JPS6153268A - Anthranilamide derivative - Google Patents
Anthranilamide derivativeInfo
- Publication number
- JPS6153268A JPS6153268A JP59175202A JP17520284A JPS6153268A JP S6153268 A JPS6153268 A JP S6153268A JP 59175202 A JP59175202 A JP 59175202A JP 17520284 A JP17520284 A JP 17520284A JP S6153268 A JPS6153268 A JP S6153268A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- value
- phenyl
- acid
- melting point
- 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.)
- Pending
Links
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 title abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 10
- -1 tetrahydroisoquinolin-2-yl Chemical group 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 24
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 239000002904 solvent Substances 0.000 abstract description 6
- 125000005843 halogen group Chemical group 0.000 abstract description 5
- 125000000217 alkyl group Chemical group 0.000 abstract description 3
- 230000003288 anthiarrhythmic effect Effects 0.000 abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 abstract description 3
- 238000010992 reflux Methods 0.000 abstract description 3
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000003533 narcotic effect Effects 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000000921 elemental analysis Methods 0.000 description 15
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RTNCJZHSKGUZKP-UHFFFAOYSA-N 2-amino-n-(2,6-dimethylphenyl)benzamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC=CC=C1N RTNCJZHSKGUZKP-UHFFFAOYSA-N 0.000 description 1
- VNRJGEMERJZKLQ-UHFFFAOYSA-N 2-piperazin-1-ylacetamide Chemical compound NC(=O)CN1CCNCC1 VNRJGEMERJZKLQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Landscapes
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
び抗潰瘍作用を有する新規なアントラニルアミド誘導体
、及びその薬理学的に許容しつる酸付加塩に関するもの
である。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel anthranilamide derivative having anti-ulcer and anti-ulcer effects, and a pharmacologically acceptable acid addition salt thereof.
発明の構成
更に詳しく言えば、発明は一般式（１）（式中、Ｒ１及
びＲ２は同一もしくけ異なって水素原子、ハロゲン原子
、低級アルキル基あるいは低級アルコキシ基を表わし、
Ｒ３け４位置換ピペラジニル基、オクタヒドロ−２にピ
リド〔１゜２−ａ）ピラジン−２−イル基あるいはテト
ラヒドロイソキノリン−２−イル基を表わす。）で示さ
れる新規なアントラニルアミド誘導体、及びその薬理学
的に許容しうる酸付加塩に関するものである０
本発明の前記一般式（１）中、Ｒ１及びＲ２で示される
ハロゲン原子としては、７ノ素、塩素。More specifically, the invention relates to the general formula (1) (wherein R1 and R2 are the same or different and represent a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group,
R3 represents a piperazinyl group substituted at the 4-position, and octahydro-2 represents a pyrido[1°2-a) pyrazin-2-yl group or a tetrahydroisoquinolin-2-yl group. ) and a pharmacologically acceptable acid addition salt thereof. In the general formula (1) of the present invention, the halogen atoms represented by R1 and R2 are 7 No element, chlorine.
臭素、ヨウ素原子等が、低級アルキル基としては、たと
えば、メチル、エチル、プロピル、イソプロピル２ ブ
チル、 ｔｅｒｔ−ブチル基等が挙げられ、低級アル
フキン基としては、たとえば、メトキシ。Examples of lower alkyl groups include methyl, ethyl, propyl, isopropyl 2-butyl, and tert-butyl groups, and examples of lower alfkyne groups include methoxy.
エトキシ、ブトキシ基が挙げられる。Examples include ethoxy and butoxy groups.
又、本発明の前記一般式（１）中、Ｒ３で示される置換
ピペラジニル基としては、たとえば、４−メチル−１−
ピペラジニル、４−エチル−１−ピペラジニル、４−ヒ
ドロキシメチル−１−ピペラジニル、４−（２−ヒドロ
キシエチル）−１−ピペラジニル、４−ベンジル−１−
ヒ°ペラジニル基等が挙げられる。Further, in the general formula (1) of the present invention, the substituted piperazinyl group represented by R3 is, for example, 4-methyl-1-
Piperazinyl, 4-ethyl-1-piperazinyl, 4-hydroxymethyl-1-piperazinyl, 4-(2-hydroxyethyl)-1-piperazinyl, 4-benzyl-1-
Examples include hyperazinyl group.
本発明の前記一般式（１）で示される化合物は、所望に
応じて薬理学的に許容しつる酸付加塩に変換することも
、又は生成した酸付加塩から、塩基を遊離きせることも
できる。The compound represented by the general formula (1) of the present invention can be converted into a pharmacologically acceptable acid addition salt as desired, or the base can be liberated from the generated acid addition salt. .
本発明の前記一般式（りで示される化合物の薬理学的に
許容しうる酸付加塩としては、たとえば、塩酸、臭化水
素酸、ヨウ化水素酸、硝酸、硫酸、（Ａ酸等の鉱酸塩、
あるいは、酢酸、マレイン酸１ フマール酸、クエン酸
、シュウ酸、酒石酸等の有機酸塩が挙げられる。Examples of the pharmacologically acceptable acid addition salts of the compound represented by the general formula (R) of the present invention include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, (mineral acid such as A acid) acid salt,
Alternatively, organic acid salts such as acetic acid, maleic acid, fumaric acid, citric acid, oxalic acid, and tartaric acid may be mentioned.
本発明の前記一般式（＋）で示される新規なアントラニ
ルアミド誘導体は、以下の様にして製造することができ
る。The novel anthranilamide derivative represented by the general formula (+) of the present invