopropylphenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyr                azine              41  72  ##STR79##     5-(3-aminophenoxy)-1-phenyl-  1Hpyrazolo[3,4-b]pyrazi                ne                 42  73  ##STR80##     5-(4-acetoamidophenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]py                razine             43  74  ##STR81##     5-(2-methoxyphenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                ine                44  75  ##STR82##     5-(4-methoxyphenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                ine                45  76  ##STR83##     5-(4-ethoxyphenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                ne                 46  77  ##STR84##     5-(4-hydroxyphenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyraz                ine                47  78  ##STR85##     5-(4-chlorophenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazi                ne                 48  79  ##STR86##     5-(4-bromophenoxy)-1-phenyl- 1Hpyrazolo[3,4-b]pyrazin                e                  49__________________________________________________________________________ 
    
     
         ______________________________________(4) A = OR.sub.6Com-                                 Exam-pound                                pleNo.   R.sub.6          Name of Compound                                No.______________________________________80    CH.sub.3         5-methoxy-1-phenyl-                                50                  1Hpyrazolo-                  [3,4-b]pyrazine81    C.sub.2 H.sub.5  5-ethoxy-1-phenyl-                                51                  1Hpyrazolo-                  [3,4-b]pyrazine82    C.sub.3 H.sub.7  5-propoxy-1-phenyl-                                52                  1Hpyrazolo-                  [3,4-b]pyrazine83    isoC.sub.3 H.sub.7                  5-isopropoxy-1-                                53                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine84    C.sub.4 H.sub.9  5-butoxy-1-phenyl-                                54                  1Hpyrazolo-                  [3,4-b]pyrazine85    isoC.sub.4 H.sub.9                  5-isobutoxy-1-                                55                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine86    secC.sub.4 H.sub.9                  5-sec-butoxy-1-                                56                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine87    C.sub.5 H.sub.11 5-pentyloxy-1-                                57                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine88    isoC.sub.5 H.sub.11                  5-isopentyloxy-1-                                58                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine89    C.sub.6 H.sub.13 5-hexyloxy-1- 59                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine90    2-C.sub.6 H.sub.13                  5-(2-hexyloxy)-1-                                60 [(C.sub.4 H.sub.9)(CH.sub.3)CH]                  phenyl-1Hpyraz-                  olo[3,4-b]pyrazine91    C.sub.8 H.sub.17 5-octyloxy-1-phenyl-                                61                  1Hpyrazolo[3,4-                  b]pyrazine92    C.sub.6 H.sub.5CH.sub.2                  5-benzyloxy-1-                                62                  phenyl-1Hpyraz-                  olo[3,4-b] pyrazine  93  ##STR87##       5-cyclohexyloxy-1- phenyl-1Hpyraz- olo[3,4-b]                  pyrazine      63  94  C.sub.3 H.sub.7CHCHCH.sub.2                  5-(trans-2-hexenyl-                                64 (trans)          oxy)-1-phenyl-                  1Hpyrazolo[3,4-                  b]pyrazine95    (CH.sub.3).sub.2 NCH.sub.2CH.sub.2                  5-(2-dimethylamino-                                65                  ethoxy)-1-phenyl-                  1Hpyrazolo[3,4-                  b]pyrazine  96  ##STR88##       5-(2-tetrahydro- furfuryloxy)-1- phenyl-1Hpyraz-                  olo[3,4-b] pyrazine                                66  97  ##STR89##       5-(2-furfuryloxy)-1- phenyl-1Hpyraz- olo[3,4-b]                  pyrazine      67______________________________________ 
    
     The compounds represented by the above formula (1) have excellent antitumor and/or antiviral activities and inhibit propagation of cancerous cells and virus. Accordingly, the compounds are useful as an antitumor or antiviral agent. 
    
    
     The preparation of the compounds of the present invention represented by the above formula (1) will now be described in detail with reference to the following Examples. 
