JPH08239366A

JPH08239366A - New parabanic acid derivative

Info

Publication number: JPH08239366A
Application number: JP34915395A
Authority: JP
Inventors: Takayuki Kotani; 孝行小谷; Kaoru Okamoto; 馨岡本; Yasuhiro Nagaki; 康弘永木
Original assignee: Nippon Zoki Pharmaceutical Co Ltd
Current assignee: Nippon Zoki Pharmaceutical Co Ltd
Priority date: 1994-12-20
Filing date: 1995-12-19
Publication date: 1996-09-17

Abstract

PURPOSE: To obtain a new compound having excellent aldose reductaseinhibiting action and high oxygen selectivity, useful as a treating and preventing agent for diabetic complication and having low toxicity and high safety. CONSTITUTION: This compound is expressed by formula I [R is H, a lower alkyl or benzyl; Xis cyano, carboxy, carbamoyl, etc.; (n) is 1-3], e.g. 3-[2-(5- trifluoromethylbenzothiazolyl)methyl]-2,4,5-trioxoimidazolidine-1-acetic acid ethylester. The compound is obtained by carrying out condensation reaction of a compound of formula II with a compound of the formula, X-CH2 -R1 (R1 is OH, a halogen, a lower alkyl-So2 -0 group, etc.), further, as necessary, hydrolyzing the resultant product. The condensation reaction can e.g. be carried out in an inert solvent such as ethanol in the presence of an alkali.

Description

Detailed Description of the Invention

【０００１】[0001]

【発明の属する技術分野】本発明は新規パラバン酸誘導
体及びその薬学的に許容される塩並びに該化合物を有効
成分として含有する医薬組成物に関する。TECHNICAL FIELD The present invention relates to a novel parabanic acid derivative, a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the compound as an active ingredient.

【０００２】[0002]

【従来の技術】糖尿病に伴う難治性慢性疾患として、糖
尿病性神経障害、糖尿病性白内障及び糖尿病性網膜症、
糖尿病性腎症、糖尿病性皮膚障害等の糖尿病性細小血管
症などが知られているが、これら糖尿病合併症の成因と
してポリオール代謝系の関与を挙げることができる。2. Description of the Related Art As intractable chronic diseases associated with diabetes, diabetic neuropathy, diabetic cataract and diabetic retinopathy,
Although diabetic microangiopathy such as diabetic nephropathy and diabetic skin disorder are known, the involvement of the polyol metabolism system can be mentioned as a cause of these diabetic complications.

【０００３】即ち、糖尿病で高血糖状態になると、ポリ
オール代謝経路を介するグルコース利用が正常状態の数
倍にもなりアルドース還元酵素によるソルビトール産生
が亢進されるため、末梢神経、網膜、腎、水晶体、動脈
等における細胞内ソルビトールの過剰蓄積が生じ、細胞
内浸透圧の異常による細胞浮腫や機能障害が引き起こさ
れると考えられている。従って、アルドース還元酵素の
阻害剤が糖尿病合併症に対する治療及び予防に有効と考
えられ研究されている。That is, when diabetes leads to a hyperglycemic state, glucose utilization via the polyol metabolic pathway is several times higher than in the normal state, and sorbitol production by aldose reductase is enhanced, so that peripheral nerves, retina, kidney, lens, It is considered that excessive accumulation of intracellular sorbitol occurs in arteries and the like, which causes cellular edema and dysfunction due to abnormal intracellular osmotic pressure. Therefore, inhibitors of aldose reductase are considered to be effective in the treatment and prevention of diabetic complications and are being studied.

【０００４】[0004]

【発明が解決しようとする課題】しかしながら、従来の
アルドース還元酵素阻害剤はポリオール代謝経路に関与
しない酵素、例えばアルデヒド還元酵素をも強く阻害し
てしまうといった問題点を有していた。However, the conventional aldose reductase inhibitors have a problem that they also strongly inhibit enzymes not involved in the polyol metabolic pathway, such as aldehyde reductase.

【０００５】そこで本発明者等は、上述の糖尿病合併症
を治療及び予防することを目的として、ソルビトールの
産生に関与するアルドース還元酵素に対して酵素選択性
の高い阻害剤について研究した結果、本発明パラバン酸
誘導体がアルドース還元酵素に対して酵素選択性が高い
優れた阻害作用を有することを見い出し本発明を完成し
た。[0007] Therefore, the present inventors have studied an inhibitor having a high enzyme selectivity for aldose reductase involved in the production of sorbitol for the purpose of treating and preventing the above-mentioned diabetic complications. Invention The inventors have found that the parabanic acid derivative has an excellent inhibitory action against aldose reductase with high enzyme selectivity and completed the present invention.

【０００６】[0006]

【課題を解決するための手段】本発明の目的は、アルド
ース還元酵素に対して酵素選択性が高く且つ優れた阻害
作用を有する新規パラバン酸誘導体及びその薬学的に許
容される塩並びに該化合物を有効成分として含有する糖
尿病合併症治療剤を提供することにある。The object of the present invention is to provide a novel parabanic acid derivative having a high enzyme selectivity for aldose reductase and an excellent inhibitory action, a pharmaceutically acceptable salt thereof, and the compound. It is intended to provide a therapeutic agent for diabetic complications, which is contained as an active ingredient.

【０００７】[0007]

【発明の実施の形態】本発明パラバン酸誘導体は下記一
般式（Ｉ）で表される化合物である。BEST MODE FOR CARRYING OUT THE INVENTION The parabanic acid derivative of the present invention is a compound represented by the following general formula (I).

【化６】〔式中、Ｒは水素、低級アルキル基又はベンジル基を表
し、Ｘはトリフルオロメチル基、シアノ基、カルボキシ
基、カルバモイル基、低級アルコキシカルボニル基又は
ニトロ基及びハロゲンで置換されているフェニル基、低
級アルキル基、低級アルコキシ基、トリフルオロメチル
基、ニトロ基及び／又はハロゲンで置換されていてもよ
いベンゾチアゾリル基、ニトロ基及び／又はハロゲンで
置換されていてもよいナフチル基若しくはピリジル基、
アントラキノニル基、フタルイミド基又はチエニル基を
表し、ｎは１乃至３の整数である。〕[Chemical 6] [Wherein, R represents hydrogen, a lower alkyl group or a benzyl group, X represents a trifluoromethyl group, a cyano group, a carboxy group, a carbamoyl group, a lower alkoxycarbonyl group or a nitro group and a phenyl group substituted with a halogen, Lower alkyl group, lower alkoxy group, trifluoromethyl group, nitro group and / or benzothiazolyl group optionally substituted with halogen, nitro group and / or naphthyl group or pyridyl group optionally substituted with halogen,
It represents an anthraquinonyl group, a phthalimido group or a thienyl group, and n is an integer of 1 to 3. ]

【０００８】本発明パラバン酸誘導体は、例えば以下の
方法により製造することができる。反応を阻害しないエ
タノール、アセトン、Ｎ，Ｎ−ジメチルホルムアミド等
の反応を阻害しない適当な溶媒中、水酸化カリウム、炭
酸水素カリウム、水素化ナトリウム等のアルカリの存在
下、一般式（II）：The parabanic acid derivative of the present invention can be produced, for example, by the following method. In the presence of an alkali such as potassium hydroxide, potassium hydrogen carbonate or sodium hydride in a suitable solvent which does not inhibit the reaction such as ethanol, acetone, N, N-dimethylformamide or the like which does not inhibit the reaction, the general formula (II):

【化７】〔式中、Ｒは水素又は低級アルキル基を表し、ｎは１乃
至３の整数である。〕で表される化合物と一般式(II
I）：[Chemical 7] [In the formula, R represents hydrogen or a lower alkyl group, and n is an integer of 1 to 3. ] And a compound represented by the general formula (II
I):

【化８】〔式中、Ｘはトリフルオロメチル基、シアノ基、カルボ
キシ基、カルバモイル基、低級アルコキシカルボニル基
又はニトロ基及びハロゲンで置換されているフェニル
基、低級アルキル基、低級アルコキシ基、トリフルオロ
メチル基、ニトロ基及び／又はハロゲンで置換されてい
てもよいベンゾチアゾリル基、ニトロ基及び／又はハロ
ゲンで置換されていてもよいナフチル基若しくはピリジ
ル基、アントラキノニル基、フタルイミド基又はチエニ
ル基を表し、Ｒ₁は水酸基、ハロゲン、低級アルキル−
ＳＯ₂−Ｏ−基又は低級アルキル基で置換されていても
よいフェニル−ＳＯ₂−Ｏ−基を表す。〕で表される化
合物とを縮合反応させることにより、一般式（Ｉ）で表
されるパラバン酸誘導体を得ることができる。反応はア
ルカリ等の種類などによって室温で攪拌するか若しくは
適宜還流して行うことができる。一般式（II）において
Ｒが低級アルキル基又はベンジル基である化合物の場合
は、上記反応終了後、例えば酢酸と濃塩酸の混合液に溶
解し加熱還流する等の通常の酸加水分解によってＲが水
素である一般式（Ｉ）で表される化合物を製造すること
ができる。Ｒが低級アルキル基である一般式（II）の化
合物を用いた場合は、副反応が起こりにくいためより好
ましい製造方法を提供可能である。Embedded image [In the formula, X is a trifluoromethyl group, a cyano group, a carboxy group, a carbamoyl group, a lower alkoxycarbonyl group or a nitro group and a phenyl group substituted with a halogen, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, A benzothiazolyl group optionally substituted with a nitro group and / or a halogen, a naphthyl group or a pyridyl group optionally substituted with a nitro group and / or a halogen, an anthraquinonyl group, a phthalimido group or a thienyl group, and R ₁ represents a hydroxyl group , Halogen, lower alkyl-
Be substituted with SO ₂ -O- group or a lower alkyl group represents a phenyl -SO ₂ -O- group. ] The paravanic acid derivative represented by the general formula (I) can be obtained by subjecting the compound represented by the formula to a condensation reaction. The reaction can be carried out at room temperature with stirring or with appropriate reflux, depending on the type of alkali and the like. In the case where R is a lower alkyl group or a benzyl group in the general formula (II), after completion of the above reaction, R is dissolved by ordinary acid hydrolysis such as dissolution in a mixed solution of acetic acid and concentrated hydrochloric acid and heating under reflux. Compounds of general formula (I) which are hydrogen can be prepared. When the compound of the general formula (II) in which R is a lower alkyl group is used, a side reaction is unlikely to occur, so that a more preferable production method can be provided.

【０００９】上記一般式（Ｉ）及び一般式（II）におい
て、Ｒは水素、低級アルキル基、好ましくはメチル、エ
チル、プロピル、イソプロピル、ブチル、イソブチル、
ｓｅｃ−ブチル、ｔｅｒｔ−ブチル等の直鎖又は分岐状
の炭素数１乃至４のアルキル基、又はベンジル基を表
し、ｎは１乃至３の整数であり、好ましくはｎは１を表
す。In the above general formulas (I) and (II), R is hydrogen, a lower alkyl group, preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
It represents a linear or branched alkyl group having 1 to 4 carbon atoms such as sec-butyl or tert-butyl, or a benzyl group, n is an integer of 1 to 3, and n is preferably 1.

【００１０】上記一般式（Ｉ）及び一般式(III) におい
て、Ｘはトリフルオロメチル基、シアノ基、カルボキシ
基、カルバモイル基、メトキシカルボニル、エトキシカ
ルボニル、プロポキシカルボニル、イソプロポキシカル
ボニル等の直鎖又は分岐状の炭素数１乃至３のアルコキ
シカルボニル基又はニトロ基及び弗素、塩素、臭素、沃
素等のハロゲン置換されているフェニル基、メチル、エ
チル、プロピル、イソプロピル等の直鎖又は分岐状の炭
素数１乃至３のアルキル基、メトキシ、エトキシ、プロ
ポキシ、イソプロポキシ等の直鎖又は分岐状の炭素数１
乃至３のアルコキシ基、トリフルオロメチル基、ニトロ
基及び／又はは弗素、塩素、臭素、沃素等のハロゲンで
置換されていてもよいベンゾチアゾリル基、弗素、塩
素、臭素、沃素等のハロゲンで置換されていてもよいナ
フチル基若しくはピリジル基、アントラキノニル基、フ
タルイミド基又はチエニル基を表す。In the above general formulas (I) and (III), X is a straight chain such as trifluoromethyl group, cyano group, carboxy group, carbamoyl group, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl or the like. A branched alkoxycarbonyl group having 1 to 3 carbon atoms or a nitro group, a halogen-substituted phenyl group such as fluorine, chlorine, bromine and iodine, and a linear or branched carbon number such as methyl, ethyl, propyl and isopropyl. 1 to 3 alkyl group, linear or branched carbon number 1 such as methoxy, ethoxy, propoxy and isopropoxy
3 to 3 alkoxy group, trifluoromethyl group, nitro group and / or benzothiazolyl group which may be substituted with halogen such as fluorine, chlorine, bromine and iodine, and halogen such as fluorine, chlorine, bromine and iodine. Optionally represents a naphthyl group, a pyridyl group, an anthraquinonyl group, a phthalimido group or a thienyl group.

【００１１】また上記一般式(III）において、Ｒ₁は水
酸基、弗素、塩素、臭素、沃素等のハロゲン、メチル、
エチル、プロピル、イソプロピル等の直鎖又は分岐状の
炭素数１乃至３のアルキル−ＳＯ₂−Ｏ−基又はメチ
ル、エチル、プロピル、イソプロピル等の直鎖又は分岐
状の炭素数１乃至３のアルキル基で置換されていてもよ
いフェニル−ＳＯ₂−Ｏ−基を表す。In the above general formula (III), R ₁ is a hydroxyl group, halogen such as fluorine, chlorine, bromine or iodine, methyl,
Ethyl, propyl, straight-chain or branched alkyl -SO ₂ -O- group or a methyl from 1 to 3 carbon atoms, ethyl, propyl, straight or branched alkyl of 1 to 3 carbon atoms isopropyl such as isopropyl, etc. Represents a phenyl-SO ₂ —O— group which may be substituted with a group.

【００１２】本発明パラバン酸誘導体は、前記一般式
（Ｉ）で表される化合物の薬学的に許容しうる塩を包含
し、例えば、ナトリウム、カリウム等のアルカリ金属、
カルシウム、マグネシウム等のアルカリ土類金属、又は
アルミニウム等の金属との塩、或いはアンモニア、有機
アミン等の塩基類との塩を挙げることができる。The parabanic acid derivative of the present invention includes a pharmaceutically acceptable salt of the compound represented by the above general formula (I), for example, an alkali metal such as sodium or potassium,
Examples thereof include salts with alkaline earth metals such as calcium and magnesium, metals with aluminum and the like, and salts with bases such as ammonia and organic amines.

【００１３】これらの塩は公知の方法により、遊離の本
発明パラバン酸誘導体より製造でき或いは相互に変換で
きる。又、本発明物質においてシス−トランス異性体、
光学異性体、配座異性体等の立体異性体が存在する場合
には、本発明はそのいずれをも包含する。These salts can be prepared from the free parabanic acid derivative of the present invention or converted into each other by known methods. Further, in the substance of the present invention, cis-trans isomer
The present invention includes any stereoisomers such as optical isomers and conformational isomers.

