JP2000309578A - Quinoxaline derivatives - Google Patents

Abstract

(57) Abstract: Formula (I) wherein A and B together form -C (O
When H) = C (X ¹ ) -C (Y ¹ ) = C (OH)-(X ¹ and Y ¹ represent a hydrogen atom, a lower alkylthio group, a lower alkenylthio group, etc.), R ¹ and R ² represents an alkyl group, an aryl group, a heterocyclic group or the like, and A and B together form —C (R ³ ) (R ⁴ )
-C (X ² ) = C (Y ² ) -C (R ⁵ ) (R ⁶ )-(X ² and Y ² represent a hydrogen atom, an amino group, a lower alkylamino group, a lower alkenylamino group, etc .; ³ and R ⁴ represent a lower alkoxy group or together represent an oxygen atom; R ⁵ and R ⁶ represent a lower alkoxy group or together represent an oxygen atom) When represented, R ¹ and R ² represent a hydrogen atom, an alkyl group, a heterocyclic group, an aryl group, etc.]
A quinoxaline derivative represented by or a salt thereof. Embedded image [Effect] It has a growth inhibitory activity on tumor cells, and is useful as an active ingredient of pharmaceuticals such as antitumor agents.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a quinoxaline derivative which exhibits a growth inhibitory activity on tumor cells and is useful as an active ingredient of a drug such as an antitumor agent.

[0002]

BACKGROUND OF THE INVENTION As quinoxaline derivatives related to the present invention, 6-bromo-7-methoxy-5,8-quinoxalinedione,
2,3-bis (acetoxymethyl) -6-methoxy-5,8-quinoxalinedione and the like are known, but these compounds are L1
210 It has been reported that it has no antitumor effect on leukemia cells [Eur. J. Med. Chem., 16 , 545 (1981)]. Also, 2,3-dimethyl-5,8-quinoxalinedione is known, but its antitumor activity has not been reported [J. Org. Chem., 32 , 54 (1967)].

[0003]

An object of the present invention is to provide a novel compound useful as an active ingredient of a drug such as an antitumor agent. The present inventors have made intensive efforts to solve the above problems, and as a result, a novel quinoxaline derivative represented by the following formula or a salt thereof has a tumor cell growth inhibitory activity, They have found that they are useful as active ingredients, and have completed the present invention.

That is, the present invention provides the following formula (I):

Embedded image [Where A and B together

Embedded image (Wherein X ¹ and Y ¹ each independently represent a hydrogen atom, a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group; Group,
R ¹ and R ² each independently represent an alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, or a substituted or unsubstituted heterocyclic thio group. Represents an unsubstituted aryloxyalkyl group (provided that when R ¹ and R ² represent an alkyl group, a substituted or unsubstituted aryl group, or an unsubstituted heterocyclic group, X ¹ and Y ¹ simultaneously represent a hydrogen atom Never); A and B together

Embedded image (Wherein X ² and Y ² are each independently a hydrogen atom, an amino group, a substituted or unsubstituted mono-lower alkylamino group,
Substituted or unsubstituted di-lower alkylamino group, substituted or unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted or unsubstituted heterocyclic amino group, substituted Or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkenylthio group, substituted or unsubstituted arylthio group, substituted or unsubstituted aralkylthio group, substituted or unsubstituted R ³ and R ⁴ each independently represent a lower alkoxy group or together represent an oxygen atom; ⁵ and either R ⁶ represents a lower alkoxy group each independently or both together an oxygen atom) Sutoki each R ¹ and R ² are independently a hydrogen atom, an alkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, halogenated alkyl group, or a substituted or unsubstituted aryloxyalkyl R ¹ and R ² together represent — (CH ₂ ) _n — (wherein _n represents an integer from 2 to 6), provided that R ¹ and R ² are simultaneously Does not indicate a hydrogen atom). Provided that when R ¹ and R ² are each independently an alkyl group, R ³ and R ⁴ together represent an oxygen atom, and R ⁵ and R ⁶ together represent an oxygen atom, One of X ² and Y ² is a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group, or a substituted or unsubstituted aralkylthio group. Represents an unsubstituted heterocyclic thio group, wherein R ¹ and R ² are each independently a phenyl group, a tolyl group, or a pyridyl group, or are both taken together as — (CH ₂ ) ₄ —
And R ³ and R ⁴ together represent an oxygen atom, and R ⁵ and R ⁶ together represent an oxygen atom;
One of X ² and Y ² is a substituted mono-lower alkylamino group, a substituted di-lower alkylamino group, a substituted or unsubstituted lower alkenylamino group, a substituted or unsubstituted aralkylamino group, a substituted or unsubstituted aryl Amino group, substituted or unsubstituted heterocyclic amino group, substituted or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkenylthio group, substituted or unsubstituted arylthio group , A substituted or unsubstituted heterocyclic thio group, or a substituted or unsubstituted alicyclic heterocyclic group] or a salt thereof.

Further, according to the present invention, the following formula (Ia) included in the above formula (I):

Embedded image (Wherein X ¹ and Y ¹ each independently represent a hydrogen atom, a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group; Group,
Or a substituted or unsubstituted heterocyclic thio group; R ¹ - ¹
And R ¹ - ² are each independently an alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group,
Or a substituted or unsubstituted aryloxyalkyl group. However, R ¹ - ¹ and R ¹ - ² alkyl group, a substituted or unsubstituted aryl group, or unsubstituted X ¹ and Y ¹ when referring to the heterocyclic group does not represent hydrogen atoms at the same time) A quinoxaline derivative or a salt thereof represented;

The following formula (Ib) included in the above formula (I):

Embedded image [Wherein X ² and Y ² are each independently a hydrogen atom, an amino group, a substituted or unsubstituted mono-lower alkylamino group,
Substituted or unsubstituted di-lower alkylamino group, substituted or unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted or unsubstituted heterocyclic amino group, substituted Or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkenylthio group, substituted or unsubstituted arylthio group, substituted or unsubstituted aralkylthio group, substituted or unsubstituted shows a heterocyclic thio group, or a substituted or unsubstituted alicyclic heterocyclic group; R ² - ¹ and R ² - ²
Are each independently a hydrogen atom, an alkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group,
Halogenated alkyl group, or a substituted or unsubstituted aryloxyalkyl groups, or R ² - ¹ and R
² - ² together - (CH _{2) n} - (wherein, n represents an integer from 2 to 6) indicates (where, R ² - ¹ and R ²
- ² never represents a hydrogen atom simultaneously); R ² - ³ and R ² - ⁴ or each independently represent a lower alkoxy group, or an oxygen atom both together; R ² - ⁵ and R ²
- ⁶ or each independently represent a lower alkoxy group, or an oxygen atom both together. However, R ² - ¹ and R ² - ² are each independently an alkyl group, R ² - ³ and R ² - ⁴ represents an oxygen atom together, and R ² - ⁵ and R ² - ⁶ is When taken together represent an oxygen atom, X ²
And Y ² is a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group, or a substituted or unsubstituted shows a heterocyclic thio group, R ² - ¹ and R ² - ² are either each independently a phenyl group, a tolyl group, or a pyridyl group, or both together - (CH _{2) 4} - are shown , R ² - ³ and R ² - ⁴ together an oxygen atom,
And R ² - ⁵ and R ² - to indicate ⁶ oxygen atoms taken together, one of X ² and Y ² is a substituted mono-lower alkylamino group, a substituted di-lower alkylamino group, a substituted or Unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted or unsubstituted heterocyclic amino group, substituted or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted A substituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted heterocyclic thio group,
Or a substituted or unsubstituted alicyclic heterocyclic group]] or a salt thereof.

According to a preferred embodiment of the present invention, (A) in the above formula (Ib), X ² is a substituted or unsubstituted mono-lower alkylamino group or a substituted or unsubstituted di-lower alkylamino group; Y ² is a hydrogen atom,
R ² - ¹ and R ² - ² are each independently a substituted or unsubstituted aryl group, or a substituted or unsubstituted aryloxy group, R ² - ³ and R ² - ⁴ together oxygen atom are shown, R ² - ⁵ and R ² - ⁶ quinoxaline derivatives or salts thereof represents an oxygen atom together;

(B) In the above formula (Ib), X ² is a mono-lower alkylamino group substituted with a di-lower alkylamino group or a morpholino group, or a di-lower alkyl group substituted with a di-lower alkylamino group or a morpholino group. an amino group, Y ² is a hydrogen atom, R ² - ¹ and R ² - ² are both a substituted aryl group, or a substituted phenoxyalkyl group, R ² - ³ and R ² - ⁴ together Indicates an oxygen atom,
R ² - ⁵ and R ² - ⁶ quinoxaline derivatives or salts thereof represents an oxygen atom together; and

(C) In the above formula (Ib), X ^{2 is} an ethylamino group substituted with a di-lower alkylamino group or a morpholino group, or an ethylmethylamino group substituted with a di-lower alkylamino group or a morpholino group. Yes, Y ²
Together ⁴ - but a hydrogen atom, R ² - ¹ and R ² - ² are both halogenated aryl group, or a benzyl group or phenoxyalkyl group substituted by a benzyloxy group, R ² - ³ and R ² It turned to represent an oxygen atom, R ² - ⁵ and R ²
A quinoxaline derivative or a salt thereof, wherein ⁶ together represent an oxygen atom;

Further, from another viewpoint, the quinoxaline derivative represented by the above formula (I), a pharmacologically acceptable salt thereof, and a hydrate and a solvate thereof are selected from the group consisting of: Provided as an active ingredient. This medicament can be used as a medicament for mammals including humans, and is useful for treating malignant tumors such as non-solid cancers or solid cancers as antitumor agents.
The medicament is preferably provided in the form of a pharmaceutical composition comprising one or more pharmaceutical additives together with the active ingredients described above.

In addition to these, the quinoxaline derivative represented by the formula (I) for producing the above-mentioned medicament, a pharmacologically acceptable salt thereof, a hydrate thereof and a solvate thereof. Use of a substance selected from the group; and a method for treating a tumor, comprising the quinoxaline derivative represented by the formula (I) and a pharmacologically acceptable salt thereof, and a hydrate and a solvate thereof. The invention provides a method comprising administering to a patient a therapeutically effective amount of a substance selected from the group consisting of:

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The meanings of the terms used in the present specification are as follows. An alkyl group or a substituent containing an alkyl moiety (eg, an aryloxyalkyl group,
Heterocyclic alkylamino group, halogenated alkyl group, etc.)
May be a straight-chain or branched chain, for example, an alkyl group or alkyl group having 1 to 20, preferably 1 to 12, more preferably 1 to 8 carbon atoms. Parts can be used. As the alkyl group, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, hexyl group, heptyl group, octyl group, nonyl Group,
Examples thereof include a decyl group, an undecyl group, a dodecyl group, and a pentadecyl group. In the case of a substituent containing an alkyl moiety, it is desirable that these alkyl groups are included as the alkyl moiety.

The lower alkyl group or the lower alkyl moiety of a substituent containing a lower alkyl moiety (eg, a lower alkoxy group, a lower alkoxycarbonyl group, a mono- or di-lower alkylamino group, a lower alkylthio group, etc.) includes, for example, Among the alkyl groups specifically exemplified above, those having about 1 to about 8 carbon atoms are preferred. In a substituent containing a plurality of lower alkyl moieties, such as a di-lower alkylamino group, the plurality of alkyl groups may be the same or different. As the lower alkenyl moiety in the substituent containing a lower alkenyl moiety (for example, a lower alkenylthio group, a lower alkenylamino group, etc.), for example, a linear or branched alkenyl group having about 2 to 6 carbon atoms is used. be able to. The number of double bonds contained in the alkenyl group is not particularly limited, but is preferably one.
As the lower alkenyl group constituting the lower alkenyl moiety, for example, vinyl group, allyl group, crotyl group, prenyl group, 3-butenyl group, 2-pentenyl group, 4-pentenyl group, 2-hexenyl group, 5-hexenyl group and the like Can be mentioned.

The aryl moiety of the aryl group or a substituent containing an aryl moiety (eg, an aryloxyalkyl group, an arylamino group, an arylthio group, etc.)
For example, a 5- to 14-membered monocyclic, bicyclic, or 3 ring
A cyclic aryl group or the like can be used. More specifically, examples of the aryl group include a phenyl group, a naphthyl group, an indenyl group, a biphenyl group, an anthryl group, and the like. Is preferred. As the aralkyl moiety in the aralkyl group, aralkyloxy group, aralkylthio group, and aralkylamino group, for example, it is preferable to use an aralkyl group having about 7 to 15 carbon atoms, and more specifically, a benzyl group as the aralkyl moiety. Phenethyl group, benzhydryl group, naphthylmethyl group and the like are preferable.

A halogen atom or a halogen atom portion of an alkyl halide may be any of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom unless otherwise specified, and when a plurality of halogen atoms are contained. They may be the same or different. Examples of the alicyclic heterocyclic group include monocyclic, bicyclic, or tricyclic containing one or more hetero atoms (such as a nitrogen atom, an oxygen atom, and a sulfur atom) as ring constituent atoms; Preferably, a monocyclic alicyclic heterocyclic group can be used. If they contain two or more heteroatoms, they may be the same or different. More specifically, as the alicyclic heterocyclic group, for example, a pyrrolidinyl group, a piperidinyl group, a piperidino group,
A piperazinyl group, a morpholino group, a thiomorpholino group, a homopiperidinyl group, a homopiperazinyl group, a tetrahydropyranyl group, or the like can be used.

The heterocyclic group in the heterocyclic group or a substituent containing a heterocyclic group (eg, a heterocyclic thio group, a heterocyclic amino group, a heterocyclic alkylamino group, etc.) includes, for example, 1
Monocyclic or bicyclic containing one or more heteroatoms (nitrogen, oxygen, sulfur, etc.) as ring constituent atoms,
Alternatively, a tricyclic heterocyclic group can be used. The heterocyclic group may be an aromatic group, but one or more rings contained in the heterocyclic group may be partially or completely saturated. As the heterocyclic group, in addition to the alicyclic heterocyclic groups specifically exemplified above, for example, a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a triazolyl group, a tetrazolyl group, a thiadiazolyl group, a pyridyl group, an indolyl group ,
Examples include a quinolyl group, an isoquinolyl group, a quinoxalinyl group, a quinazolinyl group, a thiazolyl group, a benzothiazolyl group, a benzimidazolyl group, and a benzodioxolyl group.

The substituents in the above definition will be described more specifically. As the "lower alkoxy group", for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group Group, or tert
-Butoxy group and the like. As the "mono-lower alkylamino group", for example, a methylamino group,
Ethylamino group, n-propylamino group, or n-butylamino group, and the like.Examples of the `` di-lower alkylamino group '' include, for example, dimethylamino group, diethylamino group, n-propylethylamino group, or Examples include an ethylmethylamino group. Examples of the "aralkylamino group" include, for example, a benzylamino group or a phenethylamino group.Examples of the "lower alkenylamino group" include, for example, a vinylamino group, an allylamino group, a crotylamino group, a prenylamino group,
Examples thereof include a 3-butenylamino group, a 2-pentenylamino group, a 4-pentenylamino group, a 2-hexenylamino group, and a 5-hexenylamino group. Examples of the “arylamino group” include a phenylamino group, a naphthylamino group and the like.

As the "heterocyclic amino group", for example, an amino group in which one or two, preferably one heterocyclic group specifically exemplified above is bonded can be used. As the “heterocyclic alkylamino group”, those in which one or two, preferably one heterocyclic group specifically exemplified above is bonded to the alkyl portion of the alkylamino group can be used. Specific examples include-(1-imidazolyl) -1-propylamino group, furfurylamino group, 2- (2-pyridyl) ethylamino group and the like. Examples of the "alkylthio group" include, for example, a methylthio group, an ethylthio group, and an n-propylthio group.
As the "alkenylthio group", for example, vinylthio group, allylthio group, crotylthio group, prenylthio group,
Examples thereof include a 3-butenylthio group, a 2-pentenylthio group, a 4-pentenylthio group, a 2-hexenylthio group, and a 5-hexenylthio group.