     EXAMPLES 2 THROUGH 27 
     These Examples illustrate the preparation of compounds of the formula (1) in which A stands for a group ##STR90## 
     In a sealed tube, 23.1 g (0.1 mole) of 5-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyrazine was reacted with 4 moles of an amine or nitrogen-containing heterocyclic compound shown in Table 1 at 220° C. for 3 hours, and the reaction product was dissolved in chloroform. The solution was washed with dilute hydrochloric acid and then with an aqueous 10% solution of sodium carbonate and dried with sodium sulfate. The solvent was removed by distillation and the residue was recrystallized from a recrystallization solvent shown in Table 1 to obtain a compound shown in Table 1. The melting points and IR analysis values of the so-obtained compounds are shown in Table 1. 
     
                                           TABLE 1__________________________________________________________________________Ex-am-                                                 Meltingple                                Crystal Form Yield                                               PointNo.   Intended Compound    Starting Amine                              (Recrystallization Solvent)                                           (%) (°C.)                                                    IR                                                    ν .sub.max.sup                                                    .KBr__________________________________________________________________________1  5-propylamino-1-phenyl-1H--pyrazolo                   propylamine                              yellow powder                                           78  94-95                                                    3340   [3,4-b]pyrazine                 (hexane)2  5-butylamino-1-phenyl-1H--pyrazolo                   butylamine yellow needle                                           75  90-92                                                    3410   [3,4-b]pyrazine                 (methanol)3  5-pentylamino-1-phenyl-1H--pyrazolo                   pentylamine                              light yellow needle                                           63  92-93                                                    3330   [3,4-b]pyrazine                 (hexane)4  5-hexylamino-1-phenyl-1H--pyrazolo                   hexylamine yellow column                                           59  88-89                                                    3350, 2860,   [3,4-b]pyrazine                 hexane                29305  5-decanylamino-1-phenyl-1H--pyrazolo                   decanylamine                              yellow needle                                           57       3350, 1590,   [3,4-b]pyrazine                 (methanol)            1500, 1416  5-(2-hydroxyethylamino)-1-phenyl-1H--                   2-hydroxyethylamine                              yellow powder                                           62  148-150                                                    3300, 3350   pyrazolo[3,4-b]pyrazine         (hexane)7  5-(2-hydroxypropylamino)-1-phenyl-1H-13                   2-hydroxypropylamine                              orange powder                                           65  131-132                                                    3340, 3470   pyrazolo[3,4-b]pyrazine         (methanol)8  5-(1-methylpropylamino)-1-phenyl-1H--                   1-methylpropylamine                              yellow prism 59       3310, 1590,   pryazolo[3,4-b]pyrazine         (methanol)            1510, 1419  5-(2-ethylhexylamino)-1-phenyl-1H--                   2-ethylhexylamine                              yellow needle                                           67       3340, 1590,   pyrazolo[3,4-b]pyrazine         (methanol)            1510, 14110 5-(3-carboxypropylamino)-1-phenyl-1H--                   3-carboxypropylamine                              light yellow powder                                           76  151-153                                                    1700   pyrazolo[3,4-b]pyrazine         (methanol)11 5-(5-carboxypentylamino)-1-phenyl-1H--                   5-carboxypentylamine                              light yellow needle                                           69  151-153                                                    1690   pyrazolo[3,4-b]pyrazine         (methanol)12 5-(2-chloroethylamino)-1-phenyl-1H--                   2-chloroethylamine                              yellow needle                                           54       3360, 1590,   pyrazolo[3,4-b]pyrazine         (methanol)            1480, 14113 5-(2-N,N--dimethylaminoethylamino)-1-                   