JPH0764826B2 - Benzimidazole derivative - Google Patents
Benzimidazole derivativeInfo
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- JPH0764826B2 JPH0764826B2 JP60061195A JP6119585A JPH0764826B2 JP H0764826 B2 JPH0764826 B2 JP H0764826B2 JP 60061195 A JP60061195 A JP 60061195A JP 6119585 A JP6119585 A JP 6119585A JP H0764826 B2 JPH0764826 B2 JP H0764826B2
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- benzimidazole
- benzimidazole derivative
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Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は、新規なベンズイミダゾール誘導体、更に詳細
には一般式（Ｉ）： （式中、R1はフェニル基又はベンジル基を示し、そして
R2は水素原子又はメチル基を示す）で表わされるベンズ
イミダゾール誘導体に関する。The present invention relates to a novel benzimidazole derivative, more specifically, a compound represented by the general formula (I): (Wherein R 1 represents a phenyl group or a benzyl group, and
R 2 represents a hydrogen atom or a methyl group) and is related to a benzimidazole derivative.
［従来の技術］ 従来、H+＋K+ATPアーゼは胃細胞における最終的な胃酸
分泌機構であることは当該分野において周知であり、
［スカンジナビアン・ジャーナル・オブ・ガストロエン
テロロジイ（Scand.J.Gastroenterol.）14,131〜135（1
979）］、H+＋K+ATPアーゼ阻害作用を有する物質として
ノリニウムブロマイドが知られている［プロシーディン
グ・オブ・ザ・ソサエティ・フォー・エキスプリメンタ
ル・バイオロジイ・アンド・メデシン（Proceeding of
the Society for Experimental Biology and Medicin
e），172,308〜315（1983）］。一方、２−［２−（3,5
−ジメチル−４−メトキシ）−ピリジルメチルスルフィ
ニル］−（５−メトキシ）−ベンズイミダゾール［オメ
プラゾール］はH+＋K+ATPアーゼ阻害作用を有する抗潰
瘍剤として開発されている［アメリカン・ジャーナル・
オブ・フィジオロジィ（Am.J.of Physiol.）245,G64−G
71（1983）］。[Prior Art] It is well known in the art that H + + K + ATPase is the final gastric acid secretory mechanism in gastric cells.
[Scandinavian Journal of Gastroenterology. (Scand.J.Gastroenterol.) 14 , 131-135 (1
979)], Norinium bromide is known as a substance having an H + + K + ATPase inhibitory action [Proceeding of the Society for Supplementary Biology & Medellin (Proceeding of
the Society for Experimental Biology and Medicin
e), 172 , 308-315 (1983)]. On the other hand, 2- [2- (3,5
-Dimethyl-4-methoxy) -pyridylmethylsulfinyl]-(5-methoxy) -benzimidazole [omeprazole] is being developed as an anti-ulcer drug having an H + + K + ATPase inhibitory action [American Journal
Of Physiol. 245 , G64-G
71 (1983)].
［発明が解決しようとする問題点］ 従って、優れたH+＋K+ATPアーゼ阻害作用を有する新規
な化合物の提供が望まれている。[Problems to be Solved by the Invention] Therefore, it is desired to provide a novel compound having an excellent H + + K + ATPase inhibitory action.
［問題点を解決するための手段］ 斯かる実情において、本発明者は鋭意研究を行なった結
果、前記一般式（Ｉ）式で表わされる新規なベンズイミ
ダゾール誘導体が特異的なH+＋K+ATPアーゼ阻害作用に
基づく優れた胃酸分泌抑制作用を有することを見出し、
本発明を完成した。[Means for Solving the Problems] In such a situation, the present inventors have conducted diligent research, and as a result, the novel benzimidazole derivative represented by the general formula (I) is specific to H + + K + ATP. It was found that it has an excellent gastric acid secretion inhibitory action based on an ase inhibitory action,
The present invention has been completed.
従って、本発明は抗潰瘍剤として有用なベンズイミダゾ
ール誘導体（Ｉ）を提供するものである。Therefore, the present invention provides a benzimidazole derivative (I) useful as an anti-ulcer agent.