The "arylthio group" includes, for example, a phenylthio group, a naphthylthio group and a biphenylthio group. The "aralkylthio group" includes
Examples include a benzylthio group and a phenethylthio group. As the "heterocyclic thio group", for example,
A thiol group to which a heterocyclic group specifically exemplified above is bonded can be used. Ilthio groups and the like can be used. Examples of the “aryloxyalkyl group” include a phenoxymethyl group, a phenoxyethyl group, a naphthoxymethyl group, and the like.

In the definitions of the above formulas (I), (Ia) and (Ib), a substituent is "substituted or unsubstituted"
Means that the substituent may be further substituted with one to two or more, preferably one to four, functional groups. When the substituent has two or more functional groups, those functional groups may be the same or different. Examples of such a functional group include a lower alkyl group, a halogenated alkyl group (eg, chloromethyl group, trifluoromethyl group, etc.), a hydroxyalkyl group (eg, hydroxymethyl group, etc.), a lower alkoxy group (eg, n-hexyl) Oxy group), lower alkenyl group (eg, vinyl group, allyl group, etc.), lower alkynyl group (eg, ethynyl group, propynyl group, etc.), hydroxyl group, halogen atom (eg, chlorine atom, etc.), carboxyl group, lower alkoxycarbonyl group (E.g., a methoxycarbonyl group), a lower alkanoyl group (e.g., an acetyl group), a haloalkanoyl group (e.g., a trifluoroacetyl group), an aryl group,
Aralkyl groups, aryloxy groups (such as phenoxy groups), aralkyloxy groups (such as benzyloxy groups), arylthio groups, arylalkynyl groups (such as phenylethynyl groups), lower alkanoyloxy groups (such as acetyloxy groups), Lower alkanoylamino group (eg, acetylamino group), lower alkanoyloxyalkyl group (eg, acetyloxymethyl group), aroyl group (eg, benzoyl group), heterocyclic group (eg, those exemplified above) An amino group, a mono- or di-lower alkylamino group, a carbamoyl group, a nitro group, a cyano group, a lower alkylsulfinyl group (eg, a methylsulfinyl group), a lower alkylsulfonyl group (eg, a methanesulfonyl group), a thiol group, a lower alcohol Kiruchio group, or a heterocyclic lower alkyl group (such as e.g. pyridylmethyl) and the like can be mentioned, but not limited thereto. Further, these functional groups may further have one or more other functional groups. Specific examples of such an example include a chlorophenyl group, a methylcarbamoyl group, a chlorobenzyl group, and an alkoxybenzyl group.

Examples of the functional group substituted by the substituted mono- or di-lower alkylamino group, substituted lower alkylthio group, substituted lower alkenylthio group, and substituted lower alkenylamino group include, for example, halogen atom, amino group, cyano group, aryl group, Aralkyl groups, hydroxyl groups, aralkyloxy groups, carboxyl groups, lower alkoxycarbonyl groups, lower alkanoyl groups, arylthio groups, aryloxy groups, aroyl groups, heterocyclic lower alkyl groups, mono- or di-lower alkylamino groups, and heterocyclic groups And 1 to 4 groups selected from the group consisting of 2
When it has two or more functional groups, they may be the same or different. Specific examples of the above functional groups are the same as those described above.

More specifically, "substituted alkylthio group"
As for example, a hydroxyalkylthio group such as a 2-hydroxyethylthio group, a lower alkoxycarbonylalkylthio group such as an ethoxycarbonylmethylthio group or a 2-ethoxycarbonylethylthio group, a 2-chloroethylthio group or a 3-chloro-1- Halogenated alkylthio groups such as propylthio group, 2- (N, N-dimethylamino)
Mono- or di-lower alkylaminoalkylthio groups such as an ethylthio group can be exemplified. As the "substituted mono-lower alkylamino group", for example, 2- (N, N-dimethylamino) ethylamino group, 3- (N, N-dimethylamino) -1-propylamino group, 2- (N, N Substituted with a mono- or di-lower alkylamino-substituted mono-lower alkylamino group such as -diethylamino) ethylamino group, an alicyclic heterocyclic group such as 2-morpholinoethylamino group or 2- (1-pyrrolidinyl) ethylamino group Mono-lower alkylamino group, p-
Examples thereof include a bromophenylmethylamino group, a 2- (p-hydroxyphenyl) ethylamino group, and a 3,4-methylenedioxyphenylmethylamino group. Examples of the `` substituted di-lower alkylamino group '' include, for example, 3- (N, N-dimethylamino) propyl-2-ylamino group, 4- (N, N-dimethylamino) butyl-2-ylamino group, 4- ( N, N-diethylamino) butyl-3-ylamino group, N- [2- (2-pyridyl) ethyl] -N-methylamino group and the like can be mentioned.

Further, a substituted aryl group, a substituted arylamino group, a substituted aralkylamino group, a substituted aryloxyalkyl group, a substituted arylthio group, a substituted aralkylthio group, a substituted heterocyclic thio group, a substituted heterocyclic group, a substituted heterocyclic amino group , A substituted heterocyclic alkylamino group, or a substituted alicyclic heterocyclic group as a substituent, a hydroxyl group, a halogen atom, a nitro group, an amino group, a cyano group, a mono- or di-lower alkylamino group, a carboxyl group, a lower alkyl group; Group, lower alkenyl group, lower alkynyl group, arylalkynyl group, lower alkoxy group, lower alkoxycarbonyl group, lower alkanoyl group, lower alkanoyloxy group, lower alkanoylamino group, lower alkanoyloxyalkyl group, aryl group, aryloxy group, Aralkyloxy groups, arals Group, aroyl group, a heterocyclic lower alkyl group, methylenedioxy group, and the like ethylenedioxy group.

More specifically, the “substituted aryl group” includes, for example, m-bromophenyl group, p-bromophenyl group, p-phenethylphenyl group, p-benzyloxyphenyl group, p-ethoxycarbonylphenyl group , P-acetoxyphenyl group, m-phenethylphenyl group, p-phenethylphenyl group and the like. As the “substituted arylamino group”, for example, an aralkyloxy-substituted arylamino group such as a p-benzyloxyphenylamino group, and as the “substituted arylthio group”, for example, a p-aminophenylthio group, an m-aminophenylthio group And a hydroxy-substituted arylthio group such as a p-hydroxyphenylthio group, and a lower alkoxy-substituted arylthio group such as a p-methoxyphenylthio group. Examples of the “substituted alicyclic heterocyclic group” include lower alkyl-substituted alicyclic heterocyclic groups such as a 4-methylpiperazinyl group.

The "substituted aryloxyalkyl group" includes, for example, lower alkyl-substituted aryloxyalkyl groups such as pn-propylphenoxymethyl group, lower alkoxy-substituted groups such as p-methoxyphenoxymethyl group and pn-hexyloxyphenoxymethyl group. Aryloxyalkyl group, lower alkoxycarbonyl-substituted aryloxyalkyl group such as p-methoxycarbonylphenoxymethyl group, p-benzylphenoxymethyl group, p-[(1-methyl-1-
Phenyl) ethyl-1-yl] phenoxymethyl group, p-phenethylphenoxymethyl group, aralkyl-substituted aryloxyalkyl groups such as o-benzylphenoxymethyl group,
aroyl-substituted aryloxyalkyl groups such as p-benzoylphenoxymethyl group, aralkyloxy-substituted aryloxyalkyl groups such as p-benzyloxyphenoxymethyl group, aryl-substituted aryloxyalkyl groups such as p-phenylphenoxymethyl group, p-phenoxy Other than an aryloxy-substituted aryloxyalkyl group such as a phenoxymethyl group, a p-cyanophenoxymethyl group,
and p- [2- (2-pyridyl) ethyl] phenoxymethyl group.

Preferred examples of the compound of the present invention represented by the formula (I) are shown below, but the compound of the present invention is not limited thereto. Of these, compound 22, compound 46, compound 47, compound 51, and compound 70 are particularly preferred. The compound numbers in the following table correspond to the compound numbers in the examples.

[0027]

[Table 1]

[0028]

[Table 2]

[0029]

[Table 3]

[0030]

[Table 4]

[0031]

[Table 5]

[0032]

[Table 6]

The compound represented by the formula (I) may be, for example, a base addition salt such as an acid addition salt of an organic or inorganic acid, a metal salt, an ammonium salt, an organic amine addition salt, or the like, depending on the type of the substituent. It may exist as a salt in a form such as an amino acid addition salt. Examples of the acid addition salt include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, and phosphate; or formate, acetate, benzoate, maleate, fumarate,
Organic acid salts such as succinate, tartrate, citrate, oxalate, methanesulfonate, p-toluenesulfonate, aspartate, and glutamate can be mentioned. Examples of the metal salt include lithium salts, sodium salts, alkali metal salts such as potassium salts, magnesium salts, alkaline earth metal salts such as calcium salts, aluminum salts, zinc salts, and the like. For example, ammonium, tetramethylammonium and the like can be mentioned, and as the organic amine addition salt, for example, addition salts such as morpholine and piperidine can be mentioned. Examples of the amino acid addition salt include addition salts such as glycine, phenylalanine, and lysine.

The compound represented by the above formula (I), formula (Ia) or formula (Ib) may have one or more asymmetric carbons depending on the type of the substituent, Stereoisomers such as isomers or diastereoisomers may exist. When the compound represented by the formula (I), the formula (Ia), or the formula (Ib) has a substituent containing one or more double bonds, a compound based on the double bond may be used. There are geometric isomers of Any of the above isomers or any mixture of the above isomers in pure form, racemates, etc. are included in the scope of the present invention. Further, the above formula (I), formula (Ia), or formula (Ib)
The compound represented by may exist as a tautomer, but the existence of the tautomer is obvious to those skilled in the art, and it goes without saying that any tautomer is included in the scope of the present invention. No. The compound in the free form represented by the above formula (I), formula (Ia), or formula (Ib) or a salt thereof may be present as a hydrate or a solvate, but these adducts may also be present. Included within the scope of the invention. The type of the solvent that forms the solvate is not particularly limited, and examples thereof include ethanol, acetone, and tetrahydrofuran.

The compound represented by the above formula (I), (Ia) or (Ib) can be produced, for example, by the following reaction steps. In the following production methods, if the defined groups change under the conditions of the method or are inappropriate for carrying out the method, the introduction and removal of protecting groups commonly used in organic synthetic chemistry. Release methods [for example, Protective Groups in Organic Synthesis (Protecti
ve Groups in Organic Synthesis), Green (TW
Greene), John Wiley & Sons, Inc. (1981)
Year)) can be used to obtain the desired compound. In addition, the order of the reaction steps such as introduction of a substituent can be appropriately changed as necessary. Hereinafter, formula (I), formula
(Ia) and a compound represented by the formula (Ib)
(I), compound (Ia) and compound (Ib). The same applies to compounds of other formula numbers.

<Production method 1> Compound (Ia) and compound (Ib)
Can be produced from compound (IIIa) which can be produced by a method described below or the like according to the following steps.

[0037]

Embedded image ^{(Wherein, R 1, R 2, R} 2 - 1 and R ² - ² are as defined above, R ³ represents a lower alkyl group, X ^a is a group obtained by removing a hydrogen atom from the definition of the X ² are shown, Y ^a represents a group obtained by removing a hydrogen atom from the definition of the Y ^2, the X ^1a represents a group obtained by removing a hydrogen atom from the definition of the X ^1, Y ^1a is hydrogen atom from the definition of the Y ¹ Shows the group excluding)

Step 1 In the compound (Ib), for example, X ² and Y ² represent a hydrogen atom,
R ² - ³ and R ² - ⁴ represents an oxygen atom together, and R ² - ⁵ and R ² - ⁶ compounds an oxygen atom together
(Ib-3) is a compound (IIIa) dissolved in a water-containing solvent such as water-containing acetonitrile, 1 to 20 equivalents of iodobenzene diacetate,
It can be obtained by treating with an oxidizing agent such as bis (trifluoroacetoxy) iodobenzene or cerium ammonium nitrate. The reaction temperature is preferably from -30 to 100 ° C, and the reaction time is usually from 5 minutes to 5 hours.

The compounds of at least one of X ¹ and Y ¹ is other than hydrogen atom in the Step 2 compound (Ia) (Ia-1) or compound (Ia-2) and compound (VII) (X ^a is an amino group, a substituted Or unsubstituted mono-lower alkylamino group, substituted or unsubstituted di-lower alkylamino group, substituted or unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted Or a compound having an unsubstituted heterocyclic amino group or a substituted or unsubstituted heterocyclic alkylamino group, and a compound wherein R ¹ and R ² are a hydrogen atom or a halogenated alkyl group) or a compound (VIII) (Y ^a Is an amino group, a substituted or unsubstituted mono-lower alkylamino group, a substituted or unsubstituted di-lower alkylamino group, a substituted or unsubstituted lower alkenyl group A compound that is a mino group, a substituted or unsubstituted aralkylamino group, a substituted or unsubstituted arylamino group, a substituted or unsubstituted heterocyclic amino group, or a substituted or unsubstituted heterocyclic alkylamino group, and R ¹ and Compound (Ib-3) wherein R ² is a hydrogen atom or a halogenated alkyl group) alone or in a mixed solvent of acetonitrile, tetrahydrofuran, ether, dioxane, dimethylformamide, chloroform, dichloromethane, methanol, ethanol, water and the like. 1) to 10)
It can be produced by adding an equivalent amount of ^a thiol compound represented by Xa-H or Ya-H or ^a primary or secondary amine compound. The reaction temperature is preferably −30 to 100 ° C., and the reaction is usually completed in 5 minutes to 5 hours.

In this step, the resulting compound (Ia-1)
Or compound (Ia-2) or compound (VII) or compound (VII
Compound (Ib) or compound (Ib-2) in which I) was oxidized in the reaction system, or compound (Ib-1) or compound (Ib-2) further reacted with X ^a -H ( Ia-4) may be generated. Compound (Ia-1), Compound (Ia-2), Compound (Ib-1),
Compound (Ib-2) or the formation ratio of compound (Ia-4), compound (Ib
It varies depending on the type of the substituents R ¹ and R ² of b-3), the type and amount of the amine compound or the thiol compound, and the conditions such as the reaction temperature and the reaction time. It is possible to produce the desired product at a production ratio. Further, in the compound (Ib-1) or the compound (Ib-2), X ^a and X ^b are substituted or unsubstituted lower alkylthio groups, substituted or unsubstituted lower alkenylthio groups, substituted or unsubstituted arylthio groups, 1 mol of Y ^1a -H or X is 1 mol of the compound which is a substituted or unsubstituted aralkylthio group or a substituted or unsubstituted heterocyclic thio group.
By reacting ^1a- H, X in compound (Ia)
Compounds wherein ¹ and Y ¹ are groups other than hydrogen atoms in the definitions of X ¹ and Y ² respectively can be prepared.

<Production Method 2>

Embedded image (Where X ² , Y ² , R ^2-1 , R ^2-2 , R ^2-3 , R ^2-4 , R
^2-5 , R ^2-6 and R ³ are as defined above.

The compound (Ib) can be prepared by a known method or a known method [eg, J. Med. Chem., 18 , 746 (1975)]. It can be obtained by treating with an oxidizing agent such as bis (trifluoroacetoxy) iodobenzene or cerium ammonium nitrate (Step 3). At this time, when a water-containing solvent such as water-containing acetonitrile is used, R ^2-3 and R ^2-4 , R ^2-5 and R ^2-6 are each integrated to obtain a compound (Ib) representing an oxygen atom, When an alcohol or a mixed solvent of a lower alcohol and acetonitrile or the like is used, a compound in which R ^2-3 and R ^2-4 are lower alkoxy groups, or R ^2-5 and R ^2-6 are lower alkoxy groups (I
b) is obtained. The reaction temperature is preferably from -30 to 100 ° C, and the reaction time is usually from 5 minutes to 5 hours.

<Production Method 3> Compound (IIIa) used as a starting material in the above production method can be produced, for example, by the following method.

[0044]

Embedded image ^{(Wherein, R 2 - 1, R 2} - 2 , and R ³ each have the same meanings as defined above)

Step 4 Compound (V) can be synthesized by reducing compound (IV), which can be easily synthesized by a known or known method, by an appropriate reduction method. The reduction method may be any method as long as it is a method usually used for reduction of a nitro group, for example, a method of hydrogenation or hydrazine treatment in the presence of a catalyst such as palladium or platinum, and a simple metal such as zinc or tin under acidic conditions. (Reducing agent) is used. In the hydrogenation reaction, the reaction temperature is 0 to 0 in the presence of 0.1 to 1 equivalent of the catalyst.
150 ° C. is preferable, and the reaction time is usually 10 minutes to 5 hours. Further, in the reduction reaction with a single metal, 1 to
In the presence of 50 equivalents of a reducing agent, the reaction temperature is preferably from 0 to 100 ° C, and the reaction time is usually from 10 minutes to 10 hours.

