JP2000154139A - Fused pyrazine derivative - Google Patents

Abstract

(57) [Problem] To provide an insulin secretagogue and a therapeutic agent for diabetes, which comprise a fused pyrazine derivative as an active ingredient. [Solution] [Wherein, R ^1A and R ^1B are the same or different and represent hydrogen or the like, R represents lower alkyl or the like, X ¹ , X ² , X ³ and X
⁴ is the same or different and represents CH or nitrogen, m represents 0 or 1, n represents 0 or 1, W ... V ... U is NC = O or
N = CN, A) When W… V… U is NC = O, Y… Z is CH-CH
₂ or C = CH, R ² represents a substituted or unsubstituted lower alkyl, etc., B) When W… V… U is N = CN, Y… Z is
Represents C = CH, and R ^3A and R ^3B are the same or different and represent lower alkyl, etc.] and an insulin secretagogue containing a fused pyrazine derivative or a pharmaceutically acceptable salt thereof as an active ingredient. provide.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an insulin secretagogue and a therapeutic agent for diabetes containing a fused pyrazine derivative as an active ingredient. The present invention also relates to a fused ring pyrazine derivative or a pharmaceutically acceptable salt thereof, which has a glucose concentration-dependent insulin secretion promoting action and a suitable hypoglycemic action, and is useful as a therapeutic agent for diabetes.

[0002]

BACKGROUND OF THE INVENTION Diabetes is a condition in which blood sugar levels are inappropriately elevated and are characterized by abnormal insulin secretion and various metabolic and vascular abnormalities. If various treatments are not effective or remain untreated in this condition, serious complications arise due to arterial and nervous system disorders caused by hyperglycemia. For this reason, means for lowering blood sugar levels have been studied for a long time.

[0003] Among non-insulin-dependent diabetic patients, blood glucose control can be performed by a combination of exercise therapy and a drug for lowering blood glucose levels. As a drug, an insulin secretagogue is currently widely used in clinical practice as one of oral hypoglycemic agents.
However, currently available insulin secretagogues such as sulphonylureas, such as glibenclamide, cause glucose concentration-independent insulin secretion, so that erroneous doses cause severe hypoglycemia, or It is unsatisfactory because it has an effect that cannot control blood sugar. Therefore, there is a demand for an insulin secretagogue that is effective for controlling blood sugar in diabetic patients as an insulin secretagogue by inducing insulin secretion in accordance with the blood sugar level.

[0004] For example, the following are known as condensed pyrazine derivatives. (A) U.S. Pat. No. 3,479,347 discloses that the following compounds are useful as diuretics and anti-inflammatory drugs.

[0005]

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[Wherein, R ^1a represents hydrogen, linear or branched alkyl having 1 to 8 carbon atoms, cycloalkyl or benzyl having 3 to 6 carbon atoms, and R ^2a represents linear or branched Alkyl having 1 to 8 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, phenyl, phenyl substituted with halogen (the halogen represents fluorine, chlorine, bromine or iodine), linear or branched Phenyl substituted with alkyl having 1 to 8 carbons,
Nitro-substituted phenyl or lower alkoxy wherein the alkyl moiety of the alkoxy is a straight-chain or branched
Represents phenyl, benzyl, pyridyl, furyl or thienyl substituted with） 8 alkyl). (B) U.S. Pat. No. 3,366,628 discloses that the following compounds are useful as anti-inflammatory agents.

[0007]

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Wherein R ^1b is a polyhydroxyalkyl,
Represents dihydroxy-substituted lower alkyl or trihydroxy-substituted lower alkyl, and R ^2b represents lower alkyl, phenyl, phenyl substituted with nitro, phenyl substituted with lower alkyl, phenyl substituted with halogen, phenyl substituted with lower alkoxy. Represents benzyl, pyridyl, furyl or thienyl, R ^3b and R ^6b are the same or different and represent hydrogen, halogen, lower alkyl or lower alkoxy, R ^4b and R ^5b are the same or different and are hydrogen, halogen, trifluoro Represents methyl, lower alkyl or lower alkoxy, or R ^4b and R ^5b together form a methylene chain having 3 or 4 carbon atoms.) (C) Chem. Berichte (Chem. Ber.), 108 (8)
Volume, page 2750 (1975) describes the following compounds:

[0009]

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(Wherein R ^1c represents hydrogen or methyl) (d) Synthesis, vol. 2, p. 145 (198
3 years) describes the following compounds.

[0011]

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(Wherein R ^1d represents hydrogen or methyl;
^2d represents methyl, ethyl, isobutyl, phenyl, 2-methoxyphenyl or 3-bromophenyl, and R ^3d represents hydrogen, bromine or nitro. (E) Kimiko-Farmatsveticheskij Zhurnal , 2 (11)
Volume, page 19 (1968) describes the following compounds:

[0013]

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Wherein R ^1e represents hydrogen, methyl, 4-ethoxyphenyl, 4-methylphenyl or 4-chlorophenyl, and R ^2e represents ethyl or phenyl. (F) Chemische Berichte (Chem. Ber. ), 102 (12)
Vol. 4032 (1969) describes the following two compounds.

[0015]

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However, there is no description in the above-mentioned publications or literatures on the insulin secretagogue-promoting effect and the diabetes therapeutic effect.

[0017]

SUMMARY OF THE INVENTION An object of the present invention is to provide an insulin secretagogue and a therapeutic agent for diabetes containing a fused pyrazine derivative as an active ingredient.

[0018]

According to the present invention, there is provided a compound of the formula (I)

[0019]

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[Wherein R^1AAnd R^1BAre the same or different
Hydrogen, lower alkyl, lower alkoxy, lower alkano
Iloxy, lower alkylthio, halogen, nitro, low
Lower alkanoyl, lower alkoxycarbonyl, -NR^FourR^Five
(Where R^FourAnd R^FiveAre the same or different and are hydrogen or
Represents a substituted or unsubstituted lower alkyl, R^FourAnd R^FiveBut
Substituted or unsubstituted together with an adjacent nitrogen atom
To form a heterocyclic group), -NHCOR⁶(Where R⁶Is a replacement
Or unsubstituted lower alkyl) or -CONR ^4aR^5a
(Where R^4aAnd R^5aIs the R^FourAnd R^FiveSynonymous with
Wherein R is hydrogen, substituted or unsubstituted lower
Alkyl, substituted or unsubstituted cycloalkyl, substituted
Or unsubstituted aryl or substituted or unsubstituted
Represents a heterocyclic group, X¹, X^Two, X^ThreeAnd X^FourAre the same or different
Represents CH or nitrogen, m represents 0 or 1, and n represents 0 or
Represents 1, W ... V ... U represents N-C = O or N = C-N, and A) W ... V ... U represents N-C = O (where m = 1, n = 0)
Y… Z is CH-CH_TwoOr C = CH, R^TwoIs hydrogen, substitution is
Or unsubstituted lower alkyl, substituted or unsubstituted
Chloroalkyl, substituted or unsubstituted lower alkenyl,
Substituted or unsubstituted lower alkynyl, substituted or unsubstituted
Substituted aryl, substituted or unsubstituted aralkyl or
Represents a substituted or unsubstituted heterocyclic group, and B) W ... V ... U is N = C-N (where m = 0, n = 1)
Y… Z represents C = CH, R^3AAnd R^3BAre the same or different
Is hydrogen, substituted or unsubstituted lower alkyl, substituted
Or unsubstituted cycloalkyl, substituted or unsubstituted
Aryl, substituted or unsubstituted aralkyl or substituted
Represents a substituted or unsubstituted heterocyclic group, or R^{Three A}And R^3BIs adjacent
Substituted or unsubstituted complex with the nitrogen atom
Forming a cyclic group] or a condensed pyrazine derivative represented by
Insulin containing its pharmacologically acceptable salt as the active ingredient
And a secretagogue.

The present invention also relates to a therapeutic agent for diabetes comprising, as an active ingredient, the fused pyrazine derivative represented by the above formula (I) or a pharmaceutically acceptable salt thereof.

Further, the present invention provides a compound of the formula (Ia)

[0023]

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R where R^1AyAnd R^1ByAre the same or different
Is hydrogen, lower alkyl, lower alkoxy, lower alka
Noyloxy, lower alkylthio, halogen, nitro,
Lower alkanoyl, -NR^4yR^5y(Where R^4yAnd R^5yIs
Same or different, hydrogen or substituted or unsubstituted
Represents lower alkyl, R^4yAnd R^5yIs adjacent to the nitrogen atom
Together form a substituted or unsubstituted heterocyclic group
), -NHCOR^6y(Where R ^6yIs substituted or unsubstituted low
Represents a lower alkyl) or -CONR^4ayR^5ay(Where R ^4ay
And R^5ayIs the R^4yAnd R^5yIs synonymous with)
, My represents 0 or 1, ny represents 0 or 1, W^y
… V^y… U^yRepresents N-C = O or N = C-N, A) W^y… V^y… U^yIs N-C = O (my = 1 and ny = 0 at this time)
When I) X^1y, X^2y, X^3yAnd X^4yAll represent CH, and R^yBut
Substituted or unsubstituted lower alkyl, substituted or unsubstituted
Substituted cycloalkyl, substituted or unsubstituted aryl,
Or a substituted or unsubstituted heterocyclic group,^y… Z^y
Is CH-CH_TwoOr C = CH, I-a) Y^y… Z^yIs CH-CH_TwoWhen, R^2yIs substituted or unsubstituted
Lower alkyl, substituted or unsubstituted cycloalkyl
, Substituted or unsubstituted lower alkenyl, substituted or unsubstituted
Is unsubstituted lower alkynyl, substituted or unsubstituted ant
Aralkyl or substituted or unsubstituted aralkyl or substituted
Or unsubstituted heterocyclic group, I-b) Y^y… Z^yIs C = CH, then R^2yIs substituted or unsubstituted
Cycloalkyl, substituted or unsubstituted lower alkenyl
, Substituted or unsubstituted lower alkynyl, substituted or unsubstituted
Is unsubstituted aralkyl, substituted or unsubstituted heterocycle
Group, lower alkyl [the lower alkyl is substituted or unsubstituted
Substituted cycloalkyl, substituted or unsubstituted lower alkyl
Coxy, halogen, cyano, nitro, substituted or unsubstituted
Substituted lower alkoxycarbonyl, substituted or unsubstituted
Lower alkanoyloxy, carboxy, substituted or unsubstituted
A substituted heterocyclic group, -NR^7yR^8y(Where R^7yAnd R^8yIs the same
One or different hydrogen, substituted or unsubstituted lower
Alkyl or substituted or unsubstituted cycloalkyl
Or R^7yAnd R^8yIs replaced together with the adjacent nitrogen atom
Or forming an unsubstituted heterocyclic group) and -CONR^9y
R^10y(Where R^9yAnd R^{Ten y}Are the same or different, water
Represents an alkyl or a substituted or unsubstituted lower alkyl,
R^9yAnd R^10yIs substituted together with the adjacent nitrogen atom.
Or an unsubstituted heterocyclic group).
Or differently substituted with 1-3 substituents] or
Non-hydroxy-substituted lower alkyl
The lower alkyl moiety of the lower alkyl may be substituted or unsubstituted.
Substituted cycloalkyl, substituted or unsubstituted lower alcohol
Xy, halogen, cyano, nitro, substituted or unsubstituted
Lower alkoxycarbonyl, substituted or unsubstituted lower
Higher alkanoyloxy, carboxy, substituted or unsubstituted
A substituted heterocyclic group, -NR^7yR^8y(Where R^7yAnd R^8yIs it
And -CONR, respectively.^9yR^10y(Where R
^9yAnd R^10yIs as defined above)
The same or different, and may be substituted with 0 to 2 substituents.
II) X^1y, X^2y, X^3yAnd X^4yOf which X^1yOr X^4yOne
When nitrogen is the other and CH represents the other,^y… Z^yIs CH-CH_TwoMa
Or C = CH, II-a) Y^y… Z^yIs CH-CH_TwoAnd R^yIs replaced or non-
Substituted lower alkyl, substituted or unsubstituted cycloal
Killed, substituted or unsubstituted aryl or substituted or unsubstituted
Represents an unsubstituted heterocyclic group;^2yIs replaced or non-
Substituted lower alkyl, substituted or unsubstituted cycloal
Killed, substituted or unsubstituted lower alkenyl,
Or unsubstituted lower alkynyl, substituted or unsubstituted
Reel, substituted or unsubstituted aralkyl or substituted
Or an unsubstituted heterocyclic group, II-b1) Y^y… Z^yRepresents C = CH, and R^yIs substituted lower alkyl
, Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Is unsubstituted aryl or substituted or unsubstituted heterocycle
When representing a group, R^2yIs a substituted or unsubstituted lower alkyl
, Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Is unsubstituted lower alkenyl, substituted or unsubstituted lower
Alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted
Or unsubstituted aralkyl or substituted or unsubstituted
II-b2) Y^y… Z^yRepresents C = CH, and R^yIs unsubstituted lower al
When representing a kill, R^2yIs substituted lower alkyl, substituted or
Is unsubstituted cycloalkyl, substituted or unsubstituted lower
Alkenyl, substituted or unsubstituted lower alkynyl, substituted
Substituted or unsubstituted aryl, substituted or unsubstituted aryl
Aralkyl or a substituted or unsubstituted heterocyclic group, III) X^1y, X^2y, X^3yAnd X^4yOf which X^2yOr X^3yOne
When nitrogen is the other and CH represents the other, or X^1y, X^2y, X
^3yAnd X^4yAt least two of which are nitrogen
Others represent Y when representing CH^y… Z^yIs CH-CH_TwoOr C = CH, R^y
Is substituted or unsubstituted lower alkyl, substituted or unsubstituted
Substituted cycloalkyl, substituted or unsubstituted aryl
Or a substituted or unsubstituted heterocyclic group,^2yIs
Substituted or unsubstituted lower alkyl, substituted or unsubstituted
Cycloalkyl, substituted or unsubstituted lower alkenyl
, Substituted or unsubstituted lower alkynyl, substituted or unsubstituted
Is unsubstituted aryl, substituted or unsubstituted aralkyl
Or a substituted or unsubstituted heterocyclic group;^y… V^y… U^yIs N = C-N (where my = 0 and ny = 1)
Then X^1y, X^2y, X^3yAnd X^4yAre the same or different
Represents CH or nitrogen, R^yIs a substituted or unsubstituted lower
Alkyl, substituted or unsubstituted cycloalkyl, also substituted
Or unsubstituted aryl or substituted or unsubstituted
Represents a ring group, Y^y… Z^yRepresents C = CH, and R^3AyAnd R^3ByIs
Same or different, substituted or unsubstituted lower alkyl
, Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Is unsubstituted aryl, substituted or unsubstituted aralkyl
Or a substituted or unsubstituted heterocyclic group, or R^3AyWhen
R^3ByIs substituted or unsubstituted together with the adjacent nitrogen atom.
Condensed pyrazine derivative represented by｝ forming a substituted heterocyclic group
It relates to a conductor or a pharmacologically acceptable salt thereof.

The compound represented by the formula (I) is hereinafter referred to as compound (I). The same applies to compounds of other formula numbers.

[0026]

DETAILED DESCRIPTION OF THE INVENTION In the definition of each group of formula (I) and formula (Ia), lower alkyl and lower alkoxy,
As the alkyl moiety of lower alkanoyloxy, lower alkylthio and lower alkoxycarbonyl, linear or branched alkyl having 1 to 8 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- Butyl, pentyl, hexyl, heptyl, octyl, and the like.Examples of lower alkenyl include linear or branched C2-C8, for example, vinyl, allyl,
Methacryl, butenyl, crotyl, pentenyl, hexenyl, heptenyl, octenyl and the like, and as lower alkynyl, straight-chain or branched C 2-8,
For example, ethynyl, propargyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl and the like can be mentioned. The alkylene moiety of aralkyl represents the lower alkyl obtained by removing one hydrogen. Examples of the lower alkanoyl include linear or branched C1-8 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl and octanoyl.
Examples of the cycloalkyl include a carbon ring having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Halogen includes fluorine, chlorine, bromine and iodine atoms.

The aryl part of the aryl and aralkyl includes phenyl and naphthyl. Examples of the heterocyclic group include an aromatic heterocyclic group and an alicyclic heterocyclic group, and examples of the aromatic heterocyclic group include pyridyl,
Pyrazinyl, pyrimidinyl, pyridazinyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl,
Oxazolyl, thiazolyl, thienyl, furyl, benzodioxolyl, benzodioxanyl and the like.Examples of the alicyclic heterocyclic group include, for example, pyrrolidinyl, 2,5-dioxopyrrolidinyl, thiazolidinyl, oxazolidinyl, piperidyl, Examples include piperidino, piperazinyl, homopiperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, tetrahydrofuryl, tetrahydroquinolyl, tetrahydroisoquinolyl, tetrahydroquinoxalinyl, octahydroquinolyl, dihydroindolyl, and the like.

The heterocyclic group formed together with the adjacent nitrogen atom includes, for example, pyrrolidinyl, thiazolidinyl, oxazolidinyl, piperidino, homopiperidino, piperazinyl, homopiperazinyl, morpholino, thiomorpholino, perhydroazepinyl, tetrahydroquinolyl , Tetrahydroisoquinolyl, octahydroquinolyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, purinyl, dihydroindolyl,
Pyrrolyl, pyrazolyl, triazolyl, tetrazolyl,
And imidazolyl.

In the definitions of the following substituents, lower alkyl, lower alkoxy, cycloalkyl, halogen, lower alkoxycarbonyl, lower alkanoyloxy, aryl, aralkyl, heterocyclic group, alicyclic heterocyclic group, aromatic heterocyclic group And the heterocyclic group formed together with the adjacent nitrogen atom has the same meaning as described above, and the lower alkyl part of the mono- or di-lower alkylamino has the same meaning as the lower alkyl.

Substituted lower alkyl, substituted cycloalkyl,
Substituted lower alkenyl, substituted lower alkynyl, alkylene moiety of substituted aralkyl, substituted lower alkoxy, substituted lower alkanoyloxy, substituted lower alkoxycarbonyl as substituents may be the same or different and have 1 to 3 substituents, lower alkoxy, halogen, cyano Nitro, hydroxy, lower alkoxycarbonyl, lower alkanoyloxy, carboxy, azide, cycloalkyl, substituted or unsubstituted heterocyclic group, -CONR ¹¹ R ¹² [wherein R ¹¹ and R ¹²
Are the same or different and are hydrogen, lower alkyl or substituted lower alkyl (substituents of the same substituted or lower alkyl having 1 to 3 lower alkoxy, halogen, azido, mono- or di-lower alkylamino, aryl , A heterocyclic group, etc.), or R ¹¹ and R ¹²
There together with the adjacent nitrogen atom either forms a heterocyclic group, the substituent of the substituted Hajime Tamaki (said substituted heterocyclic group together with the nitrogen atom to which R ¹¹ and R ¹² are adjacent, identical Or differently substituted 1-3 lower alkoxy, halogen,
Azide, mono- or di-lower alkylamino, aryl, heterocyclic groups, etc.), -NR ¹³ R ¹⁴
Wherein R ¹³ and R ¹⁴ are the same or different and hydrogen, a substituent A [A is lower alkyl, substituted lower alkyl (the substituent of the substituted lower alkyl is lower alkyl, hydroxy or mono- or di-lower alkylamino ), Lower alkoxy, hydroxy, lower alkoxycarbonyl, aryl, substituted aryl (substituent of said substituted aryl is lower alkyl, hydroxy or mono- or di-lower alkylamino), heterocyclic group, substituted heterocyclic group (substituted heterocyclic group) The substituent of the ring group is lower alkyl, hydroxy or mono- or di-lower alkylamino)]] or lower alkyl or substituent A (A is the same as defined above). or represents cycloalkyl, substituents a (a together with the nitrogen atom to which R ¹³ and R ¹⁴ are adjacent to each other in the same meaning Substituted to form a well heterocyclic group}, or the like at that).

The substituted aryl and the aryl moiety of the substituted aralkyl and the substituent of the substituted heterocyclic group may be the same or different and have 1 to 3 substituents, 1) lower alkyl (the lower alkyl may be the same or different and have 1 or more substituents). , Lower alkoxy, halogen, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino or a heterocyclic group, 2) lower alkoxy (the lower alkoxy may be the same or different Lower alkoxy, halogen, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino or heterocyclic group having 1 to 3 substituents), 3) halogen, 4) nitro, 5) cyano , 6) hydroxy, 7) amino, 8) lower alkoxycarbonyl, 9) cal Carboxymethyl, 10) -CONR ¹⁵ in R ¹⁶ [wherein, R ¹⁵ and R ¹⁶ are the same or different and each is hydrogen, lower alkyl, the substituent of the substituted lower alkyl (the substituted lower alkyl, the number substituted the same or different 1 to 3 A heterocyclic group represented by a lower alkoxy, halogen, azide, mono- or di-lower alkylamino, aryl, heterocyclic group or a heterocyclic group formed together with the aforementioned adjacent nitrogen atom) Or R ¹⁵ and R ¹⁶ form a heterocyclic group together with an adjacent nitrogen atom, or R ¹⁵ and R ¹⁶ form a substituted heterocyclic group together with an adjacent nitrogen atom (the substituted heterocyclic group The substituents of the ring groups may be the same or different and form lower alkoxy, halogen, azide, mono- or di-lower alkylamino, aryl or heterocyclic groups having 1 to 3 substituents)], 11) -NHCOR ¹⁷ <<wherein, R ¹⁷ is a lower alkyl Other cycloalkyl <lower alkyl or the cycloalkyl are the same or different 1 to 3 substituents, lower alkoxy, halogen, hydroxy, carboxy, -NR ¹⁸ R
^{In the} formula, R ¹⁸ and R ¹⁹ are the same or different and each represents hydrogen,
A substituent E [E is a substituted lower alkyl, wherein the substituent of the substituted lower alkyl is lower alkyl, lower alkoxy, hydroxy or mono- or di-lower alkylamino],
Lower alkoxy, hydroxy, lower alkoxycarbonyl, aryl, substituted aryl (substituent of the substituted aryl is lower alkyl, lower alkoxy, hydroxy or mono- or di-lower alkylamino), heterocyclic group, substituted heterocyclic group (the The substituent of the substituted heterocyclic group is lower alkyl, lower alkoxy, hydroxy or mono- or di-lower alkylamino) or a heterocyclic group represented by the heterocyclic group formed together with the adjacent nitrogen atom described above. A lower alkyl group which may be substituted by a substituent or a cycloalkyl which may be substituted by a substituent E (E is as defined above), or a nitrogen atom in which R ¹⁸ and R ¹⁹ are adjacent to each other. Together with a substituent E (E is as defined above) to form a heterocyclic group which may be substituted.
Aryl (the aryls may be the same or different and have 1 to 3 substituents)
Which may be substituted with lower alkoxy, halogen, hydroxy or carboxy) or a heterocyclic group (the heterocyclic group is the same or different and is substituted with lower alkoxy, halogen, hydroxy or carboxy having 1 to 3 substituents) May be substituted with>).
>, 12) aryl wherein the aryls are the same or different and have 1 to 3 substituents, lower alkyl, lower alkoxy, halogen, nitro, hydroxy, lower alkoxycarbonyl,
Carboxy, mono- or di-lower alkylamino or a heterocyclic group which may be substituted), 13) aralkyl, 14) heterocyclic group [the heterocyclic group may be the same or different and has 1 to 3 substituents, lower alkyl, (The lower alkyl may be the same or different and may be substituted with 1-3 substituted lower alkoxy, halogen, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino or alicyclic heterocyclic group) A lower alkoxy (the lower alkoxy may be the same or different and may be substituted with a lower alkoxy having 1 to 3 substituents, halogen, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino or an alicyclic heterocyclic group) Good),
Halogen, nitro, hydroxy, amino, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino, aryl (the aryls are the same or different and have 1 to 3 substituents, lower alkyl, lower alkoxy, halogen, nitro, hydroxy, lower Alkoxycarbonyl,
A carboxy, mono- or di-lower alkylamino or a heterocyclic group which may be substituted, an aralkyl group or a heterocyclic group (the heterocyclic groups may be the same or different and have 1 to 3 substituents)
Lower alkyl, lower alkoxy, halogen, nitro, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino or heterocyclic group).
15) Mono or di-lower alkylamino and the like.

As the substituents of the substituted heterocyclic group formed together with the adjacent nitrogen atom, the same or different substituents having 1 to 3 substituents, such as lower alkyl, substituted lower alkyl (substituents of the substituted lower alkyl) Examples thereof include lower or the same or different substituents having 1 to 3 lower alkoxy, halogen, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino, alicyclic heterocyclic group, etc.), lower alkoxy, substituted Lower alkoxy (the substituents of the substituted lower alkoxy may be the same or different and have 1 to 3 substituents, lower alkoxy, halogen, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino, alicyclic heterocyclic group And the like), halogen, nitro, hydroxy, amino, lower alkoxycarbonyl, Lower alkanoyloxy, carboxy, mono- or di-lower alkylamino, aryl, substituted aryl (the substituents of the substituted aryl are the same or different and have 1 to 3 substituents, lower alkyl, lower alkoxy, halogen, nitro, hydroxy, lower Alkoxycarbonyl, carboxy, mono- or di-lower alkylamino, heterocyclic group, etc.), aralkyl,
A heterocyclic group, a substituted heterocyclic group (the substituents of the substituted heterocyclic group may be the same or different and have 1 to 3 substituents, lower alkyl,
Lower alkoxy, halogen, nitro, hydroxy, lower alkoxycarbonyl, carboxy, mono- or di-lower alkylamino, heterocyclic group, etc.) or a heterocyclic group formed together with the adjacent nitrogen atom described above. And the like heterocyclic groups represented.

As the pharmacologically acceptable salt of compound (I), a non-toxic, water-soluble salt is preferable. For example, inorganic salts such as hydrochloride, hydrobromide, nitrate, sulfate, phosphate and the like can be used. Acid, acetate, benzenesulfonate, benzoate,
Acid addition salts such as citrate, fumarate, gluconate, lactate, maleate, malate, oxalate, methanesulfonate, tartrate, and other organic acid salts, sodium salts, and potassium salts Alkali metal salts, magnesium salts, etc.
Alkaline earth metal salts such as calcium salts, ammonium,
Examples thereof include ammonium salts such as tetramethylammonium, and organic amine addition salts such as morpholine addition salts and piperidine addition salts.

Next, a method for producing the compound (I) will be described.

In the following production methods, when the defined groups change under the reaction conditions or are not suitable for carrying out the method, a method commonly used in organic synthetic chemistry, for example, protection of functional groups , Deprotection [for example,
Groups in Organic Synthesis (Protec
tive Groups in Organic Synthesis), Green (TW
Greene), John Wiley & Sons, Inc. (19)
1981) can be easily implemented.

Compound (I) can be produced by a series of reactions shown below. Production Method 1: Among the compounds (I), W ... V ... U is NC = O represents a (this time is m = 1, n = 0) , the compound Y ... Z represents CH-CH ₂ (I- i) can be produced according to the following reaction steps.

[0037]

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(Wherein R ^1A , R ^1B , X ¹ , X ² , X ³ , X ⁴ , R and R ² have the same meanings as above, and R ²⁰ is hydrogen, substituted or unsubstituted lower alkyl, Substituted or unsubstituted aryl, substituted or unsubstituted aralkyl or substituted or unsubstituted heterocyclic group, and X represents halogen) substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl in the definition of R ²⁰ And the substituted or unsubstituted aralkyl and the substituted or unsubstituted heterocyclic group are as defined above. Halogen in the definition of X is as defined above.

Compound (IV) is commercially available or known method [J. Heterocyclic Chem., 33, 223]
1 (1990)]]
I) and 1 to 10 equivalents, preferably 1 to 2 equivalents of acylacrylic acid or acylacrylate (III), which are commercially available or can be produced by a known method, are mixed with methanol, ethanol, propanol, tetrahydrofuran, chloroform , N, N-dimethylformamide or the like, preferably in ethanol, at a temperature between 0 ° C. and the boiling point of the solvent to be used, for 1 to 48 hours, preferably 3 to 12 hours.

Compound (Ii) is compound (IV)
To 5 equivalents, preferably 1 to 2 equivalents of a compound (V) represented by R ² -X (wherein X is as defined above) in a solvent such as N, N-dimethylformamide, tetrahydrofuran, etc. Sodium hydride, potassium tert-butoxide, lithium amide, potassium carbonate, a base such as sodium carbonate, preferably in the presence of potassium tert-butoxide, at a temperature between 0 ° C. and the boiling point of the solvent used, preferably 1 to It is obtained by reacting for 24 hours, preferably 2 to 5 hours, or 1 to 5 equivalents, preferably 1 to 2 equivalents of R ² with compound (IV).
Compound (VI) represented by —OH and tetrahydrofuran, dioxane, dichloromethane, chloroform, diethyl ether, N, N-dimethylformamide, toluene,
In a solvent such as hexamethylphosphoric triamide, preferably in tetrahydrofuran, 1 to 5 equivalents, preferably 1
Used in the presence of ~ 2 equivalents of a condensing agent such as diethylazodicarboxylic acid, diisopropylazodicarboxylic acid, 4-methyl-1,2,4-triazolidine-3,5-dione, preferably in the presence of diethylazodicarboxylic acid at -50 ° C It can be obtained by reacting at a temperature between the boiling points of the solvents, preferably at 0 ° C. to room temperature, for 30 minutes to 24 hours, preferably 1 to 5 hours.

Production method 2: Of compound (I), W ... V ... U
Represents NC = O (where m = 1 and n = 0), and Y… Z is C =
Compound (I-ii) representing CH can be produced according to the following reaction steps.

[0042]

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Where R ^1A , R ^1B , X ¹ , X ² , X ³ , X ⁴ , X, R
And R ² are the same as defined above. Compound (VII) is obtained by converting compound (IV) obtained in Production Method 1 into a solvent such as benzene, toluene, chlorobenzene, xylene, dioxane, tetrahydrofuran, or hexane, preferably in tetrahydrofuran. 1 to 10 equivalents, preferably 1
~ 2 equivalents of 2,3-dichloro-5,6-dicyano-1,
Obtained by treating for 1 to 48 hours, preferably 1 to 10 hours at a temperature between 0 ° C. and the boiling point of the solvent used in the presence of an oxidizing agent such as 4-benzoquinone (DDQ), o-chloranil, p-chloranil and the like. Alternatively, compound (IV) is dissolved in a solvent such as water, chloroform or methylene chloride at a temperature between 0 ° C. and the boiling point of the solvent to be used, in an amount of 1 equivalent to a large excess, preferably 1 to 5 equivalents of hydrogen peroxide, m -It can be obtained by treating in the presence of a peroxide such as chloroperbenzoic acid for 1 to 24 hours, preferably 1 to 5 hours.

Compound (I-ii) can be obtained from compound (VII) in the same manner as in the production of compound (Ii) from compound (IV) in production method 1.

Production method 3: Of compound (I), W ... V ... U
Represents NC = O (where m = 1 and n = 0), and Y… Z is C = C
Compound (I-ii) representing H can also be produced according to the following reaction steps.

[0046]

Embedded image

Wherein R ^1A , R ^1B , X ¹ , X ² , X ³ , X ⁴ , X, R
And R ² have the same meanings as described above, and R ²¹ has the same meaning as the above R ^20. ) Compound (VII) can be prepared by a known method [Journal of
Heterocyclic chemistry (J. Heterocyclic)
Chem.), 32, p. 347 (1995), Journal of Heterocyclic Chemistry (J. Heterocyc)
lic Chem.), Vol. 32, p. 703 (1995)]
Commercially available or known methods [J. Heterocycli (J. Heterocycli)
Chem.), Vol. 33, p. 2231 (1990)] and 1 to 10 equivalents, preferably 1 to 10 equivalents, which are commercially available or can be prepared by known methods.
2 equivalents of compound (VIII) is added to an organic solvent such as methanol, ethanol, chloroform, N, N-dimethylformamide or tetrahydrofuran in the presence or absence of 1 equivalent to a solvent amount of an acid such as acetic acid or sulfuric acid, or It can be obtained by reacting in an acetic acid or sulfuric acid solvent at a temperature between room temperature and the boiling point of the solvent used, preferably under reflux of the solvent for 1 to 96 hours, preferably 1 to 24 hours.

Compound (I-ii) can be obtained from compound (VII) in the same manner as in the production of compound (Ii) from compound (IV) in production method 1.