本発明のベンズイミダゾール誘導体（Ｉ）は、例えば、
次の反応式に従って、２−メルカプトベンズイミダゾー
ル類（II）に２−アミノベンジル化合物（III）を反応
せしめて化合物（IV）とし、次にこれを酸化することに
より製造される。The benzimidazole derivative (I) of the present invention is, for example,
According to the following reaction formula, 2-mercaptobenzimidazoles (II) are reacted with 2-aminobenzyl compound (III) to give compound (IV), which is then oxidized.
（式中、Ｘは反応性基を示し、R1及びR2は前記と同じで
ある。） 本発明のベンズイミダゾール誘導体の製造法の原料（I
I）は、すでに公知の化合物であり、例えばオーガニッ
ク・シンセシス（Org.Synth.）第30巻、第56頁に記載の
方法によって製造される。また原料（III）のＸで表わ
される反応性基としては、塩素、臭素等のハロゲン原
子、メチルスルホニルオキシ、トルエンスルホニルオキ
シ基等のスルホニルオキシ基を挙げることができ、例え
ばＸが塩素原子の化合物はジャーナル・オブ・ザ・ケミ
カル・ソサエテイ（J.Chem.Soc.）98〜102（1942）に記
載の方法によって製造される。これらは塩の形で反応を
供することもできる。 (In the formula, X represents a reactive group, and R 1 and R 2 are the same as above.) Raw material (I of the method for producing a benzimidazole derivative of the present invention
I) is a known compound, which is produced, for example, by the method described in Organic Synthesis (Org. Synth.) Vol. 30, p. Examples of the reactive group represented by X in the raw material (III) include halogen atoms such as chlorine and bromine, and sulfonyloxy groups such as methylsulfonyloxy and toluenesulfonyloxy groups. For example, a compound in which X is a chlorine atom. Is produced by the method described in Journal of the Chemical Society (J. Chem. Soc.) 98-102 (1942). These can also be reacted in the form of salts.
化合物（II）と化合物（III）又はその塩との反応は、
トルエン、ベンゼン、エタノール、アセトン等の不活性
溶媒中、室温ないし還流下の温度で、30分ないし24時間
攪拌することによって行なわれる。この際、水酸化ナト
リウム、水酸化カリウム、炭酸カリウム、炭酸水素ナト
リウム等のアルカリ剤を存在させて、生成する酸を受容
するのが好ましい。The reaction between compound (II) and compound (III) or a salt thereof is
It is carried out by stirring in an inert solvent such as toluene, benzene, ethanol, acetone or the like at room temperature or under reflux for 30 minutes to 24 hours. At this time, it is preferable that an alkaline agent such as sodium hydroxide, potassium hydroxide, potassium carbonate or sodium hydrogencarbonate is present to receive the generated acid.
化合物（IV）のオキソ化は、常法によって行なうことが
でき、例えば過酸化水素、ｍ−クロル過安息香酸等の有
機過酸、メタ過ヨウ素酸ソーダ等の酸化剤を使用して、
化合物（IV）を酸化すればよい。反応は、クロロホル
ム、ジクロルメタン、メタノール、酢酸エチル等の不活
性溶媒中、−30℃〜50℃、好ましくは−15℃〜５℃の温
度で行なわれる。Oxidation of compound (IV) can be carried out by a conventional method, for example, using hydrogen peroxide, an organic peracid such as m-chloroperbenzoic acid, an oxidizing agent such as sodium metaperiodate,
The compound (IV) may be oxidized. The reaction is carried out in an inert solvent such as chloroform, dichloromethane, methanol and ethyl acetate at a temperature of -30 ° C to 50 ° C, preferably -15 ° C to 5 ° C.
斯くして得られる本発明化合物（Ｉ）の代表的化合物に
ついて薬理効果を試験した結果は次の通りである。The results of testing the pharmacological effects of the thus obtained representative compounds of the compound (I) of the present invention are as follows.
（１）H+＋K+ATPアーゼ阻害作用 フォルト（Forte）らの方法［ジャーナル・オブ・アプ
ライド・フィジオロジイ（J.Applied Physiol.）32,714
〜717（1972）］に従い、ウサギ胃粘膜の胃酸分泌細胞
を分離し、H+＋K+ATPアーゼを含むベシクルはフイコー
ルの不連続密度勾配中で遠心分離することにより調製し
た。5mMイミダゾール緩衝液（pH6.o）、試験物質２×10
-4Ｍを含む溶液0.5ml中で酵素を室温で25分間インキュ
ベートした後、37℃に移しさらに５分間放置した。4mM
塩化マグネシウム、80mMイミダゾール緩衝液（pH7.