【００１４】本発明化合物は、適当な医薬用の担体若し
くは希釈剤と組み合わせて医薬とすることができ、通常
の如何なる方法によっても製剤化でき、経口又は非経口
投与するための固体、半固体、液体又は気体の剤形に処
方することができる。処方にあたっては、本発明化合物
をその薬学的に許容しうる塩の形で用いてもよく、本発
明化合物を単独で若しくは適宜組み合わせて用いること
ができ、又、他の医薬活性成分との配合剤としてもよ
い。The compound of the present invention can be made into a medicine by combining with a suitable medicinal carrier or diluent, and can be formulated by any ordinary method. It can be solid, semisolid, for oral or parenteral administration, It can be formulated in liquid or gas dosage forms. In formulating, the compound of the present invention may be used in the form of a pharmaceutically acceptable salt thereof, the compound of the present invention can be used alone or in an appropriate combination, or a combination with another pharmaceutically active ingredient. It may be.

【００１５】経口投与剤としては、そのまま或いは適当
な添加剤、例えば乳糖、マンニット、トウモロコシデン
プン、バレイショデンプン等の慣用の賦形剤と共に、結
晶セルロース、セルロース誘導体、アラビアゴム、トウ
モロコシデンプン、ゼラチン等の結合剤、トウモロコシ
デンプン、バレイショデンプン、カルボキシメチルセル
ロースカリウム等の崩壊剤、タルク、ステアリン酸マグ
ネシウム等の滑沢剤、その他の増量剤、湿潤化剤、緩衝
剤、保存剤、香料等を適宜組み合わせて錠剤、散剤、顆
粒剤或いはカプセル剤とすることができる。As an orally-administered agent, as it is or together with a suitable additive such as lactose, mannitol, corn starch, potato starch and other conventional excipients, crystalline cellulose, cellulose derivative, gum arabic, corn starch, gelatin, etc. Binders, corn starch, potato starch, disintegrating agents such as potassium carboxymethyl cellulose, talc, lubricants such as magnesium stearate, other extenders, wetting agents, buffers, preservatives, perfumes and the like are appropriately combined. It can be tablets, powders, granules or capsules.

【００１６】さらに本発明化合物は、各種基剤、例えば
カカオ脂等の油脂性基剤、乳剤性基剤又はマクロゴール
等の水溶性基剤、親水性基剤等と混和して坐剤としても
よい。Further, the compound of the present invention can be mixed with various bases such as oleaginous bases such as cocoa butter, emulsion bases or water-soluble bases such as macrogol, hydrophilic bases and the like to form suppositories. Good.

【００１７】注射剤としては水性溶剤又は非水性溶剤、
例えば注射用蒸溜水、生理食塩水、リンゲル液、植物
油、合成脂肪酸グリセリド、高級脂肪酸エステル、プロ
ピレングリコール等の溶液若しくは懸濁液とすることが
できる。As an injection, an aqueous solvent or a non-aqueous solvent,
For example, it may be a solution or suspension of distilled water for injection, physiological saline, Ringer's solution, vegetable oil, synthetic fatty acid glyceride, higher fatty acid ester, propylene glycol or the like.

【００１８】吸入剤、エアゾール剤として使用するに
は、本発明化合物を溶液、懸濁液又は微小粉体の形で、
気体又は液体噴射剤と共に、且つ所望により湿潤剤又は
分散剤のような通常の補薬と共にエアゾール容器内に充
填する。本発明化合物は、ネブライザー又はアトマイザ
ーのような非加圧型の剤形にしてもよい。For use as an inhalant or an aerosol, the compound of the present invention is in the form of a solution, suspension or fine powder,
Fill in aerosol containers with a gas or liquid propellant and, if desired, conventional auxiliaries such as wetting or dispersing agents. The compound of the present invention may be in a non-pressurized dosage form such as a nebulizer or an atomizer.

【００１９】点眼剤として製剤化するには、滅菌精製
水、生理食塩水等の水性溶剤又は注射用非水性溶剤を用
いて、溶液若しくは懸濁液とすることができ、繁用され
ている保存剤、防腐剤、殺菌剤等を適宜添加することも
できる。For formulation as an eye drop, a solution or suspension can be prepared by using an aqueous solvent such as sterile purified water, physiological saline or the like or a non-aqueous solvent for injection, which is commonly used for preservation. Agents, preservatives, bactericides and the like can be added as appropriate.

【００２０】又、疾患の種類に応じて、その治療に最適
な上記以外の剤形、例えば、軟膏、パップ剤等に製剤化
することが可能である。Further, depending on the type of disease, it is possible to formulate into a dosage form other than the above-mentioned one which is most suitable for the treatment, such as an ointment or a poultice.

【００２１】本発明化合物の望ましい投与量は、投与対
象、剤形、投与方法、投与期間等によって変わるが、所
望の効果を得るには、一般に成人に対して一日に本発明
化合物を１０乃至３，０００ｍｇ、好ましくは２０乃至
１，５００ｍｇ経口投与することができる。非経口投与
（例えば注射剤）の場合、一日投与量は、前記投与量の
３乃至１０分の１の用量レベルのものが好ましい。The desired dose of the compound of the present invention varies depending on the administration subject, dosage form, administration method, administration period and the like, but in order to obtain the desired effect, generally 10 to 10 days of administration of the compound of the present invention to an adult. Oral administration can be performed at 3,000 mg, preferably 20 to 1,500 mg. In the case of parenteral administration (for example, injection), the daily dose is preferably at a dose level of 3 to 1/10 of the above dose.

【００２２】[0022]

【実施例】製造された本発明化合物は、蒸溜、クロマト
グラフィー、再結晶等の通常の手段により精製し、元素
分析、融点測定、ＩＲ、ＮＭＲ、ＭＳ等により同定を行
った。以下に、実施例により本発明化合物の製造方法の
一例を示す。EXAMPLE The produced compound of the present invention was purified by a conventional means such as distillation, chromatography, recrystallization and the like, and identified by elemental analysis, melting point measurement, IR, NMR, MS and the like. An example of a method for producing the compound of the present invention will be shown below by Examples.

【００２３】実施例１．１０ｍＬのＮ，Ｎ−ジメチルホ
ルムアミドに０．８９ｇの水素化ナトリウムを懸濁さ
せ、３．５３ｇの２，４，５−トリオキソイミダゾリジ
ン−１−酢酸エチルを溶かした５０ｍＬのＮ，Ｎ−ジメ
チルホルムアミド溶液を０℃以下にて攪拌しながら滴下
した後、室温で１時間攪拌した。反応混合物に３．７８
ｇの２−ブロモメチル−５−トリフルオロメチルベンゾ
チアゾールを溶かした４０ｍＬのＮ，Ｎ−ジメチルホル
ムアミド溶液を０℃以下にて加え、さらに２時間攪拌し
た。この反応溶液を氷冷した希塩酸に加え、固化するま
で攪拌した。固形物を濾取し水洗した後、さらにヘキサ
ンで洗浄し、エタノールより再結晶して、３−〔２−
（５−トリフルオロメチルベンゾチアゾリル）メチル〕
−２，４，５−トリオキソイミダゾリジン−１−酢酸エ
チル〔化合物１〕を得た。融点: 150.0-151.0 ℃ IR(KBr): 3001, 1742(C=O), 1430, 1333, 1234, 1115
cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.22(t,J=7.1Hz,3H,CH₃), 4.19
(q,J=7.1Hz,2H,OCH₂), 4.49(s,2H,NCH₂CO₂), 5.33(s,2
H,CH₂Ar), 7.80(d,J=8.4Hz,1H,Ar), 8.35(s,1H,Ar),8.4
0(d,J=8.4Hz,1H,Ar)Example 1 0.89 g of sodium hydride was suspended in 10 mL of N, N-dimethylformamide, and 3.53 g of 2,4,5-trioxoimidazolidine-1-ethyl acetate was dissolved. 50 mL of N, N-dimethylformamide solution was added dropwise with stirring at 0 ° C or lower, and then stirred at room temperature for 1 hour. 3.78 to the reaction mixture
40 mL of N, N-dimethylformamide solution in which g of 2-bromomethyl-5-trifluoromethylbenzothiazole was dissolved was added at 0 ° C or lower, and the mixture was further stirred for 2 hours. This reaction solution was added to ice-cooled dilute hydrochloric acid and stirred until solidified. The solid matter was collected by filtration, washed with water, further washed with hexane, and recrystallized from ethanol to give 3- [2-
(5-Trifluoromethylbenzothiazolyl) methyl]
Ethyl-2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 1] was obtained. Melting point: 150.0-151.0 ℃ IR (KBr): 3001, 1742 (C = O), 1430, 1333, 1234, 1115
cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.22 (t, J = 7.1Hz, 3H, CH ₃ ), 4.19
(q, J = 7.1Hz, 2H, OCH ₂ ), 4.49 (s, 2H, NCH ₂ CO ₂ ), 5.33 (s, 2
H, CH ₂ Ar), 7.80 (d, J = 8.4Hz, 1H, Ar), 8.35 (s, 1H, Ar), 8.4
0 (d, J = 8.4Hz, 1H, Ar)

【００２４】実施例１と同様の方法で以下の化合物が得
られた。３−（３−ピリジルメチル）−２，４，５−トリオキソ
イミダゾリジン−１−酢酸エチル〔化合物２〕融点: 112.0-113.0 ℃ IR(KBr): 1730(C=O), 1450, 1425, 1230, 1145 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.20(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.39(s,2H,NCH₂CO₂), 4.79(s,2
H,CH₂N), 7.38(dd,J=8.0,4.5Hz,1H,Ar), 7.75(ddd,J=8.
0,2.0,1.5Hz,1H,Ar), 8.51(dd,J=4.5,1.5Hz,1H,Ar), 8.
57(d,J=2.0Hz,1H,Ar)The following compounds were obtained in the same manner as in Example 1. 3- (3-Pyridylmethyl) -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 2] Melting point: 112.0-113.0 ° C IR (KBr): 1730 (C = O), 1450, 1425, 1230, 1145 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.20 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.39 (s, 2H, NCH ₂ CO ₂ ), 4.79 (s, 2
H, CH ₂ N), 7.38 (dd, J = 8.0,4.5Hz, 1H, Ar), 7.75 (ddd, J = 8.
0,2.0,1.5Hz, 1H, Ar), 8.51 (dd, J = 4.5,1.5Hz, 1H, Ar), 8.
57 (d, J = 2.0Hz, 1H, Ar)

【００２５】３−（４−ピリジルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸エチル〔化合物
３〕融点: 92.0- 94.0 ℃（分解） IR(KBr): 1740(C=O), 1720(C=O), 1520, 1440, 1400, 1
230, 1140 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.42(s,2H,NCH₂CO₂), 4.80(s,2
H,CH₂N), 7.37(d,J=5.5Hz,2H,Ar), 8.54(d,J=5.5Hz,2H,
Ar)3- (4-pyridylmethyl) -2,4,5
-Trioxoimidazolidine-1-ethyl acetate [Compound 3] Melting point: 92.0-94.0 ° C (decomposition) IR (KBr): 1740 (C = O), 1720 (C = O), 1520, 1440, 1400, 1
230, 1140 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.42 (s, 2H, NCH ₂ CO ₂ ), 4.80 (s, 2
H, CH ₂ N), 7.37 (d, J = 5.5Hz, 2H, Ar), 8.54 (d, J = 5.5Hz, 2H,
Ar)

【００２６】３−（２−チエニルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸エチル〔化合物
４〕融点: 180.5-182.5 ℃ IR(KBr): 1734(C=O), 1448, 1431, 1207, 1146, 758 cm
^-1 ¹ H-NMR (DMSO-d₆)δ: 4.42(s,2H,NCH₂CO₂), 4.86(s,2H,
CH₂N), 5.12(s,2H,OCH₂), 6.94(dd,J=5.0,3.5Hz,1H,A
r), 7.04(d,J=3.5Hz,1H,Ar), 7.29(s,5H,Ar), 7.51(d,J
=5.0Hz,1H,Ar)3- (2-thienylmethyl) -2,4,5
-Trioxoimidazolidine-1-ethyl acetate [Compound 4] Melting point: 180.5-182.5 ° C IR (KBr): 1734 (C = O), 1448, 1431, 1207, 1146, 758 cm
^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.42 (s, 2H, NCH ₂ CO ₂ ), 4.86 (s, 2H,
CH ₂ N), 5.12 (s, 2H, OCH ₂ ), 6.94 (dd, J = 5.0,3.5Hz, 1H, A
r), 7.04 (d, J = 3.5Hz, 1H, Ar), 7.29 (s, 5H, Ar), 7.51 (d, J
= 5.0Hz, 1H, Ar)

【００２７】３−〔３−（５−ブロモピリジル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸エチル〔化合物５〕融点: 137.0-139.0 ℃ IR(KBr): 1731(C=O), 1444, 1236, 1140, 1024 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.40(s,2H,NCH₂CO₂), 4.82(s,2
H,CH₂N), 8.06(dd,J=2.0,1.5Hz,1H,Ar), 8.58(d,J=1.5H
z,1H,Ar), 8.64(d,J=2.0Hz,1H,Ar)3- [3- (5-Bromopyridyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 5] Melting point: 137.0-139.0 ° C. IR (KBr): 1731 (C = O), 1444, 1236, 1140, 1024 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.40 (s, 2H, NCH ₂ CO ₂ ), 4.82 (s, 2
H, CH ₂ N), 8.06 (dd, J = 2.0,1.5Hz, 1H, Ar), 8.58 (d, J = 1.5H
z, 1H, Ar), 8.64 (d, J = 2.0Hz, 1H, Ar)

【００２８】３−〔３−（２−クロロピリジル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸エチル〔化合物６〕融点: 131.0-132.0 ℃ MS m/e: 325(M+) IR(KBr): 1736(C=O), 1425, 1238, 1151, 1074 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.42(s,2H,NCH₂CO₂), 4.81(s,2
H,CH₂N), 7.45(dd,J=7.5,4.5Hz,1H,Ar), 7.97(dd,J=7.
5,1.5Hz,1H,Ar), 8.38(dd,J=4.5,1.5Hz,1H,Ar)3- [3- (2-chloropyridyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 6] Melting point: 131.0-132.0 ° C MS m / e: 325 (M + ) IR (KBr): 1736 (C = O), 1425, 1238, 1151, 1074 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.42 (s, 2H, NCH ₂ CO ₂ ), 4.81 (s, 2
H, CH ₂ N), 7.45 (dd, J = 7.5,4.5Hz, 1H, Ar), 7.97 (dd, J = 7.
5,1.5Hz, 1H, Ar), 8.38 (dd, J = 4.5,1.5Hz, 1H, Ar)