Production method 4: Of compound (I), W ... V ... U
Represents NC = O (where m = 1 and n = 0), and Y… Z is C = C
Compound (I-ii) representing H can also be produced according to the following reaction steps.

[0050]

Embedded image

Wherein R ^1A , R ^1B , X ¹ , X ² , X ³ , X ⁴ , R and R ² have the same meanings as above, R ²² has the same meaning as R ²⁰ , and R ²³ Is a substituted or unsubstituted lower alkyl,
A substituted or unsubstituted aryl, substituted or represents a non-substituted aralkyl or a substituted or unsubstituted heterocyclic group, X ^a is as defined above X) substituted or unsubstituted lower alkyl in the definition of R ^23, substituted or Unsubstituted aryl, substituted or unsubstituted aralkyl, and substituted or unsubstituted heterocyclic group are as defined above.

Compound (X) can be prepared by a known method [Journal of Chemical Society (J. Chem. So
c.), p. 3162 (1962), Journal of Chemical Society (J. Chem. Soc.), p. 2825 (1964), Journal of Heterocyclic
Chem. (J. Heterocyclic Chem.), Vol. 27, p. 157 (1990)] and the compound (II) described above, which is commercially available or produced by a known method, and 1 to 10
Equivalent amount of pyruvate or pyruvate (IX)
And in an organic solvent such as methanol, ethanol, chloroform, N, N-dimethylformamide or tetrahydrofuran, or in an acetic acid or sulfuric acid solvent at room temperature in the presence or absence of 1 equivalent to a solvent amount of an acid such as acetic acid or sulfuric acid. ~ At a temperature between the boiling points of the solvents, preferably at room temperature, for 1 to 96 hours, preferably for 1 to 24 hours.

Compound (VII) can be prepared by a known method [Synthetic Communications (Syn. Comm.), 23
Volume, page 201 (1993)] and 1 to 5 equivalents, preferably 1 to 2 equivalents of compound (XI), which is commercially available or can be produced by a known method, with compound (X).
Compound (XII) or compound (XIII) is mixed with 3 to 10 equivalents, preferably in a solvent such as tetrahydrofuran, N, N'-dimethylpropyleneurea or N, N'-dimethylethyleneurea, or a mixed solvent thereof, preferably 3-5
In the presence of an equivalent amount of a base such as lithium amide such as lithium hexamethyldisilazane and lithium diisopropylamide, preferably in the presence of lithium diisopropylamide, at a temperature between 0 and 100 ° C., preferably at room temperature, for 1 to 48 hours, preferably 3 to 48 hours. It can be obtained by reacting for ~ 5 hours.

Compound (I-ii) can be obtained from compound (VII) in the same manner as in the production of compound (Ii) from compound (IV) in production method 1.

Production method 5: Of compound (I), W ... V ... U
Represents NC = O (where m = 1 and n = 0), and Y… Z is C = C
Compound (I-ii) representing H can also be produced according to the following reaction steps.

[0056]

Embedded image

(Wherein, R ^1A , R ^1B , X ¹ , X ² , X ³ , X ⁴ , R and R ² have the same meanings as above, R ²⁴ has the same meaning as R ²⁰ , and X ^b Has the same meaning as X). Compound (XVI) can be prepared by a known method [Journal of
Organic Chemistry (J. Org. Chem.), 21
Volume, 1326 (1956), Journal of Heterocyclic Chemistry (J. Heterocyclic Che)
m.), Vol. 32, p. 703 (1995), etc.], and halogen and nitro, such as 2-halogenated nitrobenzene or 2-chloro-3-nitropyridine, which are commercially available or can be prepared by known methods. Derivatives or aromatic heterocyclic derivatives in which the groups are adjacently substituted (XI
V) and 1 to 10 equivalents, preferably 1 to 2 equivalents of a compound (X) which is commercially available or can be prepared by known methods.
V) in an alcoholic solvent such as water or ethanol, or in an aprotic solvent such as N, N-dimethylformamide, N-methylpyrrolidone, tetrahydrofuran, or dioxane, if necessary, in the presence of an inorganic salt such as sodium hydrogen carbonate. At a temperature between 0 ° C. and the boiling point of the solvent used, for 2 to 48 hours, preferably 3 to 12 hours.

Compound (XVII) is compound (XVI)
In an alcohol solvent such as ethanol in the presence of hydrochloric acid, 1 to 10
Equivalent, preferably reduced by 1 to 3 equivalents of iron, 1 to 10 equivalents in an aqueous ammonia solution, preferably reduced by 1 to 3 equivalents of iron hydroxide, or 0.1 to 5 times by weight, Preferably reduced by a hydrogenation reaction using 0.5 to 1 times the amount of palladium-carbon or Raney nickel as a catalyst, or in an alcohol solvent such as water or ethanol, at a temperature between room temperature and the boiling point of the solvent used, preferably solvent reflux. lower, 3 to 20 equivalents, preferably 3-5 equivalents of Na ₂ S ₂
It can be obtained by reduction with O ₄ (sodium dithionite).

Compound (X) is compound (XVII)
-10 ° C., preferably 1-2 equivalents of DDQ, hydrogen peroxide, an oxidizing agent such as chromic acid, preferably -30 ° C.-70 in the presence of DDQ.
C., preferably at room temperature for 1 to 36 hours, preferably 2 to 5 hours. Compound (Ii
i) can be obtained from compound (X) in two steps by a method similar to Production Method 4.

Production method 6: Of compound (I), W ... V ... U
Represents N = CN (where m = 0 and n = 1), and Y ... Z is C = C
Compound (I-iii) representing H can be produced according to the following reaction steps.

[0061]

Embedded image

Wherein R ^1A , R ^1B , R ^3A , R ^3B , X ¹ , X ² ,
X ³ , X ⁴ , X ^a , R and R ²³ are each as defined above,
R ²⁵ represents substituted or unsubstituted aryl, substituted or unsubstituted lower alkyl or trifluoromethyl) The substituted or unsubstituted aryl, substituted or unsubstituted lower alkyl in the definition of R ²⁵ are as defined above, respectively. is there.

A known method [J. Chem. Soc., P. 3236 (195)
7), Journal of Organic Chemistry (J. Org. Chem.), Vol. 27, p. 324 (1962), etc.], and by the same method as described in Production Methods 4 and 5. The compound (X) obtained in the absence of a solvent or in an inert solvent such as 1,2-dichloroethane at a temperature between room temperature and the boiling point of the solvent to be used. 0.1 to 20 equivalents, if necessary, preferably
0.5 to 5 equivalents of a base such as triethylamine, diisopropylethylamine, N, N-dimethylaniline, or N, N-
In the presence of a reaction accelerator such as dimethylformamide, 1 to 20
Compound (XVIII) can be obtained by treating with an equivalent amount of a chlorinating agent such as phosphoryl chloride, phosphorus pentachloride or thionyl chloride, preferably phosphoryl chloride for 1 to 24 hours. In addition, a known method [Tetrahedron Letters (Te
t.Let.), vol. 23, p. 2253 (1982), tetrahedron (Tetrahedron), vol. 44, p. 6367 (1988), etc.] to give compound (X) in dichloromethane, 1,2-dichloroethane, tetrahydrofuran, In an inert solvent such as benzene, toluene and chlorobenzene, at a temperature between room temperature and the boiling point of the solvent used, 1 to 10 equivalents, preferably 1 to 5 equivalents of an organic base such as triethylamine or diisopropylethylamine, or potassium carbonate or carbonate Sodium, potassium hydrogen carbonate, sodium hydrogen carbonate, potassium hydroxide, in the presence of an inorganic base such as sodium hydroxide, 1 to 5 equivalents, preferably 1 to 2 equivalents of benzenesulfonyl chloride, p-toluenesulfonyl chloride, methanesulfonyl chloride, Reaction with a sulfonylating agent such as trifluoromethanesulfonyl chloride for 1 to 24 hours, preferably 1 to 5 hours By doing so, compound (XIX) can be obtained. Compound (XX
I) is the compound (XVIII) or (XIX) and 1-1
0 equivalents, preferably 1 to 3 equivalents of a secondary amine (XX) are mixed with a lower alcohol such as ethanol or isopropanol, or an organic solvent such as tetrahydrofuran or N, N-dimethylformamide, and optionally 1 to 5 equivalents of diisopropylethylamine. The reaction can be carried out in the presence of a base at a temperature between room temperature and the boiling point of the solvent used for several hours to several days, preferably for 5 to 48 hours.

Compound (I-iii) can be obtained from compound (XXI) in the same manner as in the production of compound (VII) from compound (X) in Production Method 4.

A part of the compound (VII) obtained by the above production method can be used as a synthetic intermediate to obtain a new compound (VII).

For example, the compound (VIIa) in which R ^1A or R ^1B is lower alkoxy is the compound (VIIb) in which R ^1A or R ^1B is halogen and the corresponding lower alcohol.
Water, methanol, ethanol, N, N-dimethylformamide, tetrahydrofuran, 1,2-dimethoxyethane,
In a solvent such as dioxane and chloroform, 1 to 10 equivalents of a base such as sodium hydride, potassium tert-butoxide, lithium diisopropylamide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. At a temperature between 0 ° C. and the boiling point of the solvent used, preferably at room temperature, in the presence of
It can be obtained by reacting for 1 hour, preferably 1 to 12 hours.

A compound wherein R ^1A or R ^1B is —NR ⁴ R ⁵ (V
IIc) is a compound (V) wherein R ^1A or R ^1B is a halogen.
IIb) and HNR ⁴ R ⁵ with water, methanol, ethanol, N,
N-dimethylformamide, tetrahydrofuran, 1,2
-1 to 10 equivalents of sodium hydride, potassium tert-butoxide, lithium diisopropylamide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, sodium hydrogencarbonate in a solvent such as dimethoxyethane, dioxane, or chloroform It can be obtained by reacting in the presence of a base such as potassium at a temperature between 0 ° C. and the boiling point of the solvent used, preferably at room temperature, for 1 to 48 hours, preferably 1 to 12 hours.

Similarly, a part of the compound (I) obtained by the above production method can be used as a synthetic intermediate to obtain a new compound (I). Substituents in compound (I)
Compounds present is carboxy in R ² (Ia), the ester group present in the corresponding substituents R ² Compound (Ib) a catalytic amount to 10 equivalents, preferably 0.5 to 2 equivalents of hydrochloric acid, sulfuric acid,
In the presence of an acid such as boron trichloride, trifluoroacetic acid, p-toluenesulfonic acid, etc., at a temperature between 0 ° C. and the boiling point of the solvent used, preferably at room temperature, for 1 to 24 hours, preferably for 1 to 5 hours. Or a compound (Ib) in the presence of a catalyst such as methanol, ethanol, water or the like in the presence of a catalytic amount of to 20 equivalents, preferably 1 to 5 equivalents of a base such as sodium hydroxide, potassium hydroxide, potassium carbonate or sodium carbonate. In a solvent, or a mixed solvent thereof, at a temperature between 0 ° C. and the boiling point of the solvent to be used, for 1 to 24 hours, preferably 1 to 5 hours, the compound (Ib) can be obtained by treating the compound (Ib) with a catalytic amount of 20 equivalents, preferably 1-5 equivalents of lithium iodide,
In the presence of an inorganic salt such as lithium bromide, pyridine, lutidine,
In a solvent such as collidine or N, N-dimethylformamide, it is obtained by a treatment for 1 to 72 hours at a temperature between room temperature and the boiling point of the solvent used, preferably at a temperature between 50 ° C. and the boiling point of the solvent used. Can be.

[0069] carbamoyl groups in substituent R ² of the compound ^{(I) (-CONR 9y R 10y} , -CONR 11 R 1 2 or -CONR ¹⁵ R
^The compound (Ic) in which ¹⁶ ) is present is the corresponding compound (Ic)
a) without solvent or in a solvent such as dichloromethane, tetrahydrofuran, N, N-dimethylformamide in an amount of 1 equivalent to
With a solvent amount of a halogenating agent such as thionyl chloride, at a temperature between 0 ° C. and the boiling point of the solvent used, for 1 to 24 hours, preferably 1 to 24 hours.
By treating for 10 hours, a compound having a chlorocarbonyl group (—COCl) in the substituent R ² is obtained. Then, N, N-dimethylformamide is added in the presence of 1 to 2 equivalents of a suitable base such as triethylamine or pyridine. , Tetrahydrofuran,
In a solvent such as dichloromethane, at a temperature between the boiling point of 0 ° C. ~ used solvents, 1 to 10 equivalents, preferably 1-2 equivalents of the amine ^{(HNR 9y R 1 0y, HNR} 11 R 12 or HNR ¹⁵ R ¹⁶⁾ and , For 1 to 24 hours, or compound (I)
a) and an amine (HNR ^9y R ^10y , HNR ¹¹ R ¹² or HNR
¹⁵ R ¹⁶ ) and dichloromethane, tetrahydrofuran,
In an inert solvent such as N, N-dimethylformamide, 1 to 5 equivalents, preferably 1 to 3 equivalents of N, N'-dicyclohexylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, carbonyldiamide Imidazole,
In the presence of a condensing agent such as 2-chloro-1-methylpyridinium iodide, and further in the presence of 1 to 5 equivalents, preferably 1 to 3 equivalents of a base such as pyridine or triethylamine, a temperature between 0 ° C. and the boiling point of the solvent used. 1-24 hours, preferably 1-4
It can also be obtained by reacting for a time.

[0070] -NR ^7y R in the substituent R ² of the compound (I)
Compound (I) in which ^8y , -NR ¹³ R ¹⁴ or -NR ¹⁸ R ¹⁹ is present
d) represents a compound (Ie) in which a halogen is present in the corresponding substituent R ² and an amine (HNR ^7y R ^8y , HNR ¹³ R ¹⁴ or HNR
¹⁸ R ¹⁹ ) in a solvent such as water, methanol, ethanol, acetonitrile, tetrahydrofuran, dichloromethane, N, N-dimethylformamide, etc. in 1 to 10 equivalents, preferably 1 to 3 equivalents of tertiary amines such as triethylamine and diisopropylethylamine. Amine or sodium carbonate, in the presence of an inorganic salt such as sodium bicarbonate, at a temperature between 0 ° C and the boiling point of the solvent used, preferably at 0 ° C to room temperature, for 1 to 24 hours, preferably 1 to 5 hours by reacting Obtainable. Compound (Id) wherein R ^7y and R ^8y , R ¹³ and R ¹⁴ or R ¹⁸ and R ¹⁹ are both hydrogen is 1 to 5 equivalents of compound (Ie) sodium azide, potassium azide and lithium azide Or with trimethylsilyl azide, water, methanol, ethanol, tetrahydrofuran, diethylene glycol dimethyl ether,
In a solvent such as N, N-dimethylformamide, or a mixed solvent thereof, at a temperature between 0 ° C and 160 ° C, preferably at a temperature between room temperature and 100 ° C, for 1 to 72 hours, preferably 10 to 72 hours. twenty four
The corresponding azide form is obtained by reacting for an hour, and then the obtained azide form is subjected to a normal pressure or pressurized hydrogen stream,
In a solvent such as methanol, ethanol, chloroform and tetrahydrofuran, in the presence of a catalyst such as palladium, nickel, and platinum, if necessary, an inorganic salt such as calcium carbonate is allowed to coexist, and at a temperature between room temperature and the boiling point of the solvent used, 1 to twenty four
Time, preferably by treating for 1-6 hours,
The obtained azide compound is dissolved in a solvent such as water, methanol, ethanol, toluene, or ether, with sodium borohydride,
It can be obtained by treating in the presence of a reducing agent such as lithium aluminum hydride, borane or triphenylphosphine at a temperature between 0 ° C. and the boiling point of the solvent to be used for 1 to 24 hours, preferably 1 to 6 hours.

In the compound (Id), R ^7y and R ^8y ,
A compound in which both R ¹³ and R ¹⁴ or R ¹⁸ and R ¹⁹ are hydrogen is a compound having a nitro group in the substituent R ² (I
f) can also be synthesized. That is, the compound (I
f) under a normal or pressurized hydrogen stream or in the presence of a formate such as formic acid or ammonium formate,
Ethanol, chloroform, in a solvent such as tetrahydrofuran, 0.01 to 5 times by weight, preferably 0.5 to 1 times by weight of palladium-carbon, nickel, platinum and the like as a catalyst, if necessary, coexist with an inorganic salt such as calcium carbonate. The compound (If) is obtained by treating at a temperature between room temperature and the boiling point of the solvent to be used for 1 to 24 hours, preferably 1 to 6 hours, or 1 to 10 equivalents, preferably 1 to 2 equivalents of compound (If). zinc,
Tin, in the presence of a reducing agent such as titanium trichloride, water, methanol, ethanol, in a solvent such as tetrahydrofuran, or in a mixed solvent thereof, at a temperature between room temperature and the boiling point of the solvent used, 1 to 12 hours, preferably It can be obtained by treating for 1 to 6 hours.

In the compound (I), -NHCO is contained in the substituent R ² .
The compound (Ig) in which R ¹⁷ is present is a compound in which R ^7y and R ^8y , R ¹³ and R ¹⁴ or R ¹⁸ and R ¹⁹ are both hydrogen and a commercially available product or a known method. 1-10 equivalents, preferably 1-2
Equivalent acid halide, acid anhydride or mixed acid anhydride is used in a solvent such as dichloromethane, N, N-dimethylformamide, tetrahydrofuran and the like in the presence of 1 to 2 equivalents of a base such as triethylamine, pyridine or the like at 0 ° C to 0 ° C. It can be obtained by reacting at a temperature between the boiling points of the solvents for 1 to 24 hours. Alternatively, R ^7y and R in compound (Id)
^8y , a compound wherein R ¹³ and R ¹⁴ or R ¹⁸ and R ¹⁹ are both hydrogen and 1 to 10 equivalents, preferably 1 to 2 equivalents of R ¹⁷ COOH, which are commercially available or can be prepared by known methods
In an inert solvent such as dichloromethane, tetrahydrofuran, N, N-dimethylformamide and the like, 1 to 5 equivalents, preferably 1 to 3 equivalents of N, N'-dicyclohexylcarbodiimide, 1-ethyl-3 In the presence of a condensing agent such as-(3-dimethylaminopropyl) carbodiimide, carbonyldiimidazole, 2-chloro-1-methylpyridinium iodide, at a temperature between 0 ° C and the boiling point of the solvent used, preferably for 1 to 24 hours. Can also be obtained by reacting for 1 to 4 hours.

The intermediates and target compounds in each of the above production methods can be purified by a purification method commonly used in synthetic organic chemistry, for example, filtration, extraction, washing, drying, concentration, recrystallization, high-performance liquid chromatography using silica gel, thin-layer chromatography. It can be purified and isolated by various chromatography methods such as chromatography and column chromatography. In addition, the intermediate can be subjected to the next reaction without purification.

Some of the compounds (I) may exist as positional isomers, geometric isomers, optical isomers or tautomers, and the present invention includes all possible isomers. Includes isomers and mixtures thereof. Compound (I)
When compound (I) is obtained in the form of a salt, it may be purified as it is, or when compound (I) is obtained in a free form, compound (I) may be dissolved in an appropriate solvent. Alternatively, they may be suspended and then isolated by adding a suitable acid or base to form a salt.

The compound (I) and its pharmacologically acceptable salts may exist in the form of adducts of water or various solvents, and these adducts are also included in the present invention.

W ... V ... U obtained by the above production method is N
-C = O (where m = 1, n = 0), X ¹ , X ² , X ³ ,
Compound (I) in which X ⁴ all represents CH and Y ... Z represents CH—CH ₂
Table 1 shows specific examples.

[0077]

[Table 1]

W ... V ... U obtained by the above production method is N
-C = O (where m = 1, n = 0), X ¹ , X ² , X ³ ,
Table 2 shows specific examples of the compound (I) in which X ⁴ all represents CH and Y ... Z represents C = CH.

[0079]

[Table 2]

[0080]

[Table 3]

[0081]

[Table 4]

[0082]

[Table 5]

[0083]

[Table 6]

[0084]

[Table 7]

[0085]

[Table 8]

[0086]

[Table 9]

[0087]

[Table 10]

[0088]

[Table 11]

W ... V ... U obtained by the above production method is N
-C = O (where m = 1, n = 0), X ¹ , X ² , X ³ ,
At least one or more of X ⁴ is nitrogen, and Y… Z is C = CH
Table 3 shows specific examples of the compound (I) representing

[0090]

[Table 12]

[0091]

[Table 13]

[0092]

[Table 14]

[0093]

[Table 15]

[0094]

[Table 16]

[0095]

[Table 17]

[0096]

[Table 18]

[0097]

[Table 19]

[0098]

[Table 20]

[0099]

[Table 21]

W ... V ... U obtained by the above production method is N
= CN (where m = 0, n = 1), X ¹ , X ² , X ³ ,
Table 4 shows specific examples of the compound (I) in which X ⁴ all represents CH and Y ... Z represents C = CH.

[0101]

[Table 22]

[0102]

[Table 23]

Next, the pharmacological action of the compound (I) will be specifically described with reference to test examples. Reported by Miyazaki et al. [Endocrinology, 127, 126
Page (1990)] The established pancreatic β-cell MIN6 cells are similar to pancreatic β-cells in the body, where insulin content and glucose-stimulated insulin secretion are close to those of pancreatic β-cells, and insulin secretion increases in response to glucose concentration. Pancreas β in the body
Well preserves the properties of cells [Ref. And Diabetologia, 36, 1139 (1993)
Year)]. In addition, in MIN6 cells, insulin secretion is promoted in response to a sulfonylurea agent used as a therapeutic agent for diabetes, for example, glibenclamide [Cellular Signaling, Vol. 5, p. 777 (1993)].

Test Example (1) Insulin Secretion-Promoting Activity in Cultured β Cells The culture of MIN6 cells and an insulin secretion test using MIN6 cells were described in the literature [Diabetologia, 36
Vol., P. 1139 (1993)]. The effect of the compound on insulin secretion activity in the presence of 14.5 mM glucose was determined by measuring the amount of insulin in the cell culture supernatant collected as follows. MIN6 cells cultured in a 24-well plate,
Buffer A containing 2 mM glucose (119 mM sodium chloride, 4.
74 mM potassium chloride, 2.54 mM calcium chloride, 1.19 mM magnesium sulfate, 1.19 mM potassium dihydrogen phosphate, 10 mM 2
-[4- (2-hydroxyethyl) -1-piperazinyl] ethanesulfonic acid, 0.1% bovine serum albumin pH 7.
3) After washing twice with 1 ml, the mixture was incubated at 37 ° C. for 45 minutes in buffer A containing 1 ml of 2 mM glucose. After incubation, the culture supernatant was replaced with buffer A containing various concentrations of the test compound and 2 mM glucose (0.9 ml) or buffer A containing 2 mM glucose (0.9 ml, control group). Incubated for 15 minutes. To this buffer A containing 127 mM glucose (0.1
MIN6 cells were stimulated with glucose (final glucose concentration: 14.5 mM). After stimulation, an additional 37
After incubation at 45 ° C for 45 minutes, the culture supernatant was collected.

On the other hand, the effect of the compound on the insulin secretion activity in the presence of 5 mM glucose was determined by measuring the amount of insulin in the cell supernatant collected as follows. In a 24-well plate, cultured MIN6 cells are washed twice with 1 ml of buffer A containing 5 mM glucose, and then buffer A (0.9 ml) containing various concentrations of test compound and 5 mM glucose or buffer containing 5 mM glucose. liquid
Replaced with A (0.9 ml, control group). Thereafter, the culture was incubated at 37 ° C. for 45 minutes (final glucose concentration: 5 mM), and the culture supernatant was collected.

The antibody-reactive insulin secreted into the culture supernatant was prepared by adding 1% bovine serum albumin and 0.1% Tween 2 to the culture supernatant.
After dilution with a phosphate buffer containing 0, 0.12% disodium ethylenediaminetetraacetate and 0.1% sodium azide, quantification was performed by radioimmunoassay. Insulin levels were expressed as rat insulin levels (ng / mL). The results are shown in Table 5 as mean values (avg) and standard error values (se) of 3-4 cases.

[0107]

[Table 24]

In this test, glibenclamide, a sulfonylurea agent, was used in the presence of 5 mM glucose and
Insulin secretion was promoted in the presence of 4.5 mM glucose. On the other hand, the compound of the present invention promoted insulin secretion only in the presence of 14.5 mM glucose. The above results suggested that, unlike the sulfonylurea agent, the compound of the present invention promotes insulin secretion depending on the glucose concentration.

The inhibitory effect of the compound of the present invention on blood glucose elevation was determined by Hill.
aire-Buys et al. [British Journal of Pharmacol
ogy), Vol. 109, p. 183 (1993)] and tested with blood glucose levels before and after glucose loading.

Test Example (2): Test for Inhibition of Elevated Blood Glucose in Normal Animals During Glucose Tolerance (Effect on Blood Glucose Level after Glucose Load in SD Rat) A test compound (100 mg / kg) was suspended in a 0.3% aqueous sodium carboxymethylcellulose solution. It was a drug solution. Glucose was dissolved in distilled water and adjusted to a concentration of 50% (W / V%).

A 10-week-old male SD rat was used for the experiment. The animals fasted for 20 hours, but had free access to water for use in the experiments. Animals were orally administered the drug solution at a dose of 100 mg / kg body weight, and the control group was similarly administered with the solvent used for the drug solution. After 40 minutes, 50 mg / k of sodium pentobarbital
Anesthesia was given by intraperitoneal administration at a dose of g body weight. After dorsal fixation, the neck was incised and the left carotid artery and the left jugular vein were cannulated. Sixty minutes after drug administration, a glucose solution was administered via the cannula inserted into the vein, and immediately thereafter 0.2 ml of saline was administered via the same cannula. Before sugar loading 1
1 minute, 3 minutes, 5 minutes, 10 minutes, 20 minutes, and 30 minutes after glucose load, blood was collected from the cannula inserted into the artery, and 3,000 minutes at 4 ° C.
After centrifugation at 15 minutes at rpm, the glucose concentration in the supernatant was determined by the glucose oxidase method [Clinical Chemistry, vol. 6, p. 466 (1960)].
Was measured. The results are shown in Table 6 as the average value of glucose concentration and the standard error (SE) value of five cases.

[0112]

[Table 25]

From the above results, it was shown that Compound 1 lowers the blood glucose level after glucose load as compared with the control group.

Compound (I) and a pharmacologically acceptable salt thereof show an insulin secretion promoting action in cultured β cells and a hypoglycemic action in rats.
Useful for the treatment of diabetes.

Compound (I) or a pharmacologically acceptable salt thereof is prepared, for example, into a commonly used dosage form such as tablets, capsules, powders, granules, syrups and injections.
It can be administered orally or by parenteral administration such as intravenous injection. For the preparation of dosage forms for oral or parenteral administration, generally known methods are applied, and the resulting preparations include, for example, various excipients, lubricants, binders, disintegrants, It may contain a turbidity agent, a tonicity agent, an emulsifier and the like.

Examples of the pharmaceutical carrier to be used include sucrose, gelatin, lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, and the like.
Alginic acid, talc, sodium citrate, calcium carbonate, calcium hydrogen phosphate, starch, polyvinylpyrrolidone, magnesium aluminate metasilicate, magnesium stearate, calcium cellulose glycolate,
Examples include urea, silicone resin, sorbitan fatty acid ester, glyceric acid ester, distilled water for injection, physiological saline, propylene glycol, polyethylene glycol, olive oil, ethanol and the like.

In order to use the compound (I) and a pharmaceutically acceptable salt thereof for the above-mentioned purpose, it is usually administered systemically or locally, orally or parenterally. The dose varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, and the like. Usually one adult at a time
Orally or parenterally, once to several times a day, or once to several times a day, or in a range of 1 to 100 mg once a day, or 1 to 100 mg per adult per day, or 1 to 24 hours a day It is continuously administered intravenously within the range. Of course, as described above, since the dose varies depending on various conditions, a dose smaller than the above-mentioned dose may be sufficient, or administration outside the range may be necessary.

[0118]

EXAMPLES The present invention will be described below in detail with reference to Examples and Examples. The proton nuclear magnetic resonance spectra ( ¹ H-NMR) used in Reference Examples and Examples were measured at 270 MHz unless otherwise specified. In the proton nuclear magnetic resonance spectrum, exchangeable hydrogen may not be clearly observed depending on the compound and measurement conditions, and in the case of hydrochloride, hydrogen on a quaternary nitrogen atom may be observed. In addition, br means a wide signal.

Reference Example 1 3- (2-oxophenethyl) -3,4-dihydro-1
H-quinoxalin-2-one 1,2-phenylenediamine (124 g, 1.14 mol) was dissolved in ethanol (1.2 L), ethyl 3-benzoylacrylate (250 ml, 1.25 mol) was added, and the mixture was stirred at room temperature for 14 hours. . The resulting precipitate was collected by filtration and dried under reduced pressure to give the title compound (161 g, 53%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.28 (dd, J = 6.9, 1
7.5Hz, 1H), 3.58 (dd, J = 4.6, 17.5Hz, 1H), 4.3
5 (m, 1H), 5.96 (s, 1H), 6.58-6.78 (m, 4H),
7.51-7.68 (m, 3H), 8.00 (d, J = 7.3 Hz, 2H), 1
0.3 (s, 1H).

Reference Example 2 3- (2-oxo-2-phenylethylidene) -3,4
-Dihydro-1H-quinoxalin-2-one 3- (2-oxophenethyl)-obtained in Reference Example 1.
3,4-dihydro-1H-quinoxalin-2-one (1.
50 g, 4.79 mmol) was dissolved in tetrahydrofuran (20 ml) and 2,3-dichloro-5,6-dicyano-1,2 was dissolved at room temperature.
4-benzoquinone (DDQ, 1.09 g, 4.79 mmol) was added and 12
Stirred for hours. An aqueous sodium hydrogen carbonate solution was added to the reaction system to adjust the pH to slightly alkaline, and the precipitated solid was collected by filtration and dried under reduced pressure to obtain the title compound (1.15 g, 91%). ¹ H-NMR (CDCl ₃ + CD ₃ OD) δ (ppm): 6.98 (s, 1H),
7.07-7.24 (m, 4H), 7.46-7.57 (m, 3H), 8.03 (d
d, J = 1.6, 8.1Hz, 2H).

Reference Example 3 6,7-dimethyl-3- (2-oxophenethyl)-
3,4-Dihydro-1H-quinoxalin-2-one By the same method as in Reference Example 1, 4,5-dimethyl-
1,2-phenylenediamine (25.0 g, 186 mmol) and ethyl 3-benzoyl acrylate (33.7 ml, 186 mmol)
From the title compound (26.7 g, 49%). ¹ H-NMR (CDCl ₃ + CD ₃ OD) δ (ppm): 2.15 (s, 6H),
3.33 (dd, J = 10.2, 18.2Hz, 1H), 3.64-3.82 (m,
1H), 4.44-4.47 (m, 1H), 6.52 (s, 1H), 6.57 (
s, 1H), 7.46-7.52 (m, 2H), 7.59-7.94 (m, 1H),
7.99 (d, J = 7.6 Hz, 2H).

Reference Example 4 6,7-dimethyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-
2-one 6,7-dimethyl-3- (2-oxophenethyl)-obtained in Reference Example 3 in the same manner as in Reference Example 2.
3,4-dihydro-1H-quinoxalin-2-one (1
0.0g, 34.0 mmol) to give the title compound (8.02 g, 81%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.28 (s, 6H), 6.80
(s, 1H), 6.98 (s, 1H), 7.01 (s, 1H), 7.44-7.5
3 (m, 3H), 8.05 (dd, J = 1.8, 7.8 Hz, 2H), 9.16
(brs, 1H), 13.9 (brs, 1H).

Reference Example 5 6,7-dichloro-3- (2-oxophenethyl)-
3,4-dihydro-1H-quinoxalin-2-one In the same manner as in Reference Example 1, 4,5-dichloro-
1,2-phenylenediamine (10.0 g, 56.5 mmol) and ethyl 3-benzoyl acrylate (10.4 ml, 56.5 mol
The title compound (13.9 g, 73%) was obtained from l). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.39 (dd, J = 6.9,
17.8Hz, 1H), 3.57 (dd, J = 4.1, 17.8Hz, 1H), 4.
41-4.46 (m, 1H), 6.39 (brs, 1H), 6.86 (s, 1H
), 6.87 (s, 1H), 7.50-7.69 (m, 3H), 7.98-8.01
(m, 2H), 10.6 (brs, 1H).