4）、20mM塩化カリウム及び4mMATPを含む溶液0.5mlを加
えて、37℃で15分間反応させたのち、24％トリクロル酢
酸1mlを加えて反応を止め、遊離した無機リンをトスキ
ー（Taussky）およびショール（Shorr）の方法［ジャー
ナル・オブ・バイオロジカル・ケミストリー（J.Biol.C
hem.）202,675−685（1953）に従って定量した。K+依存
性ATPアーゼ活性は、塩化カリウムを含まない時の活性
を差し引いて求めた。その結果を第１表に示す。(1) H + ＋ K + ATPase inhibitory action The method of Forte et al. [J. Applied Physiol.] 32,714
~ 717 (1972)], gastric acid secreting cells of rabbit gastric mucosa were isolated, and vesicles containing H + + K + ATPase were prepared by centrifugation in a discontinuous density gradient of Ficoll. 5 mM imidazole buffer (pH 6.o), test substance 2 x 10
After incubating the enzyme in 0.5 ml of a solution containing -4 M for 25 minutes at room temperature, the enzyme was transferred to 37 ° C and left for another 5 minutes. 4 mM
Magnesium chloride, 80 mM imidazole buffer (pH 7.
4), 0.5 ml of a solution containing 20 mM potassium chloride and 4 mM ATP was added, and the mixture was reacted at 37 ° C for 15 minutes. Then, 1 ml of 24% trichloroacetic acid was added to stop the reaction, and the released inorganic phosphorus was removed by using Taussky and Shawl. (Shorr) Method [Journal of Biological Chemistry (J.Biol.C
hem.) 202,675-685 (1953). The K + -dependent ATPase activity was calculated by subtracting the activity in the absence of potassium chloride. The results are shown in Table 1.
（３）急性毒性試験 体重80gから90gのウィスター（Wistar）系雄ラットに、
本発明化合物３を0.2％CMC生理食塩水に懸濁したもの
を、腹腔内投与し、７日間観察した。その結果、LD50が
300mg/kg以上であるこが確認された。 (3) Acute toxicity test For male Wistar rats weighing 80 to 90 g,
A suspension of Compound 3 of the present invention in 0.2% CMC physiological saline was intraperitoneally administered, and observed for 7 days. As a result, LD 50
It was confirmed to be 300 mg / kg or more.
本発明の化合物（Ｉ）は経口，非経口のいずれにおいて
も投与できる。経口投与剤の剤型としては、例えば、錠
剤、カプセル剤、散剤、顆粒剤およびシロップ剤等があ
げられ、非経口投与剤の剤型としては注射剤等があげら
れる。これらの調製には、通常の賦形剤、崩壊剤、結合
剤、滑沢剤、色素、希釈剤などが用いられる。賦形剤と
しては、ブドウ糖、乳糖などが、崩壊剤としては、デン
プン、カルボキシメチルセルロースカルシウムなどが、
滑沢剤としては、ステアリン酸マグネシウム、タルクな
どが、結合剤としては、ヒドロキシプロピルセルロー
ス、ゼラチン、ポリビニルピロリドンなどが用いられ
る。The compound (I) of the present invention can be administered orally or parenterally. Examples of the dosage form of the orally administered agent include tablets, capsules, powders, granules, syrups, and the like, and examples of the dosage form of the parenteral administration agent include injections and the like. Conventional excipients, disintegrants, binders, lubricants, pigments, diluents and the like are used for the preparation of these. As excipients, glucose, lactose, etc., as disintegrants, starch, carboxymethylcellulose calcium, etc.
Magnesium stearate, talc, etc. are used as lubricants, and hydroxypropyl cellulose, gelatin, polyvinylpyrrolidone, etc. are used as binders.
投与量は、通常成人において、注射剤で１日約1mg〜50m
g、経口投与で１日約10mg〜500mgであるが、年令、症状
等により増減することができる。The dosage is usually about 1 mg to 50 m per day by injection in adults.
Oral administration is about 10 mg to 500 mg per day, but it can be increased or decreased depending on the age, symptoms, etc.
次に参考例及び実施例を挙げて本発明を説明する。Next, the present invention will be described with reference to Reference Examples and Examples.