Step 5 Compound (IIIa) is obtained by converting compound (V) to methanol, ethanol,
Acetonitrile, tetrahydrofuran, ether, dioxane, dimethylformamide, chloroform, in a solvent such as ^{dichloromethane, R 2 - 1 COCOR 2 -} 2 ( wherein, R
² - ¹ and R ² - ² can be obtained by treatment with dicarbonyl compounds 1-5 equivalents represented by the same meanings as defined above, respectively). The reaction temperature is preferably from 0 to 100 ° C, and the reaction is usually completed in 5 minutes to 5 hours.

[0047] <Production Method 4> Among the compounds (IIIa) R ² - ¹ and R ² - ² is a substituted or unsubstituted aryloxy methyl compound (IIIb) is produced by the following steps from the compound (VI) You can also.

[0048]

Embedded image (Wherein, R ³ has the same meaning as described above, and Q represents a substituted or unsubstituted aryl group.)

[0049] Among R ² steps 6 Compound (III) - ¹ and R ² -. ² is a substituted or unsubstituted aryloxyalkyl group compound (IIIb) is a known compound (VI) [for example, J Chem. Soc., Perkin Tr
ans., 1 , 2443 (1996)] in an inert solvent such as acetonitrile, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, and the like, and in the presence of a base such as potassium carbonate or sodium hydride, 2 to 50 equivalents of Q-OH (formula Wherein Q has the same meaning as defined above). The amount of the base used is 1 to 5
The reaction temperature is preferably 0 to 100 ° C., and the reaction is usually performed for 5 minutes to 10 hours.

[0050] In the preparation of the compounds (Ia) or compound ^{(Ib), X 1, Y} 1, R 1, R 1 - 1, R 1 - 2, X 2, Y 2, R 2,
^{R 2 - 1, R 2 -} 2, R 2 - 3, R 2 - 4, R 2 - 5 and R ² - Conversion of functional groups ⁶ or the like, a known method other than the above process [for example, Konpurihen Comprehensive Organic Transformation
s), by RC Larock (1989)]. The isolation and purification of the product in the above production method can be carried out by appropriately combining methods used in ordinary organic synthesis, for example, filtration, extraction, washing, drying, concentration, crystallization, various types of chromatography and the like.
In addition, the intermediate produced in the above step can be subjected to the next reaction without purification. In the case of producing a salt of the compound (Ia) or the compound (Ib), if the salt of each compound is obtained in the above production method, the compound may be purified as it is, but if a compound in a free form is obtained, After dissolving or suspending the compound in free form in an appropriate solvent, the compound may be formed by adding an appropriate acid or base, and purification may be performed if necessary.

The compound represented by the above formula (I) is useful as an active ingredient of a medicine, preferably as an active ingredient of an antitumor agent. One of the preferred embodiments of the medicament of the present invention is a compound
(Ia) and a pharmacologically acceptable salt thereof, and a substance selected from the group consisting of hydrates and solvates thereof as an active ingredient. Further, another preferred embodiment of the medicament of the present invention comprises as an active ingredient a compound (Ib) and a pharmacologically acceptable salt thereof, and a substance selected from the group consisting of hydrates and solvates thereof. It is characterized by: The medicament of the present invention, as an antitumor agent,
For example, leukemia, malignant lymphoma, non-solid cancers such as myeloma, or gastric cancer, esophageal cancer, colon cancer, rectal cancer, pancreatic cancer,
It can be used for the treatment of solid cancers such as liver cancer, kidney cancer, bladder cancer, lung cancer, uterine cancer, ovarian cancer, breast cancer, prostate cancer, skin cancer, brain tumor and the like.

As the medicament of the present invention, the above-mentioned substance which is an active ingredient may be administered as it is, but generally contains the above-mentioned substance which is an active ingredient and one or more additives for pharmaceutical preparations. It is desirable to administer it in the form of a pharmaceutical composition. Such a pharmaceutical composition can be manufactured according to a method which is well known or commonly used in the field of pharmaceuticals. The medicament of the present invention in the form of a pharmaceutical composition may contain one or more active ingredients of another medicament. The medicament of the present invention is applicable to mammals including humans.

The administration route of the medicament of the present invention is not particularly limited, and the most effective administration route for treatment and / or prevention can be appropriately selected from either oral or parenteral administration. Parenteral administration can include routes of administration such as intratracheal, rectal, subcutaneous, intramuscular, and intravenous. Examples of formulations suitable for oral administration include, for example,
Tablets, granules, fine granules, powders, syrups, solutions, capsules, suspensions and the like, and examples of formulations suitable for parenteral administration include, for example, injections, drops, Examples include inhalants, sprays, suppositories, transdermal absorbents, transmucosal absorbents, and the like.

For the preparation of a liquid preparation suitable for oral administration, for example, water, saccharides such as sucrose, sorbitol, and fructose; glycols such as polyethylene glycol and propylene glycol; oils such as sesame oil, olive oil and soybean oil;
Pharmaceutical additives such as preservatives such as hydroxybenzoates can be used. For the production of solid preparations such as capsules, tablets, or granules, for example, excipients such as lactose, glucose, sucrose, mannitol; starch,
Disintegrating agents such as sodium alginate; lubricating agents such as magnesium stearate and talc; binders such as polyvinyl alcohol, hydroxypropyl cellulose and gelatin;
Surfactants such as fatty acid esters; and plasticizers such as glycerin can be used.

Among preparations suitable for parenteral administration, preparations for intravascular administration such as injections and drops can be prepared preferably using an aqueous medium isotonic with human blood. For example, an injection can be prepared as a solution, suspension, or dispersion using an aqueous solvent selected from a salt solution, a glucose solution, or a mixture of salt water and a glucose solution together with a suitable auxiliary according to a conventional method. . Suppositories for enteral administration can be prepared using carriers such as cocoa butter, hydrogenated fats or hydrogenated carboxylic acids. Sprays can be prepared using a carrier which does not irritate the oral and respiratory tract mucosa of humans and which can promote absorption by dispersing the above-mentioned substance as an active ingredient as fine particles so that absorption can be promoted. As such a carrier, for example, lactose or glycerin can be used. Depending on the properties of the substance as the active ingredient and the carrier used, the composition can be prepared as a preparation in the form of an aerosol or dry powder. For the preparation of parenteral preparations, for example, diluents, flavors, preservatives, excipients,
One or more pharmaceutical additives selected from disintegrants, lubricants, binders, surfactants, plasticizers and the like can be used. The form of the medicament of the present invention and the method for producing the medicament are not limited to those specifically described above.

The dose and frequency of administration of the medicament of the present invention are not particularly limited.
It can be appropriately selected according to various conditions such as the severity of the disease. For example, 0.01-20 per adult per day
About 0 mg / kg can be administered once a day or once every few days to once every several weeks, but the dosage and frequency of administration are not limited to this particular example. In addition, the medicament of the present invention can be used in combination with other antitumor agents, and generally, it is preferably used in combination with several kinds of antitumor agents having different mechanisms of action.

[0057]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to Examples, but the scope of the present invention is not limited to these Examples. The compound numbers in the examples correspond to the compound numbers in the above table. The physicochemical data of each compound was measured by the following instruments. ¹ H NMR: JEOL A
lpha 400 (400 MHz), JEOL Lambda 300 (300 MHz); FAB
MS: JEOL JMS-HX110. In the following examples, ordinary post-treatment means the following post-reaction treatment. After completion of the reaction in each step, if necessary, water, an acid, a buffer and the like are added to the reaction solution, and the mixture is extracted with a non-aqueous solvent such as ethyl acetate, chloroform and ether. The extract is washed with water, saline and the like, dried over anhydrous sodium sulfate and the like, and the solvent is distilled off.

Example 1 Compound 1 Compound 68 obtained in Example 50 (5.0 mg, 0.0086 mmol)
l) with chloroform (3.0 ml) and methanol (1.0 ml)
Dissolved in sodium hydrosulfite (10 mg,
0.057 mmol) and stirred at room temperature for 20 minutes. After ordinary post-treatment, the resultant was purified by thin-layer chromatography (chloroform / methanol = 9/1) to obtain Compound 1 (2.0 mg, yield: 40%). FABMS m / z: 587 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 5.00 (s, 4H), 5.49
(s, 4H), 6.85-7.50 (m, 22H)

Example 2: Compound 2 and Compound 3 Compound 68 obtained in Example 50 (150 mg, 0.26 mmo
l) was dissolved in acetonitrile (7.0 ml) and phosphate buffer (pH 7, 2.0 ml), and 2-dimethylaminoethanethiol hydrochloride (74 mg, 0.52 mmol) was added, followed by stirring at room temperature for 1.5 hours. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 9/1) to give compound 2 (5.0 mg, yield 3%) and compound 3 (33 mg, yield 16%).
I got Compound 2 FABMS m / z: 690 ( M + H) + 1 H NMR (300 MHz, CDCl 3) δ ppm: 2.40 (s, 6H), 2.51
(t, J = 6.7 Hz, 2H), 2.99 (t, J = 6.7 Hz, 2H), 5.0
0 (s, 4H), 5.50 (s, 2H), 5.54 (s, 2H), 6.80-6.95
(m, 9H), 7.24-7.45 (m, 12H) Compound 3 FABMS m / z: 793 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.36 (s, 12H), 2.4
2 (t, J = 6.0 Hz, 4H), 3.07 (t, J = 6.0 Hz, 4H), 4.
98 (s, 4H), 5.56 (s, 4H), 6.78-6.95 (m, 8H), 7.25-
7.44 (m, 10H)

Example 3: Compound 4 and Compound 5 Compound 68 obtained in Example 50 (11 mg, 0.019 mmo)
l) was dissolved in acetonitrile (3.0 ml) and phosphate buffer (pH 7, 0.5 ml), 2-mercaptoethanol (2.7 μl, 0.038 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 95/5) to give compound 4 (2.5
mg, yield 20%) and compound 5 (3.2 mg, yield 23%). Compound 4 FABMS m / z: 663 ( M + H) + 1 H NMR (300 MHz, CDCl 3) δ ppm: 3.19 (t, J = 6.0 H
z, 2H), 3.48 (brs, 1H), 3.73 (m, 2H), 5.00 (s, 4
H), 5.47 (s, 2H), 5.48 (s, 2H), 6.80-6.95 (m, 8H),
7.20-7.45 (m, 11H) Compound 5 FABMS m / z: 739 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.21 (t, J = 6.0 H
z, 4H), 3.62 (t, J = 6.0 Hz, 4H), 5.00 (s, 4H), 5.
50 (s, 4H), 6.85-6.95 (m, 8H), 7.25-7.45 (m, 10H)

Example 4: Compound 6 Compound 68 obtained in Example 50 (19 mg, 0.033 mmo
l) was dissolved in acetonitrile (3.0 ml) and phosphate buffer (pH 7, 0.5 ml), and 4-aminothiophenol (4.1 mg, 0.033 mmol) was added, followed by stirring at room temperature for 2 hours.
After ordinary post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 97/3) to give Compound 6 (8.0 mg,
Yield 34%). FABMS m / z: 710 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.83 (brs, 2H), 4.
99 (s, 2H), 5.00 (s, 2H), 5.43 (s, 2H), 5.46 (s, 2
H), 6.63-6.73 (m, 2H), 6.77 (s, 1H), 6.80-6.95 (m,
8H), 7.25-7.50 (m, 12H)

Example 5: Compound 7 and Compound 37 Compound 36 (37 mg, 0.081 mmo) obtained in Example 25
l) was dissolved in acetonitrile (5.0 ml) and phosphate buffer (pH 7, 1.0 ml), and 4-aminothiophenol (1
(0.2 mg, 0.081 mmol) and stirred at room temperature for 20 minutes. After usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 97/3) to give Compound 7 (8.0 mg,
Compound 17 (7.4 mg, 16% yield) was obtained. Compound 7 FABMS m / z: 582 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 0.87-0.95 (m, 6H),
1.50-1.57 (m, 4H), 2.48-2.55 (m, 4H), 4.88 (brs,
2H), 5.47 (s, 2H), 5.50 (s, 2H), 6.73 (m, 2H), 6.7
7 (s, 1H), 6.85-7.11 (m, 8H), 7.37 (m, 2H) Compound 37 FABMS m / z: 581 ( M + 2H) + 1 H NMR (300 MHz, CDCl 3) δ ppm: 0.90 (t, J = 7.3 H
z, 3H), 0.91 (t, J = 7.3 Hz, 3H), 1.50-1.70 (m, 4
H), 2.40-2.52 (m, 4H), 4.02 (brs, 2H), 5.54 (s, 2
H), 5.56 (s, 2H), 6.41 (s, 1H), 6.70-7.32 (m, 12H)

Example 6: Compound 8 and Compound 18 5,8-dimethoxy-2,3-diphenylquinoxaline (13 mg,
0.038 mmol) was dissolved in acetonitrile (5.0 ml), water (1.0 ml) and diammonium cerium (IV) nitrate (42
mg, 0.076 mmol) and stirred at 0 ° C. for 20 minutes. The usual post-treatment gave 2,3-diphenyl-5,8-quinoxalinedione. FABMS m / z: 314 (M + 2H) ⁺ the crude 2,3-diphenyl-5,8-quinoxalinedione obtained above was dissolved in acetonitrile (5.0 ml) and phosphate buffer (pH 7, 1.0 ml) Then, 4-aminothiophenol (4.9 mg, 0.038 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. After usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 97/3) to give compound 8 (3.0
mg, 18% yield) and compound 18 (3.0 mg, 18% yield). Compound 8 FABMS m / z: 438 ( M + H) + 1 H NMR (300 MHz, CDCl 3) δ ppm: 3.86 (brs, 2H), 6.
70 (m, 2H), 6.80 (s, 1H), 7.44 (brs, 1H), 6.35-7.5
1 (m, 12H) Compound 18 FABMS m / z: 437 (M + 2H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.01 (brs, 2H), 6.
42 (s, 1H), 6.77 (m, 2H), 7.25-7.63 (m, 12H)

Example 7: Compound 9 and Compound 10 2-methyl-5,8-dimethoxyquinoxaline (15 mg, 0.094 m
mol) in acetonitrile (2.0 ml) and water (0.2 ml)
And diammonium cerium (IV) nitrate (102 mg, 0.19
mmol) and stirred at 0 ° C. for 10 minutes. After usual work-up, 2-methyl-5,8-quinoxalinedione (5 mg, 31 yield)
%). The 2-methyl-5,8-quinoxalinedione obtained above (10
mg, 0.057 mmol) was dissolved in acetonitrile (6.0 ml) and phosphate buffer (pH 7, 2.0 ml), and 4-aminothiophenol (7.2 mg, 0.057 mmol) was added, followed by stirring at room temperature for 20 minutes. After usual post-treatment, purification was carried out by thin-layer chromatography (chloroform / methanol = 97/3) to obtain a mixture of compound 9 and compound 10 (5.0 mg, yield 30%). Compound 9 and compound 10 have a regioisomer ratio of about 4: 1.
Met. FABMS m / z: 298 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: major 2.82 (d, J =
0.7 Hz, 3H), 4.01 (brs, 2H), 6.39 (s, 1H), 6.75
(m, 2H), 7.27 (m, 2H), 8.84 (d, J = 0.7 Hz, 1H)

Example 8: Compound 11 2,3-dimethyl-5,8-quinoxalinedione (28 mg, 0.15 m
mol) was dissolved in acetonitrile (5.0 ml) and phosphate buffer (pH 7, 1.0 ml), and 4-aminothiophenol (19 mg, 0.15 mmol) was added thereto, followed by stirring at room temperature for 1 hour. After usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 97/3) to give compound 11 (13 mg,
Yield 27%). FABMS m / z: 313 (M + 2H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.69 (s, 3H), 2.72
(s, 3H), 3.85 (brs, 2H), 6.68 (m, 2H), 6.72 (s, 1
H), 7.34 (m, 2H)

Example 9: Compound 12 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(32 mg, 0.086 mmol) was dissolved in acetonitrile (5.0 ml), water (1.0 ml) and diammonium cerium nitrate (I
V) (94 mg, 0.17 mmol) was added and the mixture was stirred at room temperature for 10 minutes. After usual post-treatment, compound 12 was obtained quantitatively. FABMS m / z: 347 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.91 (s, 4H), 7.25
(s, 2H)

Example 10: Compound 13 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (100 ml), β-naphthol (96 mg, 0.67 mmol) and potassium carbonate (75 mg, 0.54 mmol) were added, and the mixture was stirred at room temperature overnight. After normal post-treatment, silica gel chromatography
(Chloroform / methanol = 98/2)
Bis (2-naphthoxymethyl) -5,8-dimethoxyquinoxaline (112 mg, 0.22 mmol, yield 83%) was obtained. FABMS m / z: 503 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.10 (s, 6H), 5.75
(s, 4H), 7.09 (s, 2H), 7.11-7.15 (m, 3H), 7.28-7.
41 (m, 4H), 7.61-7.78 (m, 7H)

The 2,3-bis (2-naphthoxymethyl) -5,8-dimethoxyquinoxaline obtained above (100 mg, 0.20 mm
ol) in a mixed solvent of acetonitrile (30 ml) and water (6.0 ml), and diammonium cerium (IV) nitrate (218 mg,
0.40 mmol) and stirred at room temperature for 30 minutes. After the usual post-treatment, 2,3-bis (2-naphthoxymethyl) -5,8-
Quinoxalinedione (107 mg, 0.23 mmol) was obtained.

