JPS5978194A - Novel derivative of 2-phenylimidazo(2,1-b)benzothiazole and its preparation - Google Patents
Novel derivative of 2-phenylimidazo(2,1-b)benzothiazole and its preparationInfo
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- JPS5978194A JPS5978194A JP57188866A JP18886682A JPS5978194A JP S5978194 A JPS5978194 A JP S5978194A JP 57188866 A JP57188866 A JP 57188866A JP 18886682 A JP18886682 A JP 18886682A JP S5978194 A JPS5978194 A JP S5978194A
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- benzothiazole
- compound
- general formula
- acid
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Abstract
Description
【発明の詳細な説明】
本発明は下記一般式(I)で示される2−フェニルイミ
ダゾ[2,1−b]ベノゾチアゾールの新規誘導体及び
その塩並びにそれらの製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel derivatives of 2-phenylimidazo[2,1-b]benozothiazole represented by the following general formula (I), salts thereof, and methods for producing them.
(式中、Aは低級アルキレン基又は低級アルケニレン基
を、nは0又は1を、Rは低級アルキル基を意味する。(In the formula, A means a lower alkylene group or a lower alkenylene group, n means 0 or 1, and R means a lower alkyl group.
以下同様) 本明細書中の一般式の基の定義において。Same below) In the definitions of groups of general formulas herein.
2低級、なる語は炭素数が1〜5個(低級アルケニレン
基におし・ては2〜5個)の直鎖状又は分枝状の炭素鎖
を意味する。従って、Rが示す低級アルキル基としては
メチル基、エチル基2プロピル基、イソプロピル基、ブ
チル基、イソブチル基、 5ee−ブチル基r t
e r t−ブチル基。The term "2-lower" means a straight or branched carbon chain having 1 to 5 carbon atoms (2 to 5 carbon atoms for lower alkenylene groups). Therefore, the lower alkyl group represented by R is a methyl group, an ethyl group, a 2-propyl group, an isopropyl group, a butyl group, an isobutyl group, and a 5ee-butyl group.
er t-butyl group.
ペノチル基、イソアミル基、ネオペンチル基等が挙げら
れる。また、Aの低級アルキレフ基としてはメチレン基
、メチルメチレ/基、エチレン基、トリメチレン基、プ
ロピレノ基、エチルメチレン基、テトラメチレフ基、メ
チルトリメチレノ基、エチルエチレン基、プロビルメチ
レ/基、イソプロピルメチレン基、ジメチルエチレン基
、エチルメチルメチレン基、ペンタメチレン基、メチル
テトラメチレン基、エチルトリメチレノ基、プロピルエ
チレン基、ブチルメチレン基、ジメチルトリメチレン基
、イソプロピルエチレン基、エチルメチルエチレン基、
ジエチルメチレ/基、メチルプロピルメチレン基等が、
更に低級アルケニレン基としては、ビニレン基、メチル
ビニレン基、フロペニレン基、ブテニレン基、メチルグ
ロペニレン基、エチルビニレン基、ジメチルビニレン基
、ペンテニレン基、メチルブテニレン基、エチルプロペ
ニレン基、プロピルビニレン基、ジメチルプロペニレン
基、エチルメチルビニレン基等が挙げられる。Examples include penotyl group, isoamyl group, neopentyl group, and the like. In addition, the lower alkylev group of A is a methylene group, a methylmethylene group, an ethylene group, a trimethylene group, a propyleno group, an ethylmethylene group, a tetramethylene group, a methyltrimethylene group, an ethylethylene group, a propylmethylene group, an isopropylmethylene group, Dimethylethylene group, ethylmethylmethylene group, pentamethylene group, methyltetramethylene group, ethyltrimethylene group, propylethylene group, butylmethylene group, dimethyltrimethylene group, isopropylethylene group, ethylmethylethylene group,
Diethylmethylene/group, methylpropylmethylene group, etc.
Furthermore, lower alkenylene groups include vinylene group, methylvinylene group, flopenylene group, butenylene group, methylgropenylene group, ethylvinylene group, dimethylvinylene group, pentenylene group, methylbutenylene group, ethylpropenylene group, propylvinylene group, dimethyl Examples include propenylene group and ethylmethylvinylene group.