2-N,N--dimethyl-                              yellow needle                                           63  121-122                                                    3250   phenyl-1H--pyrazolo[3,4-b]pyrazine                   aminoethylamine                              (hexane)14 5-bezylamino-1-phenyl-1H--pyrazolo                   benzylamine                              orange needle                                           74  130-131                                                    3340, 3050   [3,4-b]pyrazine                 (hexane)15 5-(4-nitrobenzylamine)-1-phenyl-1H--                   4-nitrobenzylamine                              yellow powder (methanol)                                           68       3300, 1520,   pyrazolo[3,4-b]pyrazine                               141016 5-(4-chlorobenzylamine)-1-phenyl-1H--                   4-chlorobenzylamine                              yellow needle (methanol)                                           63       3310, 1600,   pyrazolo[3,4-b]pyrazine                               141017 5-(3-methylbenzylamine)-1-phenyl-1H--                   3-methylbenzylamine                              yellow powder (methanol)                                           71       3330, 1600,   pyrazolo[3,4-b]pyrazine                               141018 5-dibutylamino-1-phenyl-1H-13 pyrazolo-                   dibutylamine                              yellow needle (hexane)                                           54  38-39                                                    3010, 2990,   [3,4-b]pyrazine                                       292019 5-(2-hydroxyethylamino)-1-phenyl-                   2-hydroxyethyl-                              yellow plate (hexane)                                           65  166-167                                                    3400   1H-13 pyrazolo[3,4-b]pyrazine                   methylamine20 5-benzylmethylamino-1phenyl-1H--                   benzylmethylamine                              yellow plate (hexane)                                           59  131-132                                                    3100   pyrazolo[3,4-b]pyrazine21 5-cyclopentylamino-1-phenyl-1H--                   cyclopentylamine                              yellow needle (methanol)                                           78  3350, 1600,   pyrazolo[3,4-b]pyrazine                               1490, 141022 5-cyclohexylamino-1-phenyl-1H--                   cyclohexylamine                              yellow powder (methanol)                                           69       3380, 1610,   pyrazolo[3,4-b]pyrazine                               1480, 141023 5-(4-methylcyclohexylamino)-1-phenyl-1H--                   4-methylcyclohexyl-                              yellow scale (methanol)                                           71       3400, 1590,   pyrazolo[3,4-b]pyrazine                   amine                            1500, 141024 5-hydrazine-1-phenyl-1H--pyrazolo[3,4-b]-                   hydrazine  yellow needle (methanol)                                           80  193--195                                                    3290   pyrazine25 5-piperidino-1-phenyl-1H--pyrazolo-                   piperidine yellow scale (methanol)                                           82  132-134                                                    2930, 2850   [3,4-b]pyrazine26 5-(3-carboxypiperidino)-1-phenyl-1H--                   nipecotic acid                              yellow needle (methanol)                                           68  192-194                                                    1700   pyrazolo[3,4-b]pyrazine27 5-morpholino-1-phenyl-1H--pyrazolo-                   morpholine yellow scale (methanol)                                           93  163-164                                                    2950, 2850   [3,4-b]pyrazine__________________________________________________________________________ 
    
     EXAMPLES 28 THROUGH 38 
     In a sealed tube, 1.36 g (6 millimoles) of 5-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyrazine was reacted with 25 millimoles of a phenylamine shown in Table 2 at 220° C. for 3 hours, and the reaction product was dissolved in chloroform. The solution was washed with 20 ml of 2N hydrochloric acid, then with 10 ml of an aqueous 2N solution of sodium carbonate and finally with 10 ml of water two times, and the washed solution was dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was recrystallized from a recrystallization solvent shown in Table 2 to obtain a compound shown in Table 2. The forms, yields, melting points and IR analysis values of the so-obtained compounds are shown in Table 2. 
