JP2557090B2 - Caffeic acid derivative and pharmaceutical composition containing the same - Google Patents

Caffeic acid derivative and pharmaceutical composition containing the same

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Publication number
JP2557090B2
JP2557090B2 JP63106274A JP10627488A JP2557090B2 JP 2557090 B2 JP2557090 B2 JP 2557090B2 JP 63106274 A JP63106274 A JP 63106274A JP 10627488 A JP10627488 A JP 10627488A JP 2557090 B2 JP2557090 B2 JP 2557090B2
Authority
JP
Japan
Prior art keywords
compound
group
acid derivative
caffeic acid
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
JP63106274A
Other languages
Japanese (ja)
Other versions
JPH01275552A (en
Inventor
秀連 長
勝 植田
美樹子 浜口
誠逸 室田
育男 森田
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Suntory Ltd
Original Assignee
Suntory Ltd
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Filing date
Publication date
Priority to JP63106274A priority Critical patent/JP2557090B2/en
Application filed by Suntory Ltd filed Critical Suntory Ltd
Priority to AT89107771T priority patent/ATE109770T1/en
Priority to DE68917357T priority patent/DE68917357T2/en
Priority to EP89107771A priority patent/EP0339671B1/en
Priority to AU33813/89A priority patent/AU618595B2/en
Priority to KR1019890005689A priority patent/KR900016098A/en
Priority to US07/344,583 priority patent/US5063243A/en
Publication of JPH01275552A publication Critical patent/JPH01275552A/en
Application granted granted Critical
Publication of JP2557090B2 publication Critical patent/JP2557090B2/en
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Expired - Lifetime legal-status Critical Current

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

【発明の詳細な説明】 (産業上の利用分野) 本発明は一般式(I) (式中、Xは水素原子、または水酸基を表し、R1は水素
原子、炭素数1〜20の直鎖または分岐アルキル基又はア
ルケニル基を表す。) で示されるカフェー酸誘導体および該誘導体を含む医薬
組成物に関するものである。
DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a compound represented by the general formula (I): (Wherein, X represents a hydrogen atom or a hydroxyl group, R 1 represents a hydrogen atom, a linear or branched alkyl group or alkenyl group having 1 to 20 carbon atoms), and a caffeic acid derivative represented by the formula and a derivative thereof. It relates to a pharmaceutical composition.

本発明のカフェー酸誘導体は、12−リポキシゲナーゼ
阻害作用を有し、動脈硬化の予防等、循環系疾患治療剤
として有用である。
The caffeic acid derivative of the present invention has a 12-lipoxygenase inhibitory action and is useful as a therapeutic agent for cardiovascular diseases such as prevention of arteriosclerosis.

(従来の技術) アレルギー疾患、特に喘息の原因と考えられるロイコ
トリエンは、アラキドン酸から5−リポキシゲナーゼの
作用による5−ハイドロパーオキシ−イコサテトラエン
酸(5−HPETE)、5−ヒドロキシ−イコサイテトラエ
ン酸(5−HETE)への変換を経て生成される。このよう
な知見に基づき、5−リポキシゲナーゼ阻害活性を有す
る化合物は循環器系疾患治療剤の開発を目的として数多
く報告されている。
(Prior Art) Leukotrienes, which are considered to be the cause of allergic diseases, especially asthma, include 5-hydroperoxy-icosatetraenoic acid (5-HPETE) and 5-hydroxy-icosietetraenoic acid due to the action of 5-lipoxygenase from arachidonic acid. It is generated through conversion to (5-HETE). Based on such findings, many compounds having 5-lipoxygenase inhibitory activity have been reported for the purpose of developing therapeutic agents for cardiovascular diseases.