本発明によって提供される前記一般式(I)の化合物は
酸付加塩を形成する。本発明は薬理学上許容される一般
式(I)の化合物の塩をも包含するものであり、かかる
塩としては、たとえば塩化水素酸、臭化水素酸、硫酸等
の鉱酸やメタンスルホン酸、ハラトルエンスル* 7
H等ノ有機酸との酸付加塩が挙げられる。The compounds of general formula (I) provided by the present invention form acid addition salts. The present invention also includes pharmacologically acceptable salts of the compound of general formula (I), such as mineral acids such as hydrochloric acid, hydrobromic acid, and sulfuric acid, and methanesulfonic acid. , Haratoruensur*7
Examples include acid addition salts with organic acids such as H.
また、上記一般式(Dで示される化合物中には幾何異性
体等の異性体が存在する。本発明はこれらの全ての異性
体につ℃・て包含するものである。Moreover, isomers such as geometric isomers exist in the compound represented by the above general formula (D). The present invention includes all of these isomers.
本発明化合物(I)は免疫系に作用する。たとえばタフ
バク抗原に対する細胞性免疫の代表でる遅延型アレルギ
ー反応を抑制するので、抗アレルギー剤、抗すューマチ
剤、自己免疫疾患の治療剤および臓器移植や皮ふ移植の
際の拒絶反応抑制剤として有用である。殊に、遅延型ア
レルギー抑制剤、抗リューマチ剤として有用である。す
なわち、従来、抗アレルギー剤殊に遅延型アレルギー抑
制剤としてはステロイド剤が知られて℃・るに過ぎな℃
・。抗り2.−マチ剤につし・でも同様である。しかし
、ステロイド剤は長期連用すると重篤な副作用いわゆる
ステロイド依存性を発現するため、副作用の少ない非ス
テロイド系の抗アレルギー剤、抗IJ、−マチ剤の開発
が望まれて℃・る。強力な遅延型アレルギー抑制作用を
有する本発明化合物は、これらステロイドの代替として
またステロイドと併用することによりステロイドの使用
量を軽減することができろ。Compound (I) of the present invention acts on the immune system. For example, it suppresses the delayed allergic reaction that is typical of cell-mediated immunity against Tough Bacterial antigens, so it is useful as an anti-allergic agent, an anti-seumatic agent, a therapeutic agent for autoimmune diseases, and an agent to suppress rejection reactions during organ transplants and skin transplants. be. It is particularly useful as a delayed allergy suppressant and an antirheumatic agent. That is, conventionally, steroid drugs have been known as anti-allergy agents, especially delayed-acting allergy suppressants.
・. Resistance 2. - The same goes for gusset. However, when steroids are used continuously for a long period of time, they cause a serious side effect, so-called steroid dependence, so there is a desire for the development of non-steroidal anti-allergy, anti-IJ, and anti-inflammatory agents with fewer side effects. The compound of the present invention, which has a strong delayed allergy suppressing effect, can be used as a substitute for these steroids or in combination with steroids, thereby reducing the amount of steroids used.
そして1本発明化合物(I)は毒性が極めて弱し・ので
上述した種々の用途の医薬として用℃・ることか出来る
。Since the compound (I) of the present invention has extremely low toxicity, it can be used as a medicine for the various uses mentioned above.
本発明化合物(1)は2本願出願人の先行出願(特願昭
54−106438号、特開昭56−30990号)に
開示した2−ヒドロキシフェニルイ
ミダゾ[2,1−b’3ベンゾチアゾールの水酸基が低
級アルコキシカルボニル基を有スるカルボン酸でアシル
化された新規な誘導体であって。The compound (1) of the present invention is a compound of 2-hydroxyphenylimidazo[2,1-b'3 benzothiazole] disclosed in two prior applications (Japanese Patent Application No. 106438/1982 and 30990/1983) of the present applicant. A novel derivative in which the hydroxyl group is acylated with a carboxylic acid having a lower alkoxycarbonyl group.