The 2,3-bis (2-naphthoxymethyl) -5,8-quinoxalinedione (38 mg, 0.081 mmol) obtained above was dissolved in acetonitrile (3.0 ml), and N, N-dimethylethylenediamine ( 9.0 μl, 0.081 mmol) and add 2
Stirred for 0 minutes. The reaction mixture was concentrated and dried, and the obtained residue was purified by thin-layer chromatography (chloroform / methanol = 90/10) to give Compound 13 (4.5 mg, 0.0081
mmol, 11% yield). FABMS m / z: 559 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.65
(t, J = 6.0 Hz, 2H), 3.23-3.28 (m, 2H), 5.72 (s, 2
H), 5.74 (s, 2H), 6.00 (s, 1H), 6.71 (brs, 1H), 7.0
8-7.20 (m, 2H), 7.23-7.43 (m, 5H), 7.61-7.73 (m, 7
H)

Example 11: Compound 14 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (100 ml), α-naphthol (96 mg, 0.67 mmol) and potassium carbonate (75 mg, 0.54 mmol) were added, and the mixture was stirred at room temperature overnight. After normal post-treatment, silica gel chromatography
(Chloroform / methanol = 98/2)
Bis (1-naphthoxymethyl) -5,8-dimethoxyquinoxaline (129 mg, 0.22 mmol, yield 95%) was obtained. FABMS m / z: 503 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.10 (s, 6H), 5.83
(s, 4H), 6.83 (d, J = 7.7 Hz, 2H), 7.15 (s, 2H),
7.15 (s, 2H), 7.18-7.24 (m, 2H), 7.30-7.38 (m, 2
H), 7.41-7.47 (m, 2H), 7.60-7.77 (m, 2H), 8.08-8.1
1 (m, 2H)

The 2,3-bis (1-naphthoxymethyl) -5,8-dimethoxyquinoxaline obtained above (129 mg, 0.27 mmol)
l) in a mixed solvent of acetonitrile (30 ml) and water (6.0 ml), and diammonium cerium (IV) nitrate (296 mg,
(0.54 mmol) and stirred at room temperature for 5 minutes. After the usual post-treatment, 2,3-bis (1-naphthoxymethyl) -5,8-
Quinoxalinedione (107 mg, 0.23 mmol) was obtained.

The above-obtained 2,3-bis (1-naphthoxymethyl) -5,8-quinoxalinedione (79 mg, 0.17 mmol) was dissolved in acetonitrile (35 ml), and N, N-dimethylethylenediamine was dissolved. (18 μl, 0.17 mmol) was added and the mixture was stirred at room temperature for 45 minutes. After normal workup, thin layer chromatography
(Chloroform / methanol = 90/10) to give Compound 14 (2.9 mg, 0.0050 mmol, 2.9% yield). FABMS m / z: 559 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.31 (s, 6H), 2.67
(t, J = 6.1 Hz, 2H), 3.01-3.49 (m, 2H), 5.78 (s, 2
H), 5.83 (s, 2H), 6.03 (s, 1H), 6.75 (brs, 1H), 6.7
9-6.82 (m, 3H), 7.20-7.47 (m, 6H), 7.75-7.79 (m, 2
H), 8.06-8.11 (m, 3H)

Example 12: Compound 15 1,4-dimethoxy-2,3-dinitrobenzene (1.0 g, 4.4 mm
ol) was dissolved in ethanol (150 ml), 10% palladium on carbon (100 mg) was added, and the mixture was stirred overnight at room temperature under a hydrogen atmosphere. After completion of the reaction, the mixture was filtered through celite, and dichloromethane was added to the filtrate.
Di (2-pyridyl) diketone (1.1 g,
5.3 mmol, 1.2 eq.) And further stirred at room temperature for 2 hours. The reaction mixture was concentrated and dried, and the obtained residue was subjected to silica gel chromatography (ethyl acetate / hexane = 2 /
1-ethyl acetate only) and 2,3-bis (2-pyridyl) -5,8-dimethoxyquinoxaline (582 mg, 1.7 mm
ol, yield 32%). FABMS m / z: 345 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.68 (s, 6H), 7.07
(s, 2H), 7.19-7.23 (m, 2H), 7.78-7.84 (m, 2H), 8.
04-8.07 (m, 2H), 8.31-8.32 (m, 2H)

The 2,3-bis (2-pyridyl) -5,8 obtained above
-Dimethoxyquinoxaline (54 mg, 0.16 mmol) was dissolved in a mixed solvent of acetonitrile (30 ml) and water (5.0 ml), and ceric ammonium diammonium (IV) (176 mg, 0.32 m
mol) and stirred at room temperature for 30 minutes. After normal post-processing,
Concentration gave 2,3-bis (2-pyridyl) -5,8-quinoxalinedione (40 mg, 0.13 mmol). 2,3-bis (2-pyridyl) -5,8-quinoxalinedione (40 mg, 0.13 mmol) obtained above was added to acetonitrile (15 m
l), and dissolved in N, N-dimethylethylenediamine (8.9 μl,
0.081 mmol) and stirred at room temperature for 1 hour. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 90/10) to give Compound 15 (18 mg, 0.0
45 mmol, yield 28%). FABMS m / z: 401 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.31 (s, 6H), 2.66
(t, J = 6.1 Hz, 2H), 3.25-3.31 (m, 2H), 6.04 (s, 1
H), 6.71 (brs, 1H), 7.23-7.27 (m, 2H), 7.83-7.88
(m, 2H), 8.09-8.11 (m, 1H), 8.20-8.23 (m, 1H), 8.2
7-8.31 (m, 2H)

Example 13: Compound 16 and Compound 17 1,4-dimethoxy-2,3-dinitrobenzene (1.0 g, 4.4 mm
ol) was dissolved in ethanol (150 ml), 10% palladium on carbon (100 mg) was added, and the mixture was stirred overnight at room temperature under a hydrogen atmosphere. After completion of the reaction, the mixture was filtered through celite, and dichloromethane was added to the filtrate.
Di (2-furyl) diketone (1.0 g,
5.3 mmol), and the mixture was further stirred at room temperature for 2 hours. The reaction mixture was concentrated and dried, and the resulting residue was purified by silica gel chromatography (chloroform only) to give 2,3-bis
(2-furyl) -5,8-dimethoxyquinoxaline (591 mg, 1.8
mmol, yield 35%). FABMS m / z: 323 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.06 (s, 6H), 6.53
-6.54 (m, 2H), 6.66-6.68 (m, 2H), 7.00 (s, 2H), 7.
60-7.61 (m, 2H)

The 2,3-bis (2-furyl) -5,8- obtained above
Dimethoxyquinoxaline (40 mg, 0.13 mmol) was dissolved in a mixed solvent of acetonitrile (30 ml) and water (6.0 ml),
Cerium (IV) diammonium nitrate (144 mg, 0.26 mmol)
Was added and stirred at room temperature for 30 minutes. After usual post-treatment, compound 16 (44 mg, 0.15 mmol) was obtained by concentration. FABMS m / z: 294 (M + 2H) ⁺

The compound 16 obtained above (44 mg, 0.15
was dissolved in acetonitrile (10 ml), N, N-dimethylethylenediamine (17 μl, 0.15 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. After usual post-treatment, purification was carried out by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 17 (4.0 mg, 0.010 mmol, yield 8.0%). FABMS m / z: 379 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.64
(t, J = 6.1 Hz, 2H), 3.23-3.28 (m, 2H), 5.97 (s, 1
H), 6.58-6.60 (m, 2H), 6.67 (brs, 1H), 7.01 (d, J =
3.5 Hz, 1H), 7.08 (d, J = 3.5 Hz, 1H), 6.61-7.63
(m, 2H)

Example 14: Compound 19 and Compound 20 1,4-dimethoxy-2,3-dinitrobenzene (100 mg, 0.44
mmol) was dissolved in ethanol (100 ml), 10% palladium on carbon (25 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. After completion of the reaction, the mixture was filtered through celite, bis (3-bromobenzyl) diketone (162 mg, 0.44 mmol) was added, and the mixture was further stirred at room temperature overnight. The reaction mixture is concentrated and dried, and the obtained residue is subjected to silica gel chromatography (eluted with ethyl acetate / hexane = 1/4 to ethyl acetate / hexane = 1/21).
To give 2,3-bis (3-bromophenyl) -5,8-dimethoxyquinoxaline (108 mg, 0.27 mmol, yield 50%). FABMS m / z: 501 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.01 (s, 6H), 6.99
(s, 2H), 7.04-7.09 (m, 2H), 7.20-7.22 (m, 2H), 7.
41-7.44 (m, 2H), 7.79-7.81 (m, 2H)

2,3-bis (3-bromophenyl) -5,8-dimethoxyquinoxaline obtained above (28 mg, 0.057 mmol)
Was dissolved in a mixed solvent of acetonitrile (5.0 ml) and water (1.0 ml), and ceric ammonium dinitrate (IV) (47 mg, 0.0
86 mmol) and stirred at room temperature for 1 hour. After usual work-up, concentration gave compound 19 (22 mg, 0.047 mmol). FABMS m / z: 473 (M + 3H) ⁺

The compound 19 obtained above (22 mg, 0.047
mmol) was dissolved in acetonitrile (6 ml), N, N-dimethylethylenediamine (5.1 μl, 0.047 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After ordinary post-treatment, purification was carried out by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 20 (11 mg, 0.019 mmol, yield: 33%). FABMS m / z: 557 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.31 (s, 6H), 2.66
(t, J = 6.1 Hz, 2H), 3.25-3.31 (m, 2H), 6.03 (s, 1
H), 6.73 (brs, 1H), 7.14-7.23 (m, 2H), 7.31-7.38
(m, 2H), 7.53-7.57 (m, 2H), 7.84-7.88 (m, 2H)

Example 15: Compound 21 and Compound 22 1,4-dimethoxy-2,3-dinitrobenzene (1.0 g, 4.4 mm
ol) was dissolved in ethanol (350 ml), 10% palladium carbon (100 mg) was added, and the mixture was stirred overnight at room temperature under a hydrogen atmosphere. After completion of the reaction, the mixture was filtered through celite, bis (4-bromobenzyl) diketone (1.6 g, 4.4 mmol) was added to the filtrate, and the mixture was further stirred at room temperature overnight. The reaction mixture was concentrated and dried, and the obtained residue was purified by silica gel chromatography (chloroform) to give 2,3-bis (4-bromophenyl) -5,8-dimethoxyquinoxaline (650 mg, 1.3 mmol, yield 30). %). FABMS m / z: 503 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.06 (s, 6H), 7.04
(s, 2H), 7.40-7.44 (m, 4H), 7.47-7.50 (m, 4H)

The 2,3-bis (4-bromophenyl) -5,8-dimethoxyquinoxaline obtained above (28 mg, 0.060 mmol)
Was dissolved in a mixed solvent of acetonitrile (5.0 ml) and water (1.0 ml), and cerium (IV) diammonium nitrate (49 mg, 0.0
90 mmol) and stirred at room temperature for 10 minutes. After usual work-up, concentration gave compound 21 (38 mg, 0.081 mmol). FABMS m / z: 473 (M + 3H) ⁺ Compound 21 obtained above (38 mg, 0.081 mmol) was dissolved in acetonitrile (6 ml), and N, N-dimethylethylenediamine (8.9 μl, 0.081 mmol) was added. The mixture was stirred at room temperature for 1 hour. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 22 (12 mg, 0.022 mmol, yield 36%). FABMS m / z: 556 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.65
(t, J = 6.1 Hz, 2H), 3.24-3.30 (m, 2H), 6.00 (s, 1
H), 6.71 (brs, 1H), 7.43-7.52 (m, 8H)

Example 16: Compound 23 2,3-bis (4-phenylethynylphenyl) -5,8-dimethoxyquinoxaline (2.4 mg, 0.0046) obtained in Example 22
was dissolved in a mixed solvent of methanol (1.5 ml) and ethyl acetate (1 ml), and 10% palladium on carbon (2.4 mg) and acetic acid (2.5 μl, 0.46 mmol) were added.
Stirred for days. The reaction mixture was filtered through celite, and the filtrate was concentrated and dried to obtain 2,3-bis (4-phenethylphenyl) -5,8-dimethoxyquinoxaline (2.5 mg, 0.0046 mmol, quantitative). FABMS m / z: 551 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.92 (s, 8H), 4.01
(s, 6H), 6.99 (s, 2H), 7.10 (d, J = 8.1 Hz, 4H),
7.15-7.29 (m, 10H), 7.46 (d, J = 8.1 Hz, 4H)

The 2,3-bis (4-phenethylphenyl) -5,8-dimethoxyquinoxaline obtained above (2.5 mg, 0.0046
mmol) in a mixed solvent of acetonitrile (2.0 ml) and water (0.4 ml), and diammonium cerium (IV) nitrate (5.0
mg, 0.0092 mmol) and stirred at room temperature for 2 hours. After the usual post-treatment, 2,3-bis (4-phenethylphenyl) is concentrated by
-5,8-Quinoxalinedione (3.0 mg, 0.0058 mmol) was obtained.