Reference Example 6 6,7-Dichloro-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-
2-one 6,7-Dichloro-3- (2-oxophenethyl)-obtained in Reference Example 5 in the same manner as in Reference Example 2.
3,4-dihydro-1H-quinoxalin-2-one (1
0.0 g (29.8 mmol) to give the title compound (9.40 g, 95%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 6.83 (s, 1H), 7.22
(s, 1H), 7.45-7.63 (m, 4H), 7.96-7.99 (m, 3H
), 13.5 (brs, 1H).

Reference Example 7 6,7-dimethoxy-3- (2-oxophenethyl)-
3,4-dihydro-1H-quinoxalin-2-one Concentrated hydrochloric acid (30 ml) and water (30 ml) are mixed with 4,5-dimethoxy-
1,2-Dinitrobenzene (5.00 g, 21.9 mmol) was suspended, and tin metal (13.0 g) was added at room temperature, followed by stirring for 30 minutes. The insoluble material was separated by filtration, the obtained filtrate was adjusted to pH 4 with sodium hydrogen carbonate, and the deposited precipitate was separated by filtration. Further, the obtained filtrate was adjusted to pH 12 with a 1N aqueous sodium hydroxide solution, and extracted with methylene chloride. The obtained organic layer was dried over magnesium sulfate, and the solvent was distilled off. The obtained residue (3.09 g) was dissolved in ethanol (70 ml), ethyl 3-benzoylacrylate (3.38 ml, 18.4 mmol) was added, and the mixture was stirred at room temperature overnight. The resulting precipitate was collected by filtration and dried under reduced pressure to give the title compound (1.75 g, 26%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.35 (dd, J = 10.3, 1
8.5Hz, 1H), 3.82 (s, 6H), 3.92 (dd, J = 2.1, 1
8.5Hz, 1H), 4.46 (ddd, J = 2.1, 2.1, 10.2Hz, 1H
), 4.67 (d, J = 2.1 Hz, 1H), 6.35 (s, 1H), 6.3
6 (s, 1H), 7.47-7.65 (m, 3H), 7.70 (brs, 1H
), 7.99-8.03 (m, 2H).

Reference Example 8 6,7-Dimethoxy-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one Reference Example 7 was prepared in the same manner as in Reference Example 2. 6,7-Dimethoxy-3- (2-oxophenethyl)-obtained in
3,4-dihydro-1H-quinoxalin-2-one (1.
The title compound (1.15 g, 74%) was obtained from 50 g (4.79 mmol). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.78 (s, 3H), 3.82
(s, 3H), 6.76 (s, 1H), 6.77 (s, 1H), 7.33 (
s, 1H), 7.45-7.59 (m, 3H), 7.95 (d, J = 7.9 Hz,
2H), 11.95 (brs, 1H), 14.15 (brs, 1H).

Reference Example 9 6-methyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one 3,6-dimethyl-1H-quinoxalin-2-one ( 1
3.5 g, 77.5 mmol) was suspended in tetrahydrofuran (400 ml), lithium diisopropylamide monotetrahydrofuran (155 ml, 232 mmol; 1.5 M cyclohexane solution) was added at room temperature, and the mixture was heated to the boiling point. After cooling to room temperature, ethyl benzoate (11.2 ml, 77.5 mmol) was added, and the mixture was stirred at room temperature for 2 hours. 3N Hydrochloric acid (120 ml) was added to the reaction system, extracted with tetrahydrofuran, and extracted with ethyl acetate. The obtained organic layers were mixed and washed with brine.
The obtained organic layer was dried over magnesium sulfate, the solvent was distilled off, and ethanol was added to the obtained residue for washing.
The solid was collected by filtration, and the filtered solid was heated and stirred in toluene-ethanol. The insoluble solid was collected by filtration and dried under reduced pressure to give the title compound (5.69 g, 26%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.38 (s, 3H), 6.87-
7.03 (m, 4H), 7.46-7.57 (m, 3H), 8.06 (dd, J
= 1.7, 7.9Hz, 2H), 9.90 (brs, 1H), 13.83 (brs,
1H).

Reference Example 10 6-methoxy-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-2-
On In the same manner as in Reference Example 9, 6-methoxy-3-methyl-1H-quinoxalin-2-one (12.0 g, 63.1 mmol
l) and ethyl benzoate (9.00 ml, 63.1 mmol) to give the title compound (11.1 g, 60%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.83 (s, 3H), 6.72
(d, J = 8.3 Hz, 1H), 6.74 (s, 1H), 6.98 (d, J
= 8.3Hz, 1H), 7.01 (s, 1H), 7.45-7.54 (m, 3H),
8.05 (dd, J = 1.8, 8.1Hz, 2H), 9.10 (brs, 1H
), 14.0 (brs, 1H).

Reference Example 11 7-Methyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one In the same manner as in Reference Example 9, 3,7-dimethyl -1
The title compound (12.0 g, 56%) was obtained from H-quinoxalin-2-one (13.5 g, 77.5 mmol) and ethyl benzoate (11.1 ml, 77.5 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.38 (s, 3H), 6.90-
7.03 (m, 4H), 7.45-7.54 (m, 3H), 8.05 (dd, J
= 1.7, 7.9Hz, 2H), 9.10 (brs, 1H), 13.8 (brs, 1
H).

Reference Example 12 3- [2- (2-naphthyl) -2-oxoethylidene]
-3,4-Dihydro-1H-quinoxalin-2-one In the same manner as in Reference Example 9, 3-methyl-1H-quinoxalin-2-one (20.0 g, 125 mmol) and ethyl 2-naphthoate (24.4 g, 131 mmol) from the title compound (2
9.3 g, 75%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.18 (s, 1H), 7.04-
7.33 (m, 4H), 7.53-7.64 (m, 2H), 7.88-8.02 (
m, 3H), 8.13 (dd, J = 1.8, 8.7 Hz, 1H), 8.59 (s,
1H), 9.00 (brs, 1H), 13.9 (brs, 1H).

Reference Example 13 3- [2-oxo-2- (3-pyridyl) ethylidene]
-3,4-Dihydro-1H-quinoxalin-2-one In the same manner as in Reference Example 9, 3-methyl-1H-quinoxalin-2-one (20.0 g, 125 mmol) and ethyl nicotinate (17.9 ml, 131 mmol) From the title compound (11.6
g, 35%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 6.99 (s, 1H), 7.04-
7.06 (m, 1H), 7.19-7.26 (m, 3H), 7.43 (dd, J
= 4.6, 7.9Hz, 1H), 8.30 (d, J = 7.9Hz, 1H), 8.7
5-8.77 (m, 1H), 9.00 (brs, 1H), 9.27 (d, J =
2.3Hz, 1H), 13.9 (brs, 1H).

Reference Example 14 3- [2- (2-methoxycarbonylphenyl) -2-
Oxoethylidene] -3,4-dihydro-1H-quinoxalin-2-one In the same manner as in Reference Example 9, 3-methyl-1H-quinoxalin-2-one (10.0 g, 62.4 mmol) and phthalic anhydride (9.24 g, 62.4 mmol) from 3- [2- (2-carboxyphenyl) -2-oxoethylidene] -3,4.
A crude product of -dihydro-1H-quinoxalin-2-one (24.1 g) was obtained. Methanol (250ml) and concentrated sulfuric acid (1m
l) was added and the mixture was stirred at 80 ° C for 24 hours. The precipitated solid was collected by filtration and washed with methanol. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluted with methanol / chloroform = 0 to 1/100).
The obtained solid was washed with ether and combined with the previously obtained solid to give the title compound (7.45 g, 37%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.90 (s, 3H), 6.65
(s, 1H), 7.08-7.22 (m, 4H), 7.48-7.60 (m, 2H
), 7.67 (dd, J = 1.5, 7.4Hz, 1H), 7.78 (dd, J
= 1.3, 7.3Hz, 1H), 9.90 (brs, 1H), 13.4 (brs,
1H).

Reference Example 15 3- (2-oxophenethyl) -3,4-dihydro-1
H-pyrido [3,4-b] pyrazin-2-one In the same manner as in Reference Example 1, 3,4-diaminopyridine (10.0 g, 91.6 mmol) and ethyl 3-benzoylacrylate (18.5 ml, 101 mmol). From the title compound (19.4
g, 79%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.38 (dd, J = 6.9,
17.8Hz, 1H), 3.61 (dd, J = 4.3, 17.8Hz, 1H), 4.
40-4.50 (m, 1H), 6.18 (s, 1H), 6.70 (d, J = 5.
0Hz, 1H), 7.51-7.68 (m, 3H), 7.77 (d, J = 5.0H
z, 1H), 7.91 (s, 1H), 8.00 (d, J = 7.3 Hz, 2H),
10.7 (brs, 1H).

Reference Example 16 3- (2-oxo-2-phenylethylidene) -3,4
-Dihydro-1H-pyrido [3,4-b] pyrazine-2
-On 3- (2-oxophenethyl) -3,4-dihydro-1 obtained in Reference Example 15 in the same manner as in Reference Example 2.
H-pyrido [3,4-b] pyrazin-2-one (5.00 g,
18.7 mmol) to give the title compound (4.47 g, 90%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.91 (s, 1H), 7.10
(d, J = 5.5 Hz, 1H), 7.52-7.61 (m, 3H), 7.99-8.
02 (m, 2H), 8.22 (d, J = 5.5 Hz, 1H), 8.81 (s,
1H), 12.3 (brs, 1H), 13.4 (brs, 1H).

Reference Example 17 6- (2-oxophenethyl) -5,8-dihydro-6
H-Pteridin-7-one In the same manner as in Reference Example 1, the title compound (822m
g, 67%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.50 (dd, J = 5.9,
17.8Hz, 1H), 3.63 (dd, J = 3.6, 17.8Hz, 1H), 4.
50-4.52 (m, 1H), 6.40 (brs, 1H), 7.51-7.69 (
m, 3H), 7.92 (s, 1H), 8.00 (d, J = 7.3 Hz, 2H
), 8.14 (s, 1H), 11.2 (brs, 1H).

Reference Example 18 6- (2-oxo-2-phenylethylidene) -5,8
-Dihydro-6H-pteridin-7-one 6- (2-oxophenethyl) -5,8-dihydro-6 obtained in Reference Example 17 in the same manner as in Reference Example 2.
The title compound (430 mg, 62%) was obtained from H-pteridin-7-one (700 mg, 2.61 mmol). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.92 (s, 1H), 7.52
-7.64 (m, 3H), 7.99-8.03 (m, 2H), 8.60 (s, 1H
), 8.95 (s, 1H), 12.7 (brs, 1H), 13.1 (brs, 1
H).

Reference Example 19 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one Reference Example 9 In a similar manner, the known [Journal of Heterocyclic Chemistry (J. Heterocyc
lic Chem.), 27, p. 157 (1990)] 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one.
(2.70 g, 16.7 mmol) and methyl 3-dimethylaminobenzoate (3.00 g, 16.7 mmol) to give the title compound (3.88 g, 75
%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.98 (s, 6H), 6.92
(s, 1H), 6.96 (brd, J = 7.9 Hz, 1H), 7.25 (s,
1H), 7.27 (d, J = 7.8 Hz, 1H), 7.33 (dd, J = 7.
8, 7.9Hz, 1H), 7.50 (d, J = 5.3Hz, 1H), 8.17 (
d, J = 5.3Hz, 1H), 8.29 (s, 1H), 11.90 (brs, 1
H), 13.12 (brs, 1H).

Reference Example 20 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one Reference Example 9 In a similar manner, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (1.50 g, 9.31 m
mol) and methyl 4-dimethylaminobenzoate (1.67
g, 9.31 mmol) to give the title compound (1.71 g, 60%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.04 (s, 6H), 6.78
(d, J = 8.7 Hz, 2H), 6.90 (s, 1H), 7.45 (d, J
= 5.4Hz, 1H), 7.89 (d, J = 8.7Hz, 2H), 8.15 (
d, J = 5.4Hz, 1H), 8.24 (s, 1H), 11.92 (brs, 1
H), 13.10 (brs, 1H).

Reference Example 21 2- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene] -1,4-dihydro-2
H-pyrido [3,4-b] pyrazin-3-one A mixture of 2-methyl-3-nitrobenzoic acid (20.0 g, 110 mmol) and sulfuric acid (17.0 ml, 330 mmol) was refluxed in methanol for 4.5 hours. After cooling to room temperature, the mixture was neutralized by adding a 10N aqueous sodium hydroxide solution under ice-cooling, diluted with ethyl acetate, washed with saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and crude 2-methyl-3
-Methyl nitrobenzoate (20.9 g, 97%) was obtained. The crude methyl 2-methyl-3-nitrobenzoate (20.7
g, 110 mmol) in methanol and palladium-carbon
(20 g), and the mixture was stirred overnight at room temperature under a stream of hydrogen. After filtering off the palladium-carbon, the solvent was distilled off. The obtained residue was dissolved in acetonitrile (360 ml), and a 37% aqueous solution of formaldehyde (90 ml) and sodium cyanoborohydride (22.0 g, 350 mmol) were added under ice-cooling. The mixture was stirred at room temperature for 1 hour while maintaining the liquid property of 7. After adding a saturated aqueous sodium hydrogen carbonate solution to make the mixture alkaline, dilute with ethyl acetate and wash with a saturated saline solution.
Dry over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure,
Methyl 3-dimethylamino-2-methylbenzoate (16.7
g, 79%). Hereinafter, by the same method as in Reference Example 9, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (2.00 g, 12.0 mmol) and methyl 3-dimethylamino-2-methylbenzoate ( (2.40 g, 12.0 mmol)
From the title compound (2.72 g, 70%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.35 (s, 3H), 2.66
(s, 6H), 6.49 (s, 1H), 7.12-7.30 (m, 3H), 7.
56 (d, J = 5.4Hz, 1H), 8.16 (d, J = 5.4Hz, 1H
), 8.29 (s, 1H), 12.03 (brs, 1H), 12.83 (br
s, 1H).

Reference Example 22 2- [2- (4-dimethylamino-1-naphthyl) -2
-Oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one 4-dimethylamino-1-naphthoic acid (2.50 g, 12.0 mmol
l) and a mixture of sulfuric acid (1.86 ml, 35.0 mmol) was refluxed in methanol (25 ml) for 5 hours. After cooling to room temperature, the mixture was neutralized by adding a saturated aqueous sodium hydrogen carbonate solution, diluted with ethyl acetate, washed with saturated saline, and dried over anhydrous magnesium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 10/1) to give 4-dimethylamino-1-
Methyl naphthoate (2.34 g, 85%) was obtained. Then, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (0.770 g, 4.80 mmol) was obtained in the same manner as in Reference Example 9.
l) and methyl 4-dimethylamino-1-naphthoate
(1.10 g, 4.80 mmol) gave the title compound (1.12 g, 65%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.94 (s, 6H), 6.78
(s, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.51-7.63 (
m, 3H), 7.90 (d, J = 8.0 Hz, 1H), 8.15-8.24 (m,
1H), 8.19 (d, J = 5.3 Hz, 1H), 8.29 (s, 1H),
8.66-8.75 (m, 1H), 11.82 (brs, 1H), 13.00 (br
s, 1H).

Reference Example 23 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one Reference Example 9 In a similar manner, 3-methyl-1H-pyrido [2,3-b] pyrazin-2-one (2.19 g, 14.0 m
mol) and methyl 4-dimethylaminobenzoate (2.44
g, 14.0 mmol) to give the title compound (1.37 g, 32%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.04 (s, 6H), 6.77
(d, J = 8.6 Hz, 2H), 6.80 (s, 1H), 7.09 (dd, J
= 4.7, 7.5Hz, 1H), 7.40 (d, J = 7.5Hz, 1H), 7.
88 (d, J = 8.6 Hz, 2H), 8.05 (d, J = 4.7 Hz, 1H
), 11.90 (brs, 1H), 13.35 (brs, 1H).

Reference Example 24 3- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene] -3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one In the same manner as in Reference Example 9, 3-methyl-1H-pyrido [2,3-b] pyrazin-2-one (3.00 g, 19.0 m
mol) and methyl 3-dimethylamino-2-methylbenzoate synthesized as an intermediate in Reference Example 21 (3.60 g, 19.
0 mmol) to give the title compound (2.53 g, 41%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.34 (s, 3H), 2.67
(s, 6H), 6.40 (s, 1H), 7.12-7.30 (m, 3H), 7.
17 (dd, J = 4.7, 7.9Hz, 1H), 7.46 (dd, J = 1.4,
7.9Hz, 1H), 8.10 (dd, J = 1.4, 4.7Hz, 1H), 12.0
5 (brs, 1H), 13.21 (brs, 1H).

Reference Example 25 3- [2- (2-methyl-3-pyridyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2
3-b] pyrazin-2-one By a method similar to that in Reference Example 9, 3-methyl-1H-pyrido [2,3-b] pyrazin-2-one (1.11 g, 6.86 m
mol) and methyl 2-methylnicotinate (1.04 g, 6.86
mmol) to give the title compound (1.01 g, 53%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.64 (s, 3H), 6.48
(s, 1H), 7.19 (dd, J = 4.7, 8.0 Hz, 1H), 7.35
(dd, J = 5.2, 7.9Hz, 1H), 7.48 (d, J = 8.0Hz, 1
H), 7.97 (d, J = 7.9 Hz, 1H), 8.13 (d, J = 4.7 H
z, 1H), 8.56 (d, J = 5.2 Hz, 1H), 12.12 (s, 1H
), 13.26 (s, 1H).

Reference Example 26 2- (3,3-dimethyl-2-oxobutylidene)-
1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one By a method similar to that in Reference Example 9, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one ( 3.00g, 19.0m
mol) and methyl pivalate (2.16 g, 19.0 mmol) to give the title compound (2.08 g, 45%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.17 (s, 9H), 6.41
(s, 1H), 7.45 (d, J = 5.4 Hz, 1H), 8.13 (d, J
= 5.4Hz, 1H), 8.23 (s, 1H), 11.97 (brs, 1H), 1
2.62 (brs, 1H).

Reference Example 27 2- [2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-
b] Pyrazin-3-one 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00 g, 19.0 m)
mol) and methyl 4-methoxybenzoate (3.09 g, 19.0
mmol) to give the title compound (2.06 g, 37%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.86 (s, 3H), 6.92
(s, 1H), 7.08 (d, J = 8.9 Hz, 2H), 7.50 (d, J
= 5.6Hz, 1H), 8.00 (d, J = 8.9Hz, 2H), 8.17 (
d, J = 5.6Hz, 1H), 8.27 (s, 1H), 11.81 (brs, 1
H), 13.05 (brs, 1H).

Reference Example 28 3- [2-oxo-2- (4-pyridyl) ethylidene]
-3,4-Dihydro-1H-pyrido [2,3-b] pyrazin-2-one By a method similar to that in Reference Example 9, 3-methyl-1H-pyrido [2,3-b] pyrazin-2-one (3.00g, 19.0m
mol) and methyl isonicotinate (2.61 g, 19.0 mmol)
From the title compound (3.59 g, 71%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.86 (s, 1H), 7.21
(dd, J = 4.9, 8.0Hz, 1H), 7.49 (d, J = 8.0Hz, 1
H), 7.87 (dd, J = 1.6, 4.6 Hz, 2H), 8.15 (d, J =
4.9Hz, 1H), 8.79 (dd, J = 1.6, 4.9Hz, 2H), 12.
20 (brs, 1H), 13.50 (brs, 1H).

Reference Example 29 2- {2-oxo-2- [4- (4-pyridylmethoxy) phenyl] ethylidene} -1,4-dihydro-2H
-Pyrido [3,4-b] pyrazin-3-one methyl 4-hydroxybenzoate (4.00 g, 26.3 mmol), 4
-Pyridylmethanol (4.30 g, 39.4 mmol), diethyl azodicarboxylate (7.40 ml, 39.4 mmol) and triphenylphosphine (10.3 g, 39.4 mmol) were dissolved in tetrahydrofuran (300 ml) and stirred at room temperature for 5 hours. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 1/1), and methyl 4- (4-pyridylmethoxy) benzoate was obtained.
(4.11 g, 64%). Next, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00 g, 19.0 mmol) and the above 4 were prepared in the same manner as in Reference Example 9.
Methyl-(4-pyridylmethoxy) benzoate (4.60 g, 1
9.0 mmol) to give the title compound (3.94 g, 60%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 5.31 (s, 2H), 6.93
(s, 1H), 7.18 (d, J = 8.3 Hz, 2H), 7.48 (d, J
= 5.0Hz, 2H), 7.53 (d, J = 5.1Hz, 1H), 8.02 (
d, J = 8.3Hz, 2H), 8.18 (d, J = 5.1Hz, 1H), 8.3
1 (s, 1H), 8.59 (d, J = 5.0 Hz, 2H), 12.08 (br
s, 1H), 13.04 (s, 1H).

Reference Example 30 2- [2- (4-fluorophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-
b] Pyrazin-3-one 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00 g, 19.0 m)
mol) and methyl 4-fluorobenzoate (2.93 g, 19.0
mmol) to give the title compound (2.83 g, 52%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.94 (s, 1H), 7.37
(dd, J = 7.3, 8.7Hz, 2H), 7.57 (d, J = 5.6Hz, 1
H), 8.10 (dd, J = 5.7, 8.7 Hz, 2H), 8.20 (d, J =
5.6Hz, 1H), 8.30 (s, 1H), 12.08 (brs, 1H), 1
3.03 (brs, 1H).

Reference Example 31 2- [2-oxo-2- (4-pyridyl) ethylidene]
-1,4-Dihydro-2H-pyrido [3,4-b] pyrazin-3-one By a method similar to that in Reference Example 9, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00g, 19.0m
mol) and methyl isonicotinate (2.61 g, 19.0 mmol)
From the title compound (3.07 g, 61%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.93 (s, 1H), 7.62
(d, J = 5.0 Hz, 1H), 7.87 (dd, J = 1.2, 5.0 Hz, 2
H), 8.21 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 8.
80 (dd, J = 1.2, 5.0Hz, 2H), 12.10 (brs, 1H),
13.10 (brs, 1H).

Reference Example 32 2- [2- (4-chlorophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-
b] Pyrazin-3-one By a method similar to that in Reference Example 9, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (250 mg, 1.55 m
mol) and ethyl 4-chlorobenzoate (264 mg, 1.55 mmo
From l), the title compound (307 mg, 66%) was obtained. ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.93 (s, 1H), 7.57
(d, J = 5.6 Hz, 1H), 7.61 (d, J = 8.6 Hz, 2H),
8.03 (d, J = 8.6 Hz, 2H), 8.20 (d, J = 5.6 Hz, 1H
), 8.30 (s, 1H), 12.10 (brs, 1H), 13.05 (s,
1H).

Reference Example 33 2- [2- (3-fluorophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-
b] Pyrazin-3-one 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00 g, 19.0 m)
mol) and ethyl 3-fluorobenzoate (3.13g, 19.0m
mol) to give the title compound (2.48 g, 47%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.95 (s, 1H), 7.38
(dd, J = 2.2, 8.2Hz, 1H), 7.52 (d, J = 5.0Hz, 1
H), 7.58 (dd, J = 6.1, 8.2 Hz, 1H), 7.71 (d, J =
8.2Hz, 1H), 7.86 (d, J = 7.9Hz, 1H), 8.19 (d,
J = 5.0Hz, 1H), 8.33 (s, 1H), 12.13 (brs, 1H
), 13.13 (brs, 1H).

Reference Example 34 2- [2- (2,4-dimethoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one Reference Example 9 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00 g, 19.0 m
mol) and methyl 2,4-dimethoxybenzoate (3.65
g, 19.0 mmol) to give the title compound (1.98 g, 33%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.35 (s, 3H), 3.91
(s, 3H), 6.64 (s, 1H), 6.67 (d, J = 8.3 Hz, 1H
), 7.06 (s, 1H), 7.47 (d, J = 5.3 Hz, 1H), 7.74
(d, J = 8.3 Hz, 1H), 8.15 (d, J = 5.3 Hz, 1H),
8.25 (s, 1H), 11.90 (brs, 1H), 13.01 (brs, 1H
).

Reference Example 35 2- [2- (2,5-dimethoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one Reference Example 9 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one (3.00 g, 19.0 m
mol) and methyl 2,5-dimethoxybenzoate (3.65
g, 19.0 mmol) to give the title compound (2.59 g, 43%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.75 (s, 3H), 3.88
(s, 3H), 7.05 (s, 1H), 7.06 (s, 1H), 7.37 (
d, J = 5.6Hz, 1H), 7.58 (d, J = 5.3Hz, 1H), 8.16
(d, J = 5.6 Hz, 1H), 8.39 (d, J = 5.3 Hz, 1H),
8.64 (s, 1H), 12.20 (brs, 1H), 13.07 (s, 1H).

Reference Example 36 2- [2- (2,6-dimethoxy-3-pyridyl) -2
-Oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one 2,6-dimethoxynicotinic acid (10.0 g, 55.0 mmol), methyl iodide (5.10 ml, 82.0 mmol) ) And potassium carbonate (1
5.1 g, 110 mmol) in N, N-dimethylformamide (110 ml)
And stirred at 50 ° C. for 5 hours. After allowing to cool to room temperature, water was added, the mixture was diluted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. The residue obtained by evaporating the solvent under reduced pressure is subjected to silica gel column chromatography.
(Eluted with hexane / ethyl acetate = 2/1),
Methyl 6-dimethoxynicotinate (10.9 g, quantitative) was obtained. Next, 2-methyl-4H-pyrido [3,4-b] pyrazin-3-one was prepared in the same manner as in Reference Example 9.
(3.22 g, 20.0 mmol) and methyl 2,6-dimethoxynicotinate (3.94 g, 20.0 mmol) to give the title compound (1.76 g,
27%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.97 (s, 3H), 4.05
(s, 3H), 6.55 (d, J = 8.3 Hz, 1H), 7.17 (s, 1H
), 7.49 (d, J = 5.4 Hz, 1H), 8.16 (d, J = 5.4 Hz,
1H), 8.18 (d, J = 8.3 Hz, 1H), 8.27 (s, 1H),
11.94 (brs, 1H), 13.05 (brs, 1H).

Reference Example 37 3-Methyl-2-tosyloxyquinoxaline 3-methyl-2-quinoxalinol (1.00 g, 6.24 mmol)
l), tosyl chloride (1.43 g, 7.49 mmol) and potassium carbonate (1.29 g, 9.36 mmol) in dichloroethane (15 ml)
Refluxed for 5 hours. After allowing to cool to room temperature, water was added, the mixture was diluted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. After filtering off the insolubles, the filtrate was concentrated under reduced pressure to obtain the title compound (1.93 g, 98%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.47 (s, 3H), 2.74
(s, 3H), 7.40 (d, J = 8.6 Hz, 2H), 7.63-7.74 (
m, 2H), 7.79-7.88 (m, 1H), 7.96-8.04 (m, 1H),
8.09 (d, J = 8.6 Hz, 2H).

Reference Example 38 2-Methyl-3- (4-methylpiperazin-1-yl)
Quinoxaline 3-Chloro-2-methylquinoxaline (5.00 g, 28.0 mmol) of a known [Journal of Chemical Society (J. Chem. Soc.), P.
-Dimethylformamide (120 ml), 1-methylpiperazine (9.30 ml, 84.0 mmol) was added,
Stirred for hours. Water and saline were added to the reaction system, extracted with ethyl acetate and methylene chloride, and the obtained organic layer was dried over magnesium sulfate. The solvent was distilled off, and silica gel column chromatography (methanol / chloroform = 1
/ 100-1 / 50) and purified with the title compound (5.62 g, 83
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.34 (s, 3H), 2.62-
2.66 (m, 4H), 2.70 (s, 3H), 3.40-3.44 (m, 4H
), 7.48-7.61 (m, 2H), 7.81-7.90 (m, 2H).

Reference Example 39 2-Methyl-3-thiomorpholinoquinoxaline By the same method as in Reference Example 38, the title was obtained from 2-methyl-3-chloroquinoxaline (5.00 g, 28.0 mmol) and thiomorpholine (14.1 ml, 140 mmol). Compound (2.31 g, 34
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.69 (s, 3H), 2.85-
2.88 (m, 4H), 3.62-3.66 (m, 4H), 7.50-7.63 (
m, 2H), 7.81-7.91 (m, 2H).

Reference Example 40 2-Methyl-3- (4-piperidinopiperidino) quinoxaline 3-Methyl-2-tosyloxyquinoxaline (3.00 g, 9.54 mmol) obtained in Reference Example 37 and 4-pi Peridinopiperidine (4.82 g, 28.6 mmol) was heated in N, N-dimethylformamide at 120 ° C. for 6 hours. After allowing to cool to room temperature, the mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate. After filtering off the insoluble matter, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (containing 5% triethylamine, eluted with hexane / ethyl acetate = 1/1) to give the title compound (1.13 g). , 38%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.36-3.00 (m, 19H),
2.70 (s, 3H), 7.51 (dd, J = 8.1, 8.1 Hz, 1H), 7.
59 (dd, J = 8.1, 8.1Hz, 1H), 7.81 (d, J = 8.1H
z, 1H), 7.89 (d, J = 8.1 Hz, 1H).

Reference Example 41 3-Dibutylamino-2-methylquinoxaline By the same method as in Reference Example 40, 3-methyl-2-tosyloxyquinoxaline obtained in Reference Example 37 (3.83 g,
12.2 mmol) and dibutylamine (6.2 ml, 36.5 mmol)
From the title compound (1.68 g, 51%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 0.92 (t, J = 7.2Hz,
6H), 1.20-1.66 (m, 8H), 2.70 (s, 3H), 3.39 (
t, J = 7.6Hz, 4H), 7.46 (dd, J = 8.0, 8.0Hz, 1H
), 7.56 (dd, J = 8.0, 8.0Hz, 1H), 7.78 (d, J =
8.0Hz, 1H), 7.87 (d, J = 8.0Hz, 1H).

Reference Example 42 3- (4-benzylpiperazin-1-yl) -2-methylquinoxaline By the same method as in Reference Example 40, 3-methyl-2-tosyloxyquinoxaline obtained in Reference Example 37 (4.00 g,
13.0 mmol) and 1-benzylpiperazine (6.78 ml, 3
9.0 mmol) to give the title compound (1.81 g, 44%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.60-2.93 (m, 4H),
2.69 (s, 3H), 3.28-3.61 (m, 4H), 3.69 (s, 2H
), 7.25-7.49 (m, 5H), 7.53 (dd, J = 8.1,8.1Hz,
1H), 7.61 (dd, J = 8.1, 8.1 Hz, 1H), 7.83 (d,
J = 8.1Hz, 1H), 7.90 (d, J = 8.1Hz, 1H).

Reference Example 43 3- [4- (2-methoxyphenyl) piperazine-1-
Yl] -2-methylquinoxaline In the same manner as in Reference Example 40, the 3-methyl-2-tosyloxyquinoxaline obtained in Reference Example 37 (2.00 g,
6.40 mmol) and 1- (2-methoxyphenyl) piperazine (3.69 g, 19.2 mmol) to give the title compound (1.69 g, 79
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.75 (s, 3H), 3.03-
3.42 (m, 8H), 3.90 (s, 3H), 6.82-7.11 (m, 4H
), 7.53 (dd, J = 8.0, 8.0Hz, 1H), 7.60 (dd, J
= 8.0, 8.0Hz, 1H), 7.85 (d, J = 8.0Hz, 1H), 7.9
1 (d, J = 8.0Hz, 1H).

Reference Example 44 3- [4- (tert-butoxycarbonyl) piperazine-
1-yl] -2-methylquinoxaline In the same manner as in Reference Example 40, 3-methyl-2-tosyloxyquinoxaline obtained in Reference Example 37 (2.00 g,
6.40 mmol) and 1- (tert-butoxycarbonyl)
Piperazine (3.58 g, 19.2 mmol) to give the title compound (1.22
g, 58%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.50 (s, 9H), 2.72
(s, 3H), 3.28-3.38 (m, 4H), 3.59-3.69 (m, 4H
), 7.53 (dd, J = 8.2, 8.2Hz, 1H), 7.59 (dd, J
= 8.2, 8.2Hz, 1H), 7.82 (d, J = 8.2Hz, 1H), 7.9
0 (d, J = 8.2Hz, 1H).