遅延型アレルギー抑制作用等の薬理作用がそのヒドロキ
シ化合物よりも優れて(・る点に特徴がある。It is characterized by its pharmacological effects, such as delayed allergy suppressive effect, which are superior to those of its hydroxyl compounds.
本発明化合物(1)やその酸付加塩を主成分として含有
する薬剤は任意慣用の製薬用担体や。The drug containing the compound (1) of the present invention or its acid addition salt as a main component may be carried using any conventional pharmaceutical carrier.
賦形剤を用いて任意慣用の方法で調製される。It is prepared in any conventional manner using excipients.
投与は錠剤、火剤、カプセル剤、顆粒剤等の経口投与あ
るいは静注、筋注等の注射剤、エアゾール剤、半開等の
非経口投与のいずれの形態であってもよい。投与量は症
状や投与対象の年令。Administration may be in the form of oral administration such as tablets, gunpowders, capsules, or granules, or parenteral administration such as injections such as intravenous or intramuscular injections, aerosols, or semi-open forms. The dosage depends on the symptoms and the age of the recipient.
性別等を考慮して個々の場合に応じて適宜決定されるが
2通常成人1日当り経口投与の場合5〜500mg、非
経口投与の場合2〜300■であり。The dosage is determined as appropriate for each individual case, taking into account gender, etc., but the usual daily dose for adults is 5 to 500 mg for oral administration and 2 to 300 mg for parenteral administration.
これを1日2〜3回に分けて投与する。This is administered in divided doses 2 to 3 times a day.
本発明は上記一般式(1)で示される化合物及びその塩
の製造法をも包含するものであり、以下にその代表的な
製造法を例示する。The present invention also includes a method for producing the compound represented by the above general formula (1) and a salt thereof, and typical production methods thereof are illustrated below.
第1製造法
(II)
本発明化合物(I)は式(TI)で示される 2−ヒド
ロキシフェニルイミダゾ〔2,1−b〕ベンゾチアゾー
ルと、一般式(III)で示されるモノエステル化ジカ
ルボン酸又はそのカルボキシ基における反応性誘導体と
の反応(アシル化)により製造される。First production method (II) The compound (I) of the present invention is a 2-hydroxyphenylimidazo[2,1-b]benzothiazole represented by the formula (TI) and a monoesterified dicarboxylic acid represented by the general formula (III). or by reaction (acylation) with a reactive derivative at its carboxy group.
ここに、原料化合物(Il[)のカルボキシ基における
反応性誘導体としては、酸クロライド、酸ブロマイド等
の酸ノ・ライド;酸アジド;酸無水物;アルキル炭酸、
アルキルリン酸、ジアルキル亜すン酸、硫酸等との混酸
無水物;イミダゾ−ル等トノ酸アミF” ; p−ニト
ロフェニルエステル、2.4−ジニトロフェニルエステ
ル等ノ活性エステルが挙げられる。Here, the reactive derivatives at the carboxy group of the starting compound (Il[) include acid chlorides, acid bromides, etc.; acid azides; acid anhydrides; alkyl carbonates,
Mixed acid anhydrides with alkylphosphoric acid, dialkylsulfurous acid, sulfuric acid, etc.; tonoic acids such as imidazole; and active esters such as p-nitrophenyl ester and 2,4-dinitrophenyl ester.
この反応は化合物(n)とそれに対し等モルまたは過剰
モルの化合物(I)またはその反応性誘導体を有機溶媒
中で冷却下、室温または加温下に行うのが好ましい。有
機溶媒の例としては。This reaction is preferably carried out using compound (n) and equimolar or excess molar amount of compound (I) or its reactive derivative in an organic solvent under cooling, at room temperature, or under heating. Examples of organic solvents are:
アセトン、テトラヒドロフラノ、ジクロロメタン、クロ
ロホルム、ビリジ/、ジメチルホルムアミド、テトラヒ
ドロフラノあるし・はジクロルメタンとピリジンとの混
合液等が挙げられる。Examples include acetone, tetrahydrofurano, dichloromethane, chloroform, viridi, dimethylformamide, a mixture of tetrahydrofurano or dichloromethane and pyridine.