［参考例１］（比較化合物の合成） （ｉ）２−ベンジルチオベンズイミダゾール： ２−メルカプトベンスイミダゾール5g、ベンジルクロラ
イド4.2gを水酸化ナトリウム1.47gの水5mL−エタノール
50mL溶液中に加え、１時間加熱還流した。反応混合物を
氷水中に注ぎ、析出した結晶を濾取して、7.7g（96％）
の粗結晶を得た。エタノールより再結晶し、5.9gの無色
針状晶を得た。m.p.184℃ （ii）２−ベンジルスルフィニルベンズイミダゾール： ２−ベンジルチオベンズイミダゾール4.5gをクロロホル
ム30mL中に溶解し、ｍ−クロロ過安息香酸（純度70％）
4.6gを０℃以下で少しずつ加えた。さらに20分攪拌後、
析出した結晶を濾別し、濾液を飽和炭酸水素ナトリウム
溶液、チオ硫酸ナトリウム溶液および飽和食塩水で洗浄
し、芒硝で乾燥した。溶媒を減圧留去し、4.3gの粗結晶
を得た。エタノールより再結晶し、2.0gの２−ベンジル
スルフィニルベンズイミダゾールを無色結晶として得
た。m.p.169−170℃ ［実施例１］（本発明化合物１の合成） （ｉ）２−（２−フェニルアミノベンジルチオ）ベンズ
イミダゾール ２−フェニルアミノベンジルアルコール（2.2g、10ミリ
モル）を乾燥ベンゼン（20mL）に溶解させ、塩化チオニ
ル（1.6g、13ミリモル）を加えて30分間加熱還流した。
反応液を減圧下に置いて溶媒を留去したのち、エタノー
ル（10mL）および２−メルカプトベンズイミダゾール
（1.05g、７ミリモル）を加えて室温で2.5時間攪拌し
た。エタノールを留去し、残渣をクロロホルムに溶解さ
せ、飽和重曹水および飽和食塩水で洗浄後、無水硫酸ナ
トリウムで乾燥した。溶媒を減圧留去し、残渣をシリカ
ゲルカラムクロマトグラフィー（クロロホルム／メタノ
ール＝100/1）を用いて精製し、0.53gの標題化合物を白
色結晶性粉末として得た（収率22％）。Reference Example 1 (Synthesis of Comparative Compound) (i) 2-Benzylthiobenzimidazole: 2-mercaptobensimidazole 5 g, benzyl chloride 4.2 g, sodium hydroxide 1.47 g in water 5 mL-ethanol.
It was added to 50 mL solution and heated under reflux for 1 hour. The reaction mixture was poured into ice water, and the precipitated crystals were collected by filtration to give 7.7g (96%).
The crude crystal of was obtained. Recrystallization from ethanol gave 5.9 g of colorless needle crystals. mp184 ° C (ii) 2-benzylsulfinylbenzimidazole: 4.5 g of 2-benzylthiobenzimidazole was dissolved in 30 mL of chloroform, and m-chloroperbenzoic acid (purity 70%).
4.6g was added in portions at 0 ° C or below. After stirring for another 20 minutes,
The precipitated crystals were filtered off, and the filtrate was washed with saturated sodium hydrogen carbonate solution, sodium thiosulfate solution and saturated saline, and dried with sodium sulfate. The solvent was distilled off under reduced pressure to obtain 4.3 g of crude crystals. Recrystallization from ethanol gave 2.0 g of 2-benzylsulfinylbenzimidazole as colorless crystals. mp169-170 ° C. [Example 1] (Synthesis of compound 1 of the present invention) (i) 2- (2-phenylaminobenzylthio) benzimidazole 2-phenylaminobenzyl alcohol (2.2 g, 10 mmol) was dried over benzene (20 mL). ), Thionyl chloride (1.6 g, 13 mmol) was added, and the mixture was heated under reflux for 30 minutes.
The reaction mixture was placed under reduced pressure to remove the solvent, ethanol (10 mL) and 2-mercaptobenzimidazole (1.05 g, 7 mmol) were added, and the mixture was stirred at room temperature for 2.5 hr. Ethanol was evaporated, the residue was dissolved in chloroform, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform / methanol = 100/1) to obtain 0.53 g of the title compound as a white crystalline powder (yield 22%).