The 2,3-bis (4-phenethylphenyl) -5,8-quinoxalinedione obtained above (3.0 mg, 0.0058 mmol)
Was dissolved in acetonitrile (3.0 ml), N- (2-aminoethyl) morpholine (1.5 μl, 0.011 mmol) was added, and the mixture was stirred at room temperature overnight. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 23 (1.0 mg, 0.0015 mmol, yield: 33%). FABMS m / z: 649 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.50-2.53 (m, 4H),
2.74 (t, J = 6.0 Hz, 2H), 2.93 (s, 8H), 3.25-3.26
(m, 2H), 3.71-3.73 (m, 4H), 5.97 (s, 1H), 6.94 (br
s, 1H), 7.09-7.18 (m, 4H), 7.21-7.39 (m, 10H), 7.4
7-7.54 (m, 4H)

Example 17: Compound 24 and Compound 26 2,3-bis (4-acetoxyphenyl) obtained in Example 20
-5,8-Dimethoxyquinoxaline (59 mg, 0.13 mmol) was dissolved in a mixed solvent of methanol (10 ml) and dichloromethane (3.0 ml), potassium carbonate (36 mg, 0.26 mmol) was added, and the mixture was stirred at room temperature for 2 hours. . After normal post-treatment, concentration
2,3-Bis (4-hydroxyphenyl) -5,8-dimethoxyquinoxaline (51 mg, 0.14 mmol, quantitative) was obtained. ¹ H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.05 (s, 6H), 6.76
-6.80 (m, 4H), 7.08 (s, 2H), 7.38-7.42 (m, 4H), 7.
67 (s, 2H) 2,3-bis (4-hydroxyphenyl) -5,8- obtained above
Dimethoxyquinoxaline (15 mg, 0.041 mmol) was dissolved in N, N-dimethylformamide (3 ml), and benzyl bromide (19 μl, 0.16 mmol) and potassium carbonate (34 mg, 0.25 mmol) were dissolved.
mmol) and the mixture was stirred at room temperature overnight. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 9
8/2), 2,3-bis (4-benzyloxyphenyl)
-5,8-Dimethoxyquinoxaline (21 mg, 0.037 mmol, yield 90%) was obtained. FABMS m / z: 555 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.97 (s, 6H), 5.01
(s, 4H), 6.85 (d, J = 8.5 Hz, 4H), 6.89 (s, 2H),
7.11-7.37 (m, 10H), 7.45 (d, J = 8.5 Hz, 4H)

The 2,3-bis (4-benzyloxyphenyl) -5,8-dimethoxyquinoxaline obtained above (21 mg, 0.0
38 mmol) in a mixed solvent of acetonitrile (5.0 ml) and water (1.0 ml), and diammonium cerium (IV) nitrate (46
mg, 0.084 mmol) and stirred at room temperature for 2 hours. After the usual post-treatment, the compound 24 was concentrated (25 mg, 0.048 mmol) by concentration.
I got FABMS m / z: 527 (M + 3H) ⁺

The compound 24 obtained above (25 mg, 0.048
mmol) in acetonitrile (5 ml), and N- (2-aminoethyl) morpholine (6.37 μl, 0.048 mmol) was added.
Stirred at room temperature for 15 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 26 (10 mg, 0.015 mmol, yield 41%). FABMS m / z: 653 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.50-2.52 (m, 4H),
2.71-2.75 (m, 2H), 3.25-3.26 (m, 2H), 3.72-3.75
(m, 4H), 5.09 (s, 4H), 5.94 (s, 1H), 6.71 (brs, 1
H), 6.91-6.95 (m, 4H), 7.33-7.42 (m, 10H), 7.57-7.
64 (m, 4H)

Example 18: Compound 25 Compound 24 obtained in Example 17 (18 mg, 0.033 mmol)
Was dissolved in acetonitrile (5 ml), N, N, N'-trimethylethylenediamine (14 μl, 0.033 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 25 (14 mg, 0.022 mmol, yield 33%). FABMS m / z: 625 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.08 (s, 6H), 2.45
(t, J = 5.3 Hz, 2H), 3.07 (s, 3H), 3.83 (t, J = 5.
3 Hz, 2H), 5.09 (s, 4H), 6.05 (s, 1H), 6.90-6.94
(m, 4H), 7.30-7.41 (m, 10H), 7.55-7.61 (m, 4H)

Example 19: Compound 27 and Compound 28 1,4-dimethoxy-2,3-dinitrobenzene (300 mg, 1.3 m
mol) was dissolved in ethanol (150 ml), 10% palladium on carbon (50 mg) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hours. After completion of the reaction, the mixture was filtered through celite, and dichloromethane was added to the filtrate.
(6 ml), bis (4-ethoxycarbonylbenzyl) diketone (470 mg, 1.6 mmol) was added, and the mixture was further stirred at room temperature for 6 hours. The reaction mixture was concentrated and dried, and the obtained residue was purified by silica gel chromatography (chloroform only) to give 2,3-bis (4-ethoxycarbonylphenyl) -5,8-dimethoxyquinoxaline (392 mg, 0.81 mmo
1, yield 61%). FABMS m / z: 487 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.40 (t, J = 7.1 H
z, 6H), 4.08 (s, 6H), 4.38 (q, J = 7.1 Hz, 4H), 7.0
7 (s, 2H), 7.60 (d, J = 8.3 Hz, 4H), 7.99 (d, J =
(8.3 Hz, 4H)

The 2,3-bis (4-ethoxycarbonylphenyl) -5,8-dimethoxyquinoxaline obtained above (52 mg,
0.11 mmol) in acetonitrile (4.0 ml) and water (1.0 ml)
Dissolved in a mixed solvent of cerium (IV) diammonium nitrate
(155 mg, 0.28 mmol) was added and the mixture was stirred at room temperature for 40 minutes.
After the usual post-treatment, the compound 27 (52 mg, 0.11m
mol). FABMS m / z: 457 (M + H) ⁺

The compound 27 obtained above (52 mg, 0.11
was dissolved in acetonitrile (10 ml), N, N-dimethylethylenediamine (13 μl, 0.11 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After ordinary post-treatment, purification was carried out by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 28 (29 mg, 0.053 mmol, yield 48%). FABMS m / z: 543 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.40 (t, J = 7.2 H
z, 6H), 2.31 (s, 6H), 2.66 (t, J = 6.1 Hz, 2H), 3.2
5-3.31 (m, 2H), 4.39 (q, J = 7.2 Hz, 4H), 6.03 (s,
1H), 6.73 (brs, 1H), 7.59-7.66 (m, 4H), 7.98-8.02
(m, 4H)

Example 20: Compound 29 and Compound 30 1,4-dimethoxy-2,3-dinitrobenzene (100 mg, 0.44
mmol) was dissolved in ethanol (100 ml), 10% palladium on carbon (25 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. After completion of the reaction, the mixture was filtered through celite, bis (4-acetoxybenzyl) diketone (150 mg, 0.44 mmol) was added, and the mixture was further stirred at room temperature overnight. The reaction mixture is concentrated to dryness, and the obtained residue is subjected to silica gel chromatography (eluted with ethyl acetate / hexane = 2/1 to ethyl acetate / hexane = 4/1).
To give 2,3-bis (4-acetoxyphenyl) -5,8-dimethoxyquinoxaline (141 mg, 0.31 mmol, 70% yield). FABMS m / z: 459 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.29 (s, 6H), 4.06
(s, 6H), 7.02 (s, 2H), 7.06-7.09 (m, 4H), 7.57-7.
60 (m, 4H)

The 2,3-bis (4-acetoxyphenyl) -5,8-dimethoxyquinoxaline obtained above (30 mg, 0.066 mm
ol) in a mixed solvent of acetonitrile (5.0 ml) and water (1.0 ml), and diammonium cerium (IV) nitrate (90 mg,
0.17 mmol) and stirred at room temperature for 1 hour. After usual work-up, concentration gave compound 29 (36 mg, 0.084 mmol). FABMS m / z: 430 (M + 2H) ⁺

Compound 29 obtained above (36 mg, 0.084
mmol) was dissolved in acetonitrile (6 ml), N, N-dimethylethylenediamine (9.3 μl, 0.085 mmol) was added, and the mixture was stirred at room temperature for 90 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 30 (15 mg, 0.028 mmol, yield 43%). FABMS m / z: 515 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.29 (s, 6H), 2.65
(t, J = 5.9 Hz, 2H), 3.24-3.29 (m, 2H), 5.95 (s, 1
H), 6.69 (brs, 1H), 7.08-7.12 (m, 4H), 7.59-7.67
(m, 4H)

Example 21: Compound 31 2,3-bis (3-bromophenyl) -5,8 obtained in Example 14
-Dimethoxyquinoxaline (60 mg, 0.12 mmol) and tetrakis (triphenylphosphine) -palladium (0) (140 m
g, 0.12 mmol) in N, N-dimethylformamide (8 ml), and the mixture was stirred at room temperature under an argon atmosphere for 30 minutes.
μl, 1.2 mmol) and ethynylbenzene (40 μl, 0.36 mm
ol), and the mixture was heated under reflux for 6 hours. The reaction mixture was filtered through celite, the filtrate was concentrated and dried, and the obtained residue was purified by thin-layer chromatography (ethyl acetate / hexane = 1/2) to give 2,3-bis (3-phenylethynylphenyl) -5,8-Dimethoxyquinoxaline (25 mg, 0.048 mmol) was obtained. FABMS m / z: 543 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.09 (s, 6H), 7.06
(s, 2H), 7.23-7.36 (m, 10H), 7.50-7.55 (m, 6H),
7.93-7.94 (m, 2H)

The 2,3-bis (3-phenylethynylphenyl) -5,8-dimethoxyquinoxaline obtained above (5.1 mg,
0.0094 mmol) in a mixed solvent of acetonitrile (2 ml) and water (0.4 ml) and diammonium cerium (IV) nitrate.
(10 mg, 0.018 mmol) was added and the mixture was stirred at room temperature for 2 hours. After the usual post-treatment, 2,3-bis (3-phenylethynylphenyl) -5,8-quinoxalinedione (6.0 mg, 0.012
mmol).

The 2,3-bis (3-phenylethynylphenyl) -5,8-quinoxalinedione obtained above (6.0 mg, 0.01
2 mmol) was dissolved in acetonitrile (3.0 ml), and N- (2-
(Aminoethyl) morpholine (1.8 μl, 0.012 mmol) was added, and the mixture was stirred at room temperature overnight. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 31 (3.0 mg, 0.0052 mmol, yield 53%). FABMS m / z: 641 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.52-2.55 (m, 4H),
2.76 (t, J = 6.0 Hz, 2H), 3.30-3.32 (m, 2H), 3.75-
3.77 (m, 4H), 6.03 (s, 1H), 6.79 (brs, 1H), 7.29-7.
30 (m, 2H), 7.34-7.37 (m, 7H), 7.52-7.58 (m, 7H),
7.95-8.00 (m, 2H)

Example 22: Compound 32 2,3-bis (4-bromophenyl) -5,8 obtained in Example 15
-Dimethoxyquinoxaline (30 mg, 0.060 mmol) and tetrakis (triphenylphosphine) -palladium (0) (35 m
g, 0.030 mmol) in N, N-dimethylformamide (5 ml)
And stirred for 30 minutes at room temperature under an argon atmosphere,
Copper iodide (13 mg, 0.060 mmol) and triethylamine (85
μl, 0.60 mmol) and ethynylbenzene (20 μl, 0.18
3.0 eq) and heated to reflux for 6 hours. The reaction mixture was filtered through celite, the filtrate was concentrated to dryness, and the obtained residue was subjected to thin-layer chromatography (ethyl acetate / hexane = 1 /
Purified in 4), 2,3-bis (4-phenylethynylphenyl)-
5,8-dimethoxyquinoxaline (16 mg, 0.030 mmol, yield
50%). FABMS m / z: 543 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.08 (s, 6H), 7.04
(s, 2H), 7.34-7.37 (m, 6H), 7.48-7.58 (m, 12H)

The 2,3-bis (4-phenylethynylphenyl) -5,8-dimethoxyquinoxaline obtained above (17 mg,
0.030 mmol) was dissolved in a mixed solvent of acetonitrile (15 ml), water (4.0 ml) and dichloromethane (1.0 ml). . After normal post-treatment, concentration
2,3-Bis (4-phenylethynylphenyl) -5,8-quinoxalinedione (19 mg, 0.037 mmol) was obtained.

The 2,3-bis (4-phenylethynylphenyl) -5,8-quinoxalinedione obtained above (19 mg, 0.037
mmol) was dissolved in acetonitrile (7 ml), N, N-dimethylethylenediamine (4.0 μl, 0.037 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 32 (3.5 mg, 0.0060 mmol, yield: 20%). FABMS m / z: 379 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.31 (s, 6H), 2.66
(t, J = 6.1 Hz, 2H), 3.25-3.30 (m, 2H), 6.01 (s, 1
H), 6.71 (brs, 1H), 6.35-6.37 (m, 6H), 7.49-7.65
(m, 12H)

Example 23: Compound 33 and Compound 34 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (50 ml), and phenol (63 mg, 0.67 mmol) and potassium carbonate were dissolved.
(75 mg, 0.54 mmol) was added and the mixture was stirred at room temperature overnight. After the usual post-treatment, the product was purified by silica gel chromatography (chloroform / methanol = 98/2), and 2,3-bis (phenoxymethyl) -5,8-dimethoxyquinoxaline (100 mg,
0.25 mmol, yield 92%). FABMS m / z: 403 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.07 (s, 6H), 5.60
(s, 4H), 6.93-6.98 (m, 5H), 7.06 (s, 2H), 7.20-7.
26 (m, 5H)

The 2,3-bis (phenoxymethyl) -5,8-dimethoxyquinoxaline obtained above (23 mg, 0.057 mmo
l) in a mixed solvent of acetonitrile (5.0 ml) and water (1.0 ml), and diammonium cerium (IV) nitrate (45 mg,
0.082 mmol) and stirred at room temperature for 30 minutes. After the usual post-treatment, compound 33 (18 mg, 0.048 mmol) was obtained by concentration. FABMS m / z: 375 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 5.60 (s, 4H), 6.70
-6.91 (m, 5H), 7.23-7.28 (m, 7H)

The compound 33 obtained above (14 mg, 0.038
mmol) in acetonitrile (2.0 ml), N, N-dimethylethylenediamine (3.7 μl, 0.038 mmol) was added,
Stirred at room temperature for 10 minutes. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 90/10)
Compound 34 (3.5 mg, 0.0080 mmol, 27% yield)
I got FABMS m / z: 459 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.64
(t, J = 6.0 Hz, 2H), 3.22-3.28 (m, 2H), 5.56 (s, 2
H), 5.59 (s, 2H), 6.00 (s, 1H), 6.70 (brs, 1H), 6.9
1-6.98 (m, 8H), 7.20-7.25 (m, 2H)

Example 24: Compound 35 2,3-bis (phenoxymethyl) -5,8 obtained in Example 23
-Dimethoxyquinoxaline (16 mg, 0.040 mmol) was dissolved in acetonitrile (5.0 ml), water (1.0 ml) and diammonium cerium (IV) nitrate (44 mg, 0.080 mmol) were added, and the mixture was stirred at room temperature for 10 minutes. The compound 33 was obtained by ordinary post-treatment. The obtained compound 33 was treated with acetonitrile (7.0
ml) and phosphate buffer (pH 7, 2.0 ml),
-Aminothiophenol (5.0 mg, 0.040 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. After usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 97/3) to obtain Compound 35 (7.5 mg, yield: 38%). FABMS m / z: 497 (M + 2H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.03 (brs, 2H), 5.
58 (s, 2H), 5.59 (s, 2H), 6.42 (s, 1H), 6.73-7.00
(m, 8H), 7.19-7.32 (m, 6H)

Example 25: Compound 36 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline (85 mg, 0.23 mmol) was dissolved in acetonitrile (10 ml), and 4-n-propylphenol (61 mg) was dissolved. , 0.45 mmol) and potassium carbonate (62 mg, 0.45 mmol), and the mixture was stirred at room temperature for 6 hours. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 98/2),
Bis (4-n-propylphenyloxymethyl) -5,8-dimethoxyquinoxaline (94 mg, yield 84%) was obtained. FABMS m / z: 487 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 0.90 (t, J = 7.3 H
z, 6H), 1.58 (m, 4H), 2.49 (t, J = 7.5 Hz, 4H), 4.0
6 (s, 6H), 5.57 (s, 4H), 6.86 (m, 2H), 7.02 (m, 2
H), 7.05 (s, 2H)

The 2,3-bis (4-n-propylphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (84
mg, 0.17 mmol) in acetonitrile (9.0 ml),
Water (0.5 ml) and ceric ammonium dinitrate (IV) (19
0 mg, 0.35 mmol) and stirred at room temperature for 15 minutes. The compound 36 (65 mg, yield 84%) was obtained by ordinary post-treatment. FABMS m / z: 457 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 0.91 (t, J = 7.3 H
z, 6H), 1.58 (m, 4H), 2.50 (t, J = 7.9 Hz, 4H), 5.5
7 (s, 4H), 6.85 (m, 2H), 7.03 (m, 4H), 7.23 (m, 4H)

Example 26: Compound 38 Compound 36 obtained in Example 25 (24 mg, 0.053 mmol)
l) was dissolved in acetonitrile (5.0 ml) and phosphate buffer (pH 7, 1.0 ml), and 2-dimethylaminoethanethiol hydrochloride (7.5 mg, 0.053 mmol) was added, followed by stirring at room temperature for 20 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 9/1) to obtain Compound 38 (11 mg, yield 31%). FABMS m / z: 665 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 0.90 (t, J = 7.3 H
z, 6H), 1.57 (m, 4H), 2.37 (s, 6H), 2.36-2.52 (m, 8
H), 3.08 (m, 4H), 5.59 (s, 4H), 6.80-7.05 (m, 8H)