一方、アラキドン酸から12−ハイドロパーオキシ−イ
コサテトラエン酸(12−HPETE)、12−ヒドロキシ−イ
コサテトラエン酸(12−HPETE)への変換酵素である12
−リポキシゲナーゼに関しては、多田らによる12−HETE
が虚血性心疾患の発症に関与しているという報告(Card
iovascular Research,21巻、No.8,551〜558頁,1987
年)、及び室田らによる12−HETEが内皮細胞障害活性及
び血管中膜平滑筋細胞の遊走促進作用を示し、これが動
脈硬化、賢炎等の血管病変の増悪化に関与しているとい
う報告(治療学,13巻,No.6,785〜788頁,1984年)があ
る。
On the other hand, it is a conversion enzyme from arachidonic acid to 12-hydroperoxy-icosatetraenoic acid (12-HPETE) and 12-hydroxy-icosatetraenoic acid (12-HPETE).
-For lipoxygenase, see 12-HETE by Tada et al.
Is involved in the development of ischemic heart disease (Card
iovascular Research, Volume 21, No.8, pp.551-558, 1987
, And Muroda et al. Reported that 12-HETE has an endothelial cell-damaging activity and an action of promoting migration of vascular medial smooth muscle cells, which is involved in the exacerbation of vascular lesions such as arteriosclerosis and sickness ( Therapeutics, Vol. 13, No. 6, 785-788 pages, 1984).

(発明が解決しようとする課題) 上記の知見より、12−リポキシゲナーゼ阻害活性を持
つ化合物は、循環器系疾患剤としての有用性が期待され
るが、そのような化合物としては、従来コガネバナ(Sc
utellaria baicalensis)より単離されたバイカレン(B
aicalein)以外は知られていない。なお、バイカレンは
次の構造を有する。
(Problems to be Solved by the Invention) From the above findings, a compound having 12-lipoxygenase inhibitory activity is expected to be useful as a cardiovascular disease agent, but as such a compound, a conventional Scutellaria baicalensis (Sc
Baicalen (B isolated from utellaria baicalensis)
Other than aicalein) is not known. Baicalen has the following structure.

(課題を解決するための手段) かかる状況に鑑み、本発明者らは、12−リポキシゲナ
ーゼ阻害活性を有する化合物を広くスクリーニングした
結果、一般式(I)で表されるカフェー酸誘導体が、バ
イカレンと同等またはそれ以上の阻害活性を有すること
を見出し、本発明を完成した。
(Means for Solving the Problems) In view of such circumstances, the present inventors extensively screened compounds having 12-lipoxygenase inhibitory activity, and as a result, the caffeic acid derivative represented by the general formula (I) was identified as baicalene. The present invention has been completed based on the finding that they have equivalent or higher inhibitory activity.

本発明のカフェー酸誘導体は、以下の方法により合成
することができる。即ち、一般式(II): (式中、Xは上記式(I)で定義された意味を表す。) で表されるベンズアルデヒドとシアノ酢酸又はそのアル
キルまたはアルケニルエステルとを反応に関与しない適
当な溶媒、例えば、ベンゼン、トルエン中、触媒として
の塩基、例えばピリジン、ピペリジン等を用い、通常の
クネベナーゲル(knoevenagel)、縮合反応を行うこと
により合成することができる。
The caffeic acid derivative of the present invention can be synthesized by the following method. That is, the general formula (II): (In the formula, X represents the meaning defined in the above formula (I).) In a suitable solvent which does not participate in the reaction of the benzaldehyde and the cyanoacetic acid or its alkyl or alkenyl ester, for example, in benzene or toluene. , A base such as pyridine or piperidine as a catalyst can be used to carry out an ordinary Knoevenagel condensation reaction.

尚、こうして合成された本発明の化合物の精製は、反
応液を冷却後、晶出する結晶を濾取するか、もしくはシ
リカゲルカラムクロマトグラフィー等を用いることによ
り行うことができる。
The compound of the present invention thus synthesized can be purified by cooling the reaction solution and then filtering out the crystal that crystallizes out, or by using silica gel column chromatography or the like.

式(I)において、アルキル基としては、例えばメチ
ル基、エチル基、プロピル基、イソプロピル基、n−ブ
チル基、n−ペンチル基、n−ヘキシル基、イコシル基
等が挙げられ、そしてアルケニル基としては、例えば、
アリル基、2−ブテニル基、3−ブテニル基、4−ペン
テニル基、4−ヘキセニル基、イコサ−5,8,11,14−テ
トラエニル基等をあげることができる。
In formula (I), examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an n-pentyl group, an n-hexyl group and an icosyl group, and an alkenyl group. Is, for example,
Examples thereof include an allyl group, a 2-butenyl group, a 3-butenyl group, a 4-pentenyl group, a 4-hexenyl group, and an icosa-5,8,11,14-tetraenyl group.