NMR（CDCL3）δppm; 4.48（s,2H）,6.6〜7.5（m,13H）． （ii）２−（２−フェニルアミノベンジルスルフィニ
ル）ベンズイミダゾール２−（２−フェニルアミノベン
ジルチオ）ベンズイミダゾール0.45gをクロロホルム10m
に溶解し、氷冷下ｍ−CPBAO.278g（純度80％）を少量ず
つ加えた。同温度で30分間攪拌後、飽和炭酸水素ナトリ
ウム溶液及び飽和食塩水で洗浄し、そののち芒硝で乾燥
した。溶媒を減圧留去し、残渣をアセトニトリルより結
晶化させ、0.38gの標題化合物を淡褐色結晶性粉末とし
て得た（収率80％）。 NMR (CDCL 3) δppm; 4.48 (s, 2H), 6.6~7.5 (m, 13H). (Ii) 2- (2-phenylaminobenzylsulfinyl) benzimidazole 2- (2-phenylaminobenzylthio) benzimidazole 0.45 g was added to chloroform 10 m.
The solution was dissolved in, and 278 g (purity 80%) of m-CPBAO was added little by little under ice cooling. The mixture was stirred at the same temperature for 30 minutes, washed with a saturated sodium hydrogen carbonate solution and saturated saline, and then dried with sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was crystallized from acetonitrile to obtain 0.38 g of the title compound as a pale brown crystalline powder (yield 80%).
m.p.89−92℃（分解）（クロロホルム−エーテル） IRν（KBr）cm-1： 3360,1600,1495,1410,1305,1050,750 NMR（CDCL3）δppm; 4.47及び4.78（各d,J＝14Hz,2H）， 6.5〜8.0（m,13H） ［実施例２］（本発明化合物２の合成） 実施例１と同様にして、２−［２−（Ｎ−メチル−Ｎ−
フェニルアミノ）ベンジルチオ］ベンズイミダゾール
（中間体）を経て、２−［２−（Ｎ−メチル−Ｎ−フェ
ニルアミノ）ベンジルスルフィニル］ベンズイミダゾー
ル（最終化合物）を得た。mp 89-92 ° C (decomposition) (chloroform-ether) IR ν (KBr) cm −1 : 3360,1600,1495,1410,1305,1050,750 NMR (CDCL 3 ) δppm; 4.47 and 4.78 (each d, J = 14 Hz) , 2H), 6.5 to 8.0 (m, 13H) [Example 2] (Synthesis of Compound 2 of the present invention) In the same manner as in Example 1, 2- [2- (N-methyl-N-
Phenylamino) benzylthio] benzimidazole (intermediate) gave 2- [2- (N-methyl-N-phenylamino) benzylsulfinyl] benzimidazole (final compound).
中間体 NMR（CDCL3）δppm; 3.18（s,3H）,4.40（s,2H）， 6.4〜7.6（m,13H）． 最終化合物 m.p.168−169℃（分解）（クロロホルム−アセトニトリ
ル） IRν（KBr）cm-1： 3050,1590,1485,1400,1260,1055,740 NMR（CDCL3）δppm; 3.18（s,3H）,4.32及び4.62（各d,J＝13Hz,2H）,6.3〜
7.8（m,13H）． ［実施例３］（本発明化合物３の合成） （ｉ）２−［２−（Ｎ−ベンジル−Ｎ−メチルアミノ）
ベンジルチオ］ベンズイミダゾール エタノール（10mL）に、２−（Ｎ−ベンジル−Ｎ−メチ
ルアミノ）ベンジルクロリド塩酸塩（1.7g、６ミリモ
ル）及び２−メルカプトベンズイミダゾール（0.9g、６
ミリモル）を加え、室温で３時間攪拌した。更に、エー
テル（50mL）を加え、析出した結晶を濾取した。この結
晶に酢酸エチル（200mL）及び飽和重曹水を加え、有機
層を分取し、これを飽和食塩水で洗浄したのち、無水硫
酸ナトリウムで乾燥した。溶媒を減圧留去し、残渣をエ
ーテルから結晶化させ、1.9gの標題化合物を白色結晶性
粉末として得た（収率88％）。Intermediate NMR (CDCL 3) δppm; 3.18 (s, 3H), 4.40 (s, 2H), 6.4~7.6 (m, 13H). Final compound mp168-169 ° C (decomposition) (chloroform-acetonitrile) IR ν (KBr) cm -1 : 3050,1590,1485,1400,1260,1055,740 NMR (CDCL 3 ) δppm; 3.18 (s, 3H), 4.32 And 4.62 (each d, J = 13Hz, 2H), 6.3 ~
7.8 (m, 13H). [Example 3] (Synthesis of compound 3 of the present invention) (i) 2- [2- (N-benzyl-N-methylamino)
Benzylthio] benzimidazole Ethanol (10 mL) was charged with 2- (N-benzyl-N-methylamino) benzyl chloride hydrochloride (1.7 g, 6 mmol) and 2-mercaptobenzimidazole (0.9 g, 6
Mmol) was added and the mixture was stirred at room temperature for 3 hours. Further, ether (50 mL) was added, and the precipitated crystals were collected by filtration. Ethyl acetate (200 mL) and saturated aqueous sodium hydrogen carbonate were added to the crystals, the organic layer was separated, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was crystallized from ether to give 1.9 g of the title compound as a white crystalline powder (yield 88%).