     
         TABLE 2  Exam-     Crystal Form    ple     (Recrystallization Yield Melting No. R.sub.3 R.sub.4 Intended Compound Phenylamine Solvent) (%) Point (°C.) IRν.sub.max.sup.KBr  cm.sup.-1 (NH)                                  28  ##STR91##  H 5-anilino-1-phenyl- 1Hpyrazolo[3,4-b]pyrazine  ##STR92##  yellow needle(benzene) 94 188-189 3300  29 ##STR93##  CH.sub.3 5-NMethylanilino-1-phenyl-1Hpyrazolo.sup.∥,4-b]pyrazin e  ##STR94##  yellow needle(n-hexane) 75 97-98  30 ##STR95##  H 5-(2-toluidino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR96##  yellow needle(methanol) 70 174-175 3280  31 ##STR97##  H 5-(3-toluidino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR98##  yellow needle(benzene) 80 195-196 3300  32 ##STR99##  H 5-(2,3-dimethylanilino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR100##  yellow needle(methanol) 69 163-164 3270  33 ##STR101##  H 5-(4-butylanilino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR102##  yellow scale(benzene-n-hexane) 74 150-151 3290  34 ##STR103##  H 5-(2-anisidino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR104##  yellow needle (methanol) 68 181-182 3320  35 ##STR105##  H 5-(4-phenetidino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR106##  yellow scale(methanol) 70 206-207 3340  36 ##STR107##  H 5-(4-chloroanilino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR108##  yellow powder(methanol) 72 226-227 3300  37 ##STR109##  H 5-(4-floroanilino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR110##  yellow needle(benzene) 74 201-203 3300  38 ##STR111##  H 5-(3-nitroanilino)-1-phenyl-1Hpyrazolo[3,4-b]pyrazine  ##STR112##  yellow powder(methanol) 60 261-263 3400 
    
     EXAMPLE 39 
     In 5.0 (0.053 mole) of phenol was dissolved 0.34 g (0.0085 mole) of sodium hydroxide, and 1.00 g (0.0043 mole) of 5-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyrazine was added to the solution. The mixture was maintained at 150° C. for 2 hours. The reaction mixture was dissolved in chloroform, and the resulting solution was washed with an aqueous 10% solution of sodium hydroxide and then dried. The solvent was removed by distillation, and the residue was recrystallized from a benzene-hexane mixed solvent to obtain 1.20 g (the yield was 92%) of 5-phenoxy-1-phenyl-1H-pyrazolo[3,4-b]pyrazine in the form of a colorless needle crystal. 
     EXAMPLE 40 
     In 3 ml of dimethyl sulfoxide were dissolved 2.00 g (0.0115 mole) of p-bromophenol and 0.5 g (0.009 mole) of potassium hydroxide, and 1.00 g (0.0043 mole) of 5-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyrazine was added to the solution. The mixture was maintained at 100° C. for 2 hours. The post treatments were conducted in the same manner as described in Example 39, and the resulting residue was recrystallized from hexane to obtain 1.41 g (the yield was 89%) of 5-(4-bromophenoxy)-1-phenyl-1H-pyrazolo[3,4-b]pyrazine in the form of a colorless scaly crystal. 
     EXAMPLES 41 THROUGH 49 
     The procedures of Example 40 were repeated by using phenol derivatives shown in Table 3, and the residues were recrystallized from recrystallization solvents shown in Table 3 to obtain intended compounds shown in Table 3. 
     The forms, melting points and IR analysis values of the intended compounds obtained in Examples 39 through 49 are shown in Table 3. 
     
                                           TABLE 3__________________________________________________________________________                                    FormExam-                                    (Recrystal-                                          Meltingple            Phenol                    lization                                          Point                                               IRν .sub.max.sup.KB                                               rcm.sup.-1No. R.sub.5    Derivative   Intented Compound                                    Solvent)                                          (°C.)                                               CO    Others__________________________________________________________________________39##STR113##           ##STR114##  5-phenoxy-1-phenyl-1Hpyrazolo[3,4-b]pyrazine                                    c.n.(B + H)                                          116˜167                                               13351225  40##STR115##           ##STR116##  5-(4-buromo-phenoxy-1-phenyl-1Hpyrazolo[3,4-b]                       pyrazine     c.s.(H)                                          171˜172                                               13351250  41##STR117##           ##STR118##  5-(4-methylphenoxy-1-phenyl-1Hpyrazolo[3,4-b]p                       yrazine       c.s.