また、本発明にいう薬学的に許容し得る塩とは、医学
として使用可能な塩基付加塩であって、例えばナトリウ
ム、カリウム、カルシウムとの塩等が挙げられる。ま
た、本発明化合物を循環器系疾患治療剤として用いる場
合には、前記化合物またはその薬学的に許容される塩を
単独、または公知の無害な賦形剤等と共にカプセル剤、
錠剤、注射剤等の適宜な剤形として経口的または非経口
的に投与することができる。これらの製剤は例えば次の
ようにして調整される。原体を微粉砕したのち賦形剤、
例えば乳糖、澱粉またはその誘導体、セルロース誘導体
等と混合してゼラチンカプセルに詰めカプセル剤とす
る。また錠剤とするには上記賦形剤のほかにカルボキシ
メチルセルロースナトリウム、アルギン酸、アラビアゴ
ム等の結合剤と水を加えて混練し、必要により顆粒とし
たのち、さらにタルク、ステアリン酸等の潤滑剤を添加
して通常の圧縮打錠機を用いて錠剤を調整する。注射に
よる非経口投与に際しては、本発明化合物を減菌蒸留
水、または減菌生理食塩水に溶解し、アンプルに封入し
て注射製剤とする。必要により安定化剤、緩衝物質を含
有させてもよい。
Further, the pharmaceutically acceptable salt referred to in the present invention is a base addition salt which can be used medically, and examples thereof include salts with sodium, potassium and calcium. When the compound of the present invention is used as a therapeutic agent for cardiovascular disease, the compound or a pharmaceutically acceptable salt thereof alone or together with a known harmless excipient, etc., a capsule,
It can be orally or parenterally administered in an appropriate dosage form such as tablets and injections. These formulations are prepared as follows, for example. After pulverizing the drug substance, excipients,
For example, it is mixed with lactose, starch or a derivative thereof, a cellulose derivative, etc., and packed in a gelatin capsule to obtain a capsule. In order to make tablets, in addition to the above excipients, a binder such as sodium carboxymethylcellulose, alginic acid and gum arabic and water are added and kneaded, and then kneaded into granules if necessary, and then lubricants such as talc and stearic acid are further added. Add and adjust the tablets using a conventional compression tableting machine. For parenteral administration by injection, the compound of the present invention is dissolved in sterile distilled water or sterile physiological saline and sealed in an ampoule to give an injection preparation. If necessary, a stabilizer and a buffer substance may be contained.

循環器系疾患の治療剤の有効量は、疾患の種類、およ
び症状の強さ、投与方法、患者の身体的要因に依存して
変化するが、一般に疾患の症状を抑えるのに充分な量を
投与する。
The effective amount of the therapeutic agent for cardiovascular disease varies depending on the kind of the disease, the intensity of the symptoms, the administration method, and the physical factors of the patient, but in general, an effective amount for suppressing the symptoms of the disease should be used. Administer.

次に本発明の化合物の製造を実施例により示すが、本
発明はこれらの実施例に限定されるものではない。
Next, production of the compound of the present invention will be described by way of examples, but the present invention is not limited to these examples.

実施例1 エチル 2−シアノ−3−(3,4−ジヒドロキシフェニ
ル)−2−プロペノエート(化合物1) 3,4−ジヒドロキシベンズアルデヒド2.0g(14.5mmo
l)のエタノール(10ml)溶液に、シアノ酢酸エチル1.6
g(14.5mmol)とピペリジン3滴を加え、室温で20時間
反応させた。反応液に水を加え、析出した結晶を濾取し
てエタノールと水の混液で再結晶することにより、標記
化合物2.3g(9.9mmol)を得た。なお、本発明は溶媒を
ベンゼンとし、加熱還流しても得られる。同様にして化
合物2〜6も合成した。
Example 1 Ethyl 2-cyano-3- (3,4-dihydroxyphenyl) -2-propenoate (Compound 1) 2.0 g of 3,4-dihydroxybenzaldehyde (14.5 mmo
l) in ethanol (10 ml), add 1.6 parts of ethyl cyanoacetate
g (14.5 mmol) and 3 drops of piperidine were added and reacted at room temperature for 20 hours. Water was added to the reaction solution, and the precipitated crystals were collected by filtration and recrystallized with a mixed solution of ethanol and water to obtain 2.3 g (9.9 mmol) of the title compound. The present invention can also be obtained by using benzene as a solvent and heating under reflux. Compounds 2 to 6 were also synthesized in the same manner.

