JPH0635435B2 - Succinimide derivative - Google Patents
Succinimide derivativeInfo
- Publication number
- JPH0635435B2 JPH0635435B2 JP60179356A JP17935685A JPH0635435B2 JP H0635435 B2 JPH0635435 B2 JP H0635435B2 JP 60179356 A JP60179356 A JP 60179356A JP 17935685 A JP17935685 A JP 17935685A JP H0635435 B2 JPH0635435 B2 JP H0635435B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- inventor
- ulcer
- succinimide
- 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
Links
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 title description 6
- -1 2,6-dichlorophenyl Chemical group 0.000 claims description 5
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000005504 styryl group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 16
- 208000025865 Ulcer Diseases 0.000 description 5
- 231100000397 ulcer Toxicity 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010042220 Stress ulcer Diseases 0.000 description 3
- 208000000718 duodenal ulcer Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000003699 antiulcer agent Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は、新規なコハク酸イミド誘導体に関するもので
ある。すなわち、本発明は一般式、 〔式中、Ｒは、２，４−ジクロロフエニル、３，４−ジ
クロロフエニル、２，６−ジクロロフエニル、４−メト
キシフエニル、スチリル、４−ビフエニリル、および１
−ナフチルから選ばれた基を示す〕で表わされる新規な
化合物を提供するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel succinimide derivative. That is, the present invention is a general formula, [Wherein R is 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 4-methoxyphenyl, styryl, 4-biphenylyl, and 1
-Indicating a group selected from naphthyl].
上記式(1)で表わされる化合物は、優れたストレス潰瘍
抑制作用を示し、抗潰瘍剤として有用な医薬として使用
することができる。The compound represented by the above formula (1) exhibits an excellent stress ulcer inhibitory action, and can be used as a drug useful as an anti-ulcer agent.
以下に、本発明を詳細に説明する。The present invention will be described in detail below.
まず、本発明に係る上記式(1)の化合物の製造法につい
て述べる。First, a method for producing the compound of the above formula (1) according to the present invention will be described.
本発明の一般式(1)で表わされる化合物は、例えば、次
の方法により製造することができる。The compound represented by the general formula (1) of the present invention can be produced, for example, by the following method.
1)製法１：式 で示されるコハク酸イミドと、一般式、 Ｒ−CH2−Ｘ (3) 〔式中、Ｒは、前記式(1)において定義したとおりの意
味を有し、Ｘはハロゲン原子を表わす〕の化合物とを塩
基の存在下に縮合反応に付すことにより製造することが
できる。1) Method 1: Formula In a succinimide represented by the general formula, R-CH 2 -X (3 ) [wherein, R has the meaning as defined in the formula (1), X represents a halogen atom] in It can be produced by subjecting a compound to a condensation reaction in the presence of a base.
2)製法２：式 で示される無水コハク酸と、一般式、 Ｒ−CH2-NH2 (5) 〔式中、Ｒは、前記式(1)において定義したとおりの意
味を有する〕の化合物とを反応させることにより製造す
ることができる。2) Manufacturing method 2: Formula By reacting a succinic anhydride represented by the following formula with a compound of the general formula: R—CH 2 —NH 2 (5) [wherein R has the same meaning as defined in the above formula (1)] It can be manufactured.
本発明に係る前記式(1)の化合物は、抗潰瘍剤として使
用することができる。このものは、カプセル剤、錠剤、
顆粒剤、懸濁剤もしくは乳剤等の剤形で投与することが
できる。これらの各種製剤は常法により製造される。The compound of formula (1) according to the present invention can be used as an anti-ulcer agent. This one is for capsules, tablets,
It can be administered in the form of granules, suspensions or emulsions. These various preparations are manufactured by a conventional method.
有効化合物の投与量は患者の年齢、体重、症状等に応じ
て適宜定められるが、通常、１日投与量としては10mg〜
1000mgの量である。The dose of the active compound is appropriately determined according to the age, body weight, symptom, etc. of the patient, but usually the daily dose is 10 mg to
The amount is 1000 mg.
次に、本発明に係る前記式(1)の化合物の製造方法を実
施例により説明する。Next, the method for producing the compound of formula (1) according to the present invention will be described with reference to examples.