【００２９】３−〔３−（６−クロロピリジル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸エチル〔化合物７〕融点: 81.0- 83.0 ℃ IR(KBr): 1732(C=O), 1448, 1234, 1028, 768 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.5Hz,3H,CH₃), 4.16
(q,J=7.5Hz,2H,OCH₂), 4.39(s,2H,NCH₂CO₂), 4.81(s,2
H,CH₂N), 7.53(d,J=8.0Hz,1H,Ar), 7.84(dd,J=8.0,2.5H
z,1H,Ar), 8.42(d,J=2.5Hz,1H,Ar)3- [3- (6-chloropyridyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 7] Melting point: 81.0-83.0 ° C. IR (KBr): 1732 (C = O), 1448, 1234, 1028, 768 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.5Hz, 3H, CH ₃ ), 4.16
(q, J = 7.5Hz, 2H, OCH ₂ ), 4.39 (s, 2H, NCH ₂ CO ₂ ), 4.81 (s, 2
H, CH ₂ N), 7.53 (d, J = 8.0Hz, 1H, Ar), 7.84 (dd, J = 8.0,2.5H
z, 1H, Ar), 8.42 (d, J = 2.5Hz, 1H, Ar)

【００３０】３−（２−ピリジルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸エチル〔化合物
８〕融点: 122.0-123.0 ℃ IR(KBr): 1734(C=O), 1448, 1236, 770, 513 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.55(s,2H,NCH₂CO₂), 4.88(s,2
H,CH₂N), 7.32(dd,J=7.5,4.5Hz,1H,Ar), 7.46(d,J=7.5H
z,1H,Ar), 7.81(dd,J=7.5,7.5Hz,1H,Ar), 8.50(d,J=4.5
Hz,1H,Ar)3- (2-pyridylmethyl) -2,4,5
- trioxospiro imidazolidin-1-ethyl acetate [Compound 8] mp: 122.0-123.0 ℃ IR (KBr): 1734 (C = O), 1448, 1236, 770, 513 cm -1 1 H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.55 (s, 2H, NCH ₂ CO ₂ ), 4.88 (s, 2
H, CH ₂ N), 7.32 (dd, J = 7.5,4.5Hz, 1H, Ar), 7.46 (d, J = 7.5H
z, 1H, Ar), 7.81 (dd, J = 7.5,7.5Hz, 1H, Ar), 8.50 (d, J = 4.5
Hz, 1H, Ar)

【００３１】３−（１−ナフチルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸エチル〔化合物
９〕融点: 172.0-175.0 ℃ IR(KBr): 1747(C=O), 1734(C=O), 1446, 1232, 1151, 7
97, 575 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.19(t,J=7.0Hz,3H,CH₃), 4.15
(q,J=7.0Hz,2H,OCH₂), 4.43(s,2H,NCH₂CO₂), 5.22(s,2
H,CH₂N), 7.45-7.64(m,4H,Ar), 7.91(d,J=8.6Hz,1H,A
r), 7.98(d,J=8.6Hz,1H,Ar), 8.19(d,J=8.6Hz,1H,Ar)3- (1-naphthylmethyl) -2,4,5
-Trioxoimidazolidine-1-ethyl acetate [Compound 9] Melting point: 172.0-175.0 ° C IR (KBr): 1747 (C = O), 1734 (C = O), 1446, 1232, 1151, 7
97, 575 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.19 (t, J = 7.0Hz, 3H, CH ₃ ), 4.15
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.43 (s, 2H, NCH ₂ CO ₂ ), 5.22 (s, 2
H, CH ₂ N), 7.45-7.64 (m, 4H, Ar), 7.91 (d, J = 8.6Hz, 1H, A
r), 7.98 (d, J = 8.6Hz, 1H, Ar), 8.19 (d, J = 8.6Hz, 1H, Ar)

【００３２】３−（２−ナフチルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸エチル〔化合物
１０〕融点: 149.0-150.0 ℃ IR(KBr): 1734(C=O), 1446, 1228, 1149, 766 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.19(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.43(s,2H,NCH₂CO₂), 4.92(s,2
H,CH₂N), 7.47(dd,J=8.5,1.8Hz,1H,Ar), 7.52(s,1H,A
r), 7.52(dd,J=9.5,1.8Hz,1H,Ar), 7.86-7.95(m,4H,Ar)3- (2-naphthylmethyl) -2,4,5
- trioxospiro imidazolidin-1-ethyl acetate [Compound 10] mp: 149.0-150.0 ℃ IR (KBr): 1734 (C = O), 1446, 1228, 1149, 766 cm -1 1 H-NMR (DMSO-d ₆ ) δ: 1.19 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.43 (s, 2H, NCH ₂ CO ₂ ), 4.92 (s, 2
H, CH ₂ N), 7.47 (dd, J = 8.5,1.8Hz, 1H, Ar), 7.52 (s, 1H, A
r), 7.52 (dd, J = 9.5,1.8Hz, 1H, Ar), 7.86-7.95 (m, 4H, Ar)

【００３３】３−〔２−（９，１０−アントラキノニ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物１１〕融点: 217.0-218.0 ℃ IR(KBr): 1731(C=O), 1674, 1446, 1298, 1147 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.43(s,2H,NCH₂CO₂), 4.98(s,2
H,CH₂N), 7.88-7.98(m,3H,Ar), 8.18-8.24(m,H,Ar)3- [2- (9,10-anthraquinonyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 11] Melting point: 217.0-218.0 ° C. IR (KBr): 1731 ( C = O), 1674, 1446, 1298, 1147 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.43 (s, 2H, NCH ₂ CO ₂ ), 4.98 (s, 2
H, CH ₂ N), 7.88-7.98 (m, 3H, Ar), 8.18-8.24 (m, H, Ar)

【００３４】３−（２−ベンゾチアゾリルメチル）−
２，４，５−トリオキソイミダゾリジン−１−酢酸エチ
ル〔化合物１２〕融点: 151.5-153.0 ℃ IR(KBr): 1734(C=O), 1446, 1221, 1147, 770 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.47(s,2H,NCH₂CO₂), 5.25(s,2
H,CH₂N), 7.46(ddd,J=7.7,7.7,1.2Hz,1H,Ar), 7.53(dd
d,J=7.7,7.7,1.2Hz,1H,Ar), 7.99(dd,J=7.7,1.2Hz,1H,A
r), 8.11(dd,J=7.7,1.2Hz,1H,Ar)3- (2-benzothiazolylmethyl)-
2,4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 12] Melting point: 151.5-153.0 ° C IR (KBr): 1734 (C = O), 1446, 1221, 1147, 770 cm ^-1 ¹ H- NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.47 (s, 2H, NCH ₂ CO ₂ ), 5.25 (s, 2
H, CH ₂ N), 7.46 (ddd, J = 7.7,7.7,1.2Hz, 1H, Ar), 7.53 (dd
d, J = 7.7,7.7,1.2Hz, 1H, Ar), 7.99 (dd, J = 7.7,1.2Hz, 1H, A
r), 8.11 (dd, J = 7.7,1.2Hz, 1H, Ar)

【００３５】３−（Ｎ−フタルイミドメチル）−２，
４，５−トリオキソイミダゾリジン−１−酢酸エチル
〔化合物１３〕融点: 197.0-199.0 ℃ IR(KBr): 1743(C=O), 1406, 1336, 1221, 1141, 762,
723 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.19(t,J=7.0Hz,3H,CH₃), 4.15
(q,J=7.0Hz,2H,OCH₂), 4.38(s,2H,NCH₂CO₂), 5.39(s,2
H,CH₂N), 7.82-7.96(m,4H,Ar)3- (N-phthalimidomethyl) -2,
4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 13] Melting point: 197.0-199.0 ° C IR (KBr): 1743 (C = O), 1406, 1336, 1221, 1141, 762,
723 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.19 (t, J = 7.0Hz, 3H, CH ₃ ), 4.15
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.38 (s, 2H, NCH ₂ CO ₂ ), 5.39 (s, 2
H, CH ₂ N), 7.82-7.96 (m, 4H, Ar)

【００３６】３−〔１−（２−ブロモナフチル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸エチル〔化合物１４〕融点: 184.5-185.5 ℃ IR(KBr): 1736(C=O), 1446, 1227, 1153, 771 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.44(s,2H,NCH₂CO₂), 5.04(s,2
H,CH₂N), 7.56(d,J=8.5Hz,1H,Ar), 7.64(dd,J=7.0,7.0H
z,1H,Ar), 7.72(dd,J=8.5,7.0Hz,1H,Ar), 7.95-8.05(m,
2H,Ar), 8.25(d,J=8.5Hz,1H,Ar)3- [1- (2-Bromonaphthyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 14] Melting point: 184.5-185.5 ° C. IR (KBr): 1736 (C = O), 1446, 1227, 1153, 771 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.44 (s, 2H, NCH ₂ CO ₂ ), 5.04 (s, 2
H, CH ₂ N), 7.56 (d, J = 8.5Hz, 1H, Ar), 7.64 (dd, J = 7.0,7.0H
z, 1H, Ar), 7.72 (dd, J = 8.5,7.0Hz, 1H, Ar), 7.95-8.05 (m,
2H, Ar), 8.25 (d, J = 8.5Hz, 1H, Ar)

【００３７】３−〔２−（６−ニトロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物１５〕融点: 183.0-184.0 ℃ IR(KBr): 1743(C=O), 1738(C=O), 1524(NO₂), 1444, 13
46(NO₂), 1225 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.1Hz,3H,CH₃), 4.18
(q,J=7.1Hz,2H,OCH₂), 4.48(s,2H,NCH₂CO₂), 5.34(s,2
H,CH₂Ar), 8.19(d,J=9.0Hz,1H,Ar), 8.34(dd,J=9.0,2.4
Hz,1H,Ar), 9.22(d,J=2.4Hz,1H,Ar)3- [2- (6-Nitrobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 15] Melting point: 183.0-184.0 ° C. IR (KBr): 1743 (C = O), 1738 (C = O), 1524 (NO ₂ ), 1444, 13
46 (NO ₂ ), 1225 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.1Hz, 3H, CH ₃ ), 4.18
(q, J = 7.1Hz, 2H, OCH ₂ ), 4.48 (s, 2H, NCH ₂ CO ₂ ), 5.34 (s, 2
H, CH ₂ Ar), 8.19 (d, J = 9.0Hz, 1H, Ar), 8.34 (dd, J = 9.0,2.4
Hz, 1H, Ar), 9.22 (d, J = 2.4Hz, 1H, Ar)

【００３８】３−〔２−（６−メチルベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物１６〕融点: 155.0-156.0 ℃ IR(KBr): 1738(C=O), 1443, 1402, 1234, 1147 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.1Hz,3H,CH₃), 2.44
(s,3H,CH₃), 4.18(q,J=7.1Hz,2H,OCH₂), 4.47(s,2H,NCH
₂CO₂), 5.21(s,2H,CH₂Ar), 7.34(d,J=8.2Hz,1H,Ar), 7.
86(d,J=8.2Hz,1H,Ar), 7.90(s,1H,Ar)3- [2- (6-Methylbenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 16] Melting point: 155.0-156.0 ° C. IR (KBr): 1738 (C = O), 1443, 1402, 1234, 1147 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.1Hz, 3H, CH ₃ ), 2.44
(s, 3H, CH ₃ ), 4.18 (q, J = 7.1Hz, 2H, OCH ₂ ), 4.47 (s, 2H, NCH
₂ CO ₂ ), 5.21 (s, 2H, CH ₂ Ar), 7.34 (d, J = 8.2Hz, 1H, Ar), 7.
86 (d, J = 8.2Hz, 1H, Ar), 7.90 (s, 1H, Ar)

【００３９】３−〔２−（５−クロロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物１７〕融点: 163.0-163.5 ℃ IR(KBr): 1749(C=O), 1734(C=O), 1441, 1226, 1152,
816 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.1Hz,3H,CH₃), 4.18
(q,J=7.1Hz,2H,OCH₂), 4.47(s,2H,NCH₂CO₂), 5.26(s,2
H,CH₂Ar), 7.53(dd,J=8.5,1.9Hz,1H,Ar), 8.09(d,J=1.9
Hz,1H,Ar), 8.17(d,J=8.5Hz,1H,Ar)3- [2- (5-chlorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 17] Melting point: 163.0-163.5 ° C. IR (KBr): 1749 (C = O), 1734 (C = O), 1441, 1226, 1152,
816 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.1Hz, 3H, CH ₃ ), 4.18
(q, J = 7.1Hz, 2H, OCH ₂ ), 4.47 (s, 2H, NCH ₂ CO ₂ ), 5.26 (s, 2
H, CH ₂ Ar), 7.53 (dd, J = 8.5,1.9Hz, 1H, Ar), 8.09 (d, J = 1.9
Hz, 1H, Ar), 8.17 (d, J = 8.5Hz, 1H, Ar)

【００４０】３−〔２−（６−クロロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物１８〕融点_:181.0-182.5 ℃. IR(KBr): 1734(C=O), 1444, 1405, 1240, 1148, 815 cm
^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.1Hz,3H,CH₃), 4.17
(q,J=7.1Hz,2H,OCH₂), 4.47(s,2H,NCH₂CO₂), 5.25(s,2
H,CH₂Ar), 7.56(dd,J=8.8,2.2Hz,1H,Ar), 7.99(d,J=8.8
Hz,1H,Ar), 8.29(d,J=2.2Hz,1H,Ar)3- [2- (6-chlorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 18] Melting point _: 181.0-182.5 ° C. IR (KBr) : 1734 (C = O), 1444, 1405, 1240, 1148, 815 cm
^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.1Hz, 3H, CH ₃ ), 4.17
(q, J = 7.1Hz, 2H, OCH ₂ ), 4.47 (s, 2H, NCH ₂ CO ₂ ), 5.25 (s, 2
H, CH ₂ Ar), 7.56 (dd, J = 8.8,2.2Hz, 1H, Ar), 7.99 (d, J = 8.8
Hz, 1H, Ar), 8.29 (d, J = 2.2Hz, 1H, Ar)

【００４１】３−〔２−（４−クロロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物１９〕融点: 186.5-187.5 ℃ IR(KBr): 1735(C=O), 1729(C=O), 1444, 1403, 1240, 1
147, 1102, 780, 743 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.46(s,2H,NCH₂CO₂), 5.28(s,2
H,CH₂Ar), 7.47(dd,J=8.0,8.0Hz,1H,Ar), 7.64(d,J=8.0
Hz,1H,Ar), 8.11(d,J=8.0Hz,1H,Ar)3- [2- (4-chlorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 19] Melting point: 186.5-187.5 ° C. IR (KBr): 1735 (C = O), 1729 (C = O), 1444, 1403, 1240, 1
147, 1102, 780, 743 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.46 (s, 2H, NCH ₂ CO ₂ ), 5.28 (s, 2
H, CH ₂ Ar), 7.47 (dd, J = 8.0,8.0Hz, 1H, Ar), 7.64 (d, J = 8.0
Hz, 1H, Ar), 8.11 (d, J = 8.0Hz, 1H, Ar)