化合物2: 2−シアノ−3−(3,4−ジヒドロキシフェ
ニル)−2−プロペン酸 化合物3: 2−シアノ−3−(3,4,5−ヒドロキシフェ
ニル)−2−プロペノエート 化合物4: 2−シアノ−3−(3,4,5−トリヒドロキシ
フェニル)−2−プロペン酸 化合物5: メチル 2−シアノ−3−(3,4−ジヒドロ
キシフェニル)−2−プロペノエート 化合物6: イソプロピル 2−シアノ−3−(3,4−ジ
ヒドロキシフェニル)−2−プロペノエート 実施例2 (5z,8z,11z,14z)−イコサテトラエニル 2−シアノ
−3−(3,4−ジヒドロキシフェニル)−2−プロペノ
エート(化合物7) 水素化アルミニウムリチウム90mg(2.4mmol)を無水
テトラヒドロフラン(40ml)に懸濁し、窒素気流下で0
℃に冷却し、冷却撹拌下にアラキドン酸600mg(2.0mmo
l)の無水テトラヒドロフラン(35ml)溶液を滴下し
た。0℃で1時間撹拌した後、更に室温で1時間撹拌し
た。次に水0.1mlを徐々に加え、続いて10%水酸化ナト
リウム水溶液0.1mlおよび水0.3mlを加えて1時間放置し
た。この反応液を硫酸マグネシウムで乾燥し、減圧濃縮
して、(5z,8z,11z,14z)−イコサテトラエノール510mg
(1.8mmol)を得た。
Compound 2: 2-Cyano-3- (3,4-dihydroxyphenyl) -2-propenoic acid Compound 3: 2-Cyano-3- (3,4,5-hydroxyphenyl) -2-propenoate Compound 4: 2- Cyano-3- (3,4,5-trihydroxyphenyl) -2-propenoic acid Compound 5: Methyl 2-cyano-3- (3,4-dihydroxyphenyl) -2-propenoate Compound 6: Isopropyl 2-cyano- 3- (3,4-Dihydroxyphenyl) -2-propenoate Example 2 (5z, 8z, 11z, 14z) -icosatetraenyl 2-cyano-3- (3,4-dihydroxyphenyl) -2-propenoate ( Compound 7) 90 mg (2.4 mmol) of lithium aluminum hydride was suspended in anhydrous tetrahydrofuran (40 ml), and the suspension was cooled to 0 under a nitrogen stream.
Cooled to ℃, stirred and cooled with arachidonic acid 600mg (2.0mmo
A solution of l) in anhydrous tetrahydrofuran (35 ml) was added dropwise. After stirring at 0 ° C. for 1 hour, the mixture was further stirred at room temperature for 1 hour. Next, 0.1 ml of water was gradually added, then 0.1 ml of 10% aqueous sodium hydroxide solution and 0.3 ml of water were added, and the mixture was allowed to stand for 1 hour. The reaction mixture was dried over magnesium sulfate and concentrated under reduced pressure to give (5z, 8z, 11z, 14z) -icosatetraenol 510mg.
(1.8 mmol) was obtained.

次に、この生成物をN,N−ジメチルホルムアミド(10m
l)に溶解し、0℃に冷却し、冷却撹拌下に同じ溶媒に
溶解した4mlのシアノ酢酸150mg(1.8mmol)、同じく2ml
の1−エチル−3−(3−ジメチルアミノプロピル)カ
ルボジイミド273mg(1.8mmol)、同じく2mlの4−ジメ
チルアミノピリジン21mg(0.2mmol)を順次加えた後、
1時間撹拌し、更に室温で3時間撹拌した。
The product was then added to N, N-dimethylformamide (10m
l), cooled to 0 ° C, and dissolved in the same solvent under cooling and stirring 4 ml of cyanoacetic acid 150 mg (1.8 mmol), also 2 ml.
1-ethyl-3- (3-dimethylaminopropyl) carbodiimide of 273 mg (1.8 mmol) and also 2 ml of 4-dimethylaminopyridine 21 mg (0.2 mmol) were sequentially added,
The mixture was stirred for 1 hour and further at room temperature for 3 hours.