Reference Example 45 2-Methyl-3- [4- (2-pyridyl) piperazine-
1-yl] quinoxaline In the same manner as in Reference Example 40, 3-methyl-2-tosyloxyquinoxaline obtained in Reference Example 37 (2.00 g,
6.40 mmol) and 1- (2-pyridyl) piperazine
(2.43 ml, 19.1 mmol) gave the title compound (1.23 g, 63%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.76 (s, 3H), 3.47-
3.57 (m, 4H), 3.74-3.84 (m, 4H), 6.70 (dd, J
= 5.3, 7.1Hz, 1H), 6.77 (d, J = 8.9Hz, 1H), 7.52
-7.64 (m, 3H), 7.84 (d, J = 8.0 Hz, 1H), 7.91
(d, J = 8.0 Hz, 1H), 8.24 (brd, J = 5.3 Hz, 1H).

Reference Example 46 3- [2- (2,4-Dimethoxyphenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one Reference Example 9 3-methyl-1H-pyrido [2,3-b] pyrazin-2-one (3.00 g, 19.0 m
mol) and methyl 2,4-dimethoxybenzoate (3.65
g, 19.0 mmol) to give the title compound (2.19 g, 36%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.90 (s, 3H), 3.9
6 (s, 3H), 6.67 (d, J = 7.2 Hz, 1H), 6.68 (s, 1
H), 7.04 (s, 1H), 7.10 (dd, J = 4.6, 8.6 Hz, 1H
), 7.46 (d, J = 7.2Hz, 1H), 7.80 (d, J = 8.6H
z, 1H), 8.08 (d, J = 4.6 Hz, 1H), 11.91 (brs, 1H
), 13.40 (brs, 1H).

Reference Example 47 7-chloro-2- (2-oxo-2-phenylethylidene) -1,4-dihydro-2H-pyrido [2,3-b]
Pyrazin-3-one 2,3-diamino-5-chloropyridine (2.0) of a known compound [Journal of American Chemical Society (J. Am. Chem. Soc.), Vol. 71, p. 1885 (1949)] g, 14 mmol) and ethyl 2,4-dioxo-4-phenylbutanoate (3.68 g, 16.8 mmol) which is a known compound [Chemie Berchte (Chem. Ber.), Vol. 20, p. 2178 (1887)]. The mixture was heated and refluxed for 6 hours in ethanol (60 ml) together with a 1N aqueous sulfuric acid solution (20 ml). After cooling to room temperature, the precipitated crystals were collected by filtration and washed with isopropanol. The obtained crude crystals were recrystallized from N, N-dimethylformamide to give the title compound (2.38 g, 74%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.90 (s, 1H), 7.4
9-7.68 (m, 3H), 8.01 (d, J = 8.7 Hz, 2H), 8.10
(d, J = 2.1 Hz, 1H), 8.25 (d, J = 2.1 Hz, 1H), 1
2.46 (brs, 1H), 13.39 (brs, 1H).

Reference Example 48 7-chloro-2- [2- (4-methoxyphenyl) -2
-Oxoethylidene] -1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one As in Reference Example 47, 2,3-diamino-5-chloropyridine (2.0 g, 14 mmol) And known compounds [Journal of Heterocyclic Chemistry (J. H
eterocyclic Chem.), Vol. 32, p. 347 (1995)], ethyl 4- (4-methoxyphenyl) -2,4-dioxobutanoate (4.18 g, 5.02 mmol) from the title compound (2.22 g, 48%). ) Got. ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.85 (s, 3H), 6.8
6 (s, 1H), 7.07 (d, J = 8.5 Hz, 2H), 7.99 (d, J
= 8.5Hz, 2H), 8.06 (d, J = 1.9Hz, 1H), 8.19 (
d, J = 1.9Hz, 1H), 12.44 (brs, 1H), 13.13 (br
s, 1H).

Reference Example 49 7-Chloro-2- [2- (4-fluorophenyl) -2
-Oxoethylidene] -1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one <Step 1> 4-Fluoroacetophenone (10.0 g, 72.4 m
mol) and diethyl oxalate (22.0 ml, 162 mmol) were refluxed in ethanol (70 ml) for 1 hour in the presence of sodium ethoxide (8.60 g, 126 mmol). After allowing to cool to room temperature, the mixture was added to ice water, and the precipitated crystals were collected by filtration. The obtained crude crystals were recrystallized from a mixed solvent of ethyl acetate-hexane to give 4-
Ethyl (4-fluorophenyl) -2,4-dioxobutanoate (6.82 g, 41%) was obtained. ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.15-1.29 (m, 3H
), 3.35 (s, 1H), 3.97-4.16 (m, 2H), 5.22 (s,
0.35H), 6.21 (s, 0.65H), 7.03-7.24 (m, 2H),
7.67-7.86 (m, 2H). <Step 2> 2,3-Diamino-5-chloropyridine (1.
50 g, 10.4 mmol) and ethyl 4- (4-fluorophenyl) -2,4-dioxobutanoate (2.99 g, 12.5 mmol) obtained in step 1 together with a 1N aqueous sulfuric acid solution (14 ml) in ethanol (40 ml). Heated to reflux for an hour. After cooling to room temperature, the precipitated crystals were collected by filtration and washed with isopropanol. The obtained crude crystals were recrystallized from N, N-dimethylformamide to give the title compound (1.39 g, 44%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 6.81 (s, 1H), 7.3
6 (dd, J = 9.1, 9,1Hz, 2H), 8.08 (dd, J = 5.9,
9.1Hz, 2H), 8.10 (d, J = 2.1Hz, 1H), 8.23 (d, J
= 2.1Hz, 1H), 12.26 (brs, 1H), 12.47 (brs, 1H)
).

Reference Example 50 2- [2- (1,3-benzodioxol-5-yl)
-2-oxoethylidene] -7-methyl-1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one <Step 1> In the same manner as in Step 1 of Reference Example 49,
5-acetyl-1,3-benzodioxole (12.0 g,
0.073 mol) from 4- (1,3-benzodioxole-
Ethyl 5-yl) -2,4-dioxobutanoate (4.48 g,
23%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.08-1.39 (m, 3H
), 3.35 (brs, 1H), 3.96-4.24 (m, 2H), 5.22 (
brs, 0.32H), 5.91-6.13 (m, 2H), 6.22 (brs, 0.68
H), 6.76-6.99 (m, 1H), 7.15-7.44 (m, 2H). <Step 2> In the same manner as in Step 2 of Reference Example 49,
4- (1,3-benzodioxol- obtained in step 1
Ethyl 5-yl) -2,4-dioxobutanoate (2.29 g,
7.21 mmol) and known compounds [Journal of Medicinal Chemistry (J. Med. Chem.), 33, 2
231 pages (1990)].
The title compound (1.69 g, 73%) was obtained from methylpyridine (888 mg, 8.66 mmol). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.29 (s, 3H), 6.1
4 (s, 2H), 6.78 (s, 1H), 7.04 (d, J = 8.3 Hz, 1
H), 7.47 (d, J = 1.3 Hz, 1H), 7.62 (dd, J = 1.3,
8.3Hz, 1H), 7.78 (brs, 1H), 7.93 (brs, 1H),
12.29 (brs, 1H), 13.33 (brs, 1H).

Reference Example 51 2- [2- (1-methylpyrrol-2-yl) -2-oxoethylidene] -7-piperidinocarbonyl-1,4
-Dihydro-2H-pyrido [2,3-b] pyrazine-3
-On <Step 1> Known method [Journal of Chemical
Society (J. Chem. Soc.), P. 2590 (1951
Year)] to give crude 6-chloro-5-nitronicotinic acid chloride from 6-hydroxy-5-nitronicotinic acid (3.00 g, 16.3 mmol). The prepared crude 6-chloro-5-nitronicotinic acid chloride was dissolved in dichloromethane (80 ml), and triethylamine (23.0 ml, 165 mmol) and piperidine (1.93 ml, 19.6 m) were added under ice-cooling.
mol) was added. After stirring at the same temperature for 30 minutes, the reaction solution was diluted with dichloromethane. The organic layer was washed with water and saturated saline, and then dried over anhydrous magnesium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 1/1) to give 6-chloro-5-nitro-3-piperidinocarbonylpyridine (3.17 g, 72%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.46-1.89 (m, 6H),
3.20-3.92 (m, 4H), 8.27 (d, J = 2.0 Hz, 1H), 8.
63 (d, J = 2.0Hz, 1H). <Step 2> 6-chloro-5-nitro- obtained in Step 1
3-piperidinocarbonylpyridine (3.17 g, 11.8 mmo
l) was dissolved in ethanol (40 ml) and heated to 50 ° C. At the same temperature, a concentrated aqueous ammonia solution was added until the raw materials disappeared. After cooling to room temperature, the reaction was concentrated to about one-fifth,
Diluted with chloroform. The organic layer was washed with water and saturated saline, and dried over anhydrous magnesium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 2/1) to give 6-amino-5-nitro-3-piperidinocarbonylpyridine ( 2.35 g, 78%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.48-1.82 (m, 6H),
3.15-3.97 (m, 4H), 5.88-7.96 (m, 2H), 8.48 (
d, J = 2.1Hz, 1H), 8.53 (d, J = 2.1Hz, 1H).

<Step 3> 6-amino- obtained in step 2
5-nitro-3-piperidinocarbonylpyridine (2.35
g, 9.40 mmol) was dissolved in ethanol (50 ml), palladium-carbon (1.20 g) was added, and the mixture was stirred at room temperature for 5.5 hours under a hydrogen stream. After filtering off insolubles, the solvent was distilled off under reduced pressure.
A crude product of 5,6-diamino-3-piperidinocarbonylpyridine (2.21 g, quantitative) was obtained. <Step 4> In the same manner as in Reference Example 49, 4- (1-methylpyrrole-2) was prepared from 2-acetyl-1-methylpyrrole (9.91 g, 80.5 mmol) and diethyl oxalate.
-Yl) -2,4-dioxobutanoate (3.08 g, 1
7%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.25-1.53 (m, 3H
), 3.30-3.70 (brs, 1H), 3.97 (s, 0.54H), 4.04
(s, 2.46H), 4.14-4.42 (m, 2H), 5.27 (brs, 0.1
8H), 5.97-6.20 (m, 1H), 6.24-6.39 (m, 0.82H),
6.50-6.58 (m, 0.18H), 6.62-6.79 (m, 0.82H),
6.79-6.87 (m, 0.18H), 6.87-7.03 (m, 0.82H). <Step 5> Ethyl 4- (1-methylpyrrol-2-yl) -2,4-dioxobutanoate obtained in Step 4 (2.52
g, 0.011 mol) and the crude 5,6 obtained in step 3.
-Diamino-3-piperidinocarbonylpyridine (2.21
g, 0.01 mol) to give the title compound (1.44 g, 41%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.44-1.72 (m, 6H
), 3.20-3.71 (m, 4H), 3.97 (s, 3H), 6.13-6.14
(m, 1H), 6.63 (s, 1H), 7.00-7.02 (m, 1H), 7.0
8-7.14 (m, 1H), 7.94 (d, J = 2.0 Hz, 1H), 7.99
(d, J = 2.0 Hz, 1H), 12.31 (brs, 1H), 12.64 (br
s, 1H).

Reference Example 52 2-ethoxy-6- [2- (4-fluorophenyl)-
2-oxoethylidene] -5,8-dihydro-6H-pteridin-7-one 4-amino- of a known compound [EP 385850].
2-chloro-5-nitropyrimidine (1.50 g, 7.73 mmo
l) was dissolved in ethanol (15 ml), and sodium ethoxide (631 mg, 9.27 mmol) was added under ice cooling. After heating under reflux for 4 hours, water was added under ice cooling, and the mixture was diluted with chloroform. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crudely purified 4-amino-2-
Ethoxy-5-nitropyrimidine (722 mg, 51%) was obtained. The resulting crude 4-amino-2-ethoxy-5
Nitropyrimidine (653 mg, 3.54 mmol) was added to ethanol (20
ml), palladium-carbon (330 mg) was added, and the mixture was stirred at room temperature under a hydrogen stream for 3.5 hours. After filtering off the insoluble matter,
The filtrate was concentrated under reduced pressure to give crude 4,5-diamino-2-
Ethoxypyrimidine (573 mg, quantitative) was obtained. According to a method similar to that of Reference Example 47, the obtained crudely purified 4,5-
Diamino-2-ethoxypyrimidine (573mg, 3.54mmo
l) and ethyl 4- (4-fluorophenyl) -2,4-dioxobutanoate (1.06 g, 4.46 mmol) to give the title compound (903 mg, 74%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.33 (t, J = 6.8H
z, 3H), 4.33 (q, J = 6.8 Hz, 2H), 6.80 (s, 1H),
7.34 (dd, J = 8.7, 8.7Hz, 2H), 8.06 (dd, J = 5.
8, 8.7Hz, 2H), 8.79 (s, 1H), 12.68 (brs, 1H),
13.43 (brs, 1H).

Reference Example 53 6- (Imidazol-1-yl) -2- [2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-
Dihydro-2H-pyrido [2,3-b] pyrazine-3-
2,3-Diamino-6- (imidazol-1-yl) pyridine (1.50 g, 8.56 mmol) was dissolved in ethanol (37 ml), and 1N sulfuric acid (12 ml) and 4- (4-methoxyphenyl) -2 were added. , 4-dioxobutanoate (2.57 g, 10.
(3 mmol) and heated under reflux for 3 hours. After cooling, the precipitate was collected by filtration, and the precipitate collected was dissolved in N, N-dimethylformamide.After cooling, the precipitated crystal was collected by filtration to give the title compound (0.58
g, 19%). ¹ H-NMR (CD ₃ OD) δ (ppm): 3.91 (s, 3H), 7.01
(d, J = 8.9 Hz, 2H), 7.02 (s, 1H), 7.15 (s, 1H
), 7.30 (d, J = 8.5 Hz, 1H), 7.85 (d, J = 8.5 Hz,
1H), 7.97 (s, 1H), 8.03 (d, J = 8.9 Hz, 2H),
8.40 (s, 1H).

Reference Example 54 3- {2-oxo-2- [4- (4-pyridylmethoxy) phenyl] ethylidene} -3,4-dihydro-1H
-Pyrid [2,3-b] pyrazin-2-one By a method similar to that in Reference Example 29, 3-methyl-1H-
Pyrid [2,3-b] pyrazin-2-one (2.65 g, 16.
5 mmol) and methyl 4- (4-pyridylmethoxy) benzoate (4.01 g, 16.5 mmol) obtained in Reference Example 29 to give the title compound (2.60 g, 45%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 5.38 (s, 2H), 6.96
(s, 1H), 7.20 (d, J = 8.7 Hz, 2H), 7.21 (d, J
= 8.2Hz, 1H), 7.51 (dd, J = 4.8, 8.2Hz, 1H), 7.
55 (d, J = 5.8 Hz, 2H), 8.12 (d, J = 8.7 Hz, 2H
), 8.17 (d, J = 4.8 Hz, 1H), 8.69 (d, J = 5.8 Hz,
2H), 12.08 (brs, 1H), 13.43 (s, 1H).

Example 1 1-methyl-3- (2-oxophenethyl) -3,4-
Dihydro-1H-quinoxalin-2-one (compound 1) 3- (2-oxophenethyl)-obtained in Reference Example 1
3,4-dihydro-1H-quinoxalin-2-one (1
0.0g, 37.6mmol) with N, N-dimethylformamide (100m
l), methyl iodide (2.30 ml, 37.6 mmol) and potassium carbonate (7.80 g, 56.4 mmol) were added, and the mixture was stirred at room temperature for 3 days. Water was added to the reaction system, and extracted with toluene. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluted with methylene chloride / ethyl acetate = 100/2) to give the title compound (7.50 g, 71%).
Was obtained as a pale yellow powder. ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.33 (dd, J = 10.2,
18.5Hz, 1H), 3.40 (s, 3H), 3.92 (dd, J = 2.1,
18.5Hz, 1H), 4.50 (dd, J = 2.1, 10.2Hz, 1H), 6.7
5-6.98 (m, 4H), 7.47-7.51 (m, 2H), 7.57-7.64
(m, 2H), 7.99 (dd, J = 1.3, 8.6 Hz, 2H).

Example 2 1-ethoxycarbonylmethyl-3- (2-oxophenethyl) -3,4-dihydro-1H-quinoxaline-2
-One (Compound 2) 3 obtained in Reference Example 1 in the same manner as in Example 1.
-(2-oxophenethyl) -3,4-dihydro-1H
-Quinoxalin-2-one (30.0 g, 113 mmol) and ethyl bromoacetate (10.0 ml, 113 mmol) were converted to the title compound (1
6.2 g, 43%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.30 (t, J = 7.3Hz,
3H), 3.39 (dd, J = 10.2, 18.5 Hz, 1H), 3.84 (d
d, J = 2.0, 18.5Hz, 1H), 4.26 (q, J = 7.3Hz, 2H
), 4.58 (dd, J = 2.0, 10.2Hz, 1H), 4.68 (s, 2H
), 5.00 (brs, 1H), 6.70 (dd, J = 1.3, 7.9Hz, 1H
), 6.81 (dt, J = 1.3, 7.6 Hz, 1H), 6.86 (dd, J
= 1.7, 7.9Hz, 1H), 6.95 (dt, J = 1.3, 7.6Hz, 1H
), 7.45-7.63 (m, 3H), 7.97-8.00 (m, 2H).

Example 3 1-benzyl-3- (2-oxophenethyl) -3,4
-Dihydro-1H-quinoxalin-2-one (compound 3) 3- (2-oxophenethyl)-obtained in Reference Example 1
3,4-dihydro-1H-quinoxalin-2-one (1
5.0 g, 56.3 mmol) with N, N-dimethylformamide (300 m
l), and cooled under ice-cooling with potassium tert-butoxide (6.64).
g, 59.1 mmol) and stirred for 30 minutes. A solution of benzyl bromide (6.70 ml, 56.3 mmol) in N, N-dimethylformamide (30 ml) was added dropwise over 30 minutes, and the mixture was further stirred for 20 minutes. Water was added to the reaction system, extracted with toluene, and the obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 10/1) to obtain the title compound (5.53 g, 35%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.38 (dd, J = 10.6,
18.3Hz, 1H), 3.98 (dd, J = 2.1, 18.3Hz, 1H), 4.
61 (dt, J = 2.1, 10.6Hz, 1H), 4.93 (brs, 1H),
5.10 (d, J = 16.2 Hz, 1H), 5.29 (d, J = 16.2 Hz,
1H), 6.67-6.76 (m, 2H), 6.82-6.92 (m, 2H), 7.2
1-7.36 (m, 5H), 7.48 (dt, J = 1.7,6.9Hz, 2H),
7.57-7.63 (m, 1H), 8.00 (dd, J = 1.3, 6.9 Hz, 2H
).

Example 4 3- (2-oxophenethyl) -1- (4-pyridylmethyl) -3,4-dihydro-1H-quinoxaline-2-
On (Compound 4) 3 obtained in Reference Example 1 in the same manner as in Example 1.
-(2-oxophenethyl) -3,4-dihydro-1H
-Quinoxalin-2-one (10.0 g, 37.6 mmol) and 4-pyridylmethyl chloride hydrochloride (6.17 g, 37.6 mmol)
The title compound (1.60 g, 12%) was obtained from l). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.39 (dd, J = 10.4,
18.3Hz, 1H), 3.97 (dd, J = 2.0, 18.3Hz, 1H), 4.
62 (brd, J = 10.4Hz, 1H), 4.96 (s, 1H), 5.11 (
d, J = 17.0Hz, 1H), 5.29 (d, J = 17.0Hz, 1H),
6.67-6.96 (m, 4H), 7.18 (d, J = 5.9 Hz, 2H), 7.
46-7.64 (m, 3H), 8.01 (d, J = 7.4 Hz, 2H), 8.56
(d, J = 5.9Hz, 2H).

Example 5 3- (2-oxophenethyl) -1-phenyl-3,4
-Dihydro-1H-quinoxalin-2-one (compound 5) N-phenyl-1,2-phenylenediamine (40.0 g, 2
21 mmol) was dissolved in ethanol (500 ml), ethyl 3-benzoylacrylate (30.0 g, 153 mmol) was added, and the mixture was stirred at room temperature for 10 days. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 10/1) to give the title compound (14.
0g, 17%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.41 (dd, J = 10.2,
18.5Hz, 1H), 3.98 (dd, J = 2.3, 18.5Hz, 1H), 4.
67 (ddd, J = 2.3, 2.3, 10.2Hz, 1H), 4.97 (brs, 1
H), 6.32 (d, J = 7.3 Hz, 1H), 6.65 (dt, J = 1.
3, 7.3Hz, 1H), 6.78 (dd, J = 1.3, 7.9Hz, 1H), 6.
91 (dt, J = 1.3, 7.6Hz, 1H), 7.27-7.30 (m, 2H
), 7.42-7.64 (m, 6H), 8.00 (dd, J = 1.7, 6.9H
z, 2H).

Example 6 1- (3-chloropropyl) -3- (2-oxo-2-
(Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 6) 3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline obtained in Reference Example 2 −
2-One (1.00 g, 3.78 mmol) was dissolved in N, N-dimethylformamide (15 ml), and potassium carbonate (2.61 g, 18.9 mmol) was dissolved.
l) and 1-bromo-3-chloropropane (0.410 ml, 4.16
mmol) and stirred at room temperature for 22 hours. Water was added to the reaction system, and the precipitated solid was collected by filtration. After drying the obtained solid,
Purify by silica gel column chromatography (eluted with hexane / ethyl acetate = 8/1) to give the title compound (360 mg, 3
0%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.28 (tt, J = 6.1,
7.4Hz, 2H), 3.72 (t, J = 6.1Hz, 2H), 4.41 (t, J
= 7.4Hz, 2H), 7.02 (s, 1H), 7.23-7.30 (m, 4H
), 7.45-7.54 (m, 3H), 8.04 (dd, J = 1.7, 7.9H
z, 2H), 14.1 (brs, 1H).

Example 7 3- (2-oxo-2-phenylethylidene) -1-
[3- (4-pyridylmethylamino) propyl] -3,
4-dihydro-1H-quinoxalin-2-one (compound 7) 1- (3-chloropropyl) -3- obtained in Example 6
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.00 g, 2.93 m
mol) in N, N-dimethylformamide (10 ml)
4-Pyridylmethylamine (1.49 ml, 14.7 mmol) and sodium iodide (439 mg, 2.93 mmol) were added, and the mixture was stirred at 80 ° C for 2 hours. Water was added to the reaction system, extracted with ethyl acetate,
The obtained organic layer was dried with magnesium sulfate. The solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluted with methanol / chloroform = 1/100 to 1/50) to give the title compound (845 mg, 70%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.03-2.08 (m, 3H),
2.77 (t, J = 6.9 Hz, 2H), 3.88 (s, 2H), 4.37 (
t, J = 6.9Hz, 2H), 7.02 (s, 1H), 7.16-7.25 (m,
4H), 7.33 (d, J = 5.9 Hz, 2H), 7.45-7.54 (m, 3
H), 8.04 (dd, J = 1.5, 8.1Hz, 2H), 8.57 (d, J =
5.9Hz, 2H), 14.1 (brs, 1H).

Example 8 1- (4-methoxycarbonylphenylmethyl) -3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 8) In the same manner as in Example 6, 3 obtained in Reference Example 2.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (2.70 g, 10.
2 mmol) and 4-methoxycarbonylbenzyl bromide (2.57 g, 11.2 mmol) to give the title compound (3.24 g, 77%)
I got ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.90 (s, 3H), 5.52
(s, 2H), 7.03-7.26 (m, 5H), 7.35 (d, J = 8.4H
z, 2H), 7.46-7.55 (m, 3H), 8.00 (d, J = 8.4 Hz,
2H), 8.06 (dd, J = 1.8, 8.1 Hz, 2H), 14.0 (brs,
1H).

Example 9 1- [4- (2-Methoxycarbonylphenyl) phenylmethyl] -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 9) In the same manner as in Example 6, 3 obtained in Reference Example 2
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (5.00 g, 18.
9 mmol) and 4- (2-methoxycarbonylphenyl) benzyl bromide (6.10 g, 20.8 mmol) to give the title compound (5.41 g, 58%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.60 (s, 3H), 5.52
(s, 2H), 7.02-7.54 (m, 15H), 7.82 (dd, J = 1.
3, 7.6Hz, 1H), 8.06 (dd, J = 1.8, 8.1Hz, 2H), 1
4.08 (brs, 1H).

Example 10 1- (3-chloropropyl) -6,7-dimethyl-3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 10) The 6,7-dimethyl- obtained in Reference Example 4 by the same method as in Example 6. 3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-
2-one (1.00 g, 3.40 mmol) and 3-bromo-1-
The title compound (488 mg, 39%) was obtained from chloropropane (0.400 ml, 3.74 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.21-2.33 (m, 2H),
2.29 (s, 3H), 2.33 (s, 3H), 3.72 (t, J = 6.3H
z, 2H), 4.38 (t, J = 7.3 Hz, 2H), 6.98 (s, 1H
), 7.04 (s, 1H), 7.09 (s, 1H), 7.43-7.52 (m,
3H), 8.03 (dd, J = 1.7, 7.6 Hz, 2H), 14.1 (brs,
1H).

Example 11 6,7-Dichloro-1- (3-chloropropyl) -3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (Compound 11) The 6,7-dichloro- obtained in Reference Example 6 by the same method as in Example 6. 3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-
2-one (1.00 g, 3.10 mmol) and 3-bromo-1-
The title compound (495 mg, 40%) was obtained from chloropropane (0.330 ml, 3.30 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.22-2.34 (m, 2H),
3.71 (t, J = 6.2 Hz, 2H), 4.34 (t, J = 7.4 Hz, 2H)
), 7.03 (s, 1H), 7.33 (s, 1H), 7.37 (s, 1H
), 7.45-7.55 (m, 3H), 8.03 (m, 2H), 13.9 (br
s, 1H).

Example 12 1-benzyl-6,7-dimethoxy-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H
-Quinoxalin-2-one (compound 12) 6,7-dimethoxy-3- (2-oxo-2-phenylethylidene) -3,4-dihydro- obtained in Reference Example 8.
1H-quinoxalin-2-one (500mg, 1.54mmol)
In N, N-dimethylformamide (10 ml), potassium tert-butoxide (190 mg, 1.70 mmol) and benzyl bromide (0.180 ml, 1.54 mmol) were added at room temperature, and the mixture was stirred for 12 hours. Water was added to the reaction system, and the precipitated solid was collected by filtration and dried under reduced pressure.
The obtained solid was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 3/1) to give the title compound (352 mg, 55%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.74 (s, 3H), 3.91
(s, 3H), 5.51 (s, 2H), 6.85 (s, 1H), 7.07 (
s, 1H), 7.26 (s, 1H), 7.28-7.39 (m, 5H), 7.44
-7.54 (m, 3H), 8.03-8.07 (m, 2H), 14.0 (brs,
1H).

Example 13 1- (3-Chloropropyl) -6-methyl-3- (2-
(Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 13) In the same manner as in Example 12, 6-methyl-3- (2- Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.00 g, 3.59 mmol) and 3-bromo-1-chloropropane (0.39 ml, 3.95 mmol) from the title compound (706 mg,
55%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.20-2.30 (m, 2H),
2.38 (s, 3H), 3.71 (t, J = 6.3Hz, 2H), 4.38 (
t, J = 7.4Hz, 2H), 7.00 (s, 1H), 7.04-7.06 (m,
2H), 7.18 (d, J = 8.3 Hz, 1H), 7.44-7.55 (m, 3
H), 8.04 (dd, J = 1.7, 7.9 Hz, 2H), 14.0 (brs, 1
H).

Example 14 1-benzyl-6-methoxy-3- (2-oxo-2-
Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (Compound 14) 6-methoxy-3- (2-oxo-2-) obtained in Reference Example 10 in the same manner as in Example 12. Phenylethylidene) -3,4-dihydro-1H-quinoxaline-2
The title compound (118 mg, 18%) was obtained from -one (500 mg, 1.70 mmol) and benzyl bromide (0.20 ml, 1.70 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.80 (s, 3H), 5.45
(s, 2H), 6.64 (dd, J = 2.6, 8.9 Hz, 1H), 6.76 (
d, J = 2.6Hz, 1H), 7.03 (d, J = 8.9Hz, 1H), 7.11
(s, 1H), 7.26-7.41 (m, 5H), 7.45-7.64 (m, 3H
), 8.06 (dd, J = 1.6, 7.9Hz, 2H), 14.05 (brs, 1
H).

Example 15 1- (3-Chloropropyl) -7-methyl-3- (2-
(Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 15) In the same manner as in Example 6, the 7-methyl-3- (2- The title compound (710 mg,
56%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.25-2.35 (m, 2H),
2.46 (s, 3H), 3.75 (t, J = 6.7Hz, 2H), 4.43 (
t, J = 7.3Hz, 2H), 7.01 (s, 1H), 7.06 (d, J =
7.9Hz, 1H), 7.15-7.20 (m, 2H), 7.47-7.58 (m, 3
H), 8.06 (dd, J = 1.7, 5.9 Hz, 2H), 14.18 (brs,
1H).

Example 16 3- (2-oxo-2-phenylethylidene) -1-
(4-pyridylmethyl) -3,4-dihydro-1H-quinoxalin-2-one (compound 16) By a method similar to that in Example 6, 3 obtained in Reference Example 2 was obtained.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (1.00 g, 3.7
9 mmol) and 4-pyridylmethyl chloride hydrochloride (684
mg, 4.17 mmol) to give the title compound (654 mg, 48%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.48 (s, 2H), 6.95-
7.29 (m, 7H), 7.47-7.59 (m, 3H), 8.05-8.08 (
m, 2H), 8.60 (d, J = 5.9 Hz, 2H), 14.03 (brs, 1
H).

Example 17 1- (3-Dimethylaminopropyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1
H-quinoxalin-2-one (Compound 17) 1 obtained in Example 6 in the same manner as in Example 7.
-(3-chloropropyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.00 g, 2.93 mmol) and a 50% aqueous solution of dimethylamine (4 ml) ) To the title compound (1.04 g, 87
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.99-2.09 (m, 2H),
2.38 (s, 6H), 2.54 (t, J = 6.9 Hz, 2H), 4.39 (
t, J = 7.6Hz, 2H), 7.13 (s, 1H), 7.27-7.44 (m,
4H), 7.54-7.63 (m, 3H), 8.15 (dd, J = 1.7, 7.
9Hz, 2H), 14.17 (brs, 1H).

Example 18 1- (3-Chloropropyl) -3- [2- (2-naphthyl) -2-oxoethylidene] -3,4-dihydro-1
H-quinoxalin-2-one (compound 18) 3- [2- (2-naphthyl) -2-oxoethylidene] obtained in Reference Example 12 in the same manner as in Example 6.
The title compound (12.8 g,
Quantitative). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.24-2.34 (m, 2H),
3.74 (t, J = 6.1 Hz, 2H), 4.43 (t, J = 7.6 Hz, 2H)
), 7.19 (s, 1H), 7.21-7.34 (m, 4H), 7.52-7.61
(m, 2H), 7.87-8.00 (m, 3H), 8.12 (dd, J = 1.
7, 8.6Hz, 1H), 8.58 (s, 1H), 14.1 (brs, 1H).

Example 19 3- [2- (2-naphthyl) -2-oxoethylidene]
-1- [3- (4-pyridylmethylamino) propyl]
-3,4-Dihydro-1H-quinoxalin-2-one (Compound 19) By a method similar to that in Example 7, 1- (3-chloropropyl) -3- [2- (2 -Naphthyl) -2-oxoethylidene] -3,4-dihydro-1
The title compound (625 mg, 26%) was obtained from H-quinoxalin-2-one (2.00 g, 5.12 mmol) and 4-pyridylmethylamine (2.60 ml, 25.6 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.99-2.06 (m, 2H),
2.76 (t, J = 6.4 Hz, 2H), 3.86 (s, 2H), 4.40 (
t, J = 7.1Hz, 2H), 7.19 (s, 1H), 7.17-7.32 (m,
6H), 7.53-7.61 (m, 2H), 7.87-8.01 (m, 3H),
8.13 (dd, J = 1.7, 8.6Hz, 1H), 8.55-8.58 (m, 3H
), 14.13 (brs, 1H).