【００４２】３−〔２−（６−フルオロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物２０〕融点: 154.0-155.0 ℃ IR(KBr): 1734(C=O), 1447, 1228, 1149, 770 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.1Hz,3H,CH₃), 4.17
(q,J=7.1Hz,2H,OCH₂), 4.46(s,2H,NCH₂CO₂), 5.23(s,2
H,CH₂Ar), 7.39(ddd,J=9.2,9.2,2.5Hz,1H,Ar), 8.01(d
d,J=9.2,5.0Hz,1H,Ar), 8.04(dd,J=9.2,2.5Hz,1H,Ar)3- [2- (6-Fluorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 20] Melting point: 154.0-155.0 ° C. IR (KBr): 1734 (C = O), 1447, 1228, 1149, 770 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.1Hz, 3H, CH ₃ ), 4.17
(q, J = 7.1Hz, 2H, OCH ₂ ), 4.46 (s, 2H, NCH ₂ CO ₂ ), 5.23 (s, 2
H, CH ₂ Ar), 7.39 (ddd, J = 9.2,9.2,2.5Hz, 1H, Ar), 8.01 (d
d, J = 9.2,5.0Hz, 1H, Ar), 8.04 (dd, J = 9.2,2.5Hz, 1H, Ar)

【００４３】３−〔２−（６−メトキシベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物２１〕融点: 150.5-152.0 ℃ IR(KBr): 1736(C=O), 1443, 1259, 1227, 1146, 825 cm
^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.1Hz,3H,CH₃), 3.83
(s,3H,OCH₃), 4.17(q,J=7.1Hz,2H,OCH₂), 4.46(s,2H,NC
H₂CO₂), 5.18(s,2H,CH₂Ar), 7.11(dd,J=9.0,2.6Hz,1H,A
r), 7.68(d,J=2.6Hz,1H,Ar), 7.86(d,J=9.0Hz,1H,Ar)3- [2- (6-Methoxybenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 21] Melting point: 150.5-152.0 ° C. IR (KBr): 1736 (C = O), 1443, 1259, 1227, 1146, 825 cm
^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.1Hz, 3H, CH ₃ ), 3.83
(s, 3H, OCH ₃ ), 4.17 (q, J = 7.1Hz, 2H, OCH ₂ ), 4.46 (s, 2H, NC
H ₂ CO ₂ ), 5.18 (s, 2H, CH ₂ Ar), 7.11 (dd, J = 9.0,2.6Hz, 1H, A
r), 7.68 (d, J = 2.6Hz, 1H, Ar), 7.86 (d, J = 9.0Hz, 1H, Ar)

【００４４】３−〔２−（５−ブロモベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸エチル〔化合物２２〕融点: 157.0-158.0 ℃（分解） IR(KBr): 1751(C=O), 1732(C=O), 1444, 1430 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.21(t,J=7.0Hz,3H,CH₃), 4.18
(q,J=7.0Hz,2H,OCH₂), 4.47(s,2H,NCH₂CO), 5.26(s,2H,
CH₂Ar), 7.64(dd,J=8.6,1.8Hz,1H,ArH), 8.11(d,J=8.6H
z,1H,ArH), 8.22(d,J=1.8Hz,1H,ArH)3- [2- (5-Bromobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-ethyl acetate [Compound 22] Melting point: 157.0-158.0 ° C. (decomposition) IR ( KBr): 1751 (C = O), 1732 (C = O), 1444, 1430 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.21 (t, J = 7.0Hz, 3H, CH ₃ ), 4.18
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.47 (s, 2H, NCH ₂ CO), 5.26 (s, 2H,
CH ₂ Ar), 7.64 (dd, J = 8.6,1.8Hz, 1H, ArH), 8.11 (d, J = 8.6H
z, 1H, ArH), 8.22 (d, J = 1.8Hz, 1H, ArH)

【００４５】３−（２−トリフルオロメチルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸エ
チル〔化合物２３〕融点: 173.5-174.5 ℃ MS m/z: 358(M+) IR(KBr): 1735(C=O), 1455, 1320, 1225, 1105 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.22(t,J=7.0Hz,3H,CH₃), 4.17
(q,J=7.0Hz,2H,OCH₂), 4.44(s,2H,NCH₂CO₂), 4.89(s,2
H,CH₂N), 7.54(dd,J=8.0,7.0Hz,1H,ArH), 7.59(d,J=8.0
Hz,1H,ArH), 7.66(dd,J=8.0,7.0Hz,1H,ArH), 7.78(d,J=
8.0Hz,1H,ArH)3- (2-trifluoromethylbenzyl)
-2,4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 23] Melting point: 173.5-174.5 ° C MS m / z: 358 (M +) IR (KBr): 1735 (C = O), 1455, 1320 , 1225, 1105 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.22 (t, J = 7.0Hz, 3H, CH ₃ ), 4.17
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.44 (s, 2H, NCH ₂ CO ₂ ), 4.89 (s, 2
H, CH ₂ N), 7.54 (dd, J = 8.0,7.0Hz, 1H, ArH), 7.59 (d, J = 8.0
Hz, 1H, ArH), 7.66 (dd, J = 8.0,7.0Hz, 1H, ArH), 7.78 (d, J =
(8.0Hz, 1H, ArH)

【００４６】３−（３−トリフルオロメチルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸エ
チル〔化合物２４〕融点: 109.5-110.5 ℃ MS m/z: 358(M+) IR(KBr): 1730(C=O), 1455, 1439, 1335, 1215 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.20(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.41(s,2H,NCH₂CO₂), 4.86(s,2
H,CH₂N), 7.60(dd,J=7.5,7.5Hz,1H,ArH), 7.64-7.71(m,
2H,ArH), 7.74(s,1H,ArH)3- (3-trifluoromethylbenzyl)
-2,4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 24] Melting point: 109.5-110.5 ° C MS m / z: 358 (M +) IR (KBr): 1730 (C = O), 1455, 1439 , 1335, 1215 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.20 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.41 (s, 2H, NCH ₂ CO ₂ ), 4.86 (s, 2
H, CH ₂ N), 7.60 (dd, J = 7.5,7.5Hz, 1H, ArH), 7.64-7.71 (m,
2H, ArH), 7.74 (s, 1H, ArH)

【００４７】３−（４−トリフルオロメチルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸エ
チル〔化合物２５〕融点: 138.0-139.5 ℃ MS m/z: 358(M+) IR(KBr): 2995, 1750(C=O), 1725(C=O), 1450, 1320,
1240, 1120, 775 cm^-1 ¹H-NMR (DMSO-d₆)δ: 1.20(t,J=
7.0Hz,3H,CH₃), 4.16(q,J=7.0Hz,2H,OCH₂), 4.41(s,2H,
NCH₂CO₂), 4.85(s,2H,CH₂N), 7.59(d,J=8.0Hz,2H,ArH),
7.74(d,J=8.0Hz,2H,ArH)3- (4-trifluoromethylbenzyl)
-2,4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 25] Melting point: 138.0-139.5 ° C MS m / z: 358 (M +) IR (KBr): 2995, 1750 (C = O), 1725 (C = O), 1450, 1320,
1240, 1120, 775 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.20 (t, J =
7.0Hz, 3H, CH ₃ ), 4.16 (q, J = 7.0Hz, 2H, OCH ₂ ), 4.41 (s, 2H,
NCH ₂ CO ₂ ), 4.85 (s, 2H, CH ₂ N), 7.59 (d, J = 8.0Hz, 2H, ArH),
7.74 (d, J = 8.0Hz, 2H, ArH)

【００４８】３−（３−シアノベンジル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸ベンジル〔化合
物２６〕融点: 148.5-149.0 ℃ IR(KBr): 2235(CN), 1734(C=O), 1446, 1431, 1209, 75
8 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.50(s,2H,NCH₂CO₂), 4.82(s,2H,
CH₂N), 5.20(s,2H,OCH₂), 7.33-7.44(m,5H,ArH), 7.57
(dd,J=7.9,7.9Hz,1H,ArH), 7.70(d,J=7.9Hz,1H,ArH),
7.78(d,J=7.9Hz,1H,ArH), 7.87(s,1H,ArH)3- (3-cyanobenzyl) -2,4,5
-Trioxoimidazolidine-1-benzyl acetate [Compound 26] Melting point: 148.5-149.0 ° C IR (KBr): 2235 (CN), 1734 (C = O), 1446, 1431, 1209, 75
8 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.50 (s, 2H, NCH ₂ CO ₂ ), 4.82 (s, 2H,
CH ₂ N), 5.20 (s, 2H, OCH ₂ ), 7.33-7.44 (m, 5H, ArH), 7.57
(dd, J = 7.9,7.9Hz, 1H, ArH), 7.70 (d, J = 7.9Hz, 1H, ArH),
7.78 (d, J = 7.9Hz, 1H, ArH), 7.87 (s, 1H, ArH)

【００４９】３−（４−シアノベンジル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸ベンジル〔化合
物２７〕融点: 120.5-121.0 ℃ IR(KBr): 2190(CN), 1705(C=O), 1420, 1400, 1195, 74
0 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.49(s,2H,NCH₂CO₂), 4.84(s,2H,
CH₂N), 5.20(s,2H,OCH₂), 7.30-7.40(m,5H,O-C-Ar), 7.
55(d,J=8.0Hz,2H,ArH), 7.82(d,J=8.0Hz,2H,ArH)3- (4-cyanobenzyl) -2,4,5
-Trioxoimidazolidine-1-benzyl acetate [Compound 27] Melting point: 120.5-121.0 ° C IR (KBr): 2190 (CN), 1705 (C = O), 1420, 1400, 1195, 74
0 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.49 (s, 2H, NCH ₂ CO ₂ ), 4.84 (s, 2H,
CH ₂ N), 5.20 (s, 2H, OCH ₂ ), 7.30-7.40 (m, 5H, OC-Ar), 7.
55 (d, J = 8.0Hz, 2H, ArH), 7.82 (d, J = 8.0Hz, 2H, ArH)

【００５０】３−（３−メトキシカルボニルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸エ
チル〔化合物２８〕融点: 121.0-122.0 ℃ MS m/z: 348(M+) IR(KBr): 1735(C=O), 1445, 1425, 1400, 1255, 1145,
755 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.19(t,J=7.0Hz,3H,C-CH₃), 3.86
(s,3H,O-CH₃), 4.16(q,J=7.0Hz,2H,OCH₂), 4.39(s,2H,N
CH₂CO₂), 4.82(s,2H,CH₂N), 7.52(dd,J=7.5,7.5Hz,1H,A
rH), 7.63(d,J=7.5Hz,1H,ArH), 7.90(d,J=7.5Hz,1H,Ar
H), 7.95(s,1H,ArH)3- (3-methoxycarbonylbenzyl)
-2,4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 28] Melting point: 121.0-122.0 ° C MS m / z: 348 (M +) IR (KBr): 1735 (C = O), 1445, 1425 , 1400, 1255, 1145,
755 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.19 (t, J = 7.0Hz, 3H, C-CH ₃ ), 3.86
(s, 3H, O-CH ₃ ), 4.16 (q, J = 7.0Hz, 2H, OCH ₂ ), 4.39 (s, 2H, N
CH ₂ CO ₂ ), 4.82 (s, 2H, CH ₂ N), 7.52 (dd, J = 7.5,7.5Hz, 1H, A
rH), 7.63 (d, J = 7.5Hz, 1H, ArH), 7.90 (d, J = 7.5Hz, 1H, Ar
H), 7.95 (s, 1H, ArH)

【００５１】３−（３−カルバモイルベンジル）−２，
４，５−トリオキソイミダゾリジン−１−酢酸エチル
〔化合物２９〕融点: 190.5-192.5 ℃ MS m/z: 333(M+) IR(KBr): 3450(NH₂), 1730(C=O), 1645, 1450, 1430, 1
395, 1240 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.19(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.41(s,2H,NCH₂CO₂), 4.79(s,2
H,CH₂N), 7.30-7.58(m,3H,ArH), 7.75(brs,2H,NH₂),8.0
3(s,1H,ArH)3- (3-carbamoylbenzyl) -2,
4,5-Trioxoimidazolidine-1-ethyl acetate [Compound 29] Melting point: 190.5-192.5 ° C MS m / z: 333 (M +) IR (KBr): 3450 (NH ₂ ), 1730 (C = O), 1645, 1450, 1430, 1
395, 1240 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.19 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.41 (s, 2H, NCH ₂ CO ₂ ), 4.79 (s, 2
H, CH ₂ N), 7.30-7.58 (m, 3H, ArH), 7.75 (brs, 2H, NH ₂ ), 8.0
3 (s, 1H, ArH)

【００５２】３−（３−メトキシカボニルベンジル）−
２，４，５−トリオキソイミダゾリジン−１−酢酸ベン
ジル〔化合物３０〕融点: 105.0-107.0 ℃（分解） IR(KBr): 1734(C=O), 1448, 1429, 1288, 1207 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 3.86(s,3H,OCH₃), 4.49(s,2H,NCH
₂CO₂), 4.82(s,2H,CH₂N), 5.19(s,2H,OCH₂), 7.30-7.40
(m,5H,O-C-Ar), 7.51(dd,J=7.5,7.5Hz,1H,ArH),7.62(d,
J=7.5Hz,2H,ArH), 7.90(d,J=7.5Hz,1H,ArH), 7.96(s,1
H,ArH)3- (3-methoxycarbonylbenzyl)-
2,4,5-Trioxoimidazolidine-1-benzyl acetate [Compound 30] Melting point: 105.0-107.0 ° C (decomposition) IR (KBr): 1734 (C = O), 1448, 1429, 1288, 1207 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 3.86 (s, 3H, OCH ₃ ), 4.49 (s, 2H, NCH
₂ CO ₂ ), 4.82 (s, 2H, CH ₂ N), 5.19 (s, 2H, OCH ₂ ), 7.30-7.40
(m, 5H, OC-Ar), 7.51 (dd, J = 7.5,7.5Hz, 1H, ArH), 7.62 (d,
J = 7.5Hz, 2H, ArH), 7.90 (d, J = 7.5Hz, 1H, ArH), 7.96 (s, 1
(H, ArH)

【００５３】３−（４−クロロ−３−ニトロベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸ベ
ンジル〔化合物３１〕融点: 141.0-144.0 ℃（分解） MS m/z: 369(M+) IR(KBr): 1735(C=O), 1535(NO₂), 1450, 1230 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 1.20(t,J=7.0Hz,3H,CH₃), 4.16
(q,J=7.0Hz,2H,OCH₂), 4.40(s,2H,NCH₂CO₂), 4.86(s,2
H,CH₂N), 7.70(dd,J=8.0,1.5Hz,1H,ArH), 7.78(d,J=8.0
Hz,1H,ArH), 8.08(d,J=1.5Hz,1H,ArH)3- (4-chloro-3-nitrobenzyl)
-2,4,5-Trioxoimidazolidine-1-benzyl acetate [Compound 31] Melting point: 141.0-144.0 ° C (decomposition) MS m / z: 369 (M +) IR (KBr): 1735 (C = O), 1535 (NO ₂ ), 1450, 1230 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 1.20 (t, J = 7.0Hz, 3H, CH ₃ ), 4.16
(q, J = 7.0Hz, 2H, OCH ₂ ), 4.40 (s, 2H, NCH ₂ CO ₂ ), 4.86 (s, 2
H, CH ₂ N), 7.70 (dd, J = 8.0,1.5Hz, 1H, ArH), 7.78 (d, J = 8.0
Hz, 1H, ArH), 8.08 (d, J = 1.5Hz, 1H, ArH)