(B + H)                                          144˜145                                               13351255  42##STR119##           ##STR120##  5-(4-isopropylphenoxy-1-phenyl-1Hpyrazolo[3,4-                       b]pyrazine   c.n.(H)                                          114˜115                                               13301250  43##STR121##           ##STR122##  5-(3-aminophenoxy-1-phenyl-1Hpyrazolo[3,4-b]py                       razine       c.po.(M)                                          173˜174                                               13251245  44##STR123##           ##STR124##  5-(4-acetamidophenoxy-1-phenyl-1Hpyrazolo[3,4-                       b]pyrazine   l.n.(C)                                          253˜254                                               13351250                                                     1670(CONH)  45##STR125##           ##STR126##  5-(2-methylphenoxy-1-phenyl-1Hpyrazolo[3,4-b]p                       yrazine      c.n.(M)                                          145˜146                                               13351250  46##STR127##           ##STR128##  5-(4-methylphenoxy-1-phenyl-1Hpyrazolo[3,4-b]p                       yrazine      c.s.(B)                                          163˜164                                               13351245  47##STR129##           ##STR130##  5-(4-ethoxyphenoxy-1-phenyl-1Hpyrazolo[3,4-b]p                       yrazine      c.n.(B + H)                                          160˜161                                               13351245  48##STR131##           ##STR132##  5-(4-hydroxyphenoxy-1-phenyl-1Hpyrazolo[3,4-b]                       pyrazine     c.pr.(B)                                          206˜207                                               13351245                                                     3400(OH)  49##STR133##           ##STR134##  5-(4-chlorophenoxy-1-phenyl-1Hpyrazolo[3,4-b]p                       yrazine      c.s.(H)                                          160˜161                                               13351250__________________________________________________________________________ Note c . . . colorless l . . . light yellow n . . . needle s . . . scale pr . . . prism po . . . powder B . . . benzene H . . . hexane M . . . methanol C . . . chloroform 
    
     EXAMPLES 50 THROUGH 55 
     In 50 ml of methanol was dissolved 2.1 g (0.091 mole) of metallic sodium, and then, 9.5 g (0.043 mole) of 1-phenyl-1H-phrazolo[3,4-b]pyrazine-5-carbonitrile was added to the solution. The mixture was heated under reflux for 3 hours. After completion of the reaction, the excessive amount of methanol was removed by distillation under a reduced pressure. The residue was washed with water, dried and then recrystallized from methanol to obtain 8.2 g (the yield was 84%) of 5-methoxy-1-phenyl-1H-pyrazolo[3,4-b]pyrazine in the form of a colorless needle crystal. 
     The above-mentioned procedures were repeated by using various alcohols shown in Table 4 (Examples No. 51 through 55) to obtain 1-phenyl-1H-pyrazolo[3,4-b]pyrazine derivatives having in the 5-positions --OR 6  substituents shown in Table 4. 
     The crystal forms, yields, melting points and IR analysis values of the resultant compounds are shown in Table 4. 
     EXAMPLES 56, 57 AND 58 
     In 50 ml of sec.-butanol was dissolved 2.1 g (0.091 mole) of metallic sodium, and then, 10.0 g (0.043 mole) of 5-chloro-phenyl-1H-pyrazolo[3,4-b]pyrazine was added to the solution. The mixture was heated under reflux for 2 hours. After completion of the reaction, the excessive amount of sec.-butanol was removed by distillation under a reduced pressure. The residue was washed with water, dried and then recrystallized from hexane to obtain 6.2 g (the yield was 53%) of 5-sec.-butoxy-1-phenyl-1H-pyrazolo[3,4-b]pyrazine in the form of a colorless needle crystal. 
     The above-mentioned procedures were repeated by using pentyl and iso-pentyl alcohols instead of sec.-butanol to obtain 1-phenyl-1H-pyrazolo[3,4-b]pyrazine derivatives having 5-pentyloxy and 5-iso-pentyloxy groups. 
     The crystal forms, yields, melting points and IR analysis values of the resultant compounds are shown in Table 4. 
     EXAMPLES 59 THROUGH 68 
     In 50 ml of hexanol was dissolved 2.1 g (0.091 mole) of metallic sodium, and then, 14.6 g (0.043 mole) of 5-(4-tolylsulfonyl)-1-phenyl-1H-pyrazolo[3,4-b]pyrazine was added to the solution. The mixture was heated under reflux for 2 hours. After completion of the reaction, the exessive amount of hexanol was removed by distillation under a reduced pressure. The residue was washed with water, dried and then recrystallized from a benzene/methanol (1:2) mixed solvent to obtain 11.5 g (the yield was 90%) of 5-hexyloxy-1-phenyl-1H-pyrazolo[3,4-b]pyrazine in the form of a colorless needle crystal. 