Example 20 1- [3- (4-Methylpiperazin-1-yl) propyl] -3- [2- (2-naphthyl) -2-oxoethylidene] -3,4-dihydro-1H-quinoxaline -2-
On (Compound 20) 1- (3-Chloropropyl) -3- [2- (2-naphthyl) -2-oxoethylidene] -3,4 obtained in Example 18 by the same method as in Example 7. -Dihydro-1
The title compound (999 mg, 43%) was obtained from H-quinoxalin-2-one (2.00 g, 5.12 mmol) and 1-methylpiperazine (2.84 ml, 25.6 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.95-2.02 (m, 2H),
2.30 (s, 3H), 2.32-2.54 (m, 10H), 4.32 (t, J
= 7.3Hz, 2H), 7.21 (s, 1H), 7.22-7.26 (m, 4H
), 7.52-7.60 (m, 2H), 7.87-8.03 (m, 3H), 8.12
(dd, J = 1.7, 8.6Hz, 1H), 8.58 (s, 1H), 14.13
(brs, 1H).

Example 21 1- (3-Cyclohexylaminopropyl) -3- (2
-Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 21) 1 obtained in Example 6 by the same method as in Example 7.
-(3-chloropropyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (200 mg, 0.59 mmol) and cyclohexylamine (0.20 ml, 1.77 mmol) From the title compound (11
8 mg, 50%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.02-2.02 (m, 13H),
2.41-2.48 (m, 1H), 2.76 (t, J = 6.8Hz, 2H), 4.
34 (t, J = 7.1Hz, 2H), 7.02 (s, 1H), 7.17-7.34
(m, 4H), 7.44-7.56 (m, 3H), 8.04 (dd, J = 1.
8, 8.1Hz, 2H), 14.00 (brs, 1H).

Example 22 1- (4-Carboxyphenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-
1H-quinoxalin-2-one (compound 22) 1- (4-methoxycarbonylphenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H- obtained in Example 8. Quinoxaline-2-
On (3.00 g, 7.27 mmol) in tetrahydrofuran (20 m
l) and methanol (10ml) in a mixed solvent, and water (6m
l) and lithium hydroxide monohydrate (1.25 g, 29.1 mmol) were added, and the mixture was stirred at room temperature for 24 hours. After adding an aqueous sodium hydrogen carbonate solution and ether and stirring, the insoluble matter was collected by filtration. The obtained solid was washed with 1N hydrochloric acid, collected by filtration, and dried under reduced pressure to obtain the title compound (2.47 g). Separately, the above filtrate was separated, hydrochloric acid was added to the obtained aqueous layer to adjust the pH to 1, the precipitated solid was collected by filtration, dried under reduced pressure, and combined with the crystals obtained above to give the title compound (2.65 g). , 91%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 5.55 (s, 2H), 6.9
6 (s, 1H), 7.09-7.24 (m, 4H), 7.41 (d, J = 8.3
Hz, 2H), 7.52-7.60 (m, 3H), 7.89 (d, J = 8.3 Hz,
2H), 8.00-8.03 (m, 2H), 14.00 (brs, 1H).

Example 23 4- [2-oxo-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-
1-ylmethyl] -N- (4-pyridylmethyl) benzamide (compound 23) 1- (4-carboxyphenylmethyl) -3- (2-oxo-2-phenylethylidene) obtained in Example 22
-3,4-Dihydro-1H-quinoxalin-2-one (1.00 g, 2.51 mmol) was added to N, N-dimethylformamide (20 m
l) and dissolved at room temperature in 1-hydroxybenzotriazole (423 mg, 2.76 mmol), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (529 mg,
2.76 mmol) and 4-pyridylmethylamine (0.31 ml,
3.01 mmol) and stirred for 24 hours. Water was added to the reaction system, and the precipitated crystals were collected by filtration. The collected matter was suspended in chloroform, the insoluble matter was separated by filtration, and the filtrate was dried over magnesium sulfate. The solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography (methanol / chloroform = 1).
(Elution at / 50) to give the title compound (685 mg, 56%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 4.65 (d, J = 6.3Hz,
2H), 5.52 (s, 2H), 6.51 (brt, 1H), 7.03-7.26
(m, 6H), 7.10 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H
), 7.45-7.57 (m, 3H), 7.79 (d, J = 8.4 Hz, 2H
), 8.05 (dd, J = 1.8, 8.1Hz, 2H), 8.6 (m, 2H),
14.0 (brs, 1H).

Example 24 N- (3-Dimethylaminopropyl) -4- [2-oxo-3- (2-oxo-2-phenylethylidene)-
3,4-Dihydro-1H-quinoxalin-1-ylmethyl] benzamide (Compound 24) In the same manner as in Example 23, 1- (4-carboxyphenylmethyl) -3- (2-
(Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.00 g, 2.51 mmol)
And 3-dimethylaminopropylamine (0.38 ml, 3.
01 mmol) to give the title compound (273 mg, 23%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.73 (t, J = 5.9Hz,
2H), 2.26 (s, 6H), 2.48 (t, J = 5.9 Hz, 2H), 3.
55 (dt, J = 4.6, 5.9Hz, 2H), 5.51 (s, 2H), 7.05
-7.07 (m, 2H), 7.11 (s, 1H), 7.14-7.26 (m, 2H
), 7.34 (d, J = 8.4 Hz, 2H), 7.45-7.54 (m, 3H),
7.74 (d, J = 8.4 Hz, 2H), 8.06 (dd, J = 1.7, 7.9
Hz, 2H), 8.54 (brs, 1H), 14.0 (brs, 1H).

Example 25 N- [3- (1-Imidazolyl) propyl] -4- [2
-Oxo-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-1-ylmethyl] benzamide (Compound 25) Obtained in Example 22 by a method similar to that in Example 23. 1- (4-carboxyphenylmethyl) -3- (2-
(Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.50 g, 3.76 mmol)
And 1- (3-aminopropyl) imidazole (0.54
ml, 4.51 mmol) to give the title compound (506 mg, 27%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.08-2.17 (m, 2H),
3.47 (dt, J = 6.6, 12.9Hz, 2H), 4.05 (t, J = 6.
8Hz, 2H), 5.51 (s, 2H), 6.95 (brt, 1H), 7.10
(s, 1H), 7.03-7.23 (m, 7H), 7.35 (d, J = 8.6H
z, 2H), 7.40 (d, J = 8.6 Hz, 2H), 7.46-7.54 (m,
3H), 8.06 (dd, J = 1.5, 8.1Hz, 2H), 14.05 (br
s, 1H).

Example 26 N- (2-morpholinoethyl) -4- [2-oxo-3
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-1-ylmethyl] benzamide (Compound 26) In the same manner as in Example 23, 1- (4-carboxyphenylmethyl) -3- (2-
(Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (2.00 g, 5.02 mmol)
And 4- (2-aminoethyl) morpholine (0.79 ml,
6.02 mmol) to give the title compound (723 mg, 28%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.47-2.50 (m, 4H),
2.58 (t, J = 5.6 Hz, 2H), 3.53 (dt, J = 5.6, 11.
2Hz, 2H), 3.69-3.72 (m, 4H), 5.52 (s, 2H), 6.7
2 (brt, 1H), 7.11 (s, 1H), 7.05-7.26 (m, 4H
), 7.37 (d, J = 8.6 Hz, 2H), 7.46-7.58 (m, 3H),
7.75 (d, J = 8.6 Hz, 2H), 8.06 (dd, J = 1.7, 7.9
Hz, 2H), 14.0 (brs, 1H).

Example 27 1- (3-chloropropyl) -3- [2-oxo-2-
(3-pyridyl) ethylidene] -3,4-dihydro-1
H-quinoxalin-2-one (compound 27) 3- [2-oxo-2- (3-pyridyl) ethylidene] obtained in Reference Example 13 in the same manner as in Example 6.
The title compound (4.98 g, 22.2 mmol) was prepared from -3,4-dihydro-1H-quinoxalin-2-one (15.0 g, 56.6 mmol) and 3-bromo-1-chloropropane (6.15 ml, 62.2 mmol).
6%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.22-2.33 (m, 2H),
3.73 (t, J = 6.1Hz, 2H), 4.42 (t, J = 7.6Hz, 2H
), 6.98 (s, 1H), 7.23-7.36 (m, 4H), 7.42 (dd
d, J = 0.8, 4.6, 7.9Hz, 1H), 8.28 (ddd, J = 1.7,
1.7, 7.9Hz, 1H), 8.74 (dd, J = 1.7, 4.6Hz, 1H),
9.25 (d, J = 1.7 Hz, 1H), 14.1 (brs, 1H).

Example 28 1-benzyl-3- [2- (2-methoxycarbonylphenyl) -2-oxoethylidene] -3,4-dihydro-1H-quinoxalin-2-one (Compound 28) In a similar manner, the 3- [2- (2-methoxycarbonylphenyl) -2- obtained in Reference Example 14 was obtained.
Oxoethylidene] -3,4-dihydro-1H-quinoxalin-2-one (3.00 g, 9.67 mmol) and benzyl bromide (1.27 ml, 10.6 mmol) from the title compound (1.81 g,
82%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.90 (s, 3H), 5.46
(s, 2H), 6.74 (s, 1H), 7.03-7.34 (m, 9H), 7.
47-7.59 (m, 2H), 7.68 (dd, J = 1.3, 7.3 Hz, 1H
), 7.77 (dd, J = 1.3, 7.3Hz, 1H), 13.6 (brs, 1
H).

Example 29 1-benzyl-3- [2- (2-carboxyphenyl)
-2-oxoethylidene] -3,4-dihydro-1H-
Quinoxalin-2-one (Compound 29) 1-benzyl-3- [2- (2-
Methoxycarbonylphenyl) -2-oxoethylidene] -3,4-dihydro-1H-quinoxalin-2-one (1.20 g, 2.91 mmol) in tetrahydrofuran (12 ml)
Water (2 ml) and lithium hydroxide monohydrate (488 m
g, 11.6 mmol) and stirred at room temperature for 3 hours. Water was added to the reaction solution, and after washing with ethyl acetate, the obtained aqueous layer was adjusted to pH 4 with 1N hydrochloric acid. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound (0.78 g, 67%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 5.47 (s, 2H), 6.5
1 (s, 1H), 7.11-7.31 (m, 9H), 7.55-7.73 (m, 4H
), 8.20 (brs, 1H), 13.3 (brs, 1H).

Example 30 1- (4-Nitrophenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H
-Quinoxalin-2-one (Compound 30) 3 obtained in Reference Example 2 in the same manner as in Example 6.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (1.00 g, 3.7
8 mmol) and 4-nitrobenzyl bromide (898 mg, 4.
16 mmol) to give the title compound (634 mg, 40%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.56 (s, 2H), 6.98
(d, J = 7.9 Hz, 1H), 7.06 (dd, J = 1.7, 6.9 Hz, 1H
), 7.10 (s, 1H), 7.16-7.28 (m, 2H), 7.46 (d,
J = 8.9Hz, 2H), 7.49-7.55 (m, 3H), 8.06 (dd,
J = 1.5, 8.1Hz, 2H), 8.22 (d, J = 8.9Hz, 2H), 1
4.0 (brs, 1H).

Example 31 1- (4-Aminophenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H
-Quinoxalin-2-one (compound 31) 1- (4-Nitrophenylmethyl) -3- (2-oxo-2-phenylethylidene)-obtained in Example 30
3,4-dihydro-1H-quinoxalin-2-one (10
0mg, 0.25mmol) is dissolved in N, N-dimethylformamide (2ml) and titanium trichloride solution (Kanto Chemical, dilute hydrochloric acid solution, pH
2.1) was added until the ingredients disappeared (1 ml). A saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was filtered using a radiolite, and the insolubles were washed with chloroform. The filtrate was extracted with chloroform, the obtained organic layer was dried over magnesium sulfate, the solvent was distilled off, and the mixture was concentrated under reduced pressure. The title compound (101 mg, quantitative) was obtained as crude crystals. ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.67 (brs, 2H), 5.3
5 (s, 2H), 6.63 (d, J = 8.6 Hz, 2H), 7.04-7.26
(m, 7H), 7.44-7.53 (m, 3H), 8.05 (dd, J = 1.8,
8.1Hz, 2H), 14.1 (brs, 1H).

Example 32 1- [4- (Chloroacetamido) phenylmethyl]-
3- (2-oxo-2-phenylethylidene) -3,4
-Dihydro-1H-quinoxalin-2-one (compound 3
2) 1- (4-aminophenylmethyl) -3- (2-oxo-2-phenylethylidene)-obtained in Example 31
3,4-dihydro-1H-quinoxalin-2-one (6.
70 g, 18.1 mmol) in N, N-dimethylformamide (500 ml)
Chloroacetyl chloride (2.0 ml, 1 ml)
9.9 mmol) and triethylamine (4.69 ml, 36.2 mmol) were added, and the mixture was stirred for 4 hours. Water was added to the reaction system, and the precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (7.19 g,
89%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 4.18 (s, 2H), 5.46
(s, 2H), 7.10 (s, 1H), 7.03-7.35 (m, 6H), 7.
44-7.57 (m, 5H), 8.03-8.07 (m, 2H), 8.25 (brs,
1H), 14.0 (brs, 1H).

Example 33 1- [4- (morpholinoacetamide) phenylmethyl] -3- (2-oxo-2-phenylethylidene)-
3,4-Dihydro-1H-quinoxalin-2-one (Compound 33) 1- [4- (Chloroacetamido) phenylmethyl] -3- (2-oxo-2-phenylethylidene)-obtained in Example 32 3,4-Dihydro-1H-quinoxalin-2-one (1.0 g, 2.25 mmol) was dissolved in N, N-dimethylformamide (10 ml), and diisopropylethylamine (2.0 ml, 11.3 mmol) and morpholine (0.59 ml, 6.75) were dissolved. mmo
l) was added and stirred at room temperature for 7 hours. Water was added to the reaction mixture, and extracted with chloroform. The obtained organic layer was dried over magnesium sulfate, the solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluted with chloroform) to obtain the title compound (1.02 g, 91%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.58-2.62 (m, 4H),
3.12 (s, 2H), 3.74-3.77 (m, 4H), 5.44 (s, 2H
), 7.10 (s, 1H), 7.02-7.30 (m, 6H), 7.45-7.56
(m, 5H), 8.06 (dd, J = 1.7, 7.9 Hz, 2H), 9.04
(brs, 1H), 14.05 (brs, 1H).

Example 34 3- (2-oxo-2-phenylethylidene) -1-
[4- (4-Pyridylmethylaminoacetamido) phenylmethyl] -3,4-dihydro-1H-quinoxalin-2-one (Compound 34) By a method similar to that in Example 33, 1-obtained in Example 32 [4- (chloroacetamido) phenylmethyl]
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (1.0 g,
2.25 mmol) and 4-pyridylmethylamine (0.69 ml,
6.75 mmol) to give the title compound (855 mg, 73%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.43 (s, 2H), 3.87
(s, 2H), 5.45 (s, 2H), 7.10 (s, 1H), 7.06-7.
30 (m, 8H), 7.46-7.55 (m, 5H), 8.06 (dd, J =
1.8, 8.1Hz, 2H), 8.59 (d, J = 1.5, 4.4Hz, 2H),
9.05 (brs, 1H), 14.06 (brs, 1H).

Example 35 3- (2-oxo-2-phenylethylidene) -1-
[4- (thiomorpholinoacetamido) phenylmethyl] -3,4-dihydro-1H-quinoxalin-2-one (Compound 35) 1- [4- (Chloroacetamido) phenylmethyl]
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (200 mg,
0.45mmol) and thiomorpholine (0.23ml, 2.25mmo)
The title compound (200 mg, 87%) was obtained from l). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.74-2.80 (m, 4H),
2.85-2.91 (m, 4H), 3.16 (s, 2H), 5.48 (s, 2H
), 7.14 (s, 1H), 7.06-7.34 (m, 6H), 7.49-7.59
(m, 5H), 8.10 (dd, J = 1.5, 7.8 Hz, 2H), 9.04
(brs, 1H), 14.1 (brs, 1H).

Example 36 1- [4- (2-Dimethylaminoethylaminoacetamido) phenylmethyl] -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (Compound 36) 1- [4- (Chloroacetamido) phenylmethyl] obtained in Example 32 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (150 mg,
0.34 mmol) and 2-dimethylaminoethylamine (0.18 ml, 1.68 mmol) gave the title compound (118 mg, 71%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.22 (s, 6H), 2.37-
2.41 (m, 2H), 2.71-2.75 (m, 2H), 3.37 (s, 2H
), 5.44 (s, 2H), 7.11 (s, 1H), 7.02-7.29 (m,
6H), 7.45-7.54 (m, 3H), 7.59 (d, J = 8.3 Hz, 2H
), 8.06 (dd, J = 1.6, 7.9Hz, 2H), 9.70 (brs, 1H
), 14.1 (brs, 1H).

Example 37 1- [4- (3-morpholinopropylaminoacetamido) phenylmethyl] -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one ( Compound 37) 1- [4- (chloroacetamido) phenylmethyl] obtained in Example 32 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (150 mg,
0.34 mmol) and 4- (3-aminopropyl) morpholine (0.18 ml, 1.68 mmol) to give the title compound (130 mg, 70
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.67-1.75 (m, 2H),
2.40-2.45 (m, 6H), 2.72 (t, J = 6.8 Hz, 2H), 3.
35 (s, 2H), 3.67-3.70 (m, 4H), 5.45 (s, 2H),
7.11 (s, 1H), 7.03-7.29 (m, 6H), 7.46-7.56 (
m, 5H), 8.06 (dd, J = 1.7, 7.6Hz, 2H), 9.30 (br
s, 1H), 14.1 (brs, 1H).

Example 38 1- [4- (3-Hydroxypropylaminoacetamido) phenylmethyl] -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one ( Compound 38) 1- [4- (chloroacetamido) phenylmethyl] obtained in Example 32 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (150 mg,
0.34 mmol) and 3-amino-1-propanol (0.1
The title compound (123 mg, 76%) was obtained from 3 ml, 1.68 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.72-1.79 (m, 2H),
2.82 (t, J = 6.4 Hz, 2H), 3.38 (s, 2H), 3.81 (
t, J = 5.9Hz, 2H), 5.44 (s, 2H), 7.10 (s, 1H),
7.05-7.28 (m, 6H), 7.45-7.54 (m, 3H), 7.58 (
d, J = 8.6Hz, 2H), 8.06 (dd, J = 1.7, 7.9Hz, 2H
), 9.19 (brs, 1H), 14.1 (brs, 1H).

Example 39 3- (2-oxo-2-phenylethylidene) -1-
{4- [2- (2-Pyridyl) ethylaminoacetamido] phenylmethyl} -3,4-dihydro-1H-quinoxalin-2-one (Compound 39) 1- [4- (chloroacetamido) phenylmethyl]
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (150 mg,
0.34 mmol) and 2- (2-aminoethyl) pyridine (0.12 ml, 1.01 mmol) from the title compound (204 mg,> 100%:
Oily). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.99 (t, J = 5.9Hz,
2H), 3.10 (t, J = 5.6 Hz, 2H), 3.38 (s, 2H),
5.44 (s, 2H), 7.03-7.24 (m, 9H), 7.45-7.54 (
m, 5H), 7.62 (ddd, J = 1.7, 7.6, 7.8 Hz, 1H), 8.
06 (dd, J = 1.7,8.1Hz, 2H), 8.52 (dd, J = 1.7,
5.0Hz, 1H), 9.38 (brs, 1H), 14.1 (brs, 1H).

Example 40 6-methyl-1- (4-nitrophenylmethyl) -3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 40) In the same manner as in Example 6, 6 obtained in Reference Example 9 was obtained.
From -methyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (3.00 g, 10.8 mmol) and 4-nitrobenzyl bromide (2.56 g, 11.9 mmol). The title compound (3.14 g, 71
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.35 (s, 3H), 5.54
(s, 2H), 6.87 (m, 2H), 7.09 (m, 2H), 7.43-7.
54 (m, 5H), 8.06 (dd, J = 1.8, 8.1Hz, 2H), 8.21
(d, J = 8.9 Hz, 2H), 14.0 (brs, 1H).

Example 41 1- (4-aminophenylmethyl) -6-methyl-3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 41) 6-methyl-1- (4-nitrophenylmethyl) -3 obtained in Example 40 -(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-2
-One (3.00 g, 7.26 mmol) in tetrahydrofuran (150
dissolved in titanium trichloride solution (Kanto Chemical,
Dilute hydrochloric acid solution (pH 2.1) was added until the raw materials disappeared, and the mixture was stirred for 1 hour and 30 minutes. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction system to adjust the pH to 7, ethyl acetate was added, and the precipitated crystals were collected by filtration to obtain the title compound (1.90 g). Separately, the filtrate was extracted with ethyl acetate, the obtained organic layer was dried over magnesium sulfate, and the solvent was distilled off. The obtained residue was washed with ethyl acetate, filtered, and combined with the crystals obtained above to obtain the title compound (2.51 g, 89%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.32 (s, 3H), 3.3
6 (brs, 2H), 5.45 (s, 2H), 6.90-6.98 (m, 2H),
7.08-7.18 (m, 3H), 7.28-7.40 (m, 3H), 7.50-7.6
0 (m, 3H), 7.91-8.02 (m, 2H), 13.9 (brs, 1H
).

Example 42 1- [4- (Chloroacetamido) phenylmethyl]-
6-Methyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (Compound 42) Obtained in Example 41 by a method similar to that in Example 32. 1- (4-aminophenylmethyl) -6-methyl-3
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (1.76 g, 4.5
9mmol) and chloroacetyl chloride (0.40ml, 5.05m
mol) to give the title compound (1.81 g, 86%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.34 (s, 3H), 4.17
(s, 2H), 5.43 (s, 2H), 6.63 (d, J = 8.6 Hz, 1H
), 6.86-7.12 (m, 3H), 7.27-7.31 (m, 2H), 7.45
-7.54 (m, 5H), 8.02-8.07 (m, 2H), 8.22 (brs,
1H), 14.0 (brs, 1H).

Example 43 1- [4- (2-methoxyethylaminoacetamide)
Phenylmethyl] -6-methyl-3- (2-oxo-2
-Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 43) 1- [4- (Chloroacetamido) phenylmethyl] obtained in Example 42 by the same method as in Example 33.
-6-methyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-2-
On (276 mg, 0.60 mmol) and 2-methoxyethylamine (0.26 ml, 3.00 mmol) from the title compound (106 mg, 35
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.34 (s, 3H), 2.84
(t, J = 5.0Hz, 2H), 3.37 (s, 3H), 3.38 (s, 2H
), 3.47 (t, J = 5.0 Hz, 2H), 5.42 (s, 2H), 6.87
(d, J = 6.9 Hz, 1H), 7.00-7.04 (m, 2H), 7.09
(s, 1H), 7.25-7.28 (m, 2H), 7.46-7.53 (m, 3H
), 7.57 (d, J = 8.6 Hz, 2H), 8.06 (dd, J = 1.7,
7.9Hz, 2H), 9.45 (brs, 1H), 14.0 (brs, 1H).

Example 44 1- {4- [3- (1-Imidazolyl) propylaminoacetamido] phenylmethyl} -3- (2-oxo-
2-phenylethylidene) -3,4-dihydro-1H-
Quinoxalin-2-one (Compound 44) 1- [4- (Chloroacetamido) phenylmethyl] obtained in Example 32 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (200 mg,
0.448 mmol) and 1- (3-aminopropyl) imidazole (0.16 ml, 1.34 mmol) from the title compound (170 mg, 4
0%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.94-2.04 (m, 2H),
2.69 (t, J = 7.1 Hz, 2H), 3.35 (s, 2H), 4.03 (
t, J = 6.9Hz, 2H), 5.44 (s, 2H), 6.89 (s, 1H
), 7.03-7.29 (m, 8H), 7.45-7.56 (m, 6H), 8.06
(d, J = 6.6 Hz, 2H), 8.96 (brs, 1H), 14.1 (br
s, 1H).

Example 45 1- {4- [2- (1-Methylpyrrolidin-2-yl)
Ethylaminoacetamido] phenylmethyl} -3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 45) According to a method similar to that in Example 33, 1- [4- ( Chloroacetamido) phenylmethyl]
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (200 mg,
0.448 mmol) and 2- (2-aminoethyl) -1-methylpyrrolidine (0.19 ml, 1.34 mmol) gave the title compound (177 mg, 52%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.47-1.94 (m, 6H),
2.10-2.20 (m, 2H), 2.32 (s, 3H), 2.60-2.78 (
m, 2H), 3.03-3.10 (m, 1H), 3.32 (d, J = 17.2H
z, 1H), 3.40 (d, J = 17.2 Hz, 1H), 5.45 (s, 2H
), 6.70-7.29 (m, 7H), 7.45-7.57 (m, 5H), 8.06
(dd, J = 1.7, 7.9 Hz, 2H), 9.35 (brs, 1H), 14.1
(brs, 1H).

Example 46 3- (2-oxo-2-phenylethylidene) -1-
(3-pyridylmethyl) -3,4-dihydro-1H-quinoxalin-2-one (compound 46) In the same manner as in Example 6, 3 obtained in Reference Example 2 was obtained.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (1.00 g, 3.7
9 mmol) and 3-pyridylmethyl chloride hydrochloride (684
mg, 20.8 mmol) to give the title compound (628 mg, 47%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.49 (s, 2H), 7.09
(s, 1H), 7.10-7.29 (m, 5H), 7.45-7.62 (m, 4H
), 8.03-8.06 (m, 2H), 8.55 (d, J = 4.3 Hz, 1H),
8.68 (s, 1H), 14.02 (brs, 1H).

Example 47 1- (2-Aminophenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H
-Quinoxalin-2-one (Compound 47) 3 obtained in Reference Example 2 in the same manner as in Example 6.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (10.0 g, 37.
8 mmol) and 2-nitrobenzyl bromide (8.99 g, 4
1.6 mmol) to 1- (2-nitrophenylmethyl) -3
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (4.39 g, 29
%) Of crude crystals. The title compound (3.27) was obtained from the crude crystals (4.00 g, 10.0 mmol) in the same manner as in Example 31.
g, 89%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.70 (brs, 2H),
5.50 (s, 2H), 6.94 (s, 1H), 6.82-7.00 (m, 2H
), 7.08-7.24 (m, 5H), 7.51-7.62 (m, 4H), 8.01
(dd, J = 1.5, 8.1Hz, 2H), 13.9 (brs, 1H).

Example 48 1- [2- (chloroacetamido) phenylmethyl]-
3- (2-oxo-2-phenylethylidene) -3,4
-Dihydro-1H-quinoxalin-2-one (compound 4
8) By a method similar to that in Example 32, 1- (2-aminophenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1 obtained in Example 47.
The title compound (3.55 g, 95%) was obtained from H-quinoxalin-2-one (3.10 g, 8.39 mmol) and chloroacetyl chloride (0.80 ml, 10.1 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 4.30 (s, 2H), 5.38
(s, 2H), 7.04 (s, 1H), 7.14-7.54 (m, 10H),
7.66 (d, J = 8.2 Hz, 1H), 8.02-8.04 (m, 2H), 9.3
1 (brs, 1H), 14.1 (brs, 1H).

Example 49 1- {2-[(3-methoxyphenylmethyl) aminoacetamido] phenylmethyl} -3- (2-oxo-2
-Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (Compound 49) 1- [2- (Chloroacetamido) phenylmethyl] obtained in Example 48 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (200 mg,
0.448 mmol) and 3-methoxybenzylamine (0.29
ml, 2.24 mmol) to give the title compound (206 mg, 84%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.57 (s, 2H), 3.73
(s, 3H), 3.91 (s, 2H), 5.34 (s, 2H), 6.76-7.
31 (m, 12H), 7.45-7.62 (m, 4H), 8.04 (dd, J =
1.8, 8.1Hz, 2H), 9.55 (brs, 1H), 14.1 (brs, 1
H).

Example 50 1- [4- (furfurylaminoacetamido) phenylmethyl] -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 50) 1- [4- (chloroacetamido) phenylmethyl] obtained in Example 32 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (200 mg,
0.448mmol) and furfurylamine (0.12ml, 1.34mm)
ol) to give the title compound (155 mg, 68%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.39 (s, 2H), 3.82
(s, 2H), 5.44 (s, 2H), 6.19-6.29 (m, 2H), 7.
06-7.35 (m, 8H), 7.48-7.57 (m, 5H), 8.06 (d, J
= 6.6Hz, 2H), 9.25 (brs, 1H), 14.1 (brs, 1H)
).

Example 51 1- {4-[(1-ethoxycarbonylethyl) aminoacetamido] phenylmethyl} -3- (2-oxo-
2-phenylethylidene) -3,4-dihydro-1H-
Quinoxalin-2-one (Compound 51) 1- [4- (Chloroacetamido) phenylmethyl] obtained in Example 32 by a method similar to that in Example 33.
-3- (2-oxo-2-phenylethylidene) -3,
4-dihydro-1H-quinoxalin-2-one (200 mg,
0.448 mmol) and DL-alanine ethyl ester hydrochloride (0.21 g, 1.34 mmol) to give the title compound (114 mg, 48%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.18 (d, J = 7.3H
z, 3H), 1.23 (t, J = 6.9 Hz, 3H), 2.80 (brs, 1H
), 3.21-3.40 (m, 3H), 4.09 (q, J = 6.9 Hz, 2H),
5.43 (s, 2H), 6.95 (s, 1H), 7.08-7.30 (m, 6H
), 7.50-7.59 (m, 5H), 8.00 (d, J = 6.3Hz, 2H),
9.81 (brs, 1H), 13.9 (brs, 1H).

Example 52 1- {2- [3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one-1-ylmethyl] phenyl} pyrrolidine-2,5 −
Dione (compound 52) 1- (2-aminophenylmethyl) -3- (2-oxo-2-phenylethylidene)-obtained in Example 47
3,4-dihydro-1H-quinoxalin-2-one (10
0 mg, 0.27 mmol) was dissolved in N, N-dimethylformamide (2 ml), and succinic anhydride (30 mg, 0.35 mmol) was added.
The mixture was heated and stirred at 0 ° C. for 7 hours. Evaporate the solvent, add water,
The mixture was extracted with ethyl acetate, and the obtained organic layer was washed with saturated saline and dried over magnesium sulfate. The solvent was distilled off to obtain the title compound (113 mg, 89%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.93 (d, J = 14.9Hz,
2H), 2.99 (d, J = 14.9 Hz, 2H), 5.31 (s, 2H),
7.04 (s, 1H), 7.10-7.41 (m, 6H), 7.45-7.54 (
m, 5H), 8.02-8.04 (m, 2H), 14.0 (brs, 1H).

Example 53 1- (3-methoxycarbonylphenylmethyl) -3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (compound 53) In the same manner as in Example 6, 3 obtained in Reference Example 2 was obtained.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (10.0 g, 37.
8 mmol) and 3-methoxycarbonylbenzyl bromide (9.53 g, 41.6 mmol) to give the title compound (9.74 g, 62%)
I got ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.91 (s, 3H), 5.51
(s, 2H), 7.12 (s, 1H), 7.06-7.23 (m, 4H), 7.
39-7.57 (m, 5H), 7.95-7.98 (m, 1H), 8.01 (s, 1
H), 8.07 (dd, J = 1.7, 7.9 Hz, 2H), 14.1 (brs,
1H).

Example 54 1- (3-Carboxyphenylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-
1H-quinoxalin-2-one (compound 54) 1- (3-methoxycarbonylphenylmethyl) -3 obtained in Example 53 by a method similar to that in Example 22.
-(2-oxo-2-phenylethylidene) -3,4-
Dihydro-1H-quinoxalin-2-one (4.86 g, 11.
8 mmol) to give the title compound (4.50 g, 96%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 5.65 (s, 2H), 7.0
6 (s, 1H), 7.23-7.41 (m, 3H), 7.56-7.67 (m, 6H
), 7.95 (d, J = 7.6 Hz, 1H), 8.02 (s, 1H), 8.12
(d, J = 6.3 Hz, 2H), 13.0 (brs, 1H), 14.0 (br
s, 1H).