化合物(II)を遊離の状態で使用する場合には。When compound (II) is used in the free state.
N、N’−ジシクロへキシルカルボジイミド、 N、N
’−カルボニルイミダゾール等の縮合剤を用いてピリジ
ン、 N、N−ジメチルアニリン等の塩基の存在下反応
を行うのが好ましい。この場合、縮合剤と共KN−ヒド
ロキシベンツトリアゾールを使用してもよし・。N,N'-dicyclohexylcarbodiimide, N,N
It is preferable to carry out the reaction using a condensing agent such as '-carbonylimidazole in the presence of a base such as pyridine or N,N-dimethylaniline. In this case, KN-hydroxybenztriazole may be used together with the condensing agent.
第2製造法
(TV) 誘導体 (V)(1)
本発明化合物(1)は、また一般式(IV)で示される
カルボン酸化合物又はその反応性誘導体と。Second Production Method (TV) Derivative (V) (1) The compound (1) of the present invention is also a carboxylic acid compound represented by general formula (IV) or a reactive derivative thereof.
一般式(V)で示される低級アルコールとを反応させる
ことによっても製造することができる。It can also be produced by reacting with a lower alcohol represented by general formula (V).
一般式(IV)のカルボン酸化合物の反応性誘導体とし
ては第1製造法と同様、酸クロライド、酸ブロマイド等
の酸ハライド;酸アジド;酸無水物;アルキル炭酸、ア
ルキルリン酸、ジアルキル亜すン酸、硫酸等との混酸無
水物;イミダゾール等トの酸アミド;p−ニトロフェニ
ルエステル、2.4−ジニトロフェニルエステル等トの
活性エステルが挙げられる。As in the first production method, examples of reactive derivatives of the carboxylic acid compound of general formula (IV) include acid halides such as acid chloride and acid bromide; acid azides; acid anhydrides; Examples include mixed acid anhydrides with acids, sulfuric acid, etc.; acid amides such as imidazole; and active esters such as p-nitrophenyl ester and 2,4-dinitrophenyl ester.
この反応は、第1製造法とほぼ同様の条件下に実施する
ことができる。すなわち、原料化合物(1’V)又はそ
の反応性誘導体とそれに対し等モルまたは過剰モルの原
料化合物(V)とを有機溶媒中冷却下、室温乃至加温下
に反応させることによって本発明化合物(1)を製造す
ることができる。This reaction can be carried out under substantially the same conditions as in the first production method. That is, the compound of the present invention ( 1) can be manufactured.
原料化合物(IV)を遊離の状態で使用する場合には2
反応はN、N’−ジシクロへキシルカルボジイミド、
N、N’−カルボニルイミダゾール等の縮合剤を用い
て、ピリジン、 N、N−ジメチルアニリン等の塩基
の存在下に行うのが好ましい。この場合、縮合剤と共に
N−ヒドロキシベンツトリアゾールを使用してもよ見・
。When using the raw material compound (IV) in a free state, 2
The reaction is N,N'-dicyclohexylcarbodiimide,
It is preferable to use a condensing agent such as N,N'-carbonylimidazole in the presence of a base such as pyridine or N,N-dimethylaniline. In this case, it is possible to use N-hydroxybenztriazole together with the condensing agent.
.
これらの反応に用いられる溶媒としては例えばアセトン
、テトラヒドロ7ラン2 ジクロルメタ/、クロロホル
ム、ピリジノ、ジメチルホルムアミド、テトラヒドロフ
ラノあるいはジクロルメタノとピリジンとの混合液等の
有機溶媒が有利である。Advantageous solvents used in these reactions include organic solvents such as acetone, tetrahydrol, dichloromethano, chloroform, pyridino, dimethylformamide, tetrahydrofurano or a mixture of dichloromethano and pyridine.
このようにして2種々の方法によって製造された本発明
化合物(I)はそのままあるいはその塩として、その理
化学的性状や反応条件等を考慮して、P取、溶媒による
抽出、再結晶、各種クロマトグラフィー等当分野におし
・て任意慣用の手段を適用して、単離・精製される。The compound (I) of the present invention produced by two different methods as described above, either as it is or as its salt, is subjected to P removal, solvent extraction, recrystallization, various chromatography, etc., taking into consideration its physical and chemical properties and reaction conditions. It is isolated and purified by applying any conventional means in the art, such as photography.