Example 27: Compound 39 and Compound 40 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (50 ml), 4-cyanophenol (81 mg, 0.67 mmol) and potassium carbonate (75 mg, 0.54 mmol, 2.0 eq) were added, and the mixture was stirred at room temperature overnight. After the usual post-treatment, the product was purified by silica gel chromatography (chloroform / methanol = 98/2) and 2,3-bis (4-cyanophenoxymethyl) -5,8-dimethoxyquinoxaline (113 mg, 0.25 mmol, yield) 93%). FABMS m / z: 453 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.08 (s, 6H), 5.62
(s, 4H), 6.98-7.02 (m, 4H), 7.12 (s, 2H), 7.53-7.
58 (m, 4H)

The 2,3-bis (4-cyanophenoxymethyl) -5,8-dimethoxyquinoxaline obtained above (100 mg, 0.1 mg
22 mmol) was dissolved in a mixed solvent of acetonitrile (30 ml) and water (6.0 ml), and cerium (IV) diammonium nitrate (24
2 mg, 0.44 mmol) and stirred at room temperature for 1 hour. After the usual post-treatment, concentration gave compound 39 (103 mg, 0.24 mmol).
I got FABMS m / z: 422 (M + 3H) ⁺

The compound 39 obtained above (33 mg, 0.078
mmol) in acetonitrile (3.0 ml), N, N-dimethylethylenediamine (9.0 μl, 0.078 mmol) was added,
Stirred at room temperature for 10 minutes. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 90/10)
The compound 40 (12 mg, 0.023 mmol, 32% of yield) was obtained. FABMS m / z: 509 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.32 (s, 6H), 2.66
(t, J = 5.9 Hz, 2H), 3.22-3.32 (m, 2H), 5.59 (s, 2
H), 5.62 (s, 2H), 6.03 (s, 1H), 6.80 (brs, 1H), 6.9
6-7.00 (m, 4H), 7.56-7.59 (m, 4H)

Example 28: Compound 41 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline (100 mg, 0.27 mmol) was dissolved in acetonitrile (5.0 ml), and 4-phenylphenol (99 mg, 0.58 mmol) and potassium carbonate (80 mg, 0.58 mmol), and the mixture was stirred at room temperature for 4 hours. After normal post-treatment, recrystallization (dichloromethane /
Purification with diethyl ether / hexane) and 2,3-bis (4-
(Phenylphenyloxymethyl) -5,8-dimethoxyquinoxaline (100 mg, 67% yield) was obtained. FABMS m / z: 555 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.09 (s, 6H), 5.66
(s, 4H), 6.95-7.52 (m, 20H)

The 2,3-bis (4-phenylphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (35 m
g, 0.063 mmol) was dissolved in acetonitrile (15 ml), and water (1.0 ml) and cerium (IV) diammonium nitrate (69) were dissolved.
mg, 0.13 mmol) and stirred at room temperature for 15 minutes. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 97/3) to give Compound 41 (20 mg, yield 6).
0%). FABMS m / z: 525 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 5.67 (s, 4H), 6.95
-7.60 (m, 20H)

Example 29: Compound 42 Compound 41 obtained in Example 28 (14 mg, 0.027 mmo
l) was dissolved in acetonitrile (1.5 ml), N, N-dimethylethylenediamine (2.9 μl, 0.027 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 42 (4.0 mg, yield: 24%). FABMS m / z: 611 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.65
(m, 2H), 3.25 (m, 2H), 5.63 (s, 2H), 5.66 (s, 2
H), 6.01 (s, 1H), 6.71 (br, 1H), 6.95-7.52 (m, 18H)

Example 30: Compound 43 Compound 41 obtained in Example 28 (58 mg, 0.11 mmol)
Was dissolved in acetonitrile (2.0 ml), 4-aminothiophenol (14 mg, 0.027 mmol) was added, and the mixture was stirred at room temperature for 20 minutes. After usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 43 (16 mg, yield: 22%). FABMS m / z: 650 (M + 3H) ^{+ 1} H NMR (300 MHz, DMSO-d ₆ ) δ ppm: 5.67 (s, 2H), 5.
70 (s, 2H), 5.78 (s, 2H), 6.02 (s, 1H), 6.70 (m, 2
H), 7.10-7.70 (m, 20H)

Example 31: Compound 44 and Compound 46 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(105 mg, 0.28 mmol) was dissolved in acetonitrile (50 ml), 4-benzylphenol (129 mg, 0.70 mmol) and potassium carbonate (77 mg, 0.56 mmol) were added, and the mixture was stirred at room temperature overnight. After normal post-treatment, silica gel chromatography
(Eluted with ethyl acetate / hexane = 4/1 to 2/1) to give 2,3-bis (4-benzylphenyloxymethyl) -5,8
-Dimethoxyquinoxaline (109 mg, 0.19 mmol, yield 67)
%). FABMS m / z: 583 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.88 (s, 4H), 4.06
(s, 6H), 4.71 (s, 4H), 6.84-6.88 (m, 4H), 7.01-7.
04 (m, 4H), 7.05 (s, 1H), 7.13-7.21 (m, 5H), 7.24-
7.30 (m, 5H)

The 2,3-bis (4-benzylphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (100
mg, 0.17 mmol) in acetonitrile (30 ml) and water (6.0 m
l) in a mixed solvent, and diammonium cerium nitrate (I
V) (188 mg, 0.34 mmol) was added and the mixture was stirred at room temperature for 30 minutes. After the usual work-up, compound 44 (113 mg,
0.20 mmol) was obtained. FABMS m / z: 552 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.98 (s, 4H), 5.55
(s, 4H), 6.82-6.86 (m, 4H), 7.05-7.08 (m, 4H), 7.
13-7.31 (m, 12H)

Compound 44 obtained above (21 mg, 0.038
mmol) was dissolved in acetonitrile (2 ml), N, N-dimethylethylenediamine (4.2 μl, 0.038 mmol) was added, and the mixture was stirred at room temperature for 20 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 46 (9.1 mg, 0.014 mmol, yield: 45%). FABMS m / z: 639 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.29 (s, 6H), 2.64
(t, J = 6.0 Hz, 2H), 3.22-3.27 (m, 2H), 3.89 (s, 4
H), 5.15 (s, 2H), 5.45 (s, 2H), 5.99 (s, 1H), 6.69
(brs, 1H), 6.82-6.85 (m, 4H), 7.02-7.15 (m, 4H),
7.18-7.29 (m, 10H)

Example 32: Compound 45 Compound 44 obtained in Example 31 (33 mg, 0.059 mmol)
Was dissolved in acetonitrile (4.0 ml) and diethylamine
(6.1 μl, 0.059 mmol) was added and the mixture was stirred at room temperature for 2 hours.
After the usual post-treatment, the mixture was purified by thin-layer chromatography (chloroform / methanol = 95/5) to give Compound 45 (4.5 m
g, 0.0040 mmol, 17% yield). FABMS m / z: 626 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.34 (t, J = 7.0 H
z, 6H), 3.59 (q, J = 7.0 Hz, 4H), 3.88 (s, 2H), 3.
89 (s, 2H), 5.50 (s, 2H), 5.54 (s, 2H), 6.15 (s, 1
H), 6.75-6.86 (m, 4H), 7.02-7.05 (m, 4H), 7.13-7.2
9 (m, 10H)

Example 33: Compound 47 Compound 44 obtained in Example 31 (32 mg, 0.057 mmol)
Was dissolved in acetonitrile (4.0 ml), N, N, N'-trimethylethylenediamine (7.3 μl, 0.057 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 47 (15 mg, 0.023 mmol, yield 55%). FABMS m / z: 653 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.83 (s, 6H), 2.44
(t, J = 6.1 Hz, 2H), 3.04 (s, 3H), 3.78-3.81 (m, 2
H), 3.87 (s, 2H), 3.89 (s, 2H), 5.15 (s, 2H), 5.53
(s, 2H), 6.05 (s, 1H), 6.80-6.86 (m, 4H), 7.01-7.
06 (m, 4H), 7.11-7.29 (m, 10H)

Example 34: Compound 48 Compound 44 obtained in Example 31 (27 mg, 0.049 mmol)
Was dissolved in acetonitrile (4.0 ml), N, N, N'-triethylethylenediamine (8.8 μl, 0.049 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 48 (9.4 mg, 0.014 mmol, yield 29%). FABMS m / z: 695 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 0.77 (t, J = 7.0 H
z, 6H), 1.32 (t, J = 7.0 Hz, 3H), 2.34-2.44 (m, 4
H), 2.56-2.62 (m, 2H), 3.50 (q, J = 7.0 Hz, 2H),
3.76-3.80 (m, 2H), 3.88 (s, 4H), 5.50 (s, 2H), 5.5
4 (s, 2H), 6.12 (s, 1H), 6.81-6.85 (m, 4H), 7.02-
7.05 (m, 4H), 7.13-7.29 (m, 10H)

Example 35: Compound 49 Compound 44 obtained in Example 31 (20 mg, 0.034 mmol)
Was dissolved in acetonitrile (2.0 ml) and N, N-dimethyl-1,
3-propanediamine (4.5 μl, 0.057 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 49 (2.9 mg, 0.0030 mmol, 18% yield). FABMS m / z: 655 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.84-1.90 (m, 2H),
2.32 (s, 6H), 2.53 (t, J = 6.1 Hz, 2H), 3.31-3.36
(m, 2H), 3.89 (s, 4H), 5.51 (s, 2H), 5.54 (s, 2
H), 5.94 (s, 1H), 6.82-6.84 (m, 4H), 7.02-7.05 (m,
4H), 7.13-7.31 (m, 10H)

Example 36: Compound 50 Compound 44 obtained in Example 31 (28 mg, 0.051 mmol)
Was dissolved in acetonitrile (4.0 ml), N, N, N'-trimethyl-1,3-propanediamine (7.5 μl, 0.051 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 90/1
0) to give Compound 50 (8.3 mg, 0.012 mmol, yield 34).
%). FABMS m / z: 669 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.76-1.84 (m, 8H),
2.25 (t, J = 6.1 Hz, 2H), 3.10 (s, 3H), 3.86-3.88
(m, 6H), 5.52 (s, 2H), 5.54 (s, 2H), 6.04 (s, 1H),
6.82-6.85 (m, 4H), 7.02-7.05 (m, 4H), 7.13-7.29
(m, 10H)

Example 37: Compound 51 Compound 44 obtained in Example 31 (32 mg, 0.057 mmol)
Was dissolved in acetonitrile (4.0 ml), and N- (2-aminoethyl) morpholine (7.5 μl, 0.057 mmol) was added.
Stirred for 0 minutes. After normal post-treatment, purify by thin-layer chromatography (chloroform / methanol = 95/5),
Compound 51 (5.8 mg, 0.0090 mmol, 21% yield) was obtained. FABMS m / z: 681 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.50-2.53 (m, 4H),
2.73 (t, J = 6.1 Hz, 2H), 3.25-3.31 (m, 2H), 3.73-
3.76 (m, 4H), 3.89 (s, 4H), 5.51 (s, 2H), 5.54 (s,
2H), 5.98 (s, 1H), 6.73 (brs, 1H), 6.82-6.85 (m, 4
H), 7.03-7.05 (m, 4H), 7.13-7.30 (m, 10H)

Example 38: Compound 52 Compound 44 (18 mg, 0.035 mmol) obtained in Example 31
Was dissolved in acetonitrile (4.0 ml), and 1- (2-aminoethyl) pyrrolidine (4.2 μl, 0.035 mmol) was added.
Stirred for 0 minutes. After ordinary post-treatment, purification was carried out by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 52 (13 mg, 0.019 mmol, yield 54%). FABMS m / z: 665 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.82 (m, 4H), 2.57
(m, 4H), 2.82 (t, J = 6.2 Hz, 2H), 3.29 (m, 2H),
3.89 (s, 4H), 5.51 (s, 2H), 5.54 (s, 2H), 5.99 (s,
1H), 6.71 (brs, 1H), 6.81-6.85 (m, 4H), 7.03-7.05
(m, 4H), 7.13-7.29 (m, 10H)

Example 39: Compound 53 Compound 44 obtained in Example 31 (18 mg, 0.033 mmol)
Was dissolved in acetonitrile (2 ml), N- (3-aminopropyl) morpholine (4.7 μl, 0.033 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After normal post-treatment, purify by thin-layer chromatography (chloroform / methanol = 95/5),
Compound 53 (2.8 mg, 0.0040 mmol, 17% yield) was obtained. FABMS m / z: 695 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.86-1.94 (m, 2H),
3.30-3.38 (m, 4H), 2.58-2.64 (m, 2H), 3.32-3.38
(m, 2H), 3.84-3.89 (m, 8H), 5.52 (s, 2H), 5.54 (s,
2H), 5.96 (s, 1H), 6.81-6.84 (m, 4H), 7.02-7.05
(m, 4H), 7.13-7.32 (m, 10H), 8.66 (brs, 1H)

Example 40: Compound 54 Compound 44 obtained in Example 31 (20 mg, 0.036 mmol)
Was dissolved in N, N-dimethylformamide (1 ml), 4-bromobenzylamine hydrochloride (8.0 mg, 0.036 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 95/5)
Compound 54 (1.2 mg, 0.0020 mmol, 5% yield)
I got FABMS m / z: 738 (M + 2H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.89 (s, 4H), 4.41
(d, J = 5.5 Hz, 2H), 5.51 (s, 2H), 5.54 (s, 2H),
6.00 (s, 1H), 6.37 (brs, 1H), 6.82-6.85 (m, 4H), 7.
03-7.13 (m, 4H), 7.15-7.56 (m, 14H)

Example 41: Compound 55 Compound 44 obtained in Example 31 (33 mg, 0.059 mmol)
Was dissolved in acetonitrile (4.0 ml), piperonylamine (8.0 μl, 0.059 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 90/10) to give compound 5
5 (3.5 mg, 0.0050 mmol, yield 12%) was obtained. FABMS m / z: 702 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.89 (s, 4H), 4.34
(d, J = 5.5 Hz, 2H), 5.51 (s, 2H), 5.54 (s, 2H),
6.04 (s, 1H), 6.08 (s, 2H), 6.31 (brs, 1H), 6.80-6.
84 (m, 3H), 7.02-7.06 (m, 4H), 7.13-7.16 (m, 4H),
7.18-7.35 (m, 10H)

Example 42: Compound 56 Compound 44 (43 mg, 0.077 mmol) obtained in Example 31
Was dissolved in acetonitrile (3.0 ml), furfurylamine (6.8 μl, 0.077 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual post-treatment, the compound 56 was purified by thin-layer chromatography (chloroform / methanol = 98/2),
(2.2 mg, 0.0040 mmol, 7.0% yield). FABMS m / z: 648 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.88 (s, 4H), 4.43
-4.44 (m, 2H), 5.51 (s, 2H), 5.54 (s, 2H), 6.15
(s, 1H), 6.27 (brs, 1H), 6.35-6.38 (m, 2H), 6.82
(d, J = 8.5 Hz, 4H), 7.03 (d, J = 8.5 Hz, 4H), 7.1
2-7.32 (m, 10H), 7.42-7.44 (m, 1H)

Example 43: Compound 57 Compound 44 obtained in Example 31 (16 mg, 0.029 mmol)
Was dissolved in acetonitrile (4.0 ml), 4- (2-aminoethyl) phenol (4.0 mg, 0.029 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 57 (3.0 mg, 0.0040 mmol, yield 11%). FABMS m / z: 688 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.93 (t, J = 7.1 H
z, 2H), 3.45-3.47 (m, 2H), 3.89 (s, 4H), 4.85 (br
s, 1H), 5.50 (s, 2H), 5.53 (s, 2H), 6.03 (s, 1H),
6.11 (brs, 1H), 6.79-6.84 (m, 4H), 7.02-7.07 (m, 4
H), 7.09-7.29 (m, 14H)

Example 44: Compound 58 Compound 44 (37 mg, 0.067 mmol) obtained in Example 31
Was dissolved in acetonitrile (4.0 ml), 2- (2-methylaminoethyl) pyridine (9.3 μl, 0.067 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 58 (12 mg, 0.017 mmol, yield: 34%). FABMS m / z: 689 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.10 (s, 3H), 3.21
(t, J = 7.2 Hz, 2H), 3.88 (s, 2H), 3.89 (s, 2H),
4.08-4.16 (m, 2H), 5.51 (s, 2H), 5.54 (s, 2H), 6.0
8 (s, 1H), 6.82-6.87 (m, 5H), 7.03-7.07 (m, 5H),
7.13-7.29 (m, 10H), 7.53-7.59 (m, 1H), 8.40-8.42
(m, 1H)