NMR（CDCL3）δppm; 2.66（s,3H）,4.04（s,2H）,4.56（s,2H）,6.9〜7.5
（m,13H）． （ii）２−［２−（Ｎ−ベンジル−Ｎ−メチルアミノ）
ベンジルスルフィニル］ベンズイミダゾール 実施例１の（ii）と同様にして標題化合物を得た。NMR (CDCL 3 ) δppm; 2.66 (s, 3H), 4.04 (s, 2H), 4.56 (s, 2H), 6.9 to 7.5
(M, 13H). (Ii) 2- [2- (N-benzyl-N-methylamino)
Benzylsulfinyl] benzimidazole The title compound was obtained in the same manner as in Example 1, (ii).
m.p.137℃（分解）（アセトニトリル） IRν（KBr）cm-1： 3170,1440,1400,1260,1025,940,740 NMR（CDCL3）δppm; 2.52（s,3H）,4.00（s,2H）,4.52及び4.92（各d,J＝12H
z,2H）,6.7〜7.9（m,13H）． ［実施例４］［製剤例（錠剤）］ １錠（220mg）中下記成分を含有する。mp 137 ℃ (decomposition) (acetonitrile) IRν (KBr) cm −1 : 3170,1440,1400,1260,1025,940,740 NMR (CDCL 3 ) δppm; 2.52 (s, 3H), 4.00 (s, 2H), 4.52 and 4.92 (each d, J = 12H
z, 2H), 6.7 to 7.9 (m, 13H). [Example 4] [Formulation example (tablet)] One tablet (220 mg) contains the following components.
活性成分 50mg ラクトース 103 でんぷん 50 ステアリン酸マグネシウム 2 ヒドロキシプロピルセルロース 15 ［実施例５］［製剤例（カプセル剤）］ ゼラチン硬カプセル１球中に下記成分（350mg）を含有
する。Active ingredient 50 mg Lactose 103 Starch 50 Magnesium stearate 2 Hydroxypropyl cellulose 15 [Example 5] [Formulation example (capsule)] A hard gelatin capsule contains the following ingredient (350 mg).
活性成分 40mg ラクトース 200 でんぷん 70 ポリビニルピロリドン 5 結晶セルロース 35 ［実施例６］［製剤例（顆粒）］ 顆粒1g中下記成分を含有する。Active ingredient 40 mg Lactose 200 Starch 70 Polyvinylpyrrolidone 5 Crystalline cellulose 35 [Example 6] [Formulation example (granule)] The following ingredients are contained in 1 g of granules.