以下に実施例を掲記し2本発明を更に詳細に説明する。EXAMPLES The present invention will be described in further detail with reference to Examples below.
なお2本発明の原料化合物(II)及び(IV)は前記
特願昭54−106438号や9本出願人の出願に係る
特願昭56−208609号に記載された方法により製
造される。The two raw material compounds (II) and (IV) of the present invention are produced by the method described in the above-mentioned Japanese Patent Application No. 106438/1982 and Japanese Patent Application No. 208609/1989 filed by the present applicant.
実施例 1゜
2−(m−ヒドロキシフェニル)イミダゾ[2゜1−b
]ベンゾチアゾール10g、コハク酸モノエチルエステ
ル9gをピリジン100m1K溶解した溶液に、ジシク
ロへキシルカルボジイミドl1gをピリジン10m1K
溶解した溶液をかきまぜながら15〜25Cで加え、3
時間20〜25Cでかきまぜる。析出した尿素を;戸別
し、P液を減圧濃縮する。残留物をトルエン100m乙
に溶解し、水100 mlで2回洗った後、無水硫酸マ
グネシウムで乾燥し、溶媒を留去する。アメ状残留物を
シリカゲル力ラムクロマトグンフィーに付しベンゼン−
酢酸エチル(容量比9:1)で溶出し、2−〔m−(3
−エトキ13−
ジカルボニルプロピオニルオキシ)フェニル〕イミダゾ
[2,1−b〕ベンゾチアゾール8.9gを得た。Example 1゜2-(m-hydroxyphenyl)imidazo[2゜1-b
] In a solution of 10 g of benzothiazole and 9 g of succinic acid monoethyl ester dissolved in 100 ml of pyridine, 1 g of dicyclohexylcarbodiimide was dissolved in 10 ml of pyridine.
Add the dissolved solution at 15-25C while stirring, and
Stir at 20-25C for an hour. The precipitated urea is distributed door to door, and the P solution is concentrated under reduced pressure. The residue was dissolved in 100 ml of toluene, washed twice with 100 ml of water, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The candy-like residue was subjected to silica gel column chromatography and benzene-
Elute with ethyl acetate (volume ratio 9:1) to give 2-[m-(3
8.9 g of -ethoxy13-dicarbonylpropionyloxy)phenyl]imidazo[2,1-b]benzothiazole was obtained.
融点 70〜74C(塩酸塩155〜1s9C)元素
分析値(C2,H,、N、O,Sとして)C(チ)
H(チ)N(チl S(チ)理論値 63.9
5 4,60 7,10 8.13実験値 64,0
3 4.43 7.16 8.11実施例 2゜
2− (m−ヒドロキシフェニル)イミダゾ〔2゜1−
b〕ベノゾチアゾール3.2gおよびアジピノ酸モノエ
チルエステル3.2gを用℃・実施例1と同様に処理し
て、2−(m−(5−エトキシカルボニルペンタノイル
オキシ)フェニル〕イミダゾ[2,1−b]ベノゾチア
ゾール18gを得た。Melting point 70-74C (hydrochloride 155-1s9C) Elemental analysis value (as C2, H,, N, O, S) C (chi)
H(chi) N(chil S(chi) theoretical value 63.9
5 4,60 7,10 8.13 Experimental value 64,0
3 4.43 7.16 8.11 Example 2゜2-(m-hydroxyphenyl)imidazo[2゜1-
b] 3.2 g of benozothiazole and 3.2 g of adipino acid monoethyl ester were treated in the same manner as in Example 1 at ℃ to obtain 2-(m-(5-ethoxycarbonylpentanoyloxy)phenyl]imidazo[2,1 -b] 18 g of benozothiazole was obtained.
融点 90〜92D
元素分析値(C23H22N204 Sとして)14−
C(嗟) Hfチ) N(チ) S(チ
)理論1直 65.39 5,25 6,63 7.
59実験値 65.57 5,32 6,72 7.