【００５４】実施例２．６ｍＬの酢酸と２ｍＬの濃塩酸
の混合溶液に２．１ｇの化合物１を加えて２時間還流し
た後、減圧下濃縮し、さらに６ｍＬの酢酸と２ｍＬの濃
塩酸を加えて１時間還流した。減圧下濃縮して得られた
残渣に水を加えて沈澱を濾取し、水洗、乾燥した後、エ
タノールより再結晶して、３−〔２−（５−トリフルオ
ロメチルベンゾチアゾリル）メチル〕−２，４，５−ト
リオキソイミダゾリジン−１−酢酸〔化合物３２〕を得
た。融点: 211.0-212.0 ℃ MS(EI,70eV): 387(M+,72), 258(43), 230(12), 216(1
9), 203(80), 56(100) IR(KBr): 2926(OH), 1741(C=O), 1443, 1421, 1333, 1
149, 1122 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.36(s,2H,NCH₂CO₂), 5.32(s,2H,
CH₂Ar), 7.80(d,J=8.4Hz,1H,Ar), 8.37(s,1H,Ar), 8.39
(d,J=8.4Hz,1H,Ar), 13.47(brs,1H,OH) 元素分析 (C₁₄H₈F₃N₃O₅S 0.1H₂O): 計算値(C=43.22,H=
2.12,N=10.80), 測定値(C=43.60,H=2.53,N=10.97)Example 2.6 To a mixed solution of 2.6 mL of acetic acid and 2 mL of concentrated hydrochloric acid, 2.1 g of Compound 1 was added, refluxed for 2 hours, concentrated under reduced pressure, and further added with 6 mL of acetic acid and 2 mL of concentrated hydrochloric acid. And refluxed for 1 hour. Water was added to the residue obtained by concentration under reduced pressure, the precipitate was collected by filtration, washed with water, dried and recrystallized from ethanol to give 3- [2- (5-trifluoromethylbenzothiazolyl) methyl. ] -2,4,5-Trioxoimidazolidine-1-acetic acid [Compound 32] was obtained. Melting point: 211.0-212.0 ° C MS (EI, 70eV): 387 (M +, 72), 258 (43), 230 (12), 216 (1
9), 203 (80), 56 (100) IR (KBr): 2926 (OH), 1741 (C = O), 1443, 1421, 1333, 1
149, 1122 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.36 (s, 2H, NCH ₂ CO ₂ ), 5.32 (s, 2H,
CH ₂ Ar), 7.80 (d, J = 8.4Hz, 1H, Ar), 8.37 (s, 1H, Ar), 8.39
(d, J = 8.4Hz, 1H, Ar), 13.47 (brs, 1H, OH) Elemental analysis (C ₁₄ H ₈ F ₃ N ₃ O ₅ S 0.1H ₂ O): Calculated value (C = 43.22, H =
2.12, N = 10.80), measured value (C = 43.60, H = 2.53, N = 10.97)

【００５５】同様の方法で以下の化合物が得られた。３−（３−ピリジルメチル）−２，４，５−トリオキソ
イミダゾリジン−１−酢酸〔化合物３３〕融点: 208.5-210.0 ℃（分解） IR(KBr): 3000(OH), 1735(C=O), 1705(C=O), 1605, 14
35, 1255, 1140, 755 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.29(s,2H,NCH₂CO₂), 4.82(s,2H,
CH₂N), 7.49(dd,J=7.5,5.0Hz,1H,Ar), 7.75(d,J=7.5Hz,
1H,Ar), 8.57(d,J=5.0Hz,1H,Ar), 8.63(s,1H,Ar), 13.1
6(brs,1H,OH) 元素分析 (C₁₁H₉N₃O₅): 計算値(C=50.20,H=3.45,N=15.9
6), 実測値(C=50.12,H=3.59,N=15.80)The following compounds were obtained in a similar manner. 3- (3-Pyridylmethyl) -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 33] Melting point: 208.5-210.0 ° C (decomposition) IR (KBr): 3000 (OH), 1735 (C = O), 1705 (C = O), 1605, 14
35, 1255, 1140, 755 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.29 (s, 2H, NCH ₂ CO ₂ ), 4.82 (s, 2H,
CH ₂ N), 7.49 (dd, J = 7.5,5.0Hz, 1H, Ar), 7.75 (d, J = 7.5Hz,
1H, Ar), 8.57 (d, J = 5.0Hz, 1H, Ar), 8.63 (s, 1H, Ar), 13.1
6 (brs, 1H, OH) Elemental analysis (C ₁₁ H ₉ N ₃ O ₅ ): Calculated value (C = 50.20, H = 3.45, N = 15.9
6), measured value (C = 50.12, H = 3.59, N = 15.80)

【００５６】３−（４−ピリジルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物３４〕融点: 251.0-252.0 ℃（分解） IR(KBr): 3000(OH), 1740(C=O), 1435, 1400, 1245, 11
40, 755 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.31(s,2H,NCH₂CO₂), 4.80(s,2H,
CH₂N), 7.37(d,J=5.5Hz,2H,Ar), 8.54(d,J=5.5Hz,2H,A
r), 13.30(brs,1H,OH) 元素分析 (C₁₁H₉N₃O₅): 計算値(C=50.20,H=3.45,N=15.9
6), 実測値(C=50.11,H=3.43,N=15.88)3- (4-pyridylmethyl) -2,4,5
-Trioxoimidazolidine-1-acetic acid [Compound 34] Melting point: 251.0-252.0 ° C (decomposition) IR (KBr): 3000 (OH), 1740 (C = O), 1435, 1400, 1245, 11
40, 755 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.31 (s, 2H, NCH ₂ CO ₂ ), 4.80 (s, 2H,
CH ₂ N), 7.37 (d, J = 5.5Hz, 2H, Ar), 8.54 (d, J = 5.5Hz, 2H, A
r), 13.30 (brs, 1H, OH) Elemental analysis (C ₁₁ H ₉ N ₃ O ₅ ): Calculated value (C = 50.20, H = 3.45, N = 15.9
6), measured value (C = 50.11, H = 3.43, N = 15.88)

【００５７】３−（２−チエニルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物３５〕融点: 205.5-210.0 ℃（分解） IR(KBr): 3000(OH), 1730(C=O), 1590, 1440 cm^-1 ¹ H NMR-(DMSO-d₆)δ: 4.30(s,2H,NCH₂CO₂), 4.90(s,2H,
CH₂N), 7.01(dd,J=5.0,3.5Hz,1H,Ar), 7.12(d,J=3.5Hz,
1H,Ar), 7.50(d,J=5.0Hz,1H,Ar)3- (2-thienylmethyl) -2,4,5
- trioxospiro imidazolidin-1-acetic acid [Compound 35] mp: 205.5-210.0 ℃ (decomposition) IR (KBr): 3000 ( OH), 1730 (C = O), 1590, 1440 cm -1 1 H NMR- ( DMSO-d ₆ ) δ: 4.30 (s, 2H, NCH ₂ CO ₂ ), 4.90 (s, 2H,
CH ₂ N), 7.01 (dd, J = 5.0,3.5Hz, 1H, Ar), 7.12 (d, J = 3.5Hz,
1H, Ar), 7.50 (d, J = 5.0Hz, 1H, Ar)

【００５８】３−〔３−（５−ブロモピリジル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸〔化合物３６〕融点: 221.0-222.0 ℃ IR(KBr): 3000(OH), 1734(C=O), 1448, 1138, 771 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.29(s,2H,NCH₂CO₂), 4.82(s,2H,
CH₂N), 8.06(s,1H,Ar),8.58(s,1H,Ar), 8.65(s,1H,Ar),
13.41(brs,1H,OH) 元素分析 (C₁₁H₈BrN₃O₅): 計算値(C=38.62,H=2.36,N=1
2.28), 実測値(C=38.52,H=2.41,N=12.19)3- [3- (5-Bromopyridyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 36] Melting point: 221.0-222.0 ° C. IR (KBr): 3000 (OH) , 1734 (C = O), 1448, 1138, 771 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.29 (s, 2H, NCH ₂ CO ₂ ), 4.82 (s, 2H,
CH ₂ N), 8.06 (s, 1H, Ar), 8.58 (s, 1H, Ar), 8.65 (s, 1H, Ar),
13.41 (brs, 1H, OH) Elemental analysis (C ₁₁ H ₈ BrN ₃ O ₅ ): Calculated (C = 38.62, H = 2.36, N = 1)
2.28), measured value (C = 38.52, H = 2.41, N = 12.19)

【００５９】３−〔３−（２−クロロピリジル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸〔化合物３７〕融点: 234.5-236.0 ℃ MS m/z: 297(M+) IR(KBr): 3000(OH), 1740 (C=O), 1722(C=O), 1437, 12
36, 1151, 754 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.31(s,2H,NCH₂CO₂), 4.82(s,2H,
CH₂N), 7.45(dd,J=8.0,5.0Hz,1H,Ar), 7.96(d,J=8.0Hz,
1H,Ar), 8.38(d,J=5.0Hz,1H,Ar), 13.42(brs,1H,OH) 元素分析 (C₁₁H₈ClN₃O₅): 計算値(C=44.39,H=2.71,N=1
4.12), 実測値(C=44.44,H=2.71,N=14.10)3- [3- (2-chloropyridyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 37] Melting point: 234.5-236.0 ° C. MS m / z: 297 (M +) IR (KBr): 3000 (OH), 1740 (C = O), 1722 (C = O), 1437, 12
36, 1151, 754 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.31 (s, 2H, NCH ₂ CO ₂ ), 4.82 (s, 2H,
CH ₂ N), 7.45 (dd, J = 8.0,5.0Hz, 1H, Ar), 7.96 (d, J = 8.0Hz,
1H, Ar), 8.38 (d, J = 5.0Hz, 1H, Ar), 13.42 (brs, 1H, OH) Elemental analysis (C ₁₁ H ₈ ClN ₃ O ₅ ): Calculated value (C = 44.39, H = 2.71) , N = 1
4.12), measured value (C = 44.44, H = 2.71, N = 14.10)

【００６０】３−〔３−（６−クロロピリジル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸〔化合物３８〕融点: 202.0-203.5 ℃ IR(KBr): 3100(OH), 1738(C=O), 1718(C=O), 1601, 14
50, 1390, 760 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.29(s,2H,NCH₂CO₂), 4.81(s,2H,
CH₂N), 7.53(d,J=8.2Hz,1H,Ar), 7.84(dd,J=8.2,1.7Hz,
1H,Ar), 8.42(d,J=2.5Hz,1H,Ar), 13.37(brs,1H,OH) 元素分析 (C₁₁H₈ClN₃O₅): 計算値(C=44.39,H=2.71,N=1
4.12), 実測値(C=44.68,H=2.93,N=14.12)3- [3- (6-chloropyridyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 38] Melting point: 202.0-203.5 ° C IR (KBr): 3100 (OH) , 1738 (C = O), 1718 (C = O), 1601, 14
50, 1390, 760 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.29 (s, 2H, NCH ₂ CO ₂ ), 4.81 (s, 2H,
CH ₂ N), 7.53 (d, J = 8.2Hz, 1H, Ar), 7.84 (dd, J = 8.2,1.7Hz,
1H, Ar), 8.42 (d, J = 2.5Hz, 1H, Ar), 13.37 (brs, 1H, OH) Elemental analysis (C ₁₁ H ₈ ClN ₃ O ₅ ): Calculated value (C = 44.39, H = 2.71) , N = 1
4.12), measured value (C = 44.68, H = 2.93, N = 14.12)

【００６１】３−（２−ピリジルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物３９〕融点: 251.0-253.0 ℃（分解） MS m/z: 363(M+) IR(KBr): 3000(OH), 1737(C=O), 1450, 1249, 1159, 77
5 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.33(s,2H,NCH₂CO₂), 4.88(s,2H,
CH₂N), 7.32(dd,J=7.5,3.5Hz,1H,Ar), 7.45(d,J=7.5Hz,
1H,Ar), 7.80(dd,J=7.5,7.5Hz,1H,Ar), 8.50(d,J=3.5H
z,1H,Ar), 13.43(brs,1H,OH) 元素分析 (C₁₁H₉N₃O₅): 計算値(C=50.20,H=3.45,N=15.9
6), 実測値(C=49.92,H=3.37,N=16.08)3- (2-pyridylmethyl) -2,4,5
-Trioxoimidazolidine-1-acetic acid [Compound 39] Melting point: 251.0-253.0 ° C (decomposition) MS m / z: 363 (M +) IR (KBr): 3000 (OH), 1737 (C = O), 1450, 1249, 1159, 77
5 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.33 (s, 2H, NCH ₂ CO ₂ ), 4.88 (s, 2H,
CH ₂ N), 7.32 (dd, J = 7.5,3.5Hz, 1H, Ar), 7.45 (d, J = 7.5Hz,
1H, Ar), 7.80 (dd, J = 7.5,7.5Hz, 1H, Ar), 8.50 (d, J = 3.5H
z, 1H, Ar), 13.43 (brs, 1H, OH) Elemental analysis (C ₁₁ H ₉ N ₃ O ₅ ): Calculated value (C = 50.20, H = 3.45, N = 15.9)
6), measured value (C = 49.92, H = 3.37, N = 16.08)

【００６２】３−（１−ナフチルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物４０〕融点: 225.0-228.0 ℃ IR(KBr): 3000(OH), 1738(C=O), 1722(C=O), 1444, 14
00, 1246, 1151, 798 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.34(s,2H,NCH₂CO₂), 5.21(s,2H,
CH₂N), 7.34-7.64(m,4H,Ar), 7.90(d,J=7.9Hz,1H,Ar),
7.98(d,J=7.9Hz,1H,Ar), 8.20(d,J=7.9Hz,1H,Ar)_,13.4
2(brs,1H,OH) 元素分析 (C₁₆H₁₂N₂O₅): 計算値(C=61.54,H=3.87,N=8.
97), 実測値(C=61.28,H=3.94,N=8.89)3- (1-naphthylmethyl) -2,4,5
-Trioxoimidazolidine-1-acetic acid [Compound 40] Melting point: 225.0-228.0 ° C IR (KBr): 3000 (OH), 1738 (C = O), 1722 (C = O), 1444, 14
00, 1246, 1151, 798 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.34 (s, 2H, NCH ₂ CO ₂ ), 5.21 (s, 2H,
CH ₂ N), 7.34-7.64 (m, 4H, Ar), 7.90 (d, J = 7.9Hz, 1H, Ar),
7.98 (d, J = 7.9Hz, 1H, Ar), 8.20 (d, J = 7.9Hz, 1H, Ar) _, 13.4
2 (brs, 1H, OH) Elemental analysis (C ₁₆ H ₁₂ N ₂ O ₅ ): Calculated (C = 61.54, H = 3.87, N = 8.
97), measured value (C = 61.28, H = 3.94, N = 8.89)