Example 55 4- [2-oxo-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-
1-ylmethyl] -N- (2-piperidinoethyl) benzamide hydrochloride (compound 55) By a method similar to that in Example 23, 1- (4-carboxyphenylmethyl) -3- (2-
(Oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.00 g, 2.51 mmol)
And 1- (2-aminoethyl) piperidine (0.43 ml,
3.01 mmol) to give the free base of the title compound (596 mg, 47%), which was chlorinated with 4N hydrogen chloride / ethyl acetate to give the title compound (420 mg). ¹ H-NMR (hydrochloride; DMSO-d ₆ ) δ (ppm): 1.60-1.90 (
m, 6H), 2.80-3.00 (m, 2H), 3.17-3.23 (m, 2H),
3.37-3.54 (m, 2H), 3.61-3.65 (m, 2H), 5.55 (
s, 2H), 6.96 (s, 1H), 7.09-7.22 (m, 4H), 7.44
(d, J = 8.1Hz, 2H), 7.49-7.62 (m, 3H), 7.87 (
d, J = 8.1Hz, 2H), 8.01-8.04 (m, 2H), 8.83 (br
s, 1H), 9.70 (brs, 1H), 13.9 (brs, 1H).

Example 56 1- (Carboxymethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (Compound 56) A method similar to that in Example 12. To give 3- (2-oxo-2-phenylethylidene) -3,4 obtained in Reference Example 2.
-Dihydro-1H-quinoxalin-2-one (41.6 g, 1
58 mmol) and ethyl bromoacetate (21 ml, 189 mmol) from 1- (ethoxycarbonylmethyl) -3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1.
Crude crystals of H-quinoxalin-2-one (52.3 g, 95%) were obtained. Example 22 was obtained from the crude crystals (10.0 g, 28.6 mmol).
In the same manner as above, the title compound (9.20 g, quantitative)
I got ^{1 H-NMR (DMSO-d} 6) δ (ppm): 4.88 (s, 2H), 6.8
7 (s, 1H), 7.21-7.28 (m, 3H), 7.54-7.60 (m, 4H
), 7.99 (d, J = 6.9 Hz, 2H), 13.79 (brs, 1H), 1
5.02 (s, 1H).

Example 57 3- (2-oxo-2-phenylethylidene) -1-
{2-oxo-2- [4- (pyrimidin-2-yl) piperazin-1-yl] ethyl} -3,4-dihydro-1
H-Quinoxalin-2-one (Compound 57) 1- (Carboxymethyl) -3- (2-oxo-2-) obtained in Example 56 by a method similar to that in Example 23.
Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (1.0 g, 3.11 mmol) and 2- (1
-Piperazinyl) pyrimidine dihydrochloride (1.16 g, 4.89 m
mol) to give the title compound (340 mg, 23%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.57 (m, 2H), 3.7
7 (m, 4H), 3.94 (m, 2H), 5.25 (s, 2H), 6.70
(t, J = 4.6Hz, 1H), 6.87 (s, 1H), 7.21-7.27 (
m, 3H), 7.52-7.63 (m, 4H), 8.00 (d, J = 6.6 Hz,
2H), 8.42 (d, J = 4.6 Hz, 2H), 13.82 (brs, 1H
).

Example 58 N- (3-Bromopropyl) -2- [2-oxo-3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-1-yl] acetamide (Compound 58) 1- (carboxy) obtained in Example 56 by the same method as in Example 23. Methyl) -3- (2-oxo-2-
Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (2.00 g, 6.21 mmol) and 3-bromopropylamine hydrobromide (4.27 g, 19.5 mmol)
Gave the title compound (428 mg, 16%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.85 (t, J = 6.6H
z, 1H), 1.93 (t, J = 6.6 Hz, 1H), 3.19-3.21 (m,
2H), 3.47 (t, J = 6.6 Hz, 1H), 3.58 (t, J = 6.6H
z, 1H), 4.84 (s, 2H), 6.88 (s, 1H), 7.19-7.21
(m, 3H), 7.54-7.60 (m, 4H), 8.01 (d, J = 6.3
Hz, 2H), 8.30 (brs, 1H), 13.81 (brs, 1H).

Example 59 N- [3- (1-Imidazolyl) propyl] -2- [2
-Oxo-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-1-yl] acetamide (Compound 59) Obtained in Example 56 by a method similar to that in Example 23. 1- (carboxymethyl) -3- (2-oxo-2-
Phenylethylidene) -3,4-dihydro-1H-quinoxalin-2-one (2.0 g, 6.21 mmol) and 1- (3
-Aminopropyl) imidazole (1.16ml, 9.70mmol)
From the title compound (680 mg, 26%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.82 (m, 2H), 3.0
5 (m, 3H), 3.92 (t, J = 6.9 Hz, 2H), 4.85 (s, 2
H), 6.88 (s, 2H), 7.22-7.25 (m, 3H), 7.52-7.6
0 (m, 5H), 8.00 (d, J = 6.9 Hz, 2H), 8.27 (br
s, 1H), 13.80 (brs, 1H).

Example 60 N- (3-azidopropyl) -2- [2-oxo-3-
(2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxalin-1-yl] acetamide (Compound 60) N- (3-bromopropyl) -2 obtained in Example 58
-[2-oxo-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-quinoxaline-1
-Yl] acetamide (228 mg, 0.52 mmol) and sodium azide (168 mg, 2.59 mmol) were stirred in N, N-dimethylformamide (10 ml) at room temperature for 6 hours. The reaction solution was poured into water, and the precipitated crystals were collected by filtration, washed with water, and dried under reduced pressure to obtain the title compound (77.8 mg, 37%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.64 (m, 2H), 3.1
1-3.51 (m, 4H), 4.83 (s, 2H), 6.88 (s, 1H),
7.19-7.24 (m, 3H), 7.55-7.63 (m, 4H), 8.01 (
m, 2H), 8.27 (brs, 1H), 13.80 (brs, 1H).

Example 61 4-benzyl-2- (2-oxo-2-phenylethylidene) -1,4-dihydro-2H-pyrido [2,3-
b] Pyrazin-3-one (Compound 61) A known compound [Journal of Heterocyclic Chemistry (J. He
terocyclic Chem.), 32, 347 (1995)], 2- (2-oxo-2-phenylethylidene) -1,
4-dihydro-2H-pyrido [2,3-b] pyrazine-
The title compound (1.02 g, 76%) was obtained from 3-one (1.0 g, 3.77 mmol) and benzyl bromide (0.40 ml, 3.77 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.68 (s, 2H), 7.10
(s, 1H), 7.13 (dd, J = 5.0, 7.9 Hz, 1H), 7.21-7.
30 (m, 3H), 7.46-7.57 (m, 6H), 8.03 (dd, J =
1.7, 8.3Hz, 2H), 8.22 (dd, J = 1.5, 5.0Hz, 1H),
13.9 (brs, 1H).

Example 62 1-benzyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-pyrido [3,4-
b] Pyrazin-2-one (Compound 62) A known compound [Journal of Heterocyclic Chemistry (J. Het) was prepared in the same manner as in Example 6.
3- (2-oxo-2-phenylethylidene) -3, erocyclic Chem., 31, 1065 (1994)].
4-dihydro-1H-pyrido [3,4-b] pyrazine-
The title compound (744 mg, 55%) was obtained from 2-one (1.00 g, 3.77 mmol) and benzyl bromide (0.40 ml, 3.77 mmol). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.43 (s, 2H), 7.00
(d, J = 5.6 Hz, 1H), 7.17 (s, 1H), 7.30-7.48 (
m, 5H), 7.50-7.59 (m, 3H), 8.06 (dd, J = 1.7,
8.1Hz, 2H), 8.22 (d, J = 5.6Hz, 1H), 8.54 (s,
1H), 14.0 (brs, 1H).

Example 63 3- (2-oxo-2-phenylethylidene) -1-
(4-pyridylmethyl) -3,4-dihydro-1H-pyrido [3,4-b] pyrazin-2-one (compound 63) (2-oxo-2-phenylethylidene) -3,4
-Dihydro-1H-pyrido [3,4-b] pyrazine-2
-One (1.00 g, 3.76 mmol) and 4-pyridylmethyl chloride hydrochloride (0.68 g, 4.13 mmol) to give the title compound (1
60 mg, 12%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.42 (s, 2H), 6.84
(d, J = 5.6 Hz, 1H), 7.16 (s, 1H), 7.19 (d, J =
5.8Hz, 2H), 7.48-7.57 (m, 3H), 8.05 (d, J =
6.9Hz, 2H), 8.25 (d, J = 5.6Hz, 1H), 8.57 (s,
1H), 8.62 (d, J = 5.8 Hz, 2H), 13.93 (brs, 1H
) .

Example 64 8-benzyl-6- (2-oxo-2-phenylethylidene) -5,8-dihydro-6H-pteridin-7-one (Compound 64) 6- (2-oxo-2-phenylethylidene) -5 obtained in Example 18
8-dihydro-6H-pteridin-7-one (400 mg,
1.50mmol) and benzyl bromide (0.18ml, 1.50mmo)
The title compound (362 mg, 35%) was obtained from l). ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.61 (s, 2H), 7.17
(s, 1H), 7.28-7.36 (m, 5H), 7.48-7.58 (m, 3H
), 8.02-8.05 (m, 2H), 8.56 (s, 1H), 8.80 (s,
1H), 13.8 (brs, 1H).

Example 65 4-Benzyl-2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2
H-pyrido [3,4-b] pyrazin-3-one (compound 65) By a method similar to that in Example 12, 2- [2- (3-dimethylaminophenyl) -2- obtained in Reference Example 19 Oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (400 mg, 1.30 mmol)
And benzyl bromide (0.19 ml, 1.56 mmol) to give the title compound (303 mg, 59%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.99 (s, 6H), 5.5
0 (s, 2H), 6.99 (d, J = 7.5 Hz, 1H), 7.05 (s, 1
H), 7.23-7.41 (m, 8H), 7.59 (d, J = 5.3 Hz, 1H
), 8.22 (d, J = 5.3Hz, 1H), 8.39 (s, 1H), 13.
25 (brs, 1H).

Example 66 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -4- (4-pyridylmethyl) -1,4
-Dihydro-2H-pyrido [3,4-b] pyrazine-3
-One (compound 66) 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido obtained in Reference Example 19 in the same manner as in Example 12. [3,4-b] pyrazin-3-one (400 mg, 1.30 mmol)
And 4-pyridylmethyl chloride hydrochloride (255 mg, 1.
56 mmol) to give the title compound (138 mg, 27%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.99 (s, 6H), 5.5
2 (s, 2H), 6.97 (d, J = 7.7 Hz, 1H), 7.03 (s, 1
H), 7.29 (brs, 1H), 7.31 (d, J = 7.8 Hz, 1H),
7.37 (dd, J = 7.7, 7.8Hz, 1H), 7.38 (d, J = 5.7
Hz, 2H), 7.61 (d, J = 5.5 Hz, 1H), 8.23 (d, J =
5.5Hz, 1H), 8.30 (s, 1H), 8.51 (d, J = 5.7Hz, 2
H), 13.24 (brs, 1H).

Example 67 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -4- (2-fluoroethyl) -1,4
-Dihydro-2H-pyrido [3,4-b] pyrazine-3
-One (compound 67) In the same manner as in Example 12, 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido obtained in Reference Example 19 [3,4-b] pyrazin-3-one (300 mg, 0.97 mmol)
And 1-bromo-2-fluoroethane (0.09 ml, 0.9
7 mmol) to give the title compound (191 mg, 56%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.98 (s, 6H), 4.6
0 (dt, J = 4.0, 24.8Hz, 2H), 4.76 (td, J = 4.3,
46.6Hz, 2H), 6.95 (s, 1H), 6.97 (brd, J = 7.7H
z, 1H), 7.25 (brs, 1H), 7.28 (d, J = 7.7 Hz, 1H
), 7.34 (dd, J = 7.7, 7.7Hz, 1H), 7.56 (d, J =
5.1Hz, 1H), 8.25 (d, J = 5.1Hz, 1H), 8.67 (s, 1
H), 13.21 (brs, 1H).

Example 68 4-benzyl-2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2
H-pyrido [3,4-b] pyrazin-3-one (Compound 68) The 2- [2- (4-dimethylaminophenyl) -2- obtained in Reference Example 20 by the same method as in Example 12. Oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (300 mg, 0.97 mmol)
And benzyl bromide (0.14 ml, 1.17 mmol) to give the title compound (186 mg, 48%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.4
0 (s, 2H), 6.78 (d, J = 8.8 Hz, 2H), 7.02 (s, 1
H), 7.20-7.39 (m, 5H), 7.47 (d, J = 5.1 Hz, 1H
), 7.90 (d, J = 8.8 Hz, 2H), 8.16 (d, J = 5.1H
z, 1H), 8.33 (s, 1H), 13.25 (brs, 1H).

Example 69 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -4- (2-fluoroethyl) -1,4
-Dihydro-2H-pyrido [3,4-b] pyrazine-3
-One (compound 69) 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido obtained in Reference Example 20 in the same manner as in Example 12. [3,4-b] pyrazin-3-one (300 mg, 0.97 mmol)
And 1-bromo-2-fluoroethane (0.09 ml, 1.1
6mmol) to give the title compound (63.1 mg, 18%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.04 (s, 6H), 4.5
9 (td, J = 4.6, 25.3Hz, 2H), 4.78 (td, J = 4.6,
47.4Hz, 2H), 6.78 (d, J = 7.8Hz, 2H), 6.94 (
s, 1H), 7.48 (d, J = 5.0 Hz, 1H), 7.90 (d, J =
7.8Hz, 2H), 8.23 (d, J = 5.0Hz, 1H), 8.63 (s, 1
H), 13.21 (brs, 1H).

Example 70 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -4- (3-fluoropropyl) -1,
4-dihydro-2H-pyrido [3,4-b] pyrazine-
3-one (compound 70) In the same manner as in Example 12, the 2- [2- (3-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H- obtained in Reference Example 19 was obtained. Pyrido [3,4-b] pyrazin-3-one (300 mg, 0.97 mmol)
And 1-bromo-3-fluoropropane (0.107 ml,
1.17 mmol) gave the title compound (236 mg, 66%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.97-2.20 (m, 2H
), 2.98 (s, 6H), 4.34 (t, J = 6.3 Hz, 2H), 4.60
(td, J = 5.9, 47.2Hz, 2H), 6.91-7.02 (m, 1H),
6.97 (s, 1H), 7.22-7.39 (m, 3H), 7.58 (d, J =
6.0Hz, 1H), 8.28 (d, J = 6.0Hz, 1H), 8.63 (s,
1H), 13.23 (brs, 1H).

Example 71 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -4- (4-fluorobutyl) -1,4
-Dihydro-2H-pyrido [3,4-b] pyrazine-3
-One (compound 71) 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido obtained in Reference Example 20 in the same manner as in Example 12. [3,4-b] pyrazin-3-one (300 mg, 0.97 mmol)
And 1-bromo-4-fluorobutane (0.125 ml, 1.
16mmol) to give the title compound (82.7mg, 22%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.72-1.91 (m, 4H
), 3.05 (s, 6H), 4.24 (t, J = 7.2 Hz, 2H), 4.51
(td, J = 5.8, 47.4Hz, 2H), 6.78 (d, J = 9.0Hz,
2H), 6.93 (s, 1H), 7.48 (d, J = 5.2 Hz, 1H),
7.89 (d, J = 9.0 Hz, 2H), 8.23 (d, J = 5.2 Hz, 1H
), 8.58 (s, 1H), 13.24 (brs, 1H).

Example 72 2- [2- (3-Dimethylamino-2-methylphenyl) -2-oxoethylidene] -4- (3-fluoropropyl) -1,4-dihydro-2H-pyrido [3 4-
b] pyrazin-3-one (compound 72) 2- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene]-obtained in Reference Example 21 in the same manner as in Example 12. 1,4-dihydro-2
H-pyrido [3,4-b] pyrazin-3-one (300 mg,
0.93 mmol) and 1-bromo-3-fluoropropane
(0.10 ml, 1.12 mmol) gave the title compound (225 mg, 66%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.94-2.17 (m, 2H
), 2.35 (s, 3H), 2.66 (s, 6H), 4.31 (t, J =
7.2Hz, 2H), 4.58 (td, J = 5.4, 46.9Hz, 2H), 6.53
(s, 1H), 7.13-7.30 (m, 3H), 7.64 (d, J = 5.5
Hz, 1H), 8.27 (d, J = 5.5 Hz, 1H), 8.63 (s, 1H
), 12.94 (brs, 1H).

Example 73 2- [2- (4-dimethylamino-1-naphthyl) -2
-Oxoethylidene] -4- (3-fluoropropyl)
-1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (compound 73) By the same method as in Example 12, the 2- [2- (4- Dimethylamino-1-naphthyl)-
2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (300 mg, 0.84 m
mol) and 1-bromo-3-fluoropropane (0.09m
l, 1.00 mmol) to give the title compound (192 mg, 55%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.97-2.19 (m, 2H
), 2.94 (s, 6H), 4.33 (t, J = 6.8 Hz, 2H), 4.60
(td, J = 5.8, 47.0Hz, 2H), 6.82 (s, 1H), 7.12
(d, J = 8.0Hz, 1H), 7.51-7.67 (m, 2H), 7.63 (
d, J = 5.5Hz, 1H), 7.90 (d, J = 8.0Hz, 1H), 8.15
-8.23 (m, 1H), 8.28 (d, J = 5.5 Hz, 1H), 8.63 (
s, 1H), 8.66-8.74 (m, 1H), 13.12 (s, 1H).

Example 74 1-benzyl-3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (Compound 74) The 3- [2- (4-dimethylaminophenyl) -2- obtained in Reference Example 23 in the same manner as in Example 12. Oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (300 mg, 0.97 mmol)
And benzyl bromide (0.14 ml, 1.17 mmol) to give the title compound (202 mg, 52%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.4
2 (s, 2H), 6.77 (d, J = 9.0 Hz, 2H), 6.92 (s, 1
H), 7.06 (dd, J = 5.0, 8.4 Hz, 1H), 7.18-7.37 (
m, 5H), 7.53 (d, J = 8.4 Hz, 1H), 7.90 (d, J =
9.0Hz, 2H), 8.07 (d, J = 5.0 Hz, 1H), 13.48 (br
s, 1H).

Example 75 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (3-fluoropropyl) -3,
4-dihydro-1H-pyrido [2,3-b] pyrazine-
2-one (compound 75) In the same manner as in Example 12, the 3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H- obtained in Reference Example 23 was obtained. Pyrido [2,3-b] pyrazin-2-one (300 mg, 0.97 mmol)
And 1-bromo-3-fluoropropane (0.11 ml,
1.17 mmol) gave the title compound (170 mg, 48%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.91-2.14 (m, 2H
), 3.04 (s, 6H), 4.23 (t, J = 7.0 Hz, 2H), 4.55
(td, J = 5.9, 46.9Hz, 2H), 6.74 (d, J = 9.0Hz,
2H), 6.86 (s, 1H), 7.16 (dd, J = 4.7, 8.1 Hz,
1H), 7.74 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 9.0 H
z, 2H), 8.09 (d, J = 4.7 Hz, 1H), 13.44 (brs, 1
H).

Example 76 3- [2- (3-Dimethylamino-2-methylphenyl) -2-oxoethylidene] -1- (4-pyridylmethyl) -3,4-dihydro-1H-pyrido [2 3-
b] Pyrazin-2-one (compound 76) 3- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene]-obtained in Reference Example 24 by the same method as in Example 12. 3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (300 mg,
0.93 mmol) and 4-pyridylmethyl chloride hydrochloride
(183 mg, 1.12 mmol) gave the title compound (50.3 mg, 13%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.37 (s, 3H), 2.6
7 (s, 6H), 5.44 (s, 2H), 6.51 (s, 1H), 7.14
(dd, J = 4.7, 6.3Hz, 1H), 6.99-7.28 (m, 3H),
7.35 (d, J = 6.3 Hz, 2H), 7.52 (d, J = 7.6 Hz, 1H
), 8.15 (d, J = 4.7 Hz, 1H), 8.50 (d, J = 6.3 Hz,
2H), 13.33 (brs, 1H).

Example 77 3- [2- (3-Dimethylamino-2-methylphenyl) -2-oxoethylidene] -1- (3-pyridylmethyl) -3,4-dihydro-1H-pyrido [2 3-
b] Pyrazin-2-one (compound 77) 3- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene]-obtained in Reference Example 24 by the same method as in Example 12. 3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (300 mg,
0.93 mmol) and 3-pyridylmethyl chloride hydrochloride
(183 mg, 1.12 mmol) gave the title compound (32.6 mg, 8%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.36 (s, 3H), 2.6
7 (s, 6H), 5.45 (s, 2H), 6.51 (s, 1H), 7.10-
7.27 (m, 3H), 7.15 (dd, J = 4.9, 7.0 Hz, 1H),
7.31 (dd, J = 5.1, 7.7Hz, 1H), 7.66 (d, J = 7.0
Hz, 1H), 7.72 (d, J = 7.7 Hz, 1H), 8.13 (d, J =
4.4Hz, 1H), 8.46 (d, J = 5.1Hz, 1H), 8.65 (s,
1H), 13.32 (brs, 1H).

Example 78 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (4-fluorophenylmethyl)
-3,4-Dihydro-1H-pyrido [2,3-b] pyrazin-2-one (compound 78) In the same manner as in Example 12, the 3- [2- (4- Dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.81 mmol)
And 4-fluorobenzyl bromide (0.12 ml, 0.97 m
mol) to give the title compound (313 mg, 93%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.04 (s, 6H), 5.3
9 (s, 2H), 6.79 (d, J = 9.0 Hz, 2H), 6.93 (s, 1
H), 7.09 (dd, J = 4.9, 8.3 Hz, 1H), 7.16 (dd, J
= 9.1, 9.1Hz, 2H), 7.42 (dd, J = 5.4, 9.1Hz, 2H)
), 7.57 (dd, J = 0.9, 8.3Hz, 1H), 7.91 (d, J =
9.0Hz, 2H), 8.09 (dd, J = 0.9, 4.9Hz, 1H), 13.4
8 (brs, 1H).

Example 79 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (2-fluoroethyl) -3,4
-Dihydro-1H-pyrido [2,3-b] pyrazine-2
-One (compound 79) 3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido obtained in Reference Example 23 in the same manner as in Example 12. [2,3-b] pyrazin-2-one (250 mg, 0.81 mmol)
And 1-bromo-2-fluoroethane (0.07 ml, 0.9
7 mmol) to give the title compound (133 mg, 46%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.04 (s, 6H), 4.5
3 (td, J = 4.9, 25.2Hz, 2H), 4.76 (td, J = 4.9,
47.4Hz, 2H), 6.78 (d, J = 9.1Hz, 2H), 6.86 (
s, 1H), 7.19 (dd, J = 5.2, 7.9 Hz, 1H), 7.85 (d
d, J = 0.9, 7.9Hz, 1H), 7.90 (d, J = 9.1Hz, 2H
), 8.12 (dd, J = 0.9, 5.2Hz, 1H), 13.44 (brs,
1H).

Example 80 1-benzyl-3- [2- (2-methyl-3-pyridyl) -2-oxoethylidene] -3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (compound 80) 3- [2- (2-methyl-3-pyridyl)-obtained in Reference Example 25 by a method similar to that in Example 12. 2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.89 mmol)
And benzyl bromide (0.13 ml, 1.07 mmol) to give the title compound (264 mg, 80%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.66 (s, 3H), 5.4
4 (s, 2H), 6.61 (s, 1H), 7.20 (dd, J = 4.9, 8.
1Hz, 1H), 7.23-7.42 (m, 5H), 7.38 (dd, J = 4.8,
7.7Hz, 1H), 7.64 (dd, J = 1.0, 8.1Hz, 1H), 8.0
2 (dd, J = 1.8, 7.7Hz, 1H), 8.17 (dd, J = 1.0,
4.9Hz, 1H), 8.58 (dd, J = 1.8, 4.8Hz, 1H), 13.3
9 (brs, 1H).

Example 81 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (2-pyridylmethyl) -3,4
-Dihydro-1H-pyrido [2,3-b] pyrazine-2
-One (compound 81) 3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido obtained in Reference Example 23 in the same manner as in Example 12. [2,3-b] pyrazin-2-one (300 mg, 0.97 mmol)
And 2-pyridylmethyl chloride hydrochloride (192 mg, 1.
17 mmol) to give the title compound (113 mg, 29%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.04 (s, 6H), 5.4
9 (s, 2H), 6.79 (d, J = 7.8 Hz, 2H), 6.90 (s, 1
H), 7.09 (dd, J = 5.2, 7.9 Hz, 1H), 7.30 (dd, J
= 5.2, 7.6Hz, 1H), 7.45 (d, J = 7.6Hz, 1H), 7.5
8 (d, J = 7.9 Hz, 1H), 7.78 (dd, J = 7.6, 7.6 Hz,
1H), 7.90 (d, J = 7.8 Hz, 2H), 8.09 (d, J = 5.
2Hz, 1H), 8.49 (d, J = 5.2 Hz, 1H), 13.49 (brs,
1H).

Example 82 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (3-pyridylmethyl) -3,4
-Dihydro-1H-pyrido [2,3-b] pyrazine-2
-One (compound 82) 3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido obtained in Reference Example 23 in the same manner as in Example 12. [2,3-b] pyrazin-2-one (300 mg, 0.97 mmol)
And 3-pyridylmethyl chloride hydrochloride (192 mg, 1.
17 mmol) to give the title compound (116 mg, 30%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.4
4 (s, 2H), 6.79 (d, J = 8.8 Hz, 2H), 6.92 (s, 1
H), 7.10 (dd, J = 4.6, 8.1 Hz, 1H), 7.34 (dd, J
= 4.1, 7.4Hz, 1H), 7.62 (d, J = 8.1Hz, 1H), 7.7
4 (d, J = 7.4 Hz, 1H), 7.91 (d, J = 8.8 Hz, 2H),
8.10 (d, J = 4.6 Hz, 1H), 8.49 (d, J = 4.1 Hz, 1
H), 8.67 (s, 1H), 13.47 (brs, 1H).

Example 83 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (4-pyridylmethyl) -3,4
-Dihydro-1H-pyrido [2,3-b] pyrazine-2
-One (compound 83) 3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido obtained in Reference Example 23 in the same manner as in Example 12. [2,3-b] pyrazin-2-one (300 mg, 0.97 mmol)
And 4-pyridylmethyl chloride hydrochloride (192 mg, 1.
17mmol) to give the title compound (81.6mg, 21%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.04 (s, 6H), 5.4
3 (s, 2H), 6.79 (d, J = 8.6 Hz, 2H), 6.92 (s, 1
H), 7.09 (dd, J = 5.0, 8.0 Hz, 1H), 7.36 (d, J =
5.1Hz, 2H), 7.47 (d, J = 8.0 Hz, 1H), 7.91 (d,
J = 8.6Hz, 2H), 8.10 (d, J = 5.0Hz, 1H), 8.51
(d, J = 5.1Hz, 2H), 13.49 (brs, 1H).

Example 84 3- [2- (3-Dimethylamino-2-methylphenyl) -2-oxoethylidene] -1- (2-pyridylmethyl) -3,4-dihydro-1H-pyrido [2 3-
b] Pyrazin-2-one (compound 84) 3- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene]-obtained in Reference Example 24 in the same manner as in Example 12. 3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (300 mg,
0.93 mmol) and 2-pyridylmethyl chloride hydrochloride
(183 mg, 1.12 mmol) gave the title compound (56.8 mg, 15%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.49 (s, 3H), 2.7
8 (s, 6H), 5.50 (s, 2H), 6.76 (s, 1H), 6.99
(dd, J = 5.0, 8.1Hz, 1H), 7.11-7.36 (m, 5H),
7.61 (dd, J = 1.3, 8.1Hz, 1H), 7.68 (dd, J = 1.
7, 7.6Hz, 1H), 8.12 (dd, J = 1.3, 5.0Hz, 1H),
8.57 (brd, 1H), 13.29 (brs, 1H).

Example 85 3- [2- (3-Dimethylamino-2-methylphenyl) -2-oxoethylidene] -1- (3-fluoropropyl) -3,4-dihydro-1H-pyrido [2 3-
b] Pyrazin-2-one (compound 85) 3- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene]-obtained in Reference Example 24 in the same manner as in Example 12. 3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (250 mg,
0.78 mmol) and 1-bromo-3-fluoropropane
(0.085 ml, 0.94 mmol) gave the title compound (217 mg, 73%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.04-2.33 (m, 2H
), 2.46 (s, 3H), 2.75 (s, 6H), 4.31 (t, J =
7.4Hz, 2H), 4.60 (td, J = 5.4, 46.9Hz, 2H), 6.69
(s, 1H), 7.07-7.30 (m, 3H), 7.10 (dd, J = 4.
9, 8.1Hz, 1H), 7.48 (brd, J = 8.1Hz, 1H), 8.16
(dd, J = 1.3, 4.9Hz, 1H), 13.27 (brs, 1H).

Example 86 4-Benzyl-2- (3,3-dimethyl-2-oxobutylidene) -1,4-dihydro-2H-pyrido [3,4
-B] Pyrazin-3-one (compound 86) By a method similar to that in Example 12, 2- (3,3-dimethyl-2-oxobutylidene)-obtained in Reference Example 26
The title compound (131 mg, 38) was prepared from 1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (250 mg, 1.02 mmol) and benzyl bromide (0.85 ml, 1.22 mmol).
%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.18 (s, 9H), 5.4
4 (s, 2H), 6.53 (s, 1H), 7.21-7.37 (m, 5H),
7.54 (d, J = 5.2Hz, 1H), 8.17 (d, J = 5.2Hz, 1H
), 8.33 (s, 1H), 12.74 (brs, 1H).

Example 87 4- (2-Fluoroethyl) -2- [2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazine -3-one (compound 87) In the same manner as in Example 12, the 2- [2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H- obtained in Reference Example 27 was obtained. Pyrido [3,4
-B] pyrazin-3-one (250mg, 0.85mmol) and 1-bromo-2-fluoroethane (0.076ml, 1.02mmol)
Gave the title compound (91.5 mg, 32%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.86 (s, 3H), 4.6
1 (td, J = 4.6, 25.4Hz, 2H), 4.78 (td, J = 4.6,
47.0Hz, 2H), 6.97 (s, 1H), 7.09 (d, J = 8.8 Hz,
2H), 7.57 (d, J = 5.5 Hz, 1H), 8.01 (d, J = 8.
8Hz, 2H), 8.26 (d, J = 5.5 Hz, 1H), 8.67 (s, 1H
), 13.15 (brs, 1H).

Example 88 1-benzyl-3- [2-oxo-2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (compound 88) By the same method as in Example 12, 3- [2-oxo-2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b obtained in Reference Example 28. ]
The title compound (205 mg, 6 mg) was obtained from pyrazin-2-one (250 mg, 0.94 mmol) and benzyl bromide (193 mg, 1.13 mmol).
1%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 5.47 (s, 2H), 7.0
3 (s, 1H), 7.16 (dd, J = 4.8, 8.0 Hz, 1H), 7.26
-7.35 (m, 5H), 7.63 (d, J = 8.0 Hz, 1H), 7.89 (
dd, J = 1.4, 4.6Hz, 2H), 8.16 (d, J = 4.8Hz, 1H
), 8.79 (dd, J = 1.4, 4.6Hz, 2H), 13.60 (brs, 1
H).

Example 89 1- (3-Methylphenylmethyl) -3- [2-oxo-2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazine -2-one (compound 89) In the same manner as in Example 12, 3- [2-oxo-2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido obtained in Reference Example 28. [2,3-b]
The title compound (162 mg, 47%) was obtained from pyrazin-2-one (250 mg, 0.94 mmol) and 3-methylbenzyl bromide (209 mg, 1.13 mmol). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.26 (s, 3H), 5.4
1 (s, 2H), 7.00 (s, 1H), 7.07-7.25 (m, 5H), 7.
64 (d, J = 7.9Hz, 1H), 7.91 (dd, J = 1.4, 5.2H
z, 2H), 8.18 (d, J = 4.3 Hz, 1H), 8.81 (dd, J =
1.4, 5.2Hz, 2H), 13.60 (brs, 1H).

Example 90 4-benzyl-2- {2-oxo-2- [4- (4-pyridylmethoxy) phenyl] ethylidene} -1,4-dihydro-2H-pyrido [3,4-b] pyrazine -3-one (Compound 90) In a similar manner to Example 12, 2- {2-oxo-2- [4- (4-pyridylmethoxy) phenyl] ethylidene} -1,4 obtained in Reference Example 29. -Dihydro-2H
-Pyrido [3,4-b] pyrazin-3-one (250 mg, 0.
72 mmol) and benzyl bromide (147 mg, 0.86 mmol)
To give the title compound (30 mg, 9%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 5.31 (s, 2H), 5.5
0 (s, 2H), 7.07 (s, 1H), 7.13 (d, J = 8.9 Hz, 2H
), 7.33-7.39 (m, 5H), 7.46 (d, J = 5.3 Hz, 2H
), 7.57 (d, J = 5.1 Hz, 1H), 8.05 (d, J = 8.9H
z, 2H), 8.20 (d, J = 5.1 Hz, 1H), 8.37 (brs, 1H
), 8.59 (d, J = 5.3Hz, 2H), 13.10 (brs, 1H).