41実施例 3゜
2− (m−ヒドロキシフェニル)イミダゾ〔2゜1−
b〕ベンゾチアゾール10gおよびマレイン酸モノエチ
ルエステル8.3 gを用(・実施例1と同様に処理し
て、 2−(m (cis−3−エトキシカルボニ
ルプロペノイルオキシ)フェニル〕イミタソ[2,1−
b]ベンゾチアゾール7.2gを得た。Melting point 90-92D Elemental analysis value (as C23H22N204 S) 14- C (嗟) Hf CH) N (CH) S (CH) Theory 1 straight 65.39 5,25 6,63 7.
59 Experimental value 65.57 5,32 6,72 7.
41 Example 3゜2-(m-hydroxyphenyl)imidazo[2゜1-
b] Using 10 g of benzothiazole and 8.3 g of maleic acid monoethyl ester (treated in the same manner as in Example 1, 2-(m (cis-3-ethoxycarbonylpropenoyloxy)phenyl)imitaso[2, 1-
b] 7.2 g of benzothiazole was obtained.
融点 126〜128C
元素分析値(C21Hfa N204 Sとして)C(
チ) H(チ) N(チ) Sfチ)理論値
64,27 4,11 7,14 8.17実験値
64.34 3.81 7.23 7.992− (
m−ヒドロキシフェニル)イミダゾ〔2゜1−b]ベン
ゾチアゾール4g、トリエチルアミン1.52gおよび
テトラヒドロフラン50 mlの混液にエトキサリルク
ロライド2.1 g 、テトラヒドロフラン10m1の
混液を一10C以下で加える。滴下終了後2反応液を室
温で一夜攪拌したのち減圧濃縮する。残留物をトルエン
209m1に溶解する。トルエン溶液を水洗し、無水硫
酸マグネシウムで乾燥後減圧濃縮する。残留物をカラム
クロマトグラフィー(シリカゲル80n+Z、溶出液:
トルエン:酢酸エチル=9:1)に付し、2−(m−エ
トキサリルオキシフェニル)イミダゾ[2,1−b]ベ
ンゾチアゾール2.75gを得た。Melting point 126-128C Elemental analysis value (as C21Hfa N204 S) C (
h) H (ch) N (ch) Sf h) Theoretical value
64,27 4,11 7,14 8.17 Experimental value
64.34 3.81 7.23 7.992- (
A mixture of 2.1 g of ethoxalyl chloride and 10 ml of tetrahydrofuran is added to a mixture of 4 g of m-hydroxyphenyl)imidazo[2<1-b]benzothiazole, 1.52 g of triethylamine, and 50 ml of tetrahydrofuran at a temperature below -10C. After completion of the dropwise addition, the two reaction solutions were stirred at room temperature overnight and then concentrated under reduced pressure. The residue is dissolved in 209 ml of toluene. The toluene solution is washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel 80n+Z, eluent:
Toluene:ethyl acetate=9:1) to obtain 2.75 g of 2-(m-ethoxalyloxyphenyl)imidazo[2,1-b]benzothiazole.
融点 120〜121C
元素分析値(C,、T−1,、N20.Sとして)C(
チl H(チ) N(チ) S(チ)理
論値 62,29 3.85 7.65 8.75実験
値 62.48 3.76 7,50 8.74実施例
5゜
2−(m−カルボキシアセトキシフェニル)イミダゾ[
2,1−b]ベンゾチアゾール4g、エタノール052
gおよびテトラヒドロフラン50 mlの混液に。Melting point 120-121C Elemental analysis value (as C,, T-1,, N20.S) C (
Chil H(chi) N(chi) S(chi) Theoretical value 62,29 3.85 7.65 8.75 Experimental value 62.48 3.76 7,50 8.74 Example 5゜2-(m -carboxyacetoxyphenyl)imidazo[
2,1-b]benzothiazole 4g, ethanol 052
g and 50 ml of tetrahydrofuran.