【００６３】３−（２−ナフチルメチル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物４１〕融点: 192.5-194.0 ℃ MS m/z: 312(M+) IR(KBr): 3000(OH), 1768(C=O), 1738(C=O), 1716(C=
O), 1441, 1402, 1250, 1149, 762 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.42(s,2H,NCH₂CO₂), 4.92(s,2H,
CH₂N), 7.47(dd,J=8.9,2.0Hz,1H,Ar), 7.52(s,1H,Ar),
7.52(dd,J=9.4,2.0Hz,1H,Ar), 7.86-7.94(m,4H,Ar), 1
3.46(brs,1H,OH) 元素分析 (C₁₆H₁₂N₂O₅): 計算値(C=61.54,H=3.87,N=8.
97), 実測値(C=61.24,H=4.04,N=8.76)3- (2-naphthylmethyl) -2,4,5
-Trioxoimidazolidine-1-acetic acid [Compound 41] Melting point: 192.5-194.0 ° C MS m / z: 312 (M +) IR (KBr): 3000 (OH), 1768 (C = O), 1738 (C = O ), 1716 (C =
O), 1441, 1402, 1250, 1149, 762 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.42 (s, 2H, NCH ₂ CO ₂ ), 4.92 (s, 2H,
CH ₂ N), 7.47 (dd, J = 8.9,2.0Hz, 1H, Ar), 7.52 (s, 1H, Ar),
7.52 (dd, J = 9.4,2.0Hz, 1H, Ar), 7.86-7.94 (m, 4H, Ar), 1
3.46 (brs, 1H, OH) Elemental analysis (C ₁₆ H ₁₂ N ₂ O ₅ ): Calculated value (C = 61.54, H = 3.87, N = 8.
97), measured value (C = 61.24, H = 4.04, N = 8.76)

【００６４】３−〔２−（９，１０−アントラキノニ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物４２〕融点: 236.5-238.5 ℃ IR(KBr): 3100(OH), 1736(C=O), 1674, 1446, 1300, 11
49, 711 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.32(s,2H,NCH₂CO₂), 4.98(s,2H,
CH₂N), 7.86-7.99(m,3H,Ar), 8.13-8.27(m,H,Ar), 13.4
1(brs,1H,OH) 元素分析 (C₂₀H₁₂N₂O₇ 0.5H₂O): 計算値(C=59.86,H=3.2
7,N=6.98), 実測値(C=59.91,H=3.42,N=6.82)3- [2- (9,10-anthraquinonyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 42] Melting point: 236.5-238.5 ° C. IR (KBr): 3100 (OH ), 1736 (C = O), 1674, 1446, 1300, 11
49, 711 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.32 (s, 2H, NCH ₂ CO ₂ ), 4.98 (s, 2H,
CH ₂ N), 7.86-7.99 (m, 3H, Ar), 8.13-8.27 (m, H, Ar), 13.4
1 (brs, 1H, OH) Elemental analysis (C ₂₀ H ₁₂ N ₂ O ₇ 0.5H ₂ O): Calculated value (C = 59.86, H = 3.2
7, N = 6.98), measured value (C = 59.91, H = 3.42, N = 6.82)

【００６５】３−（２−ベンゾチアゾリルメチル）−
２，４，５−トリオキソイミダゾリジン−１−酢酸〔化
合物４３〕融点: 264.0-265.0 ℃（分解） MS m/z: aaa(M+) IR(KBr): 3100(OH), 1736(C=O), 1443, 1402, 1215, 11
49, 763 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.38(s,2H,NCH₂CO₂), 5.25(s,2H,
CH₂N), 7.46(dd,J=7.4,7.4Hz,1H,Ar), 7.52(dd,J=7.4,
7.4Hz,1H,Ar), 7.99(d,J=7.4Hz,1H,Ar), 8.12(d,J=7.4H
z,1H,Ar), 13.43(brs,1H,OH) 元素分析 (C₁₃H₉N₃O₅S): 計算値(C=48.90,H=2.84,N=1
3.16), 実測値(C=48.92,H=2.90,N=13.06)3- (2-benzothiazolylmethyl)-
2,4,5-Trioxoimidazolidine-1-acetic acid [Compound 43] Melting point: 264.0-265.0 ° C (decomposition) MS m / z: aaa (M +) IR (KBr): 3100 (OH), 1736 (C = O), 1443, 1402, 1215, 11
49, 763 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.38 (s, 2H, NCH ₂ CO ₂ ), 5.25 (s, 2H,
CH ₂ N), 7.46 (dd, J = 7.4,7.4Hz, 1H, Ar), 7.52 (dd, J = 7.4,
7.4Hz, 1H, Ar), 7.99 (d, J = 7.4Hz, 1H, Ar), 8.12 (d, J = 7.4H
z, 1H, Ar), 13.43 (brs, 1H, OH) Elemental analysis (C ₁₃ H ₉ N ₃ O ₅ S): Calculated value (C = 48.90, H = 2.84, N = 1)
3.16), measured value (C = 48.92, H = 2.90, N = 13.06)

【００６６】３−（Ｎ−フタルイミドメチル）−２，
４，５−トリオキソイミダゾリジン−１−酢酸〔化合物
４４〕融点: 266.0-268.0 ℃（分解） MS m/z: 331(M+) IR(KBr): 3000(OH), 1740(C=O), 1412, 1331, 1169, 92
6, 731, 590 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.28(s,2H,NCH₂CO₂), 5.39(s,2H,
CH₂N), 7.85-7.95(m,4H,Ar), 13.41(brs,1H,OH) 元素分析 (C₁₄H₉N₃O₇): 計算値(C=50.77,H=2.74,N=12.6
9), 実測値(C=50.65,H=2.82,N=12.72)3- (N-phthalimidomethyl) -2,
4,5-Trioxoimidazolidine-1-acetic acid [Compound 44] Melting point: 266.0-268.0 ° C (decomposition) MS m / z: 331 (M +) IR (KBr): 3000 (OH), 1740 (C = O) , 1412, 1331, 1169, 92
6, 731, 590 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.28 (s, 2H, NCH ₂ CO ₂ ), 5.39 (s, 2H,
CH ₂ N), 7.85-7.95 (m, 4H, Ar), 13.41 (brs, 1H, OH) Elemental analysis (C ₁₄ H ₉ N ₃ O ₇ ): Calculated value (C = 50.77, H = 2.74, N = 12.6
9), measured value (C = 50.65, H = 2.82, N = 12.72)

【００６７】３−〔１−（２−ブロモナフチル）メチ
ル〕−２，４，５−トリオキソイミダゾリジン−１−酢
酸〔化合物４５〕融点: 205.0-210.0 ℃（分解） MS m/z: 392(M+(⁸¹Br)), 392(M+(⁷⁹Br)) IR(KBr): 3000(OH), 1738(C=O), 1720(C=O), 1433, 11
53, 760 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.33(s,2H,NCH₂CO₂), 5.04(s,2H,
CH₂N), 7.55(d,J=8.9Hz,1H,Ar), 7.64(dd,J=8.1,7.4Hz,
1H,Ar), 7.72(dd,J=8.1,7.4Hz,1H,Ar), 7.98(d,J=8.1H
z,1H,Ar), 8.00(d,J=8.1Hz,1H,Ar), 8.25(d,J=8.9Hz,1
H,Ar), 13.46(brs,1H,OH) 元素分析 (C₁₆H₁₁BrN₂O₅): 計算値(C=49.13,H=2.83,N=
7.16), 実測値(C=48.89,H=2.97,N=6.98)3- [1- (2-Bromonaphthyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 45] Melting point: 205.0-210.0 ° C. (decomposition) MS m / z: 392 (M + ( ⁸¹ Br)), 392 (M + ( ⁷⁹ Br)) IR (KBr): 3000 (OH), 1738 (C = O), 1720 (C = O), 1433, 11
53, 760 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.33 (s, 2H, NCH ₂ CO ₂ ), 5.04 (s, 2H,
CH ₂ N), 7.55 (d, J = 8.9Hz, 1H, Ar), 7.64 (dd, J = 8.1,7.4Hz,
1H, Ar), 7.72 (dd, J = 8.1,7.4Hz, 1H, Ar), 7.98 (d, J = 8.1H
z, 1H, Ar), 8.00 (d, J = 8.1Hz, 1H, Ar), 8.25 (d, J = 8.9Hz, 1
(H, Ar), 13.46 (brs, 1H, OH) Elemental analysis (C ₁₆ H ₁₁ BrN ₂ O ₅ ): Calculated value (C = 49.13, H = 2.83, N =
7.16), measured value (C = 48.89, H = 2.97, N = 6.98)

【００６８】３−〔２−（６−ニトロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物４６〕融点: 130.0-131.0 ℃ (分解) MS(EI,70eV): 364(M+,79), 235(44), 207(11), 180(4
7), 56(100) IR(KBr): 3000(OH), 1745(C=O), 1734(C=O), 1525(N
O₂), 1435, 1344(NO₂) cm^-11H-NMR (DMSO-d₆)δ: 4.36
(s,2H,NCH₂CO₂), 5.34(s,2H,CH₂Ar), 8.19(d,J=9.0Hz,1
H,Ar), 8.34(dd,J=9.0,2.3Hz,1H,Ar), 9.21(d,J=2.3Hz,
1H,Ar), 13.47(brs,1H,OH) 元素分析 (C₁₃H₈N₄O₇S): 計算値(C=42.86,H=2.21,N=1
5.38), 実測値(C=42.90,H=2.33,N=15.15)3- [2- (6-Nitrobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 46] Melting point: 130.0-131.0 ° C. (decomposition) MS (EI , 70eV): 364 (M +, 79), 235 (44), 207 (11), 180 (4
7), 56 (100) IR (KBr): 3000 (OH), 1745 (C = O), 1734 (C = O), 1525 (N
O ₂ ), 1435, 1344 (NO ₂ ) cm ^-11 H-NMR (DMSO-d ₆ ) δ: 4.36
(s, 2H, NCH ₂ CO ₂ ), 5.34 (s, 2H, CH ₂ Ar), 8.19 (d, J = 9.0Hz, 1
H, Ar), 8.34 (dd, J = 9.0,2.3Hz, 1H, Ar), 9.21 (d, J = 2.3Hz,
1H, Ar), 13.47 (brs, 1H, OH) Elemental analysis (C ₁₃ H ₈ N ₄ O ₇ S): Calculated value (C = 42.86, H = 2.21, N = 1
5.38), measured value (C = 42.90, H = 2.33, N = 15.15)

【００６９】３−〔２−（６−メチルベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物４７〕融点: 277.0-278.0 ℃ MS(EI,70eV): 333(M+,100), 204(50), 176(24), 162(2
6), 149(86), 56(63) IR(KBr): 3000(OH), 1738(C=O), 1441, 1402, 1213, 11
51, 764 cm^-1 ¹ H-NMR (DMSO-d6)δ: 2.44(s,3H,CH₃), 4.35(s,2H,NCH₂
CO₂), 5.21(s,2H,CH₂Ar), 7.34(d,J=8.3Hz,1H,Ar), 7.8
6(d,J=8.3Hz,1H,Ar), 7.89(s,1H,Ar), 13.47(brs,1H,O
H) 元素分析 (C₁₄H₁₁N₃O₅S): 計算値(C=50.45,H=3.33,N=1
2.61), 実測値(C=50.39,H=3.30,N=12.66)3- [2- (6-Methylbenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 47] Melting point: 277.0-278.0 ° C MS (EI, 70eV) : 333 (M +, 100), 204 (50), 176 (24), 162 (2
6), 149 (86), 56 (63) IR (KBr): 3000 (OH), 1738 (C = O), 1441, 1402, 1213, 11
51, 764 cm ^-1 ¹ H-NMR (DMSO-d6) δ: 2.44 (s, 3H, CH ₃ ), 4.35 (s, 2H, NCH ₂
CO ₂ ), 5.21 (s, 2H, CH ₂ Ar), 7.34 (d, J = 8.3Hz, 1H, Ar), 7.8
6 (d, J = 8.3Hz, 1H, Ar), 7.89 (s, 1H, Ar), 13.47 (brs, 1H, O
H) Elemental analysis (C ₁₄ H ₁₁ N ₃ O ₅ S): Calculated value (C = 50.45, H = 3.33, N = 1
2.61), measured value (C = 50.39, H = 3.30, N = 12.66)

【００７０】３−〔２−（５−クロロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物４８〕融点_:265.0-268.0 ℃ (分解) MS(EI,70eV): 355(M+(³⁷Cl),21), 353(M+(³⁵Cl),59), 2
24(44), 196(20), 182(19), 169(64), 56(100) IR(KBr): 3006(OH), 1782(C=O), 1741(C=O), 1429, 13
51, 1213, 1120, 886, 799, 758 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.36(s,2H,NCH₂CO₂), 5.26(s,2H,
CH₂Ar), 7.52(dd,J=8.6,2.0Hz,1H,Ar), 8.10(d,J=2.0H
z,1H,Ar), 8.16(d,J=8.6Hz,1H,Ar), 13.45(brs,1H,OH) 元素分析 (C₁₃H₈ClN₃O₅S): 計算値(C=44.14,H=2.28,N=
11.88), 実測値(C=44.20,H=2.46,N=11.80)3- [2- (5-chlorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 48] Melting point _: 265.0-268.0 ° C. (decomposition) MS (EI , 70eV): 355 (M + ( ³⁷ Cl), 21), 353 (M + ( ³⁵ Cl), 59), 2
24 (44), 196 (20), 182 (19), 169 (64), 56 (100) IR (KBr): 3006 (OH), 1782 (C = O), 1741 (C = O), 1429, 13
51, 1213, 1120, 886, 799, 758 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.36 (s, 2H, NCH ₂ CO ₂ ), 5.26 (s, 2H,
CH ₂ Ar), 7.52 (dd, J = 8.6,2.0Hz, 1H, Ar), 8.10 (d, J = 2.0H
z, 1H, Ar), 8.16 (d, J = 8.6Hz, 1H, Ar), 13.45 (brs, 1H, OH) Elemental analysis (C ₁₃ H ₈ ClN ₃ O ₅ S): Calculated value (C = 44.14, H = 2.28, N =
11.88), measured value (C = 44.20, H = 2.46, N = 11.80)

【００７１】３−〔２−（６−クロロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物４９〕融点: 265.0-266.0 ℃ MS(EI,70eV): 355(M+(³⁷Cl),32), 353(M+(³⁵Cl),82), 2
26(20), 224(52), 196(23), 182(25), 171(28), 169(7
6), 56(100) IR(KBr): 3000(OH), 1746(C=O), 1734(C=O), 1435, 13
98, 1345, 1143, 1117,757 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.36(s,2H,NCH₂CO₂), 5.25(s,2H,
CH₂Ar), 7.56(d,J=8.7Hz,1H,Ar), 7.99(d,J=8.7Hz,1H,A
r), 8.29 (s,1H,Ar), 13.45(brs,1H,OH) 元素分析 (C₁₃H₈ClN₃O₅S): 計算値(C=44.14,H=2.28,N=
11.88), 実測値(c=43.98,H=2.27,N=11.89)3- [2- (6-chlorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [compound 49] Melting point: 265.0-266.0 ° C MS (EI, 70eV) : 355 (M + ( ³⁷ Cl), 32), 353 (M + ( ³⁵ Cl), 82), 2
26 (20), 224 (52), 196 (23), 182 (25), 171 (28), 169 (7
6), 56 (100) IR (KBr): 3000 (OH), 1746 (C = O), 1734 (C = O), 1435, 13
98, 1345, 1143, 1117, 757 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.36 (s, 2H, NCH ₂ CO ₂ ), 5.25 (s, 2H,
CH ₂ Ar), 7.56 (d, J = 8.7Hz, 1H, Ar), 7.99 (d, J = 8.7Hz, 1H, A
r), 8.29 (s, 1H, Ar), 13.45 (brs, 1H, OH) Elemental analysis (C ₁₃ H ₈ ClN ₃ O ₅ S): Calculated value (C = 44.14, H = 2.28, N =
11.88), measured value (c = 43.98, H = 2.27, N = 11.89)