Example 91 1- (2-methylphenylmethyl) -3- [2-oxo-
2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (compound 91) Obtained in Reference Example 28 by a method similar to that in Example 12. 3- [2-oxo-2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b]
The title compound (161 mg, 46%) was obtained from pyrazin-2-one (250 mg, 0.94 mmol) and 2-methylbenzyl bromide (209 mg, 1.13 mmol). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.50 (s, 3H), 5.3
0 (s, 2H), 6.87 (d, J = 8.9 Hz, 1H), 6.96 (s, 1H
), 7.04 (dd, J = 4.0, 7.9Hz, 1H), 7.14-7.28 (
m, 3H), 7.45 (d, J = 7.9 Hz, 1H), 7.91 (dd, J =
1.1, 5.5Hz, 2H), 8.20 (d, J = 4.0Hz, 1H), 8.80
(dd, J = 1.1, 5.5Hz, 2H), 13.70 (brs, 1H).

Example 92 4- (2-Fluoroethyl) -2- [2- (4-fluorophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazine -3-one (compound 92) In the same manner as in Example 12, the 2- [2- (4-fluorophenyl) -2-oxoethylidene] -1,4-dihydro-2H- obtained in Reference Example 30 was obtained. Pyrido [3,4
-B] pyrazin-3-one (250mg, 0.88mmol) and 1-bromo-2-fluoroethane (0.08ml, 1.06mmol)
Gave the title compound (73.0 mg, 25%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 4.61 (td, J = 4.8,
26.0Hz, 2H), 4.78 (td, J = 4.8, 47.6Hz, 2H), 6.
98 (s, 1H), 7.38 (dd, J = 8.1, 8.1Hz, 2H), 7.62
(d, J = 5.2 Hz, 1H), 8.10 (dd, J = 5.4, 8.1 Hz,
2H), 8.28 (d, J = 5.2 Hz, 1H), 8.70 (s, 1H), 1
3.13 (brs, 1H).

Example 93 4- (tert-butoxycarbonylmethyl) -2- [2-
(4-Dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b]
Pyrazin-3-one (Compound 93) In the same manner as in Example 12, 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro- obtained in Reference Example 20. 2H-pyrido [3,4-b] pyrazin-3-one (250 mg, 0.81 mmol)
And tert-butyl bromoacetate (0.14ml, 0.97mmol)
From the title compound (114 mg, 33%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.44 (s, 9H), 3.0
4 (s, 6H), 4.98 (s, 2H), 6.79 (d, J = 8.9 Hz, 2
H), 6.94 (s, 1H), 7.51 (d, J = 5.2 Hz, 1H), 7.
90 (d, J = 8.9Hz, 2H), 8.24 (d, J = 5.2Hz, 1H
), 8.44 (s, 1H), 13.15 (brs, 1H).

Example 94 4-cyanomethyl-2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (Compound 94) In the same manner as in Example 12, 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3 , 4-b] pyrazin-3-one (250mg, 0.81mmol)
And bromoacetonitrile (0.07 ml, 0.97 mmol) gave the title compound (70.4 mg, 25%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.3
9 (s, 2H), 6.79 (d, J = 9.0 Hz, 2H), 6.95 (s, 1
H), 7.53 (d, J = 5.5 Hz, 1H), 7.90 (d, J = 9.0 H
z, 2H), 8.29 (d, J = 5.5 Hz, 1H), 8.63 (s, 1H
), 13.17 (brs, 1H).

Example 95 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -4- (4-nitrophenylmethyl)-
1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (compound 95) In the same manner as in Example 12, the 2- [2- (4-dimethyl) obtained in Reference Example 20 Aminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (250 mg, 0.81 mmol)
And 4-nitrobenzyl bromide (210mg, 0.97mmo
l) to give the title compound (215 mg, 60%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.6
1 (s, 2H), 6.78 (d, J = 8.7 Hz, 2H), 7.01 (s, 1
H), 7.51 (d, J = 5.2 Hz, 1H), 7.65 (d, J = 8.2 H
z, 2H), 7.90 (d, J = 8.7 Hz, 2H), 8.18 (d, J =
5.2Hz, 1H), 8.19 (d, J = 8.2Hz, 2H), 8.27 (s,
1H), 13.24 (brs, 1H).

Example 96 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -4- (3-trifluoromethylphenylmethyl) -1,4-dihydro-2H-pyrido [3,4
-B] Pyrazin-3-one (compound 96) 2- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -1,4 obtained in Reference Example 20 in the same manner as in Example 12. -Dihydro-2H-pyrido [3,4-b] pyrazin-3-one (250 mg, 0.81 mmol)
And 3-trifluoromethylbenzyl bromide (0.1
The title compound (213 mg, 56%) was obtained from 5 ml, 0.97 mmol). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.5
5 (s, 2H), 6.81 (d, J = 8.9 Hz, 2H), 7.01 (s, 1
H), 7.54 (d, J = 5.3 Hz, 1H), 7.60 (d, J = 7.5 H
z, 1H), 7.64-7.72 (m, 2H), 7.88 (brs, 1H), 7.
94 (d, J = 8.9 Hz, 2H), 8.21 (d, J = 5.3 Hz, 1H
), 8.34 (s, 1H), 13.24 (s, 1H).

Example 97 2- [2- (4-methoxyphenyl) -2-oxoethylidene] -4- (2-pyridylmethyl) -1,4-dihydro-2H-pyrido [3,4-b] pyrazine -3-one (compound 97) In the same manner as in Example 12, the 2- [2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H- obtained in Reference Example 27 was obtained. Pyrido [3,4
-B] pyrazin-3-one (300 mg, 1.02 mmol) and 2-pyridylmethyl chloride hydrochloride (200 mg, 1.22 mmol)
From the title compound (48.0 mg, 12%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.86 (s, 3H), 5.6
0 (s, 2H), 7.02 (s, 1H), 7.10 (d, J = 8.9 Hz, 2
H), 7.31 (dd, J = 5.1, 7.5 Hz, 1H), 7.50 (d, J =
7.5Hz, 1H), 7.59 (d, J = 5.3Hz, 1H), 7.80 (d
d, J = 7.5, 7.5Hz, 1H), 8.03 (d, J = 8.9Hz, 2H
), 8.21 (d, J = 5.3Hz, 1H), 8.40 (s, 1H), 8.4
9 (d, J = 5.1Hz, 1H), 13.18 (brs, 1H).

Example 98 4- (2-cyanophenylmethyl) -2- [2- (4-
Dimethylaminophenyl) -2-oxoethylidene]-
1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (Compound 98) The 2- [2- (4-dimethyl) obtained in Reference Example 20 in the same manner as in Example 12. Aminophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (250 mg, 0.81 mmol)
And 2-cyanobenzyl bromide (191 mg, 0.97 mmo
l) to give the title compound (197 mg, 57%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.04 (s, 6H), 5.6
1 (s, 2H), 6.79 (d, J = 9.1 Hz, 2H), 6.96 (s, 1
H), 7.35 (d, J = 7.9 Hz, 1H), 7.50 (dd, J = 6.3,
7.9Hz, 1H), 7.55 (d, J = 5.6Hz, 1H), 7.62 (d
d, J = 6.3, 7.6Hz, 1H), 7.90 (d, J = 9.1Hz, 2H
), 7.93 (d, J = 7.6Hz, 1H), 8.22 (d, J = 5.6H
z, 1H), 8.28 (s, 1H), 13.23 (brs, 1H).

Example 99 4- (4-methylphenylmethyl) -2- [2-oxo-
2- (4-pyridyl) ethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (Compound 99) Obtained in Reference Example 31 by a method similar to that in Example 12. 2- [2-oxo-2- (4-pyridyl) ethylidene] -1,4-dihydro-2H-pyrido [3,4-b]
The title compound (58.3 mg, 17%) was obtained from pyrazin-3-one (250 mg, 0.94 mmol) and 4-methylbenzyl bromide (209 mg, 1.13 mmol). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.27 (s, 3H), 5.4
7 (s, 2H), 7.07 (s, 1H), 7.14 (d, J = 7.9 Hz, 2H
), 7.27 (d, J = 7.9 Hz, 2H), 7.69 (d, J = 5.3 Hz,
1H), 7.91 (d, J = 5.1 Hz, 2H), 8.25 (d, J = 5.
3Hz, 1H), 8.44 (s, 1H), 8.82 (d, J = 5.1 Hz, 2H
), 13.24 (brs, 1H).

Example 100 4-Benzyl-2- [2- (4-chlorophenyl) -2
-Oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (compound 100) In the same manner as in Example 12, 2- [2 -(4-Chlorophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-
b] Pyrazin-3-one (250 mg, 0.83 mmol) and benzyl bromide (185 mg, 1.01 mmol) from the title compound (75.
0 mg, 22%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 5.51 (s, 2H), 7.0
7 (s, 1H), 7.27-7.46 (m, 5H), 7.60 (d, J = 5.3H
z, 1H), 7.61 (d, J = 8.4 Hz, 2H), 8.06 (d, J =
8.4Hz, 2H), 8.23 (d, J = 5.3Hz, 1H), 8.41 (br
s, 1H), 13.20 (brs, 1H).

Example 101 4- (4-Fluorobutyl) -2- [2- (3-fluorophenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazine -3-one (Compound 101) In the same manner as in Example 12, the 2- [2- (3-fluorophenyl) -2-oxoethylidene] -1,4-dihydro-2H- obtained in Reference Example 33 was obtained. Pyrido [3,4
-B] pyrazin-3-one (250 mg, 0.88 mmol) and 1
-Bromo-4-fluorobutane (178 mg, 1.15 mmol) gave the title compound (130 mg, 41%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.85-1.87 (m, 4H
), 4.28 (t, J = 5.6 Hz, 2H), 4.51 (td, J = 5.6,
48Hz, 2H), 6.99 (s, 1H), 7.39 (dd, J = 2.6,7.9H
z, 1H), 7.58 (d, J = 5.2 Hz, 1H), 7.59 (dd, J =
5.8, 7.9Hz, 1H), 7.71 (d, J = 7.9Hz, 1H), 7.86
(d, J = 8.0 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H),
8.64 (s, 1H), 13.20 (brs, 1H).

Example 102 2- [2- (2,4-Dimethoxyphenyl) -2-oxoethylidene] -4- (4-pyridylmethyl) -1,4-
Dihydro-2H-pyrido [3,4-b] pyrazine-3-
On (compound 102) 2- [2- (2,4-dimethoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazine- obtained in Reference Example 34 3-one (2
50 mg, 0.77 mmol) in tetrahydrofuran (8 ml) at room temperature with triphenylphosphine (302 mg, 1.15 mmol),
After adding pyridine methanol (126 mg, 1.15 mmol), diethyl azodicarboxylate (0.54 ml, 1.15 mmol) was added under ice cooling, and the temperature was gradually raised to room temperature, followed by stirring for 3 hours. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (eluted with methanol / chloroform = 1/100) to obtain the title compound (201 mg, 63%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.86 (s, 3H), 3.9
2 (s, 3H), 5.60 (s, 1H), 6.66 (s, 1H), 6.67
(d, J = 7.8 Hz, 1H), 7.03 (s, 1H), 7.35 (d, J =
5.9Hz, 2H), 7.55 (d, J = 5.1Hz, 1H), 7.78 (d,
J = 7.8Hz, 1H), 8.27 (d, J = 5.1Hz, 1H), 8.52
(d, J = 5.9 Hz, 2H), 8.61 (s, 1H), 13.12 (brs,
1H).

Example 103 2- [2- (2,5-Dimethoxyphenyl) -2-oxoethylidene] -4- (3-fluoropropyl) -1,
4-dihydro-2H-pyrido [3,4-b] pyrazine-
3-one (Compound 103) In the same manner as in Example 12, 2- [2- (2,5-dimethoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H obtained in Reference Example 35. -Pyrido [3,4-b] pyrazin-3-one (250 mg, 0.77 mmol)
And 1-bromo-3-fluoropropane (134 mg, 0.9
5mmol) to give the title compound (60.1mg, 22%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.98-2.17 (m, 2H
), 3.76 (s, 3H), 3.86 (s, 3H), 4.31 (t, J =
7.3Hz, 2H), 4.59 (td, J = 5.7, 47Hz, 2H), 7.06
(s, 1H), 7.08-7.16 (m, 2H), 7.22 (d, J = 1.9H
z, 1H), 7.57 (d, J = 5.3 Hz, 1H), 8.26 (d, J =
5.3Hz, 1H), 8.61 (brs, 1H), 13.10 (brs, 1H).

Example 104 4-benzyl-2- [2- (2,6-dimethoxy-3-
Pyridyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (Compound 104) Obtained in Reference Example 36 by a method similar to that in Example 12. 2- [2- (2,6-dimethoxy-3-pyridyl)-
2-oxoethylidene] -1,4-dihydro-2H-pyrido [3,4-b] pyrazin-3-one (250 mg, 0.77 m
mol) and benzyl bromide (0.11 ml, 0.92 mmol) to give the title compound (122 mg, 38%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.97 (s, 3H), 4.0
6 (s, 3H), 5.48 (s, 2H), 6.57 (d, J = 8.5 Hz, 1
H), 7.22-7.39 (m, 5H), 7.32 (s, 1H), 7.56 (
s, J = 5.4Hz, 1H), 8.20 (d, J = 5.4Hz, 1H), 8.2
1 (d, J = 8.5 Hz, 1H), 8.37 (s, 1H), 13.17 (br
s, 1H).

Example 105 2- [2- (1-Naphthyl) -2-oxoethylidene]
-3- (4-Piperidinopiperidino) -1H-quinoxaline (compound 105) n-butyllithium (1.68 N / n-hexane solution, 2.76 ml, 4.
64mmol) and diisopropylamine (0.66ml, 5.05mm
ol) prepared in Reference Example 40 in a solution of lithium diisopropylamide in tetrahydrofuran (8 ml).
-Methyl-3- (4-piperidinopiperidino) quinoxaline (630 mg, 2.02 mmol) was added at −78 ° C., and the mixture was stirred at 0 ° C. for 10 minutes. Then, at 0 ° C., methyl 1-naphthoate (564 mg, 3.03 mg) was added.
mmol) was added. After stirring at room temperature for 4 hours, water was added, the mixture was diluted with ethyl acetate, washed with water and brine, and dried over anhydrous magnesium sulfate. After filtering off insolubles, the filtrate was evaporated under reduced pressure, and the residue obtained was purified by silica gel column chromatography (containing 5% triethylamine, eluted with hexane / ethyl acetate = 1/1) to give the title compound (938 mg, Quantitative) was obtained. ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.38-2.99 (m, 15H),
3.82-3.93 (m, 2H), 4.01-4.15 (m, 2H), 6.09 (
s, 1H), 7.29-7.78 (m, 10H), 7.87-7.98 (m, 1H
), 15.51 (s, 1H).

Example 106 3- (4-Methylpiperazin-1-yl) -2- (2-
Oxo-2-phenylethylidene) -1H-quinoxaline (compound 106) By the same method as in Example 105, 2-methyl-3- (4-methylpiperazin-1-yl) quinoxaline (2.00) obtained in Reference Example 38 was obtained. g, 8.25 mmol) and ethyl benzoate (1.6 ml, 9.90 mmol) from the title compound (1.21 g, 42
%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.41 (s, 3H), 2.66-
2.69 (m, 4H), 3.30-3.90 (m, 4H), 6.37 (s, 1H
), 7.30-7.39 (m, 3H), 7.48-7.50 (m, 3H), 7.63
(d, J = 6.9 Hz, 1H), 7.95 (dd, J = 3.3, 6.6 Hz, 2
H), 15.01 (s, 1H).

Example 107 2- (2-oxo-2-phenylethylidene) -3-thiomorpholino-1H-quinoxaline (Compound 107) The 2-methyl compound obtained in Reference Example 39 in the same manner as in Example 105 -3-thiomorpholinoquinoxaline (1.
00g, 4.08mmol) and ethyl benzoate (0.70ml, 4.90m)
mol) to give the title compound (1.23 g, 88%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.89-2.93 (m, 4H),
3.72-3.76 (m, 4H), 6.33 (s, 1H), 7.29-7.43 (
m, 3H), 7.48-7.51 (m, 3H), 7.61-7.65 (m, 1H),
7.92-7.97 (m, 2H), 15.04 (s, 1H).

Example 108 3-Dibutylamino-2- [2- (1-naphthyl) -2
-Oxoethylidene] -1H-quinoxaline (Compound 1
08) 3-Dibutylamino-2-methylquinoxaline obtained in Reference Example 41 in the same manner as in Example 105 (1.
68g, 6.19mmol) and methyl 1-naphthoate (1.73g,
9.29 mmol) to give the title compound (2.63 g, quantitative). ¹ H-NMR (CDCl ₃ ) δ (ppm): 0.88 (t, J = 7.2Hz,
6H), 1.23-1.40 (m, 4H), 1.54-1.69 (m, 4H), 3.
54 (t, J = 7.3Hz, 4H), 6.19 (s, 1H), 7.24-7.97
(m, 10H), 8.86-8.94 (s, 1H), 14.92 (s, 1H).

Example 109 2- [2-oxo-2- (3,4,5-trimethoxyphenyl) ethylidene] -3-piperidino-1H-quinoxaline (Compound 109) A known compound was prepared in the same manner as in Example 105. Compound [Journal of Organic Chemistry (J. Org.
Chem.), Vol. 27, p. 324 (1962)], 2-methyl-3-piperidinoquinoxaline (1.00 g, 4.40 mmol).
And methyl 3,4,5-trimethoxybenzoate (1.41
g, 6.60 mmol) to give the title compound (1.22 g, 67%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.66-1.97 (m, 6H),
3.54-3.78 (m, 4H), 3.93 (s, 3H), 3.96 (s, 6H
), 6.40 (s, 1H), 7.21 (s, 2H), 7.24-7.43 (m,
3H), 7.98-8.10 (m, 1H), 15.34 (s, 1H).

Example 110 2- [2- (1-Methoxy-2-naphthyl) -2-oxoethylidene] -3-piperidino-1H-quinoxaline (Compound 110) A known compound was prepared in the same manner as in Example 105. Certain 2-methyl-3-piperidinoquinoxaline (1.00 g, 4.4
0 mmol) and methyl 1-methoxy-2-naphthoate
(1.43 g, 6.60 mmol) to the title compound (1.81 g, quantitative)
I got ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.64-1.90 (m, 6H),
3.43-3.59 (m, 4H), 3.98 (s, 3H), 6.84 (s, 1H
), 7.25-7.43 (m, 2H), 7.52-7.77 (m, 5H), 7.83-
7.95 (m, 2H), 8.24-8.34 (m, 1H), 15.61 (s, 1H
).

Example 111 3- (4-Benzylpiperazin-1-yl) -2- [2
-(1-Naphthyl) -2-oxoethylidene] -1H-
Quinoxaline (Compound 111) 3- (4-benzylpiperazin-1-yl) -2- obtained in Reference Example 42 by a method similar to that of Example 105.
The title compound was obtained from methylquinoxaline (1.69 g, 5.30 mmol) and methyl 1-naphthoate (1.48 g, 7.95 mmol).
(2.27 g, 91%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 2.58-2.97 (m, 4H),
3.48-3.94 (m, 6H), 6.10 (s, 1H), 7.26-7.76 (
m, 13H), 7.87-7.98 (m, 2H), 8.45-8.54 (m, 1H),
15.57 (s, 1H).

Example 112 2- [2- (4-Methoxyphenyl) -2-oxoethylidene] -3-piperidino-1H-quinoxaline (Compound 112) By a method similar to that of Example 105, the known compound 2- Methyl-3-piperidinoquinoxaline (1.00 g, 4.4
0 mmol) and methyl 4-methoxybenzoate (1.10 g, 6.
60 mmol) to give the title compound (1.59 g, quantitative). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.65-1.93 (m, 6H),
3.45-3.64 (m, 4H), 3.89 (s, 3H), 6.38 (s, 1H
), 6.98 (d, J = 8.9 Hz, 2H), 7.20-7.37 (m, 3H),
7.79-7.88 (m, 1H), 7.93 (d, J = 8.9 Hz, 2H), 1
5.36 (s, 1H).

Example 113 2- [2- (4-Fluorophenyl) -2-oxoethylidene] -3-piperidino-1H-quinoxaline (Compound 113) By a method similar to that of Example 105, the known compound 2- Methyl-3-piperidinoquinoxaline (700 mg, 3.0
8 mmol) and methyl 4-fluorobenzoate (712 mg, 4.
62 mmol) to give the title compound (384 mg, 36%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.62-1.93 (m, 6H),
3.33-3.59 (m, 4H), 6.34 (s, 1H), 7.15 (dd, J
= 8.3, 8.3Hz, 2H), 7.24-7.41 (m, 3H), 7.69-7.76
(m, 1H), 7.96 (dd, J = 5.2, 8.3 Hz, 2H), 15.55
(s, 1H).

Example 114 2- [2- (3-Dimethylaminophenyl) -2-oxoethylidene] -3-piperidino-1H-quinoxaline (Compound 114) A known compound 2 was obtained in the same manner as in Example 105. -Methyl-3-piperidinoquinoxaline (647 mg, 2.8 mg
5 mmol) and methyl 3-dimethylaminobenzoate (765
mg, 4.27 mmol) to give the title compound (1.04 g, 97%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.44-1.89 (m, 6H),
3.09 (s, 6H), 3.34-3.47 (m, 4H), 6.39 (s, 1H
), 7.19-7.46 (m, 7H), 7.58-7.67 (m, 1H), 15.66
(s, 1H).

Example 115 3- [4- (2-methoxyphenyl) piperazine-1-
Yl] -2- [2- (1-Naphthyl) -2-oxoethylidene] -1H-quinoxaline (Compound 115) In the same manner as in Example 105, 3- [4- (2 -Methoxyphenyl) piperazine-
1-yl] -2-methylquinoxaline (700 mg, 2.09 mmo
l) and methyl 1-naphthoate (584 mg, 3.14 mmol) gave the title compound (560 mg, 55%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 3.07-3.45 (m, 4H),
3.59-3.94 (m, 4H), 3.85 (s, 3H), 6.19 (s, 1H
), 6.82-7.09 (m, 2H), 7.30-7.79 (m, 10H), 7.8
4-7.98 (m, 2H), 8.50-8.58 (m, 1H), 15.68 (s,
1H).

Example 116 3- [4- (tert-butoxycarbonyl) piperazine-
1-yl] -2- [2- (1-naphthyl) -2-oxoethylidene] -1H-quinoxaline (compound 116) In the same manner as in Example 105, 3- [4- (Tert-butoxycarbonyl) piperazin-1-yl] -2-methylquinoxaline (600 mg, 1.8
3mmol) and methyl 1-naphthoate (511mg, 2.75mmo
The title compound (790 mg, 89%) was obtained from l). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.47 (s, 9H), 3.34-
3.70 (m, 8H), 6.14 (s, 1H), 7.25-7.98 (m, 10H
), 8.46-8.57 (m, 1H), 15.64 (s, 1H).

Example 117 2- [2- (1-naphthyl) -2-oxoethylidene]
-3- (1-Perhydroazepinyl) -1H-quinoxaline (Compound 117) By a method similar to that of Example 105, a known compound [Journal of Organic Chemistry (J. Org.
Chem.), 27, p. 324 (1962)], 2-methyl-3- (1-perhydroazepinyl) quinoxaline.
(489mg, 2.03mmol) and methyl 1-naphthoate (652m
g, 3.05 mmol) to give the title compound (241 mg, 30%). ¹ H-NMR (CDCl ₃ ) δ (ppm): 1.36-2.03 (m, 8H),
3.59-3.90 (m, 4H), 6.19 (s, 1H), 7.21-7.96 (
m, 10H), 8.47-8.58 (m, 1H), 15.76 (s, 1H).

Example 118 2- [2- (4-Dimethylamino-2,5-dimethylphenyl) -2-oxoethylidene] -3-piperidino-
1H-quinoxaline dihydrochloride (compound 118) 2,5-dimethyl-4-nitrobenzoic acid (280 mg, 1.42 m
mol) in ethanol (5 ml) and palladium-carbon
(140 mg), and the mixture was stirred at room temperature under a hydrogen stream for 5 hours. After filtering off the insoluble matter, the filtrate was concentrated under reduced pressure, and a mixture of the obtained residue and sulfuric acid (0.23 ml, 4.27 mmol) was treated with methanol (5 ml).
The mixture was refluxed for 6 hours. After allowing to cool to room temperature, the mixture was neutralized with a saturated aqueous solution of sodium hydrogen carbonate, diluted with ethyl acetate, washed with saturated saline, and dried over anhydrous magnesium sulfate. The residue obtained by evaporating the solvent under reduced pressure is purified by silica gel column chromatography (hexane / ethyl acetate = 2/1)
To give methyl 4-amino-2,5-dimethylbenzoate (254 mg, quantitative). Further, this compound was mixed with a 37% aqueous formaldehyde solution (1.15 ml, 14.2 mmol) and sodium cyanoborohydride (286 mg, 4.54 mmol) in acetonitrile (5 ml) under ice-cooling, and the mixture was heated to room temperature for 1 hour.
Stirred for hours. Acetic acid (0.1 ml) was added to the reaction system, which was treated with a 10N aqueous sodium hydroxide solution under ice-cooling, and then extracted with ethyl acetate. The organic layer was washed with water and saturated saline,
It was dried over magnesium sulfate. The solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 8/1) to give methyl 4-dimethylamino-2,5-dimethylbenzoate (230 mg, 78%).
I got Then, in the same manner as in Example 105,
Known compounds, 2-methyl-3-piperidinoquinoxaline (209 mg, 0.92 mmol) and 4-dimethylamino-
The crude product (360 mg) of the free base of the title compound obtained from methyl 2,5-dimethylbenzoate (230 mg, 1.11 mmol) was recrystallized (methylene chloride / hexane) to give the free base of the title compound (245 mg, 66%). ) Got. The obtained free base was converted to a hydrochloric acid with 4N hydrogen chloride / ethyl acetate to give the title compound (305m
g) was obtained. ¹ H-NMR (dihydrochloride; DMSO-d ₆ ) δ (ppm): 1.50-1.82
(m, 6H), 2.50 (s, 3H), 2.63 (s, 3H), 3.19 (
s, 6H), 3.29-3.49 (m, 4H), 5.89 (s, 1H), 7.29-
7.43 (m, 2H), 7.49 (s, 1H), 7.58 (dd, J = 1.
9, 7.7Hz, 1H), 7.64 (d, J = 7.5Hz, 1H), 7.76 (
s, 1H), 15.26 (s, 1H).

Example 119 2- [2- (1-Methoxy-2-naphthyl) -2-oxoethylidene] -3- [4- (2-pyridyl) piperazin-1-yl] -1H-quinoxaline dihydrochloride (Compound 119) In the same manner as in Example 105, 2-methyl-3- [4- (2-pyridyl) piperazin-1-yl] quinoxaline (150 mg, 0.49 mmol) obtained in Reference Example 45 and 1- Methyl methoxy-2-naphthoate (106mg, 0.49m
mol), the free base of the title compound was hydrochlorinated with 4N hydrogen chloride / ethyl acetate to give the title compound (29.9 mg, 1
2%). ¹ H-NMR _{(dihydrochloride; DMSO-d 6) δ (} ppm): 3.52-3.48
(m, 10H), 6.82 (s, 1H), 6.95-7.04 (m, 1H),
7.34-7.52 (m, 3H), 7.58-8.14 (m, 10H), 8.18-8.
26 (m, 1H), 15.35 (s, 1H).

Example 120 1-Benzyl-3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1H-pyrido [2,3-
b] Pyrazin-2-one (compound 120) Known method [Journal of heterocyclic.
2- (2-oxo-2-) obtained according to Chemistry (J. Heterocyclic Chem.), 32, 347 (1995)].
Phenylethylidene) -1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one and 3- (2-oxo-2-phenylethylidene) -3,4-dihydro-1
4: 6 of H-pyrido [2,3-b] pyrazin-2-one
(500 mg, 1.89 mmol) in N, N-dimethylformamide (20 ml) at room temperature with potassium tert-butoxide (250 mM).
g, 2.26 mmol) and benzyl bromide (0.20 ml, 1.89 mmo)
l) was added and stirred for 2 hours. Water was added to the reaction system, and the precipitated solid was collected by filtration and dried under reduced pressure. The obtained solid was purified by silica gel column chromatography (eluted with hexane / ethyl acetate = 4/1) to give the title compound (130 mg, 19%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 5.42 (s, 2H), 6.9
5 (dd, J = 5.0, 8.3Hz, 1H), 7.18 (s, 1H), 7.29
-7.38 (m, 6H), 7.46-7.56 (m, 3H), 8.08 (dd, J
= 1.5, 8.3Hz, 2H), 8.12 (dd, J = 1.5, 5.0Hz, 1H
), 13.4 (brs, 1H).

Example 121 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (2-fluorophenylmethyl)
-3,4-Dihydro-1H-pyrido [2,3-b] pyrazin-2-one (compound 121) In the same manner as in Example 12, the 3- [2- (4- Dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (300 mg, 0.97 mmol)
And 2-fluorobenzyl bromide (0.14ml, 1.17m
mol) to give the title compound (99.6 mg, 25%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.05 (s, 6H), 5.4
2 (s, 2H), 6.78 (d, J = 9.1 Hz, 2H), 6.91 (s, 1
H), 7.11 (dd, J = 5.1, 9.0Hz, 1H), 7.16-7.41 (
m, 4H), 7.52 (d, J = 9.0 Hz, 1H), 7.91 (d, J =
9.1Hz, 2H), 8.09 (d, J = 5.1Hz, 1H), 13.47 (br
s, 1H).

Example 122 1-benzyl-3- [2- (3-dimethylamino-2-
Methylphenyl) -2-oxoethylidene] -3,4-
Dihydro-1H-pyrido [2,3-b] pyrazine-2-
On (Compound 122) In the same manner as in Example 12, the 3- [2- (3-dimethylamino-2-methylphenyl) -2-oxoethylidene] -3,4-dihydro- obtained in Reference Example 24 was obtained. 1
H-pyrido [2,3-b] pyrazin-2-one (250 mg,
0.776 mmol) and benzyl bromide (0.110 ml, 0.930
mmol) to give the title compound (291 mg, 90%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.37 (s, 3H), 2.6
7 (s, 6H), 5.42 (s, 2H), 6.53 (s, 1H), 7.07-
7.37 (m, 8H), 7.14 (dd, J = 4.7, 8.0 Hz, 1H),
7.59 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 4.7 Hz, 1H
), 13.34 (brs, 1H).

Example 123 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (2-methylphenylmethyl)-
3,4-Dihydro-1H-pyrido [2,3-b] pyrazin-2-one (Compound 123) In the same manner as in Example 12, the 3- [2- (4-dimethyl) obtained in Reference Example 23 Aminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.811 mmol
l) and 2-methylbenzyl bromide (0.130 ml, 0.97
3 mmol) to give the title compound (288 mg, 86%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.44 (s, 3H), 3.0
5 (s, 6H), 5.32 (s, 2H), 6.78 (d, J = 8.5 Hz, 2
H), 6.83 (d, J = 8.0 Hz, 1H), 6.91 (s, 1H), 7.
04 (dd, J = 7.0, 8.0Hz, 1H), 7.06 (dd, J = 4.3,
8.1Hz, 1H), 7.16 (dd, J = 7.0, 7.9Hz, 1H), 7.2
6 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 8.1 Hz, 1H),
7.91 (d, J = 8.5 Hz, 2H), 8.10 (d, J = 4.3 Hz, 1H
), 13.52 (s, 1H).