実施例１ Ｎ−（４−メトキシフエニルメチル）コハク酸イミド コハク酸イミド424mg、N,N−ジメチルホルムアミド１０
ｍ、炭酸カリウム731mgおよび４−メトキシベンジル
クロライド548mgの混合物を100℃で１０時間攪拌した。
反応液を減圧下に濃縮し、酢酸エチルを加え、水洗した
のち、無水硫酸ナトリウムで乾燥した。減圧下に溶媒を
留去したのち、残留結晶を酢酸エチル−ヘキサンで再結
晶し、標題の化合物573mgを得た。Example 1 N- (4-methoxyphenylmethyl) succinimide Succinimide 424 mg, N, N-dimethylformamide 10
A mixture of m, 731 mg of potassium carbonate and 548 mg of 4-methoxybenzyl chloride was stirred at 100 ° C for 10 hours.
The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, the mixture was washed with water, and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the residual crystals were recrystallized from ethyl acetate-hexane to give the title compound (573 mg).
融点 127.6〜128.8℃ Massスペクトル(m/e)；219(M+),191,190,176,160,148,1
34,121,55 実施例２〜７ 実施例１に準拠した反応操作により、コハク酸イミドと
各化合物ごとに反応するクロライドとを用いて下記表１
中に掲げた各化合物を製造した。Melting point 127.6-128.8 ° C Mass spectrum (m / e); 219 (M + ), 191,190,176,160,148,1
34,121,55 Examples 2 to 7 By the reaction procedure based on Example 1, succinimide and chlorides that react with each compound were used to give the following Table 1.
Each compound listed therein was prepared.
表１中に、各実施例で得られた化合物を式(1)中のＲを
もつて示し、その化合物の融点およびMassスペクトルを
掲げた。In Table 1, the compounds obtained in each Example are shown with R in the formula (1), and the melting points and Mass spectra of the compounds are listed.
本発明に係る化合物についてストレス潰瘍抑制作用に関
する試験を行なつた。以下にその試験例ならびにデータ
を示す。 The compound according to the present invention was tested for its stress ulcer inhibitory action. The test examples and data are shown below.
試験方法 水浸拘束によるストレス潰瘍抑制効果 高木、岡部ら；JaP.J.Pharmacol.,18,9(1968)に記載の
方法に従い、体重240ｇ前後のWistar系雄性ラツトを１
８時間絶食後、供試化合物を経口投与した。３０分後、
ラツトをストレスケージに入れ、23±１℃の水槽内に胸
部まで浸し、ストレス負荷した。６時間後、ラツトを殺
し、そして、その胃を摘出し、１０ｍの生理食塩水を
注入した。５％ホルマリンで５分間固定後、大湾に沿つ
て胃を切り開き、腺胃部にみられる潰瘍の長径を測定
し、その総和を１匹当りの潰瘍係数とした。供試化合物
は５％アラビアゴム溶液に懸濁し、５０mg/kgまたは１
００mg/kgの割合で経口投与した。こうして得られた抗
潰瘍作用は次式を用いて計算し、１群９〜10匹の平均値
として表２に示した。Stress ulcer inhibiting effect Takagi by the test method water immersion restraint, Okabe et al;. JaP.J.Pharmacol, 18, according to the method described in 9 (1968), before and after weighing 240g male Wistar rat 1
After fasting for 8 hours, the test compound was orally administered. 30 minutes later
The rat was placed in a stress cage, and the chest was immersed in a water tank at 23 ± 1 ° C. to apply stress. Six hours later, the rat was killed and the stomach was removed and injected with 10 m of saline. After fixing with 5% formalin for 5 minutes, the stomach was cut open along the bay, the major axis of the ulcer found in the glandular stomach was measured, and the total was taken as the ulcer index per animal. The test compound is suspended in 5% gum arabic solution to give 50 mg / kg or 1
It was orally administered at a rate of 00 mg / kg. The anti-ulcer action thus obtained was calculated using the following formula and shown in Table 2 as an average value of 9 to 10 animals per group.