【００７２】３−〔２−（４−クロロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物５０〕融点_:238.0-240.0 ℃ MS(EI,70eV): 355(M+(³⁷Cl),32), 353(M+(³⁵Cl),82), 2
26(16), 224(41), 196(17), 182(17), 171(24), 169(6
4), 56(100) IR(KBr): 2900(OH), 1732(C=O), 1442, 1401, 1201, 11
46, 1108, 778, 762, 607 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.35(s,2H,NCH₂CO₂), 5.27(s,2H,
CH₂Ar), 7.47(dd,J=8.0,8.0Hz,1H,Ar), 7.63(d,J=8.0H
z,1H,Ar), 8.11(d,J=8.0Hz,1H,Ar), 13.41(brs,1H,OH) 元素分析 (C₁₃H₈ClN₃O₅S): 計算値(C=44.14,H=2.28,N=
11.88), 実測値(C=44.32,H=2.47,N=11.56)3- [2- (4-chlorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 50] Melting point _: 238.0-240.0 ° C MS (EI, 70eV) : 355 (M + ( ³⁷ Cl), 32), 353 (M + ( ³⁵ Cl), 82), 2
26 (16), 224 (41), 196 (17), 182 (17), 171 (24), 169 (6
4), 56 (100) IR (KBr): 2900 (OH), 1732 (C = O), 1442, 1401, 1201, 11
46, 1108, 778, 762, 607 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.35 (s, 2H, NCH ₂ CO ₂ ), 5.27 (s, 2H,
CH ₂ Ar), 7.47 (dd, J = 8.0,8.0Hz, 1H, Ar), 7.63 (d, J = 8.0H
z, 1H, Ar), 8.11 (d, J = 8.0Hz, 1H, Ar), 13.41 (brs, 1H, OH) Elemental analysis (C ₁₃ H ₈ ClN ₃ O ₅ S): Calculated value (C = 44.14, H = 2.28, N =
11.88), measured value (C = 44.32, H = 2.47, N = 11.56)

【００７３】３−〔２−（６−フルオロベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物５１〕融点: 261.0-262.0 ℃ MS(EI,70eV): 337(M+,72), 208(57), 180(30), 166(3
4), 153(100) IR(KBr): 2900(OH), 1744(C=O), 1721(C=O), 1521, 143
9, 1406, 1204, 1154, 1116, 769, 631 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.34(s,2H,NCH₂CO₂), 5.22(s,2H,
CH₂Ar), 7.34-7.41(m,1H,Ar), 7.97-8.06(m,2H,Ar), 1
3.43(brs,1H,OH) 元素分析 (C₁₃H₈FN₃O₅S): 計算値(C=46.29,H=2.39,N=1
2.46), 実測値(C=46.59,H=2.59,N=12.68)3- [2- (6-Fluorobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 51] Melting point: 261.0-262.0 ° C MS (EI, 70eV) : 337 (M +, 72), 208 (57), 180 (30), 166 (3
4), 153 (100) IR (KBr): 2900 (OH), 1744 (C = O), 1721 (C = O), 1521, 143
9, 1406, 1204, 1154, 1116, 769, 631 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.34 (s, 2H, NCH ₂ CO ₂ ), 5.22 (s, 2H,
CH ₂ Ar), 7.34-7.41 (m, 1H, Ar), 7.97-8.06 (m, 2H, Ar), 1
3.43 (brs, 1H, OH) Elemental analysis (C ₁₃ H ₈ FN ₃ O ₅ S): Calculated value (C = 46.29, H = 2.39, N = 1
2.46), measured value (C = 46.59, H = 2.59, N = 12.68)

【００７４】３−〔２−（６−メトキシベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物５２〕融点_:270.0-271.0 ℃ MS(EI,70eV): 349(M+,100), 220(47), 192(28), 178(2
8), 165(74), 56(53) IR(KBr): 3000(OH), 1734(C=O), 1443, 1421, 1223, 1
149 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 3.83(s,3H,OCH₃), 4.34(s,2H,NCH
₂CO₂), 5.18(s,2H,CH₂Ar), 7.11(dd,J=8.9,2.4Hz,1H,A
r), 7.67(d,J=2.4Hz,1H,Ar), 7.87(d,J=8.9Hz,1H,Ar) 元素分析 (C₁₄H₁₁N₃O₆ 0.1H₂O): 計算値(C=47.89,H=3.2
2,N=12.97), 実測値(C=47.87,H=3.10,N=11.53)3- [2- (6-methoxybenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 52] Melting point _: 270.0-271.0 ° C MS (EI, 70eV) : 349 (M +, 100), 220 (47), 192 (28), 178 (2
8), 165 (74), 56 (53) IR (KBr): 3000 (OH), 1734 (C = O), 1443, 1421, 1223, 1
149 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 3.83 (s, 3H, OCH ₃ ), 4.34 (s, 2H, NCH
₂ CO ₂ ), 5.18 (s, 2H, CH ₂ Ar), 7.11 (dd, J = 8.9,2.4Hz, 1H, A
r), 7.67 (d, J = 2.4Hz, 1H, Ar), 7.87 (d, J = 8.9Hz, 1H, Ar) Elemental analysis (C ₁₄ H ₁₁ N ₃ O ₆ 0.1H ₂ O): Calculated value ( C = 47.89, H = 3.2
2, N = 12.97), measured value (C = 47.87, H = 3.10, N = 11.53)

【００７５】３−〔２−（５−ブロモベンゾチアゾリ
ル）メチル〕−２，４，５−トリオキソイミダゾリジン
−１−酢酸〔化合物５３〕融点_:272.0-273.0 ℃（分解） MS(EI,70eV) m/z: 293(M+,10), 275(4), 157(100), 136
(36), 120(28), 90(54),74(47), 56(43) IR(KBr): 3000(OH), 1740(C=O), 1428, 1400, 1211 cm
^-1 ¹ H-NMR (DMSO-d₆)δ: 4.34(s,2H,NCH₂CO), 5.26(s,2H,C
H₂Ar), 7.64(dd,J=8.6,1.6Hz,1H,ArH), 8.11(d,J=8.6H
z,1H,ArH), 8.23(d,J=1.6Hz,1H,ArH), 13.20(brs,1H,CO
OH) 元素分析 (C₁₃H₈BrN₃O₅S): 計算値(C=39.21,H=2.03,N=
10.55), 実測値(C=39.41,H=1.86,N=10.12)3- [2- (5-Bromobenzothiazolyl) methyl] -2,4,5-trioxoimidazolidine-1-acetic acid [Compound 53] Melting point _: 272.0-273.0 ° C. (decomposition) MS (EI , 70eV) m / z: 293 (M +, 10), 275 (4), 157 (100), 136
(36), 120 (28), 90 (54), 74 (47), 56 (43) IR (KBr): 3000 (OH), 1740 (C = O), 1428, 1400, 1211 cm
^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.34 (s, 2H, NCH ₂ CO), 5.26 (s, 2H, C
H ₂ Ar), 7.64 (dd, J = 8.6,1.6Hz, 1H, ArH), 8.11 (d, J = 8.6H
z, 1H, ArH), 8.23 (d, J = 1.6Hz, 1H, ArH), 13.20 (brs, 1H, CO
OH) Elemental analysis (C ₁₃ H ₈ BrN ₃ O ₅ S): Calculated value (C = 39.21, H = 2.03, N =
10.55), measured value (C = 39.41, H = 1.86, N = 10.12)

【００７６】３−（２−トリフルオロメチルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸
〔化合物５４〕融点: 217.0-219.0 ℃ MS m/z: 262(M+) IR(KBr): 3100(OH), 1720(C=O), 1445, 1425, 1310, 11
80, 1150, 1105, 765 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.33(s,2H,NCH₂CO₂), 4.90(s,2H,
CH₂N), 7.61-7.43(m,2H,ArH), 7.66(dd,J=8.5,7.0Hz,1
H,ArH), 7.78(d,J=8.5Hz,1H,ArH), 13.40(brs,1H,COOH) 元素分析 (C₁₃H₉F₃N₂O₅): 計算値(C=47.28,H=2.75,N=8.
48), 実測値(C=47.35,H=2.84,N=8.40)3- (2-trifluoromethylbenzyl)
-2,4,5-Trioxoimidazolidine-1-acetic acid [Compound 54] Melting point: 217.0-219.0 ° C MS m / z: 262 (M +) IR (KBr): 3100 (OH), 1720 (C = O) , 1445, 1425, 1310, 11
80, 1150, 1105, 765 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.33 (s, 2H, NCH ₂ CO ₂ ), 4.90 (s, 2H,
CH ₂ N), 7.61-7.43 (m, 2H, ArH), 7.66 (dd, J = 8.5,7.0Hz, 1
H, ArH), 7.78 (d, J = 8.5Hz, 1H, ArH), 13.40 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₉ F ₃ N ₂ O ₅ ): Calculated value (C = 47.28, H = 2.75, N = 8.
48), measured value (C = 47.35, H = 2.84, N = 8.40)

【００７７】３−（３−トリフルオロメチルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸
〔化合物５５〕融点: 190.0-192.5 ℃ MS m/z: 330(M+) IR(KBr): 3000(OH), 1730(C=O), 1455, 1440, 1335, 1
225, 1100 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.32(s,2H,NCH₂CO₂), 4.87(s,2H,
CH₂N), 7.60(dd,J=7.5,7.5Hz,1H,ArH), 7.64-7.72(m,2
H,ArH), 7.74(s,1H,ArH), 13.44(brs,1H,COOH) 元素分析 (C₁₃H₉F₃N₂O₅): 計算値(C=47.28,H=2.75,N=8.
48), 実測値(C=47.17,H=2.61,N=8.31)3- (3-trifluoromethylbenzyl)
-2,4,5-trioxoimidazolidine-1-acetic acid [Compound 55] Melting point: 190.0-192.5 ° C MS m / z: 330 (M +) IR (KBr): 3000 (OH), 1730 (C = O) , 1455, 1440, 1335, 1
225, 1100 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.32 (s, 2H, NCH ₂ CO ₂ ), 4.87 (s, 2H,
CH ₂ N), 7.60 (dd, J = 7.5,7.5Hz, 1H, ArH), 7.64-7.72 (m, 2
H, ArH), 7.74 (s, 1H, ArH), 13.44 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₉ F ₃ N ₂ O ₅ ): Calculated value (C = 47.28, H = 2.75, N = 8.
48), measured value (C = 47.17, H = 2.61, N = 8.31)

【００７８】３−（４−トリフルオロメチルベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸
〔化合物５６〕融点: 190.0-192.0 ℃ MS m/z: 330(M+) IR(KBr): 3000(OH), 1715(C=O), 1440, 1325, 1140, 1
065 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.29(s,2H,NCH₂CO₂), 4.85(s,2H,
CH₂N), 7.58(d,J=7.9Hz,2H,ArH), 7.73(d,J=7.9Hz,2H,A
rH), 13.45(brs,1H,COOH) 元素分析 (C₁₃H₉F₃N₂O₅): 計算値(C=47.28,H=2.75,N=8.
48), 実測値(C=47.14,H=2.75,N=8.41)3- (4-trifluoromethylbenzyl)
-2,4,5-Trioxoimidazolidine-1-acetic acid [Compound 56] Melting point: 190.0-192.0 ° C MS m / z: 330 (M +) IR (KBr): 3000 (OH), 1715 (C = O) , 1440, 1325, 1140, 1
065 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.29 (s, 2H, NCH ₂ CO ₂ ), 4.85 (s, 2H,
CH ₂ N), 7.58 (d, J = 7.9Hz, 2H, ArH), 7.73 (d, J = 7.9Hz, 2H, A
rH), 13.45 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₉ F ₃ N ₂ O ₅ ): Calculated value (C = 47.28, H = 2.75, N = 8.
48), measured value (C = 47.14, H = 2.75, N = 8.41)

【００７９】３−（３−シアノベンジル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物５７〕融点: 181.0-181.5 ℃ MS m/z: 287(M+) IR(KBr): 3100(OH), 2231(CN), 1738(C=O), 1714(C=O),
1446, 1257, 1151 cm^-11H-NMR (DMSO-d₆)δ: 4.28(s,2
H,NCH₂CO₂), 4.82(s,2H,CH₂N), 7.58(dd,J=7.3,7.3Hz,1
H,ArH), 7.71(d,J=7.3Hz,1H,ArH), 7.78(d,J=7.3Hz,1H,
ArH), 7.85(s,1H,ArH), 13.48(brs,1H,COOH) 元素分析 (C₁₃H₉N₃O₅): 計算値(C=54.36,H=3.16,N=14.6
3), 実測値(C=54.36,H=3.13,N=14.57)3- (3-cyanobenzyl) -2,4,5
-Trioxoimidazolidine-1-acetic acid [Compound 57] Melting point: 181.0-181.5 ° C MS m / z: 287 (M +) IR (KBr): 3100 (OH), 2231 (CN), 1738 (C = O), 1714 (C = O),
1446, 1257, 1151 cm ^-11 H-NMR (DMSO-d ₆ ) δ: 4.28 (s, 2
H, NCH ₂ CO ₂ ), 4.82 (s, 2H, CH ₂ N), 7.58 (dd, J = 7.3,7.3Hz, 1
H, ArH), 7.71 (d, J = 7.3Hz, 1H, ArH), 7.78 (d, J = 7.3Hz, 1H,
ArH), 7.85 (s, 1H, ArH), 13.48 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₉ N ₃ O ₅ ): Calculated value (C = 54.36, H = 3.16, N = 14.6
3), measured value (C = 54.36, H = 3.13, N = 14.57)

【００８０】３−（４−シアノベンジル）−２，４，５
−トリオキソイミダゾリジン−１−酢酸〔化合物５８〕融点: 175.0-176.0 ℃ MS m/z: 287(M+) IR(KBr): 3000(OH), 2250(CN), 1730(C=O), 1440, 140
0, 1205, 760 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.30(s,2H,NCH₂CO₂), 4.85(s,2H,
CH₂N), 7.56(d,J=7.9Hz,2H,ArH), 7.84(d,J=7.9Hz,2H,A
rH), 13.41(brs,1H,COOH) 元素分析 (C₁₃H₉N₃O₅): 計算値(C=54.36,H=3.16,N=14.6
3), 実測値(C=53.98,H=3.24,N=14.42)3- (4-cyanobenzyl) -2,4,5
-Trioxoimidazolidine-1-acetic acid [Compound 58] Melting point: 175.0-176.0 ° C MS m / z: 287 (M +) IR (KBr): 3000 (OH), 2250 (CN), 1730 (C = O), 1440, 140
0, 1205, 760 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.30 (s, 2H, NCH ₂ CO ₂ ), 4.85 (s, 2H,
CH ₂ N), 7.56 (d, J = 7.9Hz, 2H, ArH), 7.84 (d, J = 7.9Hz, 2H, A
rH), 13.41 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₉ N ₃ O ₅ ): Calculated value (C = 54.36, H = 3.16, N = 14.6
3), measured value (C = 53.98, H = 3.24, N = 14.42)