Example 124 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (4-methylphenylmethyl)-
3,4-Dihydro-1H-pyrido [2,3-b] pyrazin-2-one (Compound 124) In the same manner as in Example 12, the 3- [2- (4-dimethyl) obtained in Reference Example 23 Aminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.811 mmol
l) and 4-methylbenzyl bromide (180mg, 0.973m
mol) to give the title compound (263 mg, 79%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.26 (s, 3H), 3.0
5 (s, 6H), 5.37 (s, 2H), 6.79 (d, J = 8.9 Hz, 2
H), 6.93 (s, 1H), 7.08 (dd, J = 4.9, 8.2 Hz 1H
), 7.13 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 H
z, 2H), 7.55 (d, J = 8.2 Hz, 1H), 7.91 (d, J =
8.9Hz, 2H), 8.08 (d, J = 4.9Hz, 1H), 13.48 (s,
1H).

Example 125 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (3-fluorophenylmethyl)
-3,4-Dihydro-1H-pyrido [2,3-b] pyrazin-2-one (compound 125) In the same manner as in Example 12, the 3- [2- (4- Dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.811 mmol)
l) and 3-fluorobenzyl bromide (0.120 ml, 0.
973 mmol) to give the title compound (333 mg, 99%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.04 (s, 6H), 5.4
1 (s, 2H), 6.79 (d, J = 9.2 Hz, 2H), 6.92 (s, 1
H), 7.04-7.15 (m, 1H), 7.09 (dd, J = 4.9, 8.0H
z, 1H), 7.16-7.30 (m, 2H), 7.38 (ddd, J = 6.0,
8.0, 8.0Hz, 1H), 7.52 (d, J = 8.0Hz, 1H), 7.91
(d, J = 9.2Hz, 2H), 8.09 (dd, J = 1.2, 4.9Hz, 1H
), 13.48 (brs, 1H).

Example 126 1- (4-Methylphenylmethyl) -3- [2-oxo-
2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (compound 126) Obtained in Reference Example 28 by a method similar to that in Example 12. 3- [2-oxo-2- (4-pyridyl) ethylidene]
From -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.910 mmol) and 4-methylbenzylbromide (209 mg, 1.13 mmol), the title compound (226 mg, 65%) I got ^{1 H-NMR (DMSO-d} 6) δ (ppm): 2.29 (s, 3H), 5.4
3 (s, 2H), 7.04 (s, 1H), 7.11-7.25 (m, 5H),
7.62 (d, J = 8.3 Hz, 1H), 7.88 (dd, J = 1.4, 5.3
Hz, 2H), 8.16 (d, J = 4.5 Hz, 1H), 8.79 (dd, J
= 1.4, 5.3Hz, 2H), 13.60 (brs, 1H).

Example 127 3- [2- (4-Dimethylaminophenyl) -2-oxoethylidene] -1- (2-pyridylmethyl) -3,4
-Dihydro-1H-pyrido [2,3-b] pyrazine-2
-One trihydrochloride (compound 127) 3- [2- (4-dimethylaminophenyl) -2-oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b obtained in Reference Example 23 ] Pyrazin-2-one
(400mg, 1.30mmol), 2-pyridylmethanol (0.190m
l, 1.95 mmol) and triphenylphosphine (510 mg,
1.95 mmol) in tetrahydrofuran (13 ml)
Diethyl azodicarboxylate (0.910ml, 1.95mmo
l) was added. After stirring at room temperature for 10 hours, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluted with chloroform / methanol = 50/1) to give the free base of the title compound (197 mg, 38 %). The obtained free base (241 mg, 0.61 mmol) was suspended in ethyl acetate (30 ml), and a 4N hydrogen chloride / ethyl acetate solution (4.5 ml) was added at room temperature. After stirring at the same temperature for 0.5 hour, the precipitated crystals were collected by filtration, washed with ethyl acetate, and dried under reduced pressure to obtain the title compound (258 mg, 80%). ¹ H-NMR (as free base; DMSO-d ₆ ) δ (ppm): 3.0
4 (s, 6H), 5.49 (s, 2H), 6.79 (d, J = 7.8 Hz, 2
H), 6.90 (s, 1H), 7.09 (dd, J = 5.2, 7.9 Hz, 1H
), 7.30 (dd, J = 5.2, 7.6Hz, 1H), 7.45 (d, J =
7.6Hz, 1H), 7.58 (d, J = 7.9Hz, 1H), 7.78 (d
d, J = 7.6, 7.6Hz, 1H), 7.90 (d, J = 7.8Hz, 2H),
8.09 (d, J = 5.2 Hz, 1H), 8.49 (d, J = 5.2 Hz, 1
H), 13.49 (s, 1H).

Example 128 1-Benzyl-3- {2-oxo-2- [4- (4-pyridylmethoxy) phenyl] ethylidene} -3,4-dihydro-1H-pyrido [2,3-b] pyrazine -2-one (compound 128) In the same manner as in Example 1, 3- {2-oxo-2- [4- (4-pyridylmethoxy) phenyl] ethylidene} -3,4 obtained in Reference Example 54. -Dihydro-1H
-Pyrido [2,3-b] pyrazin-2-one (250 mg, 0.
720 mmol) and benzyl bromide (147 mg, 0.860 mmol)
Afforded the title compound (122 mg, 39%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 5.30 (s, 2H), 5.4
3 (s, 2H), 6.97 (s, 1H), 7.12 (dd, J = 4.5, 7.
7Hz, 1H), 7.17 (d, J = 9.1 Hz, 2H), 7.23-7.39 (
m, 5H), 7.46 (d, J = 5.1 Hz, 2H), 7.59 (d, J =
7.7Hz, 1H), 8.05 (d, J = 9.1Hz, 2H), 8.12 (d,
J = 4.5Hz, 1H), 8.60 (d, J = 5.1Hz, 2H), 13.50
(brs, 1H).

Example 129 1- (2-Fluorophenylmethyl) -3- [2-oxo-2- (4-pyridyl) ethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazine -2-one (Compound 129) 3- [2-oxo-2- (4-pyridyl) ethylidene] obtained in Reference Example 28 in the same manner as in Example 12.
From the -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.940 mmol) and 2-fluorobenzyl bromide (214 mg, 1.13 mmol), the title compound (165 mg, 47%) ). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 5.45 (s, 2H), 6.9
7 (s, 1H), 7.08 (dd, J = 4.6, 7.3 Hz, 1H), 7.21
-7.39 (m, 4H), 7.63 (d, J = 7.3 Hz, 1H), 7.91 (d
d, J = 1.5, 4.5Hz, 2H), 8.21 (d, J = 4.6Hz, 1H
), 8.80 (dd, J = 1.5, 4.5 Hz, 2H), 13.60 (brs, 1
H).

Example 130 1-Benzyl-3- [2- (2,4-dimethoxyphenyl) -2-oxoethylidene] -3,4-dihydro-1
H-pyrido [2,3-b] pyrazin-2-one (compound 130) 3- [2- (2,4-dimethoxyphenyl) -2 obtained in Reference Example 46 by a method similar to that in Example 12. -Oxoethylidene] -3,4-dihydro-1H-pyrido [2,3-b] pyrazin-2-one (250 mg, 0.730 mmol
l) and benzyl bromide (171 mg, 0.950 mmol) gave the title compound (220 mg, 73%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 3.87 (s, 3H), 3.9
4 (s, 3H), 5.42 (s, 2H), 6.64 (d, J = 7.5 Hz, 1
H), 6.65 (s, 1H), 7.06 (dd, J = 4.6, 8.1 Hz, 1H
), 7.16 (s, 1H), 7.26-7.34 (m, 5H), 7.54 (d,
J = 7.5Hz, 1H), 7.79 (d, J = 8.1Hz, 1H), 8.08 (
d, J = 4.6Hz, 1H), 13.40 (brs, 1H).

Example 131 7-Chloro-2- (2-oxo-2-phenylethylidene) -4- [2- (3-thienyl) ethyl] -1,4-
Dihydro-2H-pyrido [2,3-b] pyrazine-3-
On (compound 131) 7-chloro-2- (2-oxo-2-phenylethylidene) -1,4-dihydro-2H-pyrido [2, obtained in Reference Example 47 in the same manner as in Example 127. 3-
b] pyrazin-3-one (250 mg, 0.834 mmol) and 3
-(2-hydroxyethyl) thiophene (0.140 ml, 1.2
5 mmol) to give the title compound (237 mg, 70%) as pale yellow crystals. ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.98 (t, J = 7.9H
z, 2H), 4.51 (t, J = 7.9 Hz, 2H), 6.95 (s, 1H),
7.06 (dd, J = 1.1, 5.2Hz, 1H), 7.28 (dd, J = 1.
1, 2.0Hz, 1H), 7.49 (dd, J = 2.0, 5.2Hz, 1H),
7.52-7.67 (m, 3H), 7.98-8.04 (m, 2H), 8.22 (
d, J = 2.1Hz, 1H), 8.33 (d, J = 2.1Hz, 1H), 13.
28 (brs, 1H).

Example 132 7-Chloro-2- (2-oxo-2-phenylethylidene) -4- [2- (2-pyridyl) ethyl] -1,4-
Dihydro-2H-pyrido [2,3-b] pyrazine-3-
On (compound 132) 7-chloro-2- (2-oxo-2-phenylethylidene) -1,4-dihydro-2H-pyrido [2, obtained in Reference Example 47 in the same manner as in Example 127. 3-
b] pyrazin-3-one (250 mg, 0.834 mmol) and 2
-(2-hydroxyethyl) pyridine (0.140ml, 1.26m
mol) yielded the title compound (83.2 mg, 24%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 3.11 (t, J = 7.6H
z, 2H), 4.65 (t, J = 7.6 Hz, 2H), 6.94 (s, 1H),
7.22 (dd, J = 5.0, 7.6Hz, 1H), 7.31 (d, J = 7.6
Hz, 1H), 7.51-7.66 (m, 3H), 7.71 (dd, J = 7.6,
7.6Hz, 1H), 8.01 (d, J = 7.2Hz, 2H), 8.20 (d,
J = 2.2Hz, 1H), 8.33 (d, J = 2.2Hz, 1H), 8.48
(d, J = 5.0 Hz, 1H), 13.29 (brs, 1H).

Compound 133 7-Chloro-2- [2- (4-methoxyphenyl) -2
-Oxoethylidene] -4- [2- (2-methoxyphenyl) ethyl] -1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one (compound 133) Same as in Example 127 According to the method, 7-chloro-2- [2- (4-methoxyphenyl) obtained in Reference Example 48
-2-oxoethylidene] -1,4-dihydro-2H-
Pyrido [2,3-b] pyrazin-3-one (250 mg, 0.7
58 mmol) and 2- (2-methoxyphenyl) ethanol (0.160 ml, 1.14 mmol) to give the title compound (144.9 mg, 41
%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.95 (t, J = 7.2H
z, 2H), 3.72 (s, 3H), 3.86 (s, 3H), 4.52 (t,
J = 7.2Hz, 2H), 6.83 (dd, J = 7.4, 7.4Hz, 1H),
6.88 (s, 1H), 6.89 (d, J = 7.4Hz, 1H), 7.03-7.
21 (m, 2H), 7.08 (d, J = 8.8 Hz, 2H), 8.00 (d,
J = 8.8Hz, 2H), 8.13 (d, J = 2.1Hz, 1H), 8.23
(d, J = 2.1Hz, 1H), 13.23 (brs, 1H).

Example 134 4- (2-butynyl) -7-chloro-2- [2- (4-
Fluorophenyl) -2-oxoethylidene] -1,4
-Dihydro-2H-pyrido [2,3-b] pyrazine-3
-One (compound 134) 7-chloro-2- [2- (4-fluorophenyl)-obtained in Reference Example 49 by a method similar to that in Example 12.
2-oxoethylidene] -1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one (250 mg, 0.787
mmol) and 1-bromo-2-butyne (0.0830 ml, 0.95
0 mmol) to give the title compound (126 mg, 43%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.67-1.80 (m, 3H
), 4.94-5.01 (m, 2H), 6.94 (s, 1H), 7.38 (dd,
J = 8.8, 8.8Hz, 2H), 8.10 (dd, J = 6.6, 8.8Hz,
2H), 8.25 (d, J = 2.1 Hz, 1H), 8.33 (d, J = 2.1
Hz, 1H), 13.15 (brs, 1H).

Example 135 2- [2- (1,3-benzodioxol-5-yl)
-2-oxoethylidene] -4-benzyl-7-methyl-1,4-dihydro-2H-pyrido [2,3-b] pyrazin-3-one (Compound 135) In the same manner as in Example 12, reference was made. 2- [2- (1,3-benzodioxol-5-yl) -2-oxoethylidene] -7-methyl-1,4-obtained in Example 50
Dihydro-2H-pyrido [2,3-b] pyrazine-3-
ON (250 mg, 0.773 mmol) and benzyl bromide (0.
110 ml (0.92 mmol) gave the title compound (127 mg, 40%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.30 (s, 3H), 5.5
2 (s, 2H), 6.14 (s, 2H), 6.85 (s, 1H), 7.05
(d, J = 8.1Hz, 1H), 7.18-7.38 (m, 5H), 7.48 (
d, J = 1.7Hz, 1H), 7.63 (dd, J = 1.7, 8.1Hz, 1H
), 7.88 (d, J = 1.4 Hz, 1H), 8.01 (d, J = 1.4 Hz,
1H), 13.45 (brs, 1H).

Example 136 2- [2- (1,3-benzodioxol-5-yl)
-2-oxoethylidene] -7-methyl-4- [2-
(4-pyridyl) ethyl] -1,4-dihydro-2H-
Pyrido [2,3-b] pyrazin-3-one (compound 13
6) In the same manner as in Example 127, 2- [2- (1,3-benzodioxol-5-yl) -2-oxoethylidene] -7-methyl-1, obtained in Reference Example 50. 4-
Dihydro-2H-pyrido [2,3-b] pyrazine-3-
On (250 mg, 0.773 mmol) and 4- (2-hydroxyethyl) pyridine (0.130 ml, 1.16 mmol) gave the title compound (172 mg, 52%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.32 (s, 3H), 3.0
0 (t, J = 7.4 Hz, 2H), 4.56 (t, J = 7.4 Hz, 2H),
6.15 (s, 2H), 6.82 (s, 1H), 7.06 (d, J = 8.1H
z, 1H), 7.28 (d, J = 6.9 Hz, 2H), 7.47 (d, J =
1.8Hz, 1H), 7.63 (dd, J = 1.8, 8.1Hz, 1H), 7.86
(brs, 1H), 8.05 (brs, 1H), 8.47 (d, J = 6.9H
z, 2H), 13.42 (s, 1H).

Example 137 4-Benzyl-2- [2- (1-methylpyrrole-2-)
Yl) -2-oxoethylidene] -7-piperidinocarbonyl-1,4-dihydro-2H-pyrido [2,3-
b] Pyrazin-3-one (compound 137) 2- [2- (1-methylpyrrol-2-yl) -2- obtained in Reference Example 51 in the same manner as in Example 12.
Oxoethylidene] -7-piperidinocarbonyl-1,
4-dihydro-2H-pyrido [2,3-b] pyrazine-
From the 3-one (250 mg, 0.659 mmol) and benzyl bromide (0.0940 ml, 0.789 mmol), the title compound (247 mg, 80
%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.44-1.70 (m, 6H
), 3.40-3.68 (m, 4H), 3.98 (s, 3H), 5.50 (s,
2H), 6.16 (dd, J = 2.4, 3.9 Hz, 1H), 6.71 (s, 1H
), 7.05 (dd, J = 1.7, 3.9 Hz, 1H), 7.15 (dd, J
= 1.7, 2.4Hz, 1H), 7.19-7.41 (m, 5H), 8.07 (d,
J = 1.3Hz, 1H), 8.09 (d, J = 1.3Hz, 1H), 12.74
(brs, 1H).

Example 138 4-Allyl-2- [2- (1-methylpyrrol-2-yl) -2-oxoethylidene] -7-piperidinocarbonyl-1,4-dihydro-2H-pyrido [2 , 3-b]
Pyrazin-3-one (Compound 138) 2- [2- (1-Methylpyrrol-2-yl) -2- obtained in Reference Example 51 by a method similar to that in Example 12.
Oxoethylidene] -7-piperidinocarbonyl-1,
4-dihydro-2H-pyrido [2,3-b] pyrazine-
From the 3-one (250 mg, 0.659 mmol) and allyl bromide (0.0680 ml, 0.789 mmol), the title compound (196 mg, 71
%). ^{1 H-NMR (DMSO-d} 6) δ (ppm): 1.44-1.73 (m, 8H
), 3.22-3.75 (m, 2H), 3.98 (s, 3H), 4.86-4.94
(m, 2H), 5.09-5.20 (m, 2H), 5.87-6.02 (m, 1H
), 6.16 (dd, J = 2.5, 4.2Hz, 1H), 6.69 (s, 1H
), 7.03 (dd, J = 1.8, 4.2Hz, 1H), 7.15 (dd, J =
1.8, 2.5Hz, 1H), 8.03 (d, J = 1.8Hz, 1H), 8.08
(d, J = 1.8 Hz, 1H), 12.73 (brs, 1H).

Example 139 8- [3- (3,4-Dimethoxyphenyl) propyl]
-2-ethoxy-6- [2- (4-fluorophenyl)
-2-oxoethylidene] -5,8-dihydro-6H-
Pteridin-7-one (Compound 139) 2-ethoxy-6- [2- (4-fluorophenyl) -2-oxoethylidene] -5,8 obtained in Reference Example 52 by a method similar to that in Example 127. -Dihydro-6
H-pteridin-7-one (250 mg, 0.761 mmol) and 3- (3,4-dimethoxyphenyl) propanol (0.
210 ml (1.14 mmol) gave the title compound (237 mg, 62%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 2.64 (t, J = 7.6H
z, 3H), 1.89-2.06 (m, 2H), 2.56-2.70 (m, 2H),
3.32 (s, 3H), 3.33 (s, 3H), 4.03 (q, J = 7.6H
z, 2H), 4.23 (t, J = 7.2 Hz, 2H), 6.71 (brd, J
= 8.2Hz, 1H), 6.80 (s, 1H), 6.83 (s, 1H), 7.3
6 (dd, J = 8.8, 8.8Hz, 2H), 7.42 (brd, J = 8.2H
z, 1H), 8.06 (dd, J = 6.4, 8.8 Hz, 2H), 8.85 (
s, 1H), 13.62 (s, 1H).

Example 140 2-ethoxy-6- [2- (4-fluorophenyl)-
2-oxoethylidene] -8- [2- (2-methoxyphenyl) ethyl] -5,8-dihydro-6H-pteridin-7-one (Compound 140) In the same manner as in Example 127, refer to Reference Example 52. The obtained 2-ethoxy-6- [2- (4-fluorophenyl) -2-oxoethylidene] -5,8-dihydro-6
H-pteridin-7-one (250 mg, 0.761 mmol) and 2- (2-methoxyphenyl) ethanol (0.160 ml,
1.14 mmol) gave the title compound (128 mg, 37%). ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 1.35 (t, J = 7.1H
z, 3H), 2.98 (t, J = 6.9 Hz, 2H), 3.69 (s, 3H),
4.32 (q, J = 7.1 Hz, 2H), 4.45 (t, J = 6.9 Hz, 2
H), 6.80-6.91 (m, 2H), 6.84 (s, 1H), 7.10-7.2
1 (m, 2H), 7.36 (dd, J = 8.9, 8.9Hz, 2H), 8.06
(dd, J = 5.2, 8.9Hz, 2H), 8.84 (s, 1H), 13.62
(brs, 1H).

Example 141 4-Benzyl-6- (imidazol-1-yl) -2-
[2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H-pyrido [2,3-b]
Pyrazin-3-one (Compound 141) 6- (Imidazol-1-yl) -2- [2- (4-) obtained in Reference Example 53 in the same manner as in Example 12.
Methoxyphenyl) -2-oxoethylidene] -1,4
-Dihydro-2H-pyrido [2,3-b] pyrazine-3
-One (250 mg, 0.690 mmol) and benzyl bromide (1
The title compound (98.0 mg, 31%) was obtained from 42 mg (0.830 mmol). ¹ H-NMR (CD ₃ OD) δ (ppm): 3.90 (s, 3H), 5.65
(s, 2H), 6.99 (d, J = 8.9 Hz, 2H), 7.08 (s, 1H
), 7.17 (s, 1H), 7.27-7.37 (m, 5H), 7.49 (d,
J = 8.3Hz, 1H), 7.63 (s, 1H), 7.71 (d, J = 8.
3Hz, 1H), 8.02 (d, J = 8.9Hz, 2H), 8.28 (s, 1H
).

Example 142 4- (2-Butynyl) -6- (imidazol-1-yl) -2- [2- (4-methoxyphenyl) -2-oxoethylidene] -1,4-dihydro-2H- Pyrid [2,3-b] pyrazin-3-one (compound 142) 6- (Imidazol-1-yl) -2- [2- (4) obtained in Reference Example 53 by a method similar to that of Example 141.
-Methoxyphenyl) -2-oxoethylidene] -1,
4-dihydro-2H-pyrido [2,3-b] pyrazine-
3-one (250 mg, 0.690 mmol) and 1-bromo-2-
From butyne (110 mg, 0.830 mmol) to the title compound (82.0 mg, 2
9%). ¹ H-NMR (CD ₃ OD) δ (ppm): 1.79 (t, J = 2.5Hz,
3H), 3.91 (s, 3H), 5.14 (d, J = 2.5 Hz, 2H), 7.
00 (dd, J = 2.0, 8.9Hz, 2H), 7.07 (s, 1H), 7.19
(s, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.58 (d, J
= 8.3Hz, 1H), 7.73 (s, 1H), 8.03 (dd, J = 2.
0, 8.9Hz, 2H), 8.42 (s, 1H).

Formulation Example 1 Tablet A tablet having the following composition is prepared by a conventional method. Prescription Compound 1 20 mg Lactose 143.4 mg Potato starch 30 mg Hydroxypropylcellulose 6 mg Magnesium stearate 0.6 mg Total 200 mg

Formulation Example 2 Capsule A capsule having the following composition is prepared by a conventional method. Prescription Compound 11 20 mg Avicel 99.5 mg Magnesium stearate 0.5 mg Total 120 mg

Formulation Example 3 Injection An injection having the following composition is prepared by a conventional method. Formulation Compound 14 2 mg Purified soybean oil 200 mg Purified egg yolk lecithin 24 mg Glycerin for injection 50 mg Distilled water for injection 1.72 ml Total 2.00 ml

[0319]

Industrial Applicability According to the present invention, it is possible to provide an insulin secretagogue and an antidiabetic agent containing a condensed pyrazine derivative as an active ingredient.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat ゛ (Reference) A61K 31/55 A61K 31/55 A61P 5/50 A61P 5/50 C07D 241/44 C07D 241/44 401/04 401/04 401/06 401/06 401/12 401/12 403/04 403/04 403/10 403/10 403/12 403/12 405/12 405/12 471/04 120 471/04 120 (72) Inventor Miho Suda 343-1 Nakadokari, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture (72) Inventor Hideaki Kusaka 410-1, Narimeri, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture (72) Inventor Hiroshi Yano 343-1 Nakadori-cho, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture (72) Inventor Satoshi Nakanishi 279-241, Shioka-cho, Kohoku-ku, Yokohama-shi, Kanagawa-ken

Claims (3)

[Claims] 1. A compound of the formula (I)[Where R^1AAnd R^1BAre the same or different hydrogen, lower
Alkyl, lower alkoxy, lower alkanoyloxy,
Lower alkylthio, halogen, nitro, lower alkanoy
, Lower alkoxycarbonyl, -NR^FourR^Five(Where R^FourYou
And R^FiveAre the same or different and are hydrogen or substituted or
Represents unsubstituted lower alkyl, or R^FourAnd R^FiveIs adjacent to nitrogen
Form a substituted or unsubstituted heterocyclic group together with the atom
), -NHCOR⁶(Where R⁶Is substituted or unsubstituted
Represents lower alkyl) or -CONR ^4aR^5a(Where R^4aYou
And R^5aIs the R^FourAnd R^FiveIs synonymous with)
R is hydrogen, substituted or unsubstituted lower alkyl,
Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Represents a substituted aryl or a substituted or unsubstituted heterocyclic group.
Then X¹, X^Two, X^ThreeAnd X^FourAre the same or different CH or
Represents nitrogen, m represents 0 or 1, n represents 0 or 1, W
... V ... U represents N-C = O or N = C-N. A) When W ... V ... U is N-C = O (where m = 1 and n = 0)
Y… Z is CH-CH_TwoOr C = CH, R^TwoIs hydrogen, substitution is
Or unsubstituted lower alkyl, substituted or unsubstituted
Chloroalkyl, substituted or unsubstituted lower alkenyl,
Substituted or unsubstituted lower alkynyl, substituted or unsubstituted
Substituted aryl, substituted or unsubstituted aralkyl or
Represents a substituted or unsubstituted heterocyclic group, and B) W ... V ... U is N = C-N (where m = 0, n = 1)
Y… Z represents C = CH, R^3AAnd R^3BAre the same or different
Is hydrogen, substituted or unsubstituted lower alkyl, substituted
Or unsubstituted cycloalkyl, substituted or unsubstituted
Aryl, substituted or unsubstituted aralkyl or substituted
Represents a substituted or unsubstituted heterocyclic group, or R^{Three A}And R^3BIs adjacent
Substituted or unsubstituted complex with the nitrogen atom
Forming a cyclic group] or a condensed pyrazine derivative represented by
Insulin containing its pharmacologically acceptable salt as the active ingredient
Secretagogues. 2. A therapeutic agent for diabetes comprising the fused ring pyrazine derivative according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient. 3. The compound of formula (Ia)中 where R^1AyAnd R^1ByAre the same or different hydrogen, low
Lower alkyl, lower alkoxy, lower alkanoyl oxy
Si, lower alkylthio, halogen, nitro, lower alk
Noil, -NR^4yR^5y(Where R^4yAnd R^5yAre the same or
Differently, hydrogen or substituted or unsubstituted lower alkyl
Or R^4yAnd R^5yTogether with the adjacent nitrogen atom
To form a substituted or unsubstituted heterocyclic group), -NHCO
R^6y(Where R ^6yRepresents a substituted or unsubstituted lower alkyl
Represents) or -CONR^4ayR^5ay(Where R ^4ayAnd R^5ayIs
Each of the above R^4yAnd R^5yIs synonymous with) and my is
Represents 0 or 1, ny represents 0 or 1, W^y… V^y… U^yIs N-
C = O or N = C-N, A) W^y… V^y… U^yIs N-C = O (my = 1 and ny = 0 at this time)
When I) X^1y, X^2y, X^3yAnd X^4yAll represent CH, and R^yBut
Substituted or unsubstituted lower alkyl, substituted or unsubstituted
Substituted cycloalkyl, substituted or unsubstituted aryl,
Or a substituted or unsubstituted heterocyclic group,^y… Z^y
Is CH-CH_TwoOr C = CH, I-a) Y^y… Z^yIs CH-CH_TwoWhen, R^2yIs substituted or unsubstituted
Lower alkyl, substituted or unsubstituted cycloalkyl
, Substituted or unsubstituted lower alkenyl, substituted or unsubstituted
Is unsubstituted lower alkynyl, substituted or unsubstituted ant
Aralkyl or substituted or unsubstituted aralkyl or substituted
Or unsubstituted heterocyclic group, I-b) Y^y… Z^yIs C = CH, then R^2yIs substituted or unsubstituted
Cycloalkyl, substituted or unsubstituted lower alkenyl
, Substituted or unsubstituted lower alkynyl, substituted or unsubstituted
Is unsubstituted aralkyl, substituted or unsubstituted heterocycle
Group, lower alkyl [the lower alkyl is substituted or unsubstituted
Substituted cycloalkyl, substituted or unsubstituted lower alkyl
Coxy, halogen, cyano, nitro, substituted or unsubstituted
Substituted lower alkoxycarbonyl, substituted or unsubstituted
Lower alkanoyloxy, carboxy, substituted or unsubstituted
A substituted heterocyclic group, -NR^7yR^8y(Where R^7yAnd R^8yIs the same
One or different hydrogen, substituted or unsubstituted lower
Alkyl or substituted or unsubstituted cycloalkyl
Or R^7yAnd R^8yIs replaced together with the adjacent nitrogen atom
Or forming an unsubstituted heterocyclic group) and -CONR^9y
R^10y(Where R^9yAnd R^{Ten y}Are the same or different, water
Represents an alkyl or a substituted or unsubstituted lower alkyl,
R^9yAnd R^10yIs substituted together with the adjacent nitrogen atom.
Or an unsubstituted heterocyclic group).
Or differently substituted with 1-3 substituents] or
Non-hydroxy-substituted lower alkyl
The lower alkyl moiety of the lower alkyl may be substituted or unsubstituted.
Substituted cycloalkyl, substituted or unsubstituted lower alcohol
Xy, halogen, cyano, nitro, substituted or unsubstituted
Lower alkoxycarbonyl, substituted or unsubstituted lower
Higher alkanoyloxy, carboxy, substituted or unsubstituted
A substituted heterocyclic group, -NR^7yR^8y(Where R^7yAnd R^8yIs it
And -CONR, respectively.^9yR^10y(Where R
^9yAnd R^10yIs as defined above)
The same or different, and may be substituted with 0 to 2 substituents.
II) X^1y, X^2y, X^3yAnd X^4yOf which X^1yOr X^4yOne
When nitrogen is the other and CH represents the other,^y… Z^yIs CH-CH_TwoMa
Or C = CH, II-a) Y^y… Z^yIs CH-CH_TwoAnd R^yIs replaced or non-
Substituted lower alkyl, substituted or unsubstituted cycloal
Killed, substituted or unsubstituted aryl or substituted or unsubstituted
Represents an unsubstituted heterocyclic group;^2yIs replaced or non-
Substituted lower alkyl, substituted or unsubstituted cycloal
Killed, substituted or unsubstituted lower alkenyl,
Or unsubstituted lower alkynyl, substituted or unsubstituted
Reel, substituted or unsubstituted aralkyl or substituted
Or an unsubstituted heterocyclic group, II-b1) Y^y… Z^yRepresents C = CH, and R^yIs substituted lower alkyl
, Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Is unsubstituted aryl or substituted or unsubstituted heterocycle
When representing a group, R^2yIs a substituted or unsubstituted lower alkyl
, Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Is unsubstituted lower alkenyl, substituted or unsubstituted lower
Alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted
Or unsubstituted aralkyl or substituted or unsubstituted
II-b2) Y^y… Z^yRepresents C = CH, and R^yIs unsubstituted lower al
When representing a kill, R^2yIs substituted lower alkyl, substituted or
Is unsubstituted cycloalkyl, substituted or unsubstituted lower
Alkenyl, substituted or unsubstituted lower alkynyl, substituted
Substituted or unsubstituted aryl, substituted or unsubstituted aryl
Aralkyl or a substituted or unsubstituted heterocyclic group, III) X^1y, X^2y, X^3yAnd X^4yOf which X^2yOr X^3yOne
When nitrogen is the other and CH represents the other, or X^1y, X^2y, X
^3yAnd X^4yAt least two of which are nitrogen
Others represent Y when representing CH^y… Z^yIs CH-CH_TwoOr C = CH, R^y
Is substituted or unsubstituted lower alkyl, substituted or unsubstituted
Substituted cycloalkyl, substituted or unsubstituted aryl
Or a substituted or unsubstituted heterocyclic group,^2yIs
Substituted or unsubstituted lower alkyl, substituted or unsubstituted
Cycloalkyl, substituted or unsubstituted lower alkenyl
, Substituted or unsubstituted lower alkynyl, substituted or unsubstituted
Is unsubstituted aryl, substituted or unsubstituted aralkyl
Or a substituted or unsubstituted heterocyclic group;^y… V^y… U^yIs N = C-N (where my = 0 and ny = 1)
Then X^1y, X^2y, X^3yAnd X^4yAre the same or different
Represents CH or nitrogen, R^yIs a substituted or unsubstituted lower
Alkyl, substituted or unsubstituted cycloalkyl, also substituted
Or unsubstituted aryl or substituted or unsubstituted
Represents a ring group, Y^y… Z^yRepresents C = CH, and R^3AyAnd R^3ByIs
Same or different, substituted or unsubstituted lower alkyl
, Substituted or unsubstituted cycloalkyl, substituted or unsubstituted
Is unsubstituted aryl, substituted or unsubstituted aralkyl
Or a substituted or unsubstituted heterocyclic group, or R^3AyWhen
R^3ByIs substituted or unsubstituted together with the adjacent nitrogen atom.
Condensed pyrazine derivative represented by｝ forming a substituted heterocyclic group
Conductor or a pharmacologically acceptable salt thereof.