     The above-mentioned procedures were repeated by using various alcohols shown in Table 4 (Examples 60 through 68) to obtain 1-phenyl-1H-pyrazolo[3,4-b]pyrazine derivatives having in the 5-positions --OR 6  substituents shown in Table 4. 
     The crystal forms, yields, melting points and IR analysis values of the resultant compounds are shown in Table 4. 
     
                                           TABLE 4__________________________________________________________________________                                     Crystal                                     formExam-                                     (Recrystal-    IRνKBrple                                       lization  Melting                                                    max (cm.sup.-1)No. R.sub.6      Alcohol       OR.sub.6   Solvent)                                           Yield                                               point                                                    =c-o-__________________________________________________________________________50  CH.sub.3     CH.sub.3 OH   5-methyl-  c.n.  84  105-107                                                    1255                                     (MeOH)51  C.sub.2 H.sub.5            C.sub.2 H.sub.5 OH                          5-ethoxy-  y.n.  82  139-140                                                    1255                                     (MeOH)52  C.sub.3 H.sub.7            C.sub.3 H.sub.7 OH                          5-propoxy- c.n.  89  98-99                                                    1250                                     (MeOH)53  iso C.sub.3 H.sub.7            iso C.sub.3 H.sub.7 OH                          5-isoproxy-                                     ly.cu.                                           86  86-87                                                    1255                                     (Hexane)54  C.sub.4 H.sub.9            C.sub.4 H.sub.9 OH                          5-butoxy-  c.sc. 90  96-98                                                    1243                                     (MeOH)55  iso C.sub.4 H.sub.9            iso C.sub.4 H.sub.9 OH                          5-isobutoxy-                                     c.p.  88  110-111                                                    1252                                     (MeOH)56  sec C.sub.4 H.sub.9            sec C.sub.4 H.sub.9 OH                          5-sec-butoxy-                                     c.n.  53  61-62                                                    1255                                     (Hexane)57  C.sub.5 H.sub.11            C.sub.5 H.sub.11 OH                          5-pentyloxy-                                     c.sc. 85  98-99                                                    1250                                     (MeOH)58  iso C.sub.5 H.sub.11            iso C.sub.5 H.sub.11 OH                          5-isopentyloxy-                                     ly.n. 83  84-85                                                    1250                                     (MeOH)59  C.sub.6 H.sub.13            C.sub.6 H.sub.13 OH                          5-hexyloxy-                                     c.sc. 90  107-108                                                    1250                                     (MeOH +                                     Benzene)                                     (1:2)60  2-C.sub.6 H.sub.13            2-C.sub.6 H.sub.13 OH                          5-(2-hexyloxy)-                                     c.liquid                                           60       124961  C.sub.8 H.sub.17            C.sub.8 H.sub.17 OH                          5-octyloxy-                                     c.sc. 81  110-111                                                    1249                                     (MeOH)  62##STR135##             ##STR136##   5-benzyloxy-                                     c.sc.(MeOH)                                           90  92-93                                                    1252  63##STR137##             ##STR138##   5-cyclohexyloxy-                                     c.sc.(MeOH)                                           71  96-97                                                    1249  64    C.sub.3 H.sub.7CHCHCH.sub.2            C.sub.3 H.sub.7CHCHCH.sub.2 OH                          5-(trans-2-                                     c.n.  93  55-56                                                    1250                          hexenyloxy)-                                     (Hexane)65  (CH.sub.3).sub.2 NCH.sub.2CH.sub.2            (CH.sub.3).sub.2 NCH.sub.2CH.sub.2 OH                          5-(2-dimethyl-                                     c.n.  94  86-87                                                    1255                          aminoethyloxy)-                                     (Hexane)  67##STR139##             ##STR140##   5-(2-tetrahydro-furfuryloxy)                                     c.leaflet(Hexane)                                           79  88-89                                                    1243  68##STR141##             ##STR142##   5-(2-furfuryloxy)-                                     c.n(MeOH)                                           91  125-126                                                    1251__________________________________________________________________________ Note c . . . Colorless n . . . needle ly . . . light yellow y . . . yellow sc . . . scale cu . . . cubic p . . . plate