【００８１】３−（３−カルボキシベンジル）−２，
４，５−トリオキソイミダゾリジン−１−酢酸〔化合物
５９〕融点: 244.5-245.0 ℃ MS m/z: 287(M+) IR(KBr): 3000(OH), 1730(C=O), 1705(C=O), 1450, 143
0, 1400, 1260, 1155 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.29(s,2H,NCH₂CO₂), 4.81(s,2H,
CH₂N), 7.50(dd,J=8.0,8.0Hz,1H,ArH), 7.59(d,J=8.0H
z,1H,ArH), 7.88(d,J=8.0Hz,1H,ArH), 7.94(s,1H,ArH),
13.14(brs,1H,COOH) 元素分析 (C₁₃H₁₀N₂O₇): 計算値(C=50.99,H=3.29,N=9.
15), 実測値(C=50.87,H=3.40,N=9.08)3- (3-carboxybenzyl) -2,
4,5-Trioxoimidazolidine-1-acetic acid [Compound 59] Melting point: 244.5-245.0 ° C MS m / z: 287 (M +) IR (KBr): 3000 (OH), 1730 (C = O), 1705 ( C = O), 1450, 143
0, 1400, 1260, 1155 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.29 (s, 2H, NCH ₂ CO ₂ ), 4.81 (s, 2H,
CH ₂ N), 7.50 (dd, J = 8.0,8.0Hz, 1H, ArH), 7.59 (d, J = 8.0H
z, 1H, ArH), 7.88 (d, J = 8.0Hz, 1H, ArH), 7.94 (s, 1H, ArH),
13.14 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₁₀ N ₂ O ₇ ): Calculated value (C = 50.99, H = 3.29, N = 9.
15), measured value (C = 50.87, H = 3.40, N = 9.08)

【００８２】３−（３−カルバモイルベンジル）−２，
４，５−トリオキソイミダゾリジン−１−酢酸〔化合物
６０〕融点: 234.5-236.0 ℃ IR(KBr): 3450(NH₂), 3000(OH), 1730(C=O), 1450, 14
25, 1400, 1145, 765 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.30(s,2H,NCH₂CO₂), 4.39(s,2H,
CH₂N), 7.60-7.29(m,3H,ArH), 7.74(brs,2H,NH₂), 8.00
(s,1H,ArH), 13.32(brs,1H,COOH) 元素分析 (C₁₃H₁₁N₃O₆): 計算値(C=51.15,H=3.63,N=1
3.77), 実測値(C=50.74,H=3.62,N=13.48)3- (3-carbamoylbenzyl) -2,
4,5-Trioxoimidazolidine-1-acetic acid [Compound 60] Melting point: 234.5-236.0 ° C IR (KBr): 3450 (NH ₂ ), 3000 (OH), 1730 (C = O), 1450, 14
25, 1400, 1145, 765 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.30 (s, 2H, NCH ₂ CO ₂ ), 4.39 (s, 2H,
CH ₂ N), 7.60-7.29 (m, 3H, ArH), 7.74 (brs, 2H, NH ₂ ), 8.00
(s, 1H, ArH), 13.32 (brs, 1H, COOH) Elemental analysis (C ₁₃ H ₁₁ N ₃ O ₆ ): Calculated value (C = 51.15, H = 3.63, N = 1)
3.77), measured value (C = 50.74, H = 3.62, N = 13.48)

【００８３】３−（３−メトキシカボニルベンジル）−
２，４，５−トリオキソイミダゾリジン−１−酢酸〔化
合物６１〕融点: 89.0-90.0 ℃（分解） MS m/z: 332(M+) IR(KBr): 3100(OH), 1728(C=O), 1443, 1406, 1302, 12
09, 1149, 756 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 3.86(s,3H,OCH₃), 4.30(s,2H,NCH
₂CO₂), 4.82(s,2H,CH₂N), 7.52(dd,J=8.0,8.0Hz,1H,O-C
-Ar), 7.63(d,J=8.0,2H,ArH), 7.90(d,J=8.0Hz,1H,Ar
H), 7.96(s,1H,ArH), 13.39(brs,1H,COOH) 元素分析 (C₁₄H₁₂N₂O₇): 計算値(C=52.51,H=3.77,N=8.
49), 実測値(C=52.60,H=3.77,N=8.49)3- (3-methoxycarbonylbenzyl)-
2,4,5-Trioxoimidazolidine-1-acetic acid [Compound 61] Melting point: 89.0-90.0 ° C (decomposition) MS m / z: 332 (M +) IR (KBr): 3100 (OH), 1728 (C = O), 1443, 1406, 1302, 12
09, 1149, 756 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 3.86 (s, 3H, OCH ₃ ), 4.30 (s, 2H, NCH
₂ CO ₂ ), 4.82 (s, 2H, CH ₂ N), 7.52 (dd, J = 8.0,8.0Hz, 1H, OC
-Ar), 7.63 (d, J = 8.0,2H, ArH), 7.90 (d, J = 8.0Hz, 1H, Ar
H), 7.96 (s, 1H, ArH), 13.39 (brs, 1H, COOH) Elemental analysis (C ₁₄ H ₁₂ N ₂ O ₇ ): Calculated value (C = 52.51, H = 3.77, N = 8.
49), measured value (C = 52.60, H = 3.77, N = 8.49)

【００８４】３−（４−クロロ−３−ニトロベンジル）
−２，４，５−トリオキソイミダゾリジン−１−酢酸
〔化合物６２〕融点: 178.0-181.0 ℃（分解） MS m/z: 332(M+) IR(KBr): 3000(OH), 1730(C=O), 1710(C=O), 1535(N
O₂), 1435, 1345(NO₂), 1255, 1145 cm^-1 ¹ H-NMR (DMSO-d₆)δ: 4.29(s,2H,NCH₂CO₂), 4.86(s,2H,
CH₂N), 7.70(dd,J=8.0,1.5Hz,1H,ArH), 7.78(d,J=8.0H
z,1H,ArH), 8.06(d,J=1.5Hz,1H,ArH) 元素分析 (C₁₂H₈ClN₃O₇): 計算値(C=42.19,H=2.36,N=1
2.30), 実測値(C=42.10,H=2.37,N=12.26)3- (4-chloro-3-nitrobenzyl)
-2,4,5-Trioxoimidazolidine-1-acetic acid [Compound 62] Melting point: 178.0-181.0 ° C (decomposition) MS m / z: 332 (M +) IR (KBr): 3000 (OH), 1730 (C = O), 1710 (C = O), 1535 (N
O ₂ ), 1435, 1345 (NO ₂ ), 1255, 1145 cm ^-1 ¹ H-NMR (DMSO-d ₆ ) δ: 4.29 (s, 2H, NCH ₂ CO ₂ ), 4.86 (s, 2H,
CH ₂ N), 7.70 (dd, J = 8.0,1.5Hz, 1H, ArH), 7.78 (d, J = 8.0H
z, 1H, ArH), 8.06 (d, J = 1.5Hz, 1H, ArH) Elemental analysis (C ₁₂ H ₈ ClN ₃ O ₇ ): Calculated value (C = 42.19, H = 2.36, N = 1)
2.30), measured value (C = 42.10, H = 2.37, N = 12.26)

【００８５】[0085]

【作用】以下に、本発明化合物の薬理作用について述べ
る。（１）アルドース還元酵素阻害作用ラット水晶体より調製したアルドース還元酵素を用い
て、本発明化合物のアルドース還元酵素阻害作用を調べ
た。即ち、リン酸緩衝液、ＮＡＤＰＨ及びアルドース還
元酵素から成る反応系に、被検薬を加え、数分間吸光度
の安定を確認した後、グリセルアルデヒドを添加して３
４０ｎｍの吸光度の経時的な減少を測定することにより
被検薬のアルドース還元酵素に対する阻害能を測定し
た。The pharmacological action of the compound of the present invention will be described below. (1) Aldose Reductase Inhibitory Action The aldose reductase inhibitory action of the compound of the present invention was examined using aldose reductase prepared from rat lens. That is, a test drug was added to a reaction system consisting of a phosphate buffer solution, NADPH and aldose reductase, and the stability of the absorbance was confirmed for several minutes, and then glyceraldehyde was added to the reaction system.
The ability of the test drug to inhibit aldose reductase was measured by measuring the decrease in absorbance at 40 nm with time.

【００８６】結果の一例を第１表に示す。尚、表中のア
ルドース還元酵素に対する阻害率は、被検薬濃度１×１
０^-7Ｍにおける値である。Table 1 shows an example of the results. In addition, the inhibition rate for aldose reductase in the table is the test drug concentration of 1 × 1.
It is a value at 0 ^-7 M.

【表１】 [Table 1]

【００８７】[0087]

【発明の効果】以上の薬理試験の結果から明らかなよう
に、本発明パラバン酸誘導体は優れたアルドース還元酵
素阻害作用を示し、且つ毒性が低く、糖尿病合併症に対
する医薬として非常に有用なものである。即ち、細胞内
ソルビトールの過剰蓄積に起因する糖尿病性神経障害、
糖尿病性白内障或いは糖尿病性網膜症、糖尿病性腎症、
糖尿病性皮膚障害等の糖尿病性細小血管症など各種糖尿
病合併症を治療、予防するための薬剤として有用であ
る。As is clear from the results of the above-mentioned pharmacological tests, the parabanic acid derivative of the present invention exhibits an excellent aldose reductase inhibitory action, has low toxicity, and is extremely useful as a drug for diabetic complications. is there. That is, diabetic neuropathy caused by excessive accumulation of intracellular sorbitol,
Diabetic cataract or diabetic retinopathy, diabetic nephropathy,
It is useful as a drug for treating and preventing various diabetic complications such as diabetic microangiopathy such as diabetic skin disorder.

【００８８】ラット腎臓のアルデヒド還元酵素に対する
本発明化合物の阻害作用を、１×１０^-4Ｍの被検薬濃度
にて測定したが、ほとんど阻害はみられなかった。この
ように、糖尿病合併症を誘因するソルビトールの産生に
関与するアルドース還元酵素に対して高い酵素選択性を
有する本発明化合物は、低毒性で安全性が高いため、長
期投与を要する慢性的な上記疾患の治療に特に有利であ
る。The inhibitory effect of the compound of the present invention on the aldehyde reductase of rat kidney was measured at a test drug concentration of 1 × 10 ^-4 M, but almost no inhibition was observed. As described above, the compound of the present invention having a high enzyme selectivity for aldose reductase involved in the production of sorbitol which induces diabetic complications, has low toxicity and high safety, and thus chronic chronic administration requiring long-term administration. It is particularly advantageous for the treatment of diseases.

───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.⁶ 識別記号庁内整理番号ＦＩ技術表示箇所Ｃ０７Ｄ 403/06 ２０９Ｃ０７Ｄ 403/06 ２０９ 409/06 ２３３ 409/06 ２３３ 417/06 ２３３ 417/06 ２３３ //(Ｃ０７Ｄ 401/06 213:16 233:96） (Ｃ０７Ｄ 401/06 213:61 233:96） (Ｃ０７Ｄ 409/06 233:96 333:10） (Ｃ０７Ｄ 417/06 233:96 277:64） (Ｃ０７Ｄ 417/06 233:96 277:68） (72)発明者永木康弘兵庫県加東郡社町木梨字川北山442番１日本臓器製薬株式会社生物活性科学研究所内─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication location C07D 403/06 209 C07D 403/06 209 409/06 233 409/06 233 417/06 233 417/06 233 // (C07D 401/06 213: 16 233: 96) (C07D 401/06 213: 61 233: 96) (C07D 409/06 233: 96 333: 10) (C07D 417/06 233: 96 277: 64) ) (C07D 417/06 233: 96 277: 68) (72) Inventor Yasuhiro Nagaki 442-1, Kawakitayama, Kinashi, Kato-gun, Hyogo, Japan

Claims

[Reference number] PC-248 [Claims]

1. A parabanic acid derivative represented by the general formula (I) and a pharmaceutically acceptable salt thereof. Embedded image [Wherein, R represents hydrogen, a lower alkyl group or a benzyl group, X represents a trifluoromethyl group, a cyano group, a carboxy group, a carbamoyl group, a lower alkoxycarbonyl group or a nitro group and a phenyl group substituted with a halogen, Lower alkyl group, lower alkoxy group, trifluoromethyl group, nitro group and / or benzothiazolyl group optionally substituted with halogen, nitro group and / or naphthyl group or pyridyl group optionally substituted with halogen,
It represents an anthraquinonyl group, a phthalimido group or a thienyl group, and n is an integer of 1 to 3. ]

2. The parabanic acid derivative according to claim 1, wherein X is a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, a nitro group and / or a benzothiazolyl group optionally substituted with halogen.

3. The parabanic acid derivative according to claim 1, wherein X is a nitro group and / or a naphthyl group optionally substituted with halogen.

4. The parabanic acid derivative according to claim 1, wherein X is a nitro group and a phenyl group substituted with halogen.

5. A therapeutic agent for diabetic complications, which comprises as an active ingredient at least one of the parabanic acid derivative represented by the general formula (I) and a pharmaceutically acceptable salt thereof. Embedded image [Wherein, R represents hydrogen, a lower alkyl group or a benzyl group, X represents a trifluoromethyl group, a cyano group, a carboxy group, a carbamoyl group, a lower alkoxycarbonyl group or a nitro group and a phenyl group substituted with a halogen, Lower alkyl group, lower alkoxy group, trifluoromethyl group, nitro group and / or benzothiazolyl group optionally substituted with halogen, nitro group and / or naphthyl group or pyridyl group optionally substituted with halogen,
It represents an anthraquinonyl group, a phthalimido group or a thienyl group, and n is an integer of 1 to 3. ]

6. A compound represented by the general formula (II): [In the formula, R represents hydrogen, a lower alkyl group or a benzyl group, and n is an integer of 1 to 3. ] And a compound represented by the general formula (III): [In the formula, X is a trifluoromethyl group, a cyano group, a carboxy group, a carbamoyl group, a lower alkoxycarbonyl group or a nitro group and a phenyl group substituted with a halogen, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, Benzothiazolyl group optionally substituted with nitro group and / or halogen, naphthyl group or pyridyl group optionally substituted with nitro group and / or halogen, anthraquinonyl group, phthalimido group or thienyl group, R ₁ is a hydroxyl group , Halogen, lower alkyl-
Be substituted with SO ₂ -O- group or a lower alkyl group represents a phenyl -SO ₂ -O- group. ] The method for producing a parabanic acid derivative represented by the general formula (I), which comprises subjecting the compound represented by the formula to a condensation reaction and further hydrolyzing it as desired. Embedded image [In the Formula, R, X, and n are the same as the above. ]