活性成分 200mg ラクトース 450 トウモロコシデンプン 300 ヒドロキシプロピルセルロース 50Active ingredient 200 mg Lactose 450 Corn starch 300 Hydroxypropyl cellulose 50
───────────────────────────────────────────────────── フロントページの続き (72)発明者 山川 富雄 埼玉県草加市神明１―12―４ 阿部コーポ 202号 (72)発明者 野村 豊 埼玉県草加市八幡町899 (72)発明者 林 正敏 東京都新宿区市谷台町６ (56)参考文献 特開 昭61−56168（ＪＰ，Ａ) ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Tomio Yamakawa 1-12-4 Shinmei Soka-shi, Saitama Prefecture Abe Corp. No. 202 (72) Inventor Yutaka Nomura 899 Hachiman-cho, Soka-shi, Saitama Prefecture (72) Masatoshi Hayashi Tokyo 6, Tanidaicho, Shinjuku-ku, Tokyo (56) References Japanese Patent Laid-Open No. 61-56168 (JP, A)
Claims (1)
R2は水素原子又はメチル基を示す。）で表わされるベン
ズイミダゾール誘導体。1. The following general formula (I): (Wherein R 1 represents a phenyl group or a benzyl group, and
R 2 represents a hydrogen atom or a methyl group. ) A benzimidazole derivative represented by:
Priority Applications (17)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60061195A JPH0764826B2 (en) | 1985-03-26 | 1985-03-26 | Benzimidazole derivative |
| AU46409/85A AU4640985A (en) | 1984-08-31 | 1985-08-19 | Benzimidazole derivatives |
| BE0/215506A BE903128A (en) | 1984-08-31 | 1985-08-27 | BENZIMIDAZOLE DERIVATIVES PROCESS FOR THEIR PREPARATION AND ANTI-ULCER AGENTS CONTAINING THEM |
| ES546445A ES8703142A1 (en) | 1984-08-31 | 1985-08-27 | Benzimidazole derivatives |
| GB08521493A GB2163747B (en) | 1984-08-31 | 1985-08-29 | Benzimidazole derivatives, and antiulcer agents containing the same |
| CH3709/85A CH665417A5 (en) | 1984-08-31 | 1985-08-29 | BENZIMIDAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND ANTI-ULCER AGENTS CONTAINING THESE DERIVATIVES. |
| KR1019850006307A KR920004936B1 (en) | 1984-08-31 | 1985-08-30 | Method for producing of benzimidazole derivatives |
| IT67743/85A IT1189601B (en) | 1984-08-31 | 1985-08-30 | Benzyl sulphinyl benzimidazole |
| AR85301474A AR242195A1 (en) | 1984-08-31 | 1985-08-30 | A procedure for the preparation of benzimidazole derivatives and their salts. |
| SE8504048A SE500669C2 (en) | 1984-08-31 | 1985-08-30 | Benzimidazoles |
| FR858512961A FR2569691B1 (en) | 1984-08-31 | 1985-08-30 | BENZIMIDAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND ANTI-ULCER AGENTS CONTAINING THEM |
| NL8502384A NL8502384A (en) | 1984-08-31 | 1985-08-30 | BENZIMIDAZOLE DERIVATIVES, PHARMACEUTICAL PREPARATIONS WITH AN ACTION AGAINST SILES CONTAINING THEM AND METHODS FOR PREPARING THESE DERIVATIVES |
| DE3531487A DE3531487C2 (en) | 1984-08-31 | 1985-08-30 | benzimidazole derivatives |
| MX206462A MX159807A (en) | 1984-08-31 | 1985-08-30 | PROCEDURE FOR PREPARING BENZMIDAZOLE DERIVATIVES |
| BR8504252A BR8504252A (en) | 1984-08-31 | 1985-08-30 | BENZIMIDAZOL DERIVATIVE, PROCESS FOR THE PREPARATION OF A BENZIMIDAZOL DERIVATIVE AND AN ANTI ULCEROSAL AGENT |
| AU41271/89A AU4127189A (en) | 1984-08-31 | 1989-09-11 | Benzimidazole derivatives, process for preparing the same and antiulcer agents containing the same |
| AU29750/92A AU647978B2 (en) | 1984-08-31 | 1992-11-27 | Benzimidazole derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60061195A JPH0764826B2 (en) | 1985-03-26 | 1985-03-26 | Benzimidazole derivative |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1340694A Division JPH0670018B2 (en) | 1989-12-28 | 1989-12-28 | Benzimidazole derivative, method for producing the same, and antiulcer agent containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61221176A JPS61221176A (en) | 1986-10-01 |
| JPH0764826B2 true JPH0764826B2 (en) | 1995-07-12 |
Family
ID=13164144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60061195A Expired - Lifetime JPH0764826B2 (en) | 1984-08-31 | 1985-03-26 | Benzimidazole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0764826B2 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8417271D0 (en) * | 1984-07-06 | 1984-08-08 | Fisons Plc | Biologically active nitrogen heterocycles |
-
1985
- 1985-03-26 JP JP60061195A patent/JPH0764826B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61221176A (en) | 1986-10-01 |
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