ジシクロへキシルカルボジイミド2.3g、 テトラ
ヒドロフラフ10mtの混液を10C以下で加える。滴
下終了後、室温で一夜攪拌し、生じたジシクロヘキシル
尿素を沢去し、母液を減圧濃縮する。残留物をカラムク
ロマトグラフィー(シリカゲル80m1゜溶出液:トル
エン:酢酸エチル−9:1)に付し油状の2−(m−エ
トキシカルボニルアセトキシフェニル)イミダゾ[2,
1−b]ベノゾチアゾー17−
ル2.0 gを得た。Add a mixture of 2.3 g of dicyclohexylcarbodiimide and 10 mt of tetrahydrofluff at 10C or less. After completion of the dropwise addition, the mixture was stirred overnight at room temperature, the dicyclohexylurea formed was removed, and the mother liquor was concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel 80ml, eluent: toluene:ethyl acetate - 9:1) to obtain an oily 2-(m-ethoxycarbonylacetoxyphenyl)imidazo[2,
1-b] Benozothiazole 17-2.0 g was obtained.
核磁気共鳴スペクトル(CDCl5)
δ(ppm) : 1.33 (t、 3H,−CH2
Cul)3.61 (S、 2H,coc3co )実
施例 6
2− (m−ヒドロキシフェニル)イミダゾ〔2゜1−
b〕ベンゾチアゾール11.5g、およびフマール酸モ
ノエチルエステル9.2gを用いて、実施例1と同様に
処理して、 2− (m −(trans −3−エ
トキシカルボニルプロペノイルオキシ)フェニル〕イミ
ダゾ[2,1−b〕ベンゾチアゾール7.3gを得た。Nuclear magnetic resonance spectrum (CDCl5) δ (ppm): 1.33 (t, 3H, -CH2
Cul) 3.61 (S, 2H, coc3co) Example 6 2-(m-hydroxyphenyl)imidazo[2゜1-
b] 2-(m-(trans-3-ethoxycarbonylpropenoyloxy)phenyl)imidazo 7.3 g of [2,1-b]benzothiazole was obtained.
融点 130〜130.5tl?
18−
元素分析値(C21HI3 N204 Sとして)C(
係) H(チ) N(チ) S(チ)理論値
64,27 4,11 7,14 8.17実験値 6
4,38 3.95 7,19 8.21特許出願人
山之内製薬株式会社
代理人 佐々木晃−
−19=Melting point 130-130.5tl? 18- Elemental analysis value (as C21HI3 N204 S) C(
) H (chi) N (chi) S (chi) Theoretical value
64,27 4,11 7,14 8.17 Experimental value 6
4,38 3.95 7,19 8.21 Patent applicant
Yamanouchi Pharmaceutical Co., Ltd. Agent Akira Sasaki - -19=
Claims (1)
を、nは0又は1を、Rは低級アルキル基を意味する) で示される2−フェニルイミダゾ[2,1−b〕ベンゾ
チアゾールの新規誘導体又はその塩。 2式 で示される2−ヒドロキシフェニルイミダゾ[:2,1
−b〕ベンゾチアゾールと、一般式%式% (式中、Aは低級アルキレン基又は低級アルケニレン基
を、nはO又は1を、Rは低級アルキル基を意味する。 以下同様) ゛で示されるモノエステル化ジカル
ボン酸又はその反応性誘導体とを反応させることを特徴
とする一般式 で示される2−フェニルイミダゾ[2,1−b〕ベンゾ
チアゾールの新規誘導体又はその塩の製造法。 3、一般式 (式中、Aは低級アルキレン基又は低級アルケニレン基
を、nはO又は1を意味する。 以下同様) で示されるカルボン酸化合物又はその反応性誘導体と一
般式 %式% (Rは低級アルキル基を意味する。以下同様)で示され
る低級アルコールとを反応させることを特徴とする一般
式 で示される2−フェニルイミダゾ[2,1,−b〕ベン
ゾチアゾールの新規誘導体又はその塩の製造法。[Claims] 1 2-phenylimidazo[2, 1-b] A novel derivative of benzothiazole or a salt thereof. 2-hydroxyphenylimidazo [:2,1
-b] Benzothiazole and the general formula % (In the formula, A means a lower alkylene group or a lower alkenylene group, n means O or 1, and R means a lower alkyl group. The same applies hereinafter) A method for producing a novel 2-phenylimidazo[2,1-b]benzothiazole derivative or a salt thereof represented by the general formula, which comprises reacting a monoesterified dicarboxylic acid or a reactive derivative thereof. 3. A carboxylic acid compound or its reactive derivative represented by the general formula (wherein A represents a lower alkylene group or a lower alkenylene group, and n represents O or 1. The same applies hereinafter) and the general formula % formula % (R means a lower alkyl group (hereinafter the same applies) A novel derivative of 2-phenylimidazo[2,1,-b]benzothiazole represented by the general formula or a salt thereof, which is characterized by reacting with a lower alcohol represented by manufacturing method.