続いて反応液を減圧濃縮した後、水を加え、ジエチル
エーテルで抽出した。有機層を硫酸マグネシウムで乾燥
して、減圧濃縮後、カラムクロマトグラフィーで精製し
て、(5z,8z,11z,14z)−イコサテトラエニルシアノア
セテート300mg(0.8mmol)を得た。
Subsequently, the reaction solution was concentrated under reduced pressure, water was added, and the mixture was extracted with diethyl ether. The organic layer was dried over magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain (5z, 8z, 11z, 14z) -icosatetraenyl cyanoacetate 300 mg (0.8 mmol).

この生成物を、ベンゼン10mlに溶解し、3,4−ジヒド
ロキシベンズアルデヒド116mg(0.8mmol)のジエチルエ
ーテル溶液(10ml)とピペリジン1滴を加え、生成する
水を除きながら、1.5時間還流させた。反応液を冷却
し、減圧濃縮することにより標記化合物240mg(0.5mmo
l)を得た。
This product was dissolved in 10 ml of benzene, and a solution of 116 mg (0.8 mmol) of 3,4-dihydroxybenzaldehyde in diethyl ether (10 ml) and 1 drop of piperidine were added, and the mixture was refluxed for 1.5 hours while removing water produced. The reaction mixture was cooled and concentrated under reduced pressure to give 240 mg (0.5 mmo) of the title compound.
l) got.

同様に、アラキドン酸に代えて、アラキジン酸を用い
ることにより、イコシル 2−シアノ−3−(3,4−ジ
ヒドロキシフェニル)−2−プロペノエート(化合物
8)を合成した。
Similarly, icosyl 2-cyano-3- (3,4-dihydroxyphenyl) -2-propenoate (Compound 8) was synthesized by using arachidic acid instead of arachidonic acid.

以上で合成した化合物1〜8の収率、性状等を第1表
に示す。
Table 1 shows yields, properties, etc. of the compounds 1 to 8 synthesized above.

次に、本発明の治療剤の製剤例を示す。 Next, preparation examples of the therapeutic agent of the present invention will be shown.

製剤例1(カプセル剤) 化合物1 10g 乳糖 30g トウモロコシデンプン 30g 結晶セルロース 28gステアリン酸マグネシウム 2g 全量 100g 上記成分を常法により顆粒化した後、ゼラチン硬カプ
セル200個に充填した。得られた製剤は、1カプセル中
に有効成分50mgを含有する。
Formulation Example 1 (Capsule) Compound 1 10 g Lactose 30 g Corn starch 30 g Crystalline cellulose 28 g Magnesium stearate 2 g Total amount 100 g The above components were granulated by a conventional method and filled into 200 gelatin hard capsules. The resulting formulation contains 50 mg of active ingredient in a capsule.

製剤例2(錠剤) 化合物1 20g 乳糖 40g トウモロコシデンプン 20g ヒドロキシプロピルセルロース 18gタルク 2g 全量 100g 上記成分を混和機で十分に混和した後、打錠して、50
0mgの錠剤200個を製造した。こうして1浄財中に有効成
分100mgを含有する本発明の製剤を得た。
Formulation Example 2 (tablets) Compound 1 20 g Lactose 40 g Corn starch 20 g Hydroxypropyl cellulose 18 g Talc 2 g Total amount 100 g After thoroughly mixing the above ingredients in a kneader, tableting, 50
200 0 mg tablets were produced. Thus, a preparation of the present invention containing 100 mg of the active ingredient in one purified product was obtained.

薬理試験例 方法 本発明化合物の12−のリポキシゲナーゼ阻害活性を以
下の薬理試験によって測定した。
Example of Pharmacological Test Method The 12-lipoxygenase inhibitory activity of the compound of the present invention was measured by the following pharmacological test.

ラットの腹部大動脈より、クエン酸血を採取した。常
法に従い洗浄血小板を調整し、0.45%NaClを含むリン酸
バッファー(pH=8.0)で希釈し、酵素液とした。その
酵素液に被験化合物(10μN)を添加し、さらに
14C〕アラキドン酸0.2μCi、アラキドン酸3μgを添
加し、37℃にて3〜5分間反応させた。その反応液を薄
層クロマトグラムで展開し、ラジオクロマトスキャナー
により12−HETEを同定し、その産生量の減少を12−リポ
キシゲナーゼ阻害活性の指標にした。
Citrated blood was collected from the abdominal aorta of the rat. Washed platelets were prepared according to a conventional method and diluted with a phosphate buffer (pH = 8.0) containing 0.45% NaCl to obtain an enzyme solution. A test compound (10 µN) was added to the enzyme solution, 0.2 µCi of [ 14 C] arachidonic acid and 3 µg of arachidonic acid were further added, and the mixture was reacted at 37 ° C for 3 to 5 minutes. The reaction solution was developed with a thin-layer chromatogram, 12-HETE was identified by a radiochromatographic scanner, and the decrease in the production amount was used as an index of 12-lipoxygenase inhibitory activity.