Example 45: Compound 59 Compound 44 (24 mg, 0.043 mmol) obtained in Example 31
Was dissolved in acetonitrile (4.0 ml), and 2- (2-aminoethyl) pyridine (5.2 μl, 0.043 mmol) was added.
Stirred for minutes. After normal post-treatment, purify by thin-layer chromatography (chloroform / methanol = 90/10),
Compound 59 (7.4 mg, 0.011 mmol, yield 34%) was obtained. FABMS m / z: 673 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.18 (t, J = 6.3 H
z, 2H), 3.64-3.70 (m, 2H), 3.88 (s, 4H), 5.50 (s, 2
H), 5.53 (s, 2H), 6.04 (s, 1H), 6.81-6.84 (m, 4H),
7.01-7.05 (m, 4H), 7.13-7.29 (m, 12H), 7.60-7.68
(m, 1H), 8.59-8.61 (m, 1H)

Example 46: Compound 60 and Compound 61 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (50 ml), 4-cumylphenol (143 mg, 0.67 mmol) and potassium carbonate (75 mg, 0.54 mmol) were added, and the mixture was stirred at room temperature overnight. After normal post-treatment, silica gel chromatography
(Chloroform / methanol = 98/2)
Bis (4-cumylphenyloxymethyl) -5,8-dimethoxyquinoxaline (151 mg, 0.24 mmol, yield 88%) was obtained. FABMS m / z: 639 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.63 (s, 12H), 4.0
4 (s, 6H), 5.57 (s, 4H), 6.83-6.87 (m, 4H), 7.03-
7.06 (m, 4H), 7.09 (s, 2H), 7.12-7.27 (m, 10H) 2,3-bis (4-cumylphenyloxymethyl)-obtained above
5,8-Dimethoxyquinoxaline (30 mg, 0.047 mmol) was dissolved in a mixed solvent of acetonitrile (5.0 ml) and water (1.0 ml), and diammonium cerium (IV) nitrate (64 mg, 0.12 mm
ol) and stirred at room temperature for 2 hours. After usual work-up, concentration gave Compound 60 (46 mg, 0.077 mmol). FABMS m / z: 611 (M + 3H) ⁺

Compound 60 obtained above (46 mg, 0.077
mmol) was dissolved in acetonitrile (5 ml), N, N-dimethylethylenediamine (8.3 μl, 0.077 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After ordinary post-treatment, purification was carried out by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 61 (14 mg, 0.020 mmol, yield: 44%). FABMS m / z: 697 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.63 (s, 12H), 2.2
9 (s, 6H), 2.64 (t, J = 6.1 Hz, 2H), 3.22-3.27 (m,
2H), 5.52 (s, 2H), 5.55 (s, 2H), 5.99 (s, 1H), 6.7
8 (brs, 1H), 6.78-6.83 (m, 4H), 7.07-7.10 (m, 4H),
7.15-7.25 (m, 10H)

Example 47: Compound 62 and Compound 63 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (100 ml), and p-hydroxybenzophenone (134 mg, 0.67 mmo
l) and potassium carbonate (120 mg, 0.81 mmol) were added, and the mixture was stirred at room temperature overnight. After the usual post-treatment, purification by silica gel chromatography (chloroform / methanol = 98/2) yielded 2,3-bis (4-benzoylphenyloxymethyl) -5,8
-Dimethoxyquinoxaline (121 mg, 0.20 mmol, yield 73
%). FABMS m / z: 611 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.09 (s, 6H), 5.69
(s, 4H), 7.00-7.05 (m, 4H), 7.11 (s, 2H), 7.43-7.
48, (m, 4H), 7.53-7.59 (m, 2H), 7.70-7.73 (m, 4H),
7.75-7.80 (m, 4H)

The 2,3-bis (4-benzoylphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (73
mg, 0.12 mmol) in acetonitrile (30 ml), water (6.0
dissolved in a mixed solvent of
Cerium (IV) diammonium nitrate (164 mg, 0.30 mmol)
Was added and stirred at room temperature for 2 hours. After usual work-up, concentration gave compound 62 (51 mg, 0.088 mmol). FABMS m / z: 583 (M + 3H) ⁺

The compound 62 obtained above (29 mg, 0.050
mmol) in acetonitrile (5.0 ml), and N, N-dimethylethylenediamine (5.5 μl, 0.050 mmol) was added.
Stirred at room temperature for 1 hour. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 63 (8.0 mg, 0.012 mmol, yield: 24%). FABMS m / z: 667 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.65
(t, J = 6.0 Hz, 2H), 3.24-3.29 (m, 2H), 5.66 (s, 2
H), 5.68 (s, 2H), 6.03 (s, 1H), 6.75 (brs, 1H), 6.9
8-7.01 (m, 4H), 7.44-7.48 (m, 4H), 7.54-7.59 (m, 2
H), 7.70-7.73 (m, 4H), 7.77-7.80 (m, 4H)

Example 48: Compound 64 and Compound 65 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(100 mg, 0.27 mmol) was dissolved in acetonitrile (50 ml), 4-phenoxyphenol (127 mg, 0.67 mmol) and potassium carbonate (75 mg, 0.54 mmol, 2.0 eq) were added, and the mixture was stirred at room temperature overnight. After the usual post-treatment, purification by silica gel chromatography (chloroform / methanol = 98/2) yielded 2,3-bis (4-phenoxyphenyloxymethyl)-
5,8-dimethoxyquinoxaline (121 mg, 0.21 mmol, yield
78%). FABMS m / z: 587 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.08 (s, 6H), 5.60
(s, 4H), 6.90-6.93 (m, 12H), 7.00-7.08 (m, 4H),
7.27-7.32 (m, 4H)

The 2,3-bis (4-phenoxyphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (30
mg, 0.051 mmol) in acetonitrile (5.0 ml) and water (1.0
cerium diammonium nitrate
(IV) (56 mg, 0.10 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual work-up, Compound 64 (17 mg,
0.031 mmol). FABMS m / z: 557 (M + H) ⁺

The compound 64 obtained above (17 mg, 0.031
mmol) was dissolved in acetonitrile (2.0 ml), and N, N-dimethylethylenediamine (3.8 μl, 0.031 mmol) was added.
Stirred at room temperature for 15 minutes. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 90/10)
Compound 65 (7.4 mg, 0.012 mmol, 34% yield)
I got FABMS m / z: 643 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.65
(t, J = 6.0 Hz, 2H), 3.23-3.28 (m, 2H), 5.56 (s, 2
H), 5.58 (s, 2H), 6.00 (s, 1H), 6.70 (brs, 1H), 6.9
1-6.94 (m, 14H), 7.02-7.08 (m, 2H), 7.27-7.33 (m,
2H)

Example 49: Compound 66 and Compound 67 trans-4-hydroxystilbene (1.0 g, 5.0 mmol)
Dissolved in ethanol (150 ml) and 10% palladium on carbon
(100 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours.
After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was concentrated and dried. The crude product 4-phenethylphenol (870 mg, 4.4 mmol, yield
88%). ¹ H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.80-2.88 (m, 8H),
6.73-6.76 (m, 2H), 7.02-7.15 (m, 2H), 7.17-7.30
(m, 5H)

2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline (100 mg, 0.27 mmol) was added to acetonitrile
(50 ml), and the above-obtained 4-phenethylphenol (134 mg, 0.67 mmol) and potassium carbonate (75 mg,
(0.54 mmol) and the mixture was stirred at room temperature overnight. After the usual post-treatment, purification by silica gel chromatography (chloroform / methanol = 98/2) yielded 2,3-bis (4-phenethylphenyloxymethyl) -5,8-dimethoxyquinoxaline.
(108 mg, 0.18 mmol, 66% yield). FABMS m / z: 611 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.80-2.87 (m, 8H),
4.07 (s, 6H), 5.57 (s, 4H), 6.72-6.77 (m, 2H), 6.
85-6.89 (m, 4H), 6.95-7.07 (m, 5H), 7.12-7.20 (m,
5H), 7.23-7.30 (m, 4H)

The 2,3-bis (4-phenethylphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (39
mg, 0.064 mmol) in acetonitrile (30 ml) and water (6.0
cerium diammonium nitrate
(IV) (88 mg, 0.16 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After usual work-up, compound 66 (44 mg,
0.077 mmol). FABMS m / z: 683 (M + 3H) ⁺

The compound 66 obtained above (44 mg, 0.077
was dissolved in acetonitrile (4.0 ml), N, N-dimethylethylenediamine (8.3 μl, 0.077 mmol) was added,
Stirred at room temperature for 30 minutes. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 90/10)
Compound 67 (4.3 mg, 0.0060 mmol, yield 9.4)
%). FABMS m / z: 667 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 14H), 2.6
4 (t, J = 6.0 Hz, 2H), 3.21-3.25 (m, 2H), 5.53 (s,
2H), 5.56 (s, 2H), 5.99 (s, 1H), 6.70 (brs, 1H), 6.
83-6.86 (m, 4H), 7.03-7.06 (m, 4H), 7.13-7.29 (m,
10H),

Example 50: Compound 68 2,3-Bis (bromomethyl) -5,8-dimethoxyquinoxaline (38 mg, 0.10 mmol) was dissolved in acetonitrile (10 ml), and 4-benzyloxyphenol (41 mg, 0.20 mmol)
And potassium carbonate (28 mg, 0.20 mmol).
Stirred for hours. After normal post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 98/2),
-Bis (4-benzyloxyphenyloxymethyl) -5,8-dimethoxyquinoxaline (45 mg, yield 73%) was obtained. FABMS m / z: 615 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.06 (s, 6H), 4.98
(s, 4H), 5.54 (s, 4H), 6.75-6.95 (m, 8H), 7.04
(s, 2H), 7.25-7.40 (m, 10H)

2,3-bis (4-benzyloxyphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above
(130 mg, 0.21 mmol) was dissolved in acetonitrile (12 ml), and water (1.0 ml) and cerium diammonium nitrate (I
V) (232 mg, 0.42 mmol) was added and the mixture was stirred at room temperature for 15 minutes. The compound 68 (40 mg, yield 33) was subjected to usual post-treatment.
%). FABMS m / z: 587 (M + 3H) ⁺ , 586 (M + 2H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 4.99 (s, 4H), 5.54
(s, 4H), 6.86 (m, 8H), 7.25-7.39 (m, 12H)

Example 51: Compound 69 Compound 68 obtained in Example 50 (10 mg, 0.017 mmol)
l) was dissolved in acetonitrile (2.0 ml) and N, N-dimethyl
-1,3-Propanediamine (1.7 mg, 0.017 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 69 (4.0 mg, yield 34%). FABMS m / z: 685 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.87 (m, 2H), 2.32
(s, 6H), 2.52 (m, 2H), 3.35 (m, 2H), 4.99 (s, 4
H), 5.49 (s, 2H), 5.53 (s, 2H), 5.95 (s, 1H), 6.75
6.90 (m, 8H), 7.25-7.43 (m, 10H), 8.78 (brs, 1H)

Example 52: Compound 70 Compound 68 obtained in Example 50 (9.2 mg, 0.016 mmol)
l) was dissolved in acetonitrile (2.0 ml), N, N-dimethylethylenediamine (1.7 μl, 0.038 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 70 (4.0 mg, yield 38%). FABMS m / z: 671 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.31 (s, 6H), 2.65
(t, J = 6.0Hz, 2H), 3.20 (m, 2H), 4.98 (s, 2H),
4.99 (s, 2H), 5.50 (s, 2H), 5.53 (s, 2H), 5.99 (s,
1H), 6.71 (br, 1H), 6.80-6.90 (m, 8H), 7.23-7.44
(m, 10H)

Example 53: Compound 71 Compound 68 obtained in Example 50 (10 mg, 0.017 mmol)
l) was dissolved in acetonitrile (2.0 ml), N, N-diethylethylenediamine (2.0 mg, 0.017 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After ordinary post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 71 (4.0 mg, yield 33%). FABMS m /
z: 699 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.06 (t, J = 7.1 H
z, 6H), 2.59 (q, J = 7.1 Hz, 4H), 2.77 (t, J = 6.2
Hz, 2H), 3.21 (br, 2H), 4.99 (s, 4H), 5.50 (s, 2
H), 5.53 (s, 2H), 5.98 (s, 1H), 6.75-6.98 (m, 9H),
7.20-7.60 (m, 10H)

Example 54: Compound 72 Compound 68 obtained in Example 50 (10 mg, 0.017 mmol)
l) was dissolved in acetonitrile (2.0 ml), 1- (3-aminopropyl) imidazole (2.1 mg, 0.017 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. After usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 72 (4.0 mg, yield 34%). FABMS m / z: 708 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.24 (m, 2H), 3.26
(m, 2H), 4.11 (t, J = 6.8 Hz, 2H), 4.98 (s, 2H),
4.99 (s, 2H), 5.49 (s, 2H), 5.52 (s, 2H), 5.97 (s,
1H), 6.07 (br, 1H), 6.80-7.70 (m, 21H)

Example 55: Compound 73 Compound 68 obtained in Example 50 (9.5 mg, 0.016 mmol)
l) was dissolved in acetonitrile (2.0 ml), N-methylpiperazine (1.8 μl, 0.016 mmol) was added, and the mixture was stirred at room temperature for 50 minutes. After usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 95/5) to obtain Compound 73 (5.3 mg, yield 48%). FABMS m / z: 685 (M + 3H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.36 (s, 3H), 2.60
(m, 4H), 3.66 (m, 4H), 4.98 (s, 2H), 4.99 (s, 2
H), 5.69 (s, 2H), 5.51 (s, 2H), 6.26 (s, 1H), 6.80-
6.93 (m, 8H), 7.25-7.45 (m, 10H)

Example 56: Compound 74 and Compound 75 Palladium acetate (123 mg, 0.55 mol) and tri-o-tolylphosphine (670 mg, 2.2 mmol) were dissolved in N, N-dimethylformamide (10 ml). 1 at room temperature under argon atmosphere
Stirred for hours. Then, p-iodophenol (300 mg,
1.4 mmol), 2-vinylpyridine (0.60 ml, 5.5 mmol) and triethylamine (0.80 ml, 5.5 mmol) were added, and the mixture was heated under reflux for 3 hours. The reaction mixture was filtered through celite, the filtrate was concentrated and dried, and the resulting residue was subjected to silica gel chromatography.
(Chloroform only ~ chloroform / methanol = 97 /
(Eluted with 3) to give 2- [2- (4-hydroxyphenyl) vinyl] pyridine (224 mg, 1.1 mmol, 83% yield). ¹ H NMR (300 MHz, CDCl ₃ ) δ ppm: 6.78 (d, J = 8.6 H
z, 2H), 7.03 (d, J = 15 Hz, 1H), 7.19-7.23 (m, 1
H), 7.45 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 15 Hz, 1
H), 7.56-7.59 (m, 1H), 7.74-7.80 (m, 1H), 7.89 (s,
1H), 8.44-8.55 (m, 1H)

The 2- [2- (4-hydroxyphenyl) vinyl] pyridine (220 mg, 1.1 mmol) obtained above was added to ethanol
(50 ml), 10% palladium carbon (50 mg) was added, and the mixture was stirred overnight at room temperature under a hydrogen atmosphere. The reaction mixture was filtered through celite, the filtrate was concentrated to dryness, and the crude product 2- [2- (4-
Hydroxyphenyl) ethyl] pyridine (206 mg, 1.0 mm
ol, yield 94%). ¹ H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.86-2.91 (m, 2H),
2.93-3.03 (m, 2H), 6.62-6.68 (m, 2H), 6.93-6.98
(m, 2H), 7.18-7.25 (m, 2H), 7.66-7.72 (m, 1H), 7.8
9 (s, 1H), 8.42-8.43 (m, 1H)