抑制率（％）＝〔｛（コントロール群の潰瘍係数）−
（各群の潰瘍係数）｝÷（コントロール群の潰瘍係
数）〕×100 試験結果 Inhibition rate (%) = [{(ulcer index of control group)-
(Ulcer index of each group) ÷ (ulcer index of control group)] × 100 test results
───────────────────────────────────────────────────── フロントページの続き (72)発明者 菅井 三郎 埼玉県岩槻市大字柏崎1470番地の６ (72)発明者 岡崎 徳二 東京都日野市平山６丁目３番地の３ (72)発明者 梶原 良夫 東京都北区赤羽南１丁目11番５―903号 (72)発明者 木村 智憲 埼玉県大宮市大字東門前１番２号 (72)発明者 河田 登美枝 東京都千代田区九段南３丁目９番11号 マ ートルコート麹町702号 (72)発明者 神原 俊文 神奈川県横浜市保土ヶ谷区月見台40番地 ビユーハイム月見台102号 (72)発明者 内藤 泰男 埼玉県川口市大字行衛164 (72)発明者 吉田 誠一郎 東京都小平市仲町80番地 (72)発明者 赤星 三彌 東京都調布市富士見町４丁目18番地９ (72)発明者 池上 四郎 東京都八王子市打越町908番地51 (56)参考文献 特開 昭53−28162（ＪＰ，Ａ) 特公 昭43−11312（ＪＰ，Ｂ１) 米国特許4008222（ＵＳ，Ａ) ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Saburo Sugai, 1470 Kashiwazaki, Iwatsuki City, Saitama Prefecture (72) Inventor Tokuji Okazaki 3-3, Hirayama, Hino City, Tokyo (72) Inventor Yoshio Kajiwara Tokyo 1-11-5-903, Akabane Minami, Kita-ku (72) Inventor Tomonori Kimura 1-2-2, Tomonmae, Omiya-shi, Saitama Prefecture (72) Inventor Tomie Kawada 3--9-11, Dandan, Chiyoda-ku, Tokyo Myrtle Court Kojimachi No. 702 (72) Inventor Toshifumi Kamihara 40 Tsukimidai, Hodogaya-ku, Yokohama, Kanagawa 102 Bieuheim Tsukimidai 102 (72) Inventor Yasuo Naito Kawaguchi City Saitama 164 (72) Inventor Seiichiro Yoshida Kodaira, Tokyo 80, Nakamachi, Ichi (72) Sanya Akahoshi, 4-18, Fujimi-cho, Chofu-shi, Tokyo 9 (72) Inventor, Shiro Ikegami 908, Uchikoshi-cho, Hachioji, Tokyo 51 (56) References Patent Sho 53-28162 (JP, A) Tokuoyake Akira 43-11312 (JP, B1) U.S. Patent 4,008,222 (US, A)
Claims (1)
クロロフエニル、２，６−ジクロロフエニル、４−メト
キシフエニル、スチリル、４−ビフエニリル、および１
−ナフチルから選ばれた基を示す〕で表わされるコハク
酸イミド誘導体。1. A formula: [Wherein R is 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 4-methoxyphenyl, styryl, 4-biphenylyl, and 1
-Indicating a group selected from naphthyl]].
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60179356A JPH0635435B2 (en) | 1985-08-16 | 1985-08-16 | Succinimide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60179356A JPH0635435B2 (en) | 1985-08-16 | 1985-08-16 | Succinimide derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6239565A JPS6239565A (en) | 1987-02-20 |
| JPH0635435B2 true JPH0635435B2 (en) | 1994-05-11 |
Family
ID=16064411
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60179356A Expired - Lifetime JPH0635435B2 (en) | 1985-08-16 | 1985-08-16 | Succinimide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0635435B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9277339B2 (en) | 2011-11-24 | 2016-03-01 | Toyota Jidosha Kabushiki Kaisha | Sound source detection apparatus |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4008222A (en) | 1966-12-16 | 1977-02-15 | Bayer Aktiengesellschaft | Anthraquinone dyestuffs |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5328162A (en) * | 1976-08-26 | 1978-03-16 | Kissei Pharmaceut Co Ltd | Novel succinic acid imide derivatives and their preparation |
-
1985
- 1985-08-16 JP JP60179356A patent/JPH0635435B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4008222A (en) | 1966-12-16 | 1977-02-15 | Bayer Aktiengesellschaft | Anthraquinone dyestuffs |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9277339B2 (en) | 2011-11-24 | 2016-03-01 | Toyota Jidosha Kabushiki Kaisha | Sound source detection apparatus |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6239565A (en) | 1987-02-20 |
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