結果 対照(被験薬無添加)の12−HETE生成量を100%とし
たとき、本発明の化合物1、5および6を夫々添加する
と、12−HETEの生成量が夫々38.1%、36.0%および31.4
%と有意な12−リポキシゲナーゼ阻害活性が認められ
た。
Results When the amount of 12-HETE produced in the control (without addition of the test drug) was 100%, the amounts of 12-HETE produced were 38.1%, 36.0% and 31.4% when the compounds 1, 5 and 6 of the present invention were added, respectively.
%, A significant 12-lipoxygenase inhibitory activity was observed.

───────────────────────────────────────────────────── フロントページの続き (72)発明者 室田 誠逸 東京都文京区小石川3―8―11―301 (72)発明者 森田 育男 東京都板橋区蓮根3―12―27―320 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Seiko Murota 3-8-11-301 Koishikawa, Bunkyo-ku, Tokyo (72) Inventor Ikuo Morita 3-12-27-320 Hasune, Itabashi-ku, Tokyo

Claims (2)

(57)【特許請求の範囲】(57) [Claims] 【請求項1】一般式(I): (式中、Xは水素原子、または水酸基を表し、R1は水素
原子、炭素数1〜20の直鎖または分岐アルキル基又はア
ルケニル基を表す。) で示されるカフェー酸誘導体およびその薬学的に許容し
うる塩。
1. General formula (I): (In the formula, X represents a hydrogen atom or a hydroxyl group, R 1 represents a hydrogen atom, a linear or branched alkyl group or alkenyl group having 1 to 20 carbon atoms.) And a pharmaceutically acceptable derivative thereof. Acceptable salt.
【請求項2】請求項1記載の化合物を有効成分として含
有する循環器系疾患治療剤。
2. A therapeutic agent for a circulatory disease comprising the compound according to claim 1 as an active ingredient.
JP63106274A 1988-04-28 1988-04-28 Caffeic acid derivative and pharmaceutical composition containing the same Expired - Lifetime JP2557090B2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP63106274A JP2557090B2 (en) 1988-04-28 1988-04-28 Caffeic acid derivative and pharmaceutical composition containing the same
DE68917357T DE68917357T2 (en) 1988-04-28 1989-04-28 Derivatives of caffeine acid and pharmaceutical compositions containing them.
EP89107771A EP0339671B1 (en) 1988-04-28 1989-04-28 Derivative of caffeic acid and pharmaceutical composition containing the same
AU33813/89A AU618595B2 (en) 1988-04-28 1989-04-28 Derivative of caffeic acid and pharmaceutical composition containing the same
AT89107771T ATE109770T1 (en) 1988-04-28 1989-04-28 CAFFEINEIC ACID DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
KR1019890005689A KR900016098A (en) 1988-04-28 1989-04-28 Derivatives of Caffeic Acid and Pharmaceutical Compositions Containing the Same
US07/344,583 US5063243A (en) 1988-04-28 1989-04-28 Derivative of caffeic acid and pharmaceutical composition containing the same

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP63106274A JP2557090B2 (en) 1988-04-28 1988-04-28 Caffeic acid derivative and pharmaceutical composition containing the same

Publications (2)

Publication Number Publication Date
JPH01275552A JPH01275552A (en) 1989-11-06
JP2557090B2 true JP2557090B2 (en) 1996-11-27

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Country Status (1)

Country Link
JP (1) JP2557090B2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2138021A1 (en) 1993-04-13 1994-10-27 Koichi Hashimoto Coumarin derivative and use thereof
DE4446329A1 (en) * 1994-12-23 1996-06-27 Basf Ag Salts of aromatic hydroxyl compounds and their use as brighteners

Also Published As

Publication number Publication date
JPH01275552A (en) 1989-11-06

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