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57188866A JPS5978194A (en) | 1982-10-27 | 1982-10-27 | Novel derivative of 2-phenylimidazo(2,1-b)benzothiazole and its preparation |
US06/449,759 US4464384A (en) | 1981-12-23 | 1982-12-14 | 2-Phenylimidazo[2,1-b]benzothiazole compounds, salts thereof, process of producing them, and pharmaceutical compositions containing them |
DE8282306804T DE3276580D1 (en) | 1981-12-23 | 1982-12-20 | 2-phenylimidazo(2,1-b)benzothiazole compounds, salts thereof, process for producing them, and pharmaceutical compositions containing them |
EP82306804A EP0082712B1 (en) | 1981-12-23 | 1982-12-20 | 2-phenylimidazo(2,1-b)benzothiazole compounds, salts thereof, process for producing them, and pharmaceutical compositions containing them |
AT82306804T ATE27819T1 (en) | 1981-12-23 | 1982-12-20 | 2-PHENYLIMIDAZO (2,1-B)BENZOTHIAZOLE COMPOUNDS, THEIR SALTS, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
CA000418482A CA1190231A (en) | 1981-12-23 | 1982-12-21 | Process for preparing 2-phenylimidazo 2,1-b benzothiazole compounds and salts thereof |
ES518488A ES8406495A1 (en) | 1981-12-23 | 1982-12-22 | 2-Phenylimidazo(2,1-b)benzothiazole compounds, salts thereof, process for producing them, and pharmaceutical compositions containing them. |
DK567482A DK567482A (en) | 1981-12-23 | 1982-12-22 | METHOD FOR PREPARING 2-PHENYLIMIDAZO (2,1-B) BENZOTHIAZOL COMPOUNDS |
NO824331A NO824331L (en) | 1981-12-23 | 1982-12-22 | PROCEDURE FOR PREPARING 2-PHENYLIMIDAZO (2,1-B) BENZOTHIAZOLE COMPOUNDS |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57188866A JPS5978194A (en) | 1982-10-27 | 1982-10-27 | Novel derivative of 2-phenylimidazo(2,1-b)benzothiazole and its preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS5978194A true JPS5978194A (en) | 1984-05-04 |
Family
ID=16231234
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP57188866A Pending JPS5978194A (en) | 1981-12-23 | 1982-10-27 | Novel derivative of 2-phenylimidazo(2,1-b)benzothiazole and its preparation |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5978194A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4968708A (en) * | 1988-06-22 | 1990-11-06 | Nikken Chemicals Co., Ltd. | Imidazo[2,1-B]benzothiazole compounds and antiulcer compositions containing the same |
JP2009530300A (en) * | 2006-03-17 | 2009-08-27 | アムビト ビオスシエンセス コルポラチオン | Imidazolothiazole compounds for treating diseases |
-
1982
- 1982-10-27 JP JP57188866A patent/JPS5978194A/en active Pending
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4968708A (en) * | 1988-06-22 | 1990-11-06 | Nikken Chemicals Co., Ltd. | Imidazo[2,1-B]benzothiazole compounds and antiulcer compositions containing the same |
JP2009530300A (en) * | 2006-03-17 | 2009-08-27 | アムビト ビオスシエンセス コルポラチオン | Imidazolothiazole compounds for treating diseases |
JP2011037858A (en) * | 2006-03-17 | 2011-02-24 | Ambit Biosciences Corp | Imidazolothiazole compound for treating disease |
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