2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline (97 mg, 0.26 mmol) was added to acetonitrile
(50 ml) and the crude product obtained above, 2- [2- (4-hydroxyphenyl) ethyl] pyridine (129 mg, 0.65 mmo
l, 2.5 eq) and potassium carbonate (75 mg, 0.54 mmol) were added, and the mixture was stirred at room temperature overnight. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 95/5) to give 2,3-bis [4- [2- (2-pyridyl) ethyl] phenyloxymethyl] -5,8- Dimethoxyquinoxaline (33 mg, 0.054
mmol, 21% yield). FABMS m / z: 613 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.93-3.07 (m, 8H),
4.07 (s, 6H), 5.56 (s, 4H), 6.85-6.88 (m, 4H), 7.
01-7.12 (m, 10H), 7.50-7.56 (m, 2H), 7.54-7.56 (m,
2H)

The 2,3-bis [4- [2- (2-pyridyl) ethyl] phenyloxymethyl] -5,8-dimethoxyquinoxaline (23 mg, 0.038 mmol) obtained above was treated with acetonitrile (4.0 mg).
The mixture was dissolved in a mixed solvent of water (0.8 ml) and water (0.8 ml), ceric ammonium dinitrate (IV) (42 mg, 0.076 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual post-treatment, compound 74 (17 mg, 0.29 mmol) was obtained by concentration. FABMS m / z: 583 (M + H) ⁺

The compound 74 obtained above (17 mg, 0.029
mmol) in acetonitrile (2.0 ml), N, N-dimethylethylenediamine (3.1 μl, 0.029 mmol) was added,
Stirred at room temperature for 20 minutes. After normal post-treatment, thin-layer chromatography (chloroform / methanol = 90/10)
Compound 75 (3.2 mg, 0.0050 mmol, 17% yield)
I got FABMS m / z: 669 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.64
(t, J = 5.9 Hz, 2H), 3.00-3.06 (m, 8H), 3.24-3.26
(m, 2H), 5.52 (s, 2H), 5.55 (s, 2H), 5.99 (s, 1H),
6.70 (brs, 1H), 6.81-6.85 (m, 4H), 7.02-7.12 (m,
8H), 7.52-7.57 (m, 2H), 8.54-8.55 (m, 2H)

Example 57: Compound 76 and Compound 77 2,3-bis (bromomethyl) -5,8-dimethoxyquinoxaline
(117 mg, 0.31 mmol) was dissolved in acetonitrile (50 ml), and 2-hydroxydiphenylmethane (144 mg, 0.78 mmo
l) and potassium carbonate (86 mg, 0.62 mmol) were added, and the mixture was stirred at room temperature overnight. After the usual post-treatment, purification by silica gel chromatography (chloroform / methanol = 98/2) yielded 2,3-bis (2-benzylphenyloxymethyl) -5,8-
Dimethoxyquinoxaline (130 mg, 0.22 mmol, 72% yield)
I got FABMS m / z: 583 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.84 (s, 4H), 4.09
(s, 6H), 5.12 (s, 4H), 6.68-6.71 (m, 2H), 6.84-6.
89 (m, 2H), 6.96-6.99 (m, 4H), 7.05-7.20 (m, 12H)

The 2,3-bis (2-benzylphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained above (200
mg, 0.34 mmol) in acetonitrile (40 ml) and water (8.0 m
l) in a mixed solvent, and diammonium cerium nitrate (I
V) (373 mg, 0.68 mmol) was added and the mixture was stirred at room temperature for 2 hours.
After the usual work-up, the compound 76 (142 mg, 0.26
mmol). FABMS m / z: 555 (M + 3H) ⁺

The compound 76 obtained above (30 mg, 0.055
mmol) was dissolved in acetonitrile (2 ml), N, N-dimethylethylenediamine (6.0 μl, 0.016 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After the usual post-treatment, purification was performed by thin-layer chromatography (chloroform / methanol = 90/10) to obtain Compound 77 (10 mg, 0.016 mmol, 29% yield). FABMS m / z: 639 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 2.30 (s, 6H), 2.65
(t, J = 6.0 Hz, 2H), 3.24-3.29 (m, 2H), 3.85 (s, 4
H), 5.00 (s, 2H), 5.05 (s, 2H), 6.01 (s, 1H), 6.50
(brs, 1H), 6.66-6.72 (m, 3H), 6.88-6.98 (m, 6H),
7.08-7.17 (m, 9H)

Example 58: Compound 78 6,7,8,9-Tetrahydro-1,4-phenazinedione (37 mg,
0.17 mmol) was dissolved in acetonitrile (10 ml) and phosphate buffer (pH 7, 2.0 ml), and 4-aminothiophenol (22 mg, 0.017 mmol) was added, followed by stirring at room temperature for 10 minutes. After ordinary post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 97/3) to give compound 78 (1
9 mg, yield 33%). FABMS m / z: 338 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 1.95-2.08 (m, 4H),
3.13-3.25 (m, 4H), 4.01 (brs, 2H), 6.34 (s, 1H),
6.76 (m, 2H), 7.28 (m, 2H)

Example 59: Compound 79 and Compound 81 2,3-bis (phenoxymethyl) -5,8 obtained in Example 23
-Dimethoxyquinoxaline (50 mg, 0.12 mmol) was dissolved in methanol (8.0 ml), and cerium diammonium nitrate was dissolved.
(IV) (230 mg, 0.42 mmol) was added, and the mixture was stirred at room temperature for 40 minutes. After the usual post-treatment, the product was purified by thin-layer chromatography (chloroform / methanol = 98/2) to give Compound 79.
(10 mg, 0.029 mmol, 24% yield) and Compound 81 (17 mg,
0.029 mmol, 31% yield). Compound 79 FABMS m / z: 419 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.43 (s, 6H), 5.54
(s, 2H), 5.57 (s, 2H), 6.70 (d, J = 11 Hz, 1H),
6.91-6.99 (m, 5H), 7.16 (d, J = 11 Hz, 1H), 7.20-
7.29 (m, 5H) Compound 81 FABMS m / z: 464 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.34 (s, 12H), 5.1
5 (s, 4H), 6.42 (s, 2H), 6.90-6.97 (m, 6H), 7.20-
7.26 (m, 4H)

Example 60: Compound 80 2,3-Bis (4-benzyloxyphenyloxymethyl) -5,8-dimethoxyquinoxaline obtained in Example 50 (21 m
g, 0.034 mmol) in acetonitrile (2.5 ml),
Methanol (0.7 ml) and diammonium cerium (IV) nitrate (46 mg, 0.084 mmol) were added, and the mixture was stirred at room temperature for 3.5 hours. Compound 80 (4.4 mg, yield 21) after the usual post-treatment
%). FABMS m / z: 631 (M + H) ^{+ 1} H NMR (300 MHz, CDCl ₃ ) δ ppm: 3.41 (s, 6H), 4.99
(s, 2H), 5.00 (s, 2H), 5.47 (s, 2H), 5.50 (s, 2
H), 6.70 (d, J = 10.6 Hz, 1H), 6.80-6.90 (m, 8H),
7.15 (d, J = 10.6 Hz, 1H), 7.25-7.42 (m, 10H)

Test Example 1: Growth Inhibition Test on Human Lung Cancer A549 Cells 1000 human lung cancer A549 cells were seeded per well in a 96-well microplate (Nunc # 167008) and incubated at 37 ° C. in a 5% CO 2 incubator at 24 ° C. For a time, preculture was performed in RPMI 1640 medium containing 10% fetal calf serum (FCS).
Then, a 10 mM solution of each test compound in DMSO was serially diluted with a culture medium, and 50 μl was added to each well.
μl was added. After culturing at 37 ° C for an additional 72 hours, 5- (4,5-dimethylthiazol-2-yl)-dissolved in the culture medium to a final concentration of 1 mg / ml 5 hours before the end of the culture.
2,5-diphenyltetrazolium bromide (3- (4,5-dimet
hylthiazol-2-yl) -2,5-diphenyltetorazorium bromido
(Sigma), hereinafter abbreviated as MTT] was dispensed at 50 μl per well. After culture, add 150 μl DMSO per well
Agitate vigorously using a plate mixer
MTT-formazan crystals were completely dissolved, and the absorbance at 550 nm was measured using a microplate reader MTP-32 (Corona Electric). The cell growth inhibitory activity was represented by a 50% growth inhibitory concentration (IC ₅₀ ). The results are shown in Table 3.

[0164]

[Table 7]

[0165]

Industrial Applicability The compound of the present invention has a growth inhibitory activity on tumor cells and is useful as an active ingredient of pharmaceuticals such as antitumor agents.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 401/12 C07D 401/12 405/04 405/04 405/12 405/12 (72) Inventor Shunichi Ikeda 1-53-1, Takasu-cho, Sakai-shi, Osaka F-term (reference) in Kyowa Hakko Kogyo Co., Ltd. Sakai Laboratory 4C063 AA01 AA03 BB01 BB08 BB09 CC34 CC75 CC81 DD12 DD34 EE01 4C086 AA01 AA03 BC52 GA02 GA07 GA08 GA12 NA14 ZA01 ZA59 ZA66 ZA75 ZA81 ZA89 ZB21 ZB26 ZB27

Claims (8)

[Claims] 1. The following formula (I): [Wherein A and B together form (Wherein X ¹ and Y ¹ each independently represent a hydrogen atom, a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group; Group,
R ¹ and R ² each independently represent an alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, or a substituted or unsubstituted heterocyclic thio group. Represents an unsubstituted aryloxyalkyl group (provided that when R ¹ and R ² represent an alkyl group, a substituted or unsubstituted aryl group, or an unsubstituted heterocyclic group, X ¹ and Y ¹ are simultaneously hydrogen atoms There is no); A and B together (Wherein X ² and Y ² are each independently a hydrogen atom, an amino group, a substituted or unsubstituted mono-lower alkylamino group,
Substituted or unsubstituted di-lower alkylamino group, substituted or unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted or unsubstituted heterocyclic amino group, substituted Or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkenylthio group, substituted or unsubstituted arylthio group, substituted or unsubstituted aralkylthio group, substituted or unsubstituted R ³ and R ⁴ each independently represent a lower alkoxy group or together represent an oxygen atom; ⁵ and either R ⁶ represents a lower alkoxy group each independently or both together an oxygen atom) Sutoki each R ¹ and R ² are independently a hydrogen atom, an alkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, halogenated alkyl group, or a substituted or unsubstituted aryloxyalkyl R ¹ and R ² together represent — (CH ₂ ) _n — (wherein _n represents an integer from 2 to 6), provided that R ¹ and R ² are simultaneously Does not indicate a hydrogen atom). Provided that when R ¹ and R ² are each independently an alkyl group, R ³ and R ⁴ together represent an oxygen atom, and R ⁵ and R ⁶ together represent an oxygen atom, One of X ² and Y ² is a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group, or a substituted or unsubstituted aralkylthio group. Represents an unsubstituted heterocyclic thio group, wherein R ¹ and R ² are each independently a phenyl group, a tolyl group, or a pyridyl group, or are both taken together as — (CH ₂ ) ₄ —
And R ³ and R ⁴ together represent an oxygen atom, and R ⁵ and R ⁶ together represent an oxygen atom;
One of X ² and Y ² is a substituted mono-lower alkylamino group, a substituted di-lower alkylamino group, a substituted or unsubstituted lower alkenylamino group, a substituted or unsubstituted aralkylamino group, a substituted or unsubstituted aryl Amino group, substituted or unsubstituted heterocyclic amino group, substituted or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkenylthio group, substituted or unsubstituted arylthio group , A substituted or unsubstituted heterocyclic thio group, or a substituted or unsubstituted alicyclic heterocyclic group]] or a salt thereof. 2. The following formula (Ia): (Wherein X ¹ and Y ¹ each independently represent a hydrogen atom, a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group; Group,
Or a substituted or unsubstituted heterocyclic thio group; R ¹ - ¹
And R ¹ - ² are each independently an alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group,
Or a substituted or unsubstituted aryloxyalkyl group. However, R ¹ - ¹ and R ¹ - ² alkyl group, a substituted or unsubstituted aryl group, or unsubstituted X ¹ and Y ¹ when referring to the heterocyclic group are not hydrogen atoms at the same time) The represented quinoxaline derivative or a salt thereof. 3. The following formula (Ib): [Wherein X ² and Y ² are each independently a hydrogen atom, an amino group, a substituted or unsubstituted mono-lower alkylamino group,
Substituted or unsubstituted di-lower alkylamino group, substituted or unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted or unsubstituted heterocyclic amino group, substituted Or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkenylthio group, substituted or unsubstituted arylthio group, substituted or unsubstituted aralkylthio group, substituted or unsubstituted shows a heterocyclic thio group, or a substituted or unsubstituted alicyclic heterocyclic group; R ² - ¹ and R ² - ²
Are each independently a hydrogen atom, an alkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group,
Halogenated alkyl group, or a substituted or unsubstituted aryloxyalkyl groups, or R ² - ¹ and R
² - ² together - (CH _{2) n} - (wherein, n represents an integer from 2 to 6) indicates (where, R ² - ¹ and R ²
- ² never represents a hydrogen atom simultaneously); R ² - ³ and R ² - ⁴ or each independently represent a lower alkoxy group, or an oxygen atom both together; R ² - ⁵ and R ²
- ⁶ or each independently represent a lower alkoxy group, or an oxygen atom both together. However, R ² - ¹ and R ² - ² are each independently an alkyl group, R ² - ³ and R ² - ⁴ represents an oxygen atom together, and R ² - ⁵ and R ² - ⁶ is When taken together represent an oxygen atom, X ²
And Y ² is a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted aralkylthio group, or a substituted or unsubstituted shows a heterocyclic thio group, R ² - ¹ and R ² - ² are either each independently a phenyl group, a tolyl group, or a pyridyl group, or both together - (CH _{2) 4} - are shown , R ² - ³ and R ² - ⁴ together an oxygen atom,
And R ² - ⁵ and R ² - to indicate ⁶ oxygen atoms taken together, one of X ² and Y ² is a substituted mono-lower alkylamino group, a substituted di-lower alkylamino group, a substituted or Unsubstituted lower alkenylamino group, substituted or unsubstituted aralkylamino group, substituted or unsubstituted arylamino group, substituted or unsubstituted heterocyclic amino group, substituted or unsubstituted heterocyclic alkylamino group, substituted or unsubstituted A substituted lower alkylthio group, a substituted or unsubstituted lower alkenylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted heterocyclic thio group,
Or a substituted or unsubstituted alicyclic heterocyclic group]] or a salt thereof. Wherein X ² is substituted or unsubstituted mono-lower alkylamino group, or a substituted or unsubstituted di-lower alkylamino group, Y ² is a hydrogen atom, R ² - ¹ and R ² - ² There are each independently a substituted or unsubstituted aryl group, or a substituted or unsubstituted aryloxy group, R ² - ³ and R ² - ⁴ together an oxygen atom, R ² - ⁵ and R ² - ⁶ quinoxaline derivatives or salts thereof according to claim 3, an oxygen atom together. 5. A mono-lower alkylamino group wherein X ² is substituted with a di-lower alkylamino group or a morpholino group,
Or a di-lower alkylamino group or substituted di-lower alkylamino group morpholino group, Y ² is a hydrogen atom, R ² - ¹ and R ² - ² are both a substituted aryl group, or a substituted phenoxyalkyl group Yes, R ^{2 -3} and R ^{2 -4}
There an oxygen atom together, R ² - ⁵ and R ² - ⁶ quinoxaline derivatives or salts thereof according to claim 3, an oxygen atom together. 6. X ^{2 is} an ethylamino group substituted with a di-lower alkylamino group or a morpholino group, or an ethylmethylamino group substituted with a di-lower alkylamino group or a morpholino group, and Y ² is a hydrogen atom. Yes, R ²
- ¹ and R ² - ² are both halogenated aryl group, or a benzyl group or phenoxyalkyl group substituted by a benzyloxy group, R ² - ³ and R ² - ⁴ together an oxygen atom, R ² - ⁵ and R ² - ⁶ quinoxaline derivatives or salts thereof according to claim 3, an oxygen atom together. 7. The quinoxaline derivative according to any one of claims 1 to 6, and a pharmaceutically acceptable salt thereof,
And a medicament comprising, as an active ingredient, a substance selected from the group consisting of hydrates and solvates thereof. 8. A quinoxaline derivative according to any one of claims 1 to 6 and a pharmaceutically acceptable salt thereof,
And an antitumor agent comprising a substance selected from the group consisting of hydrates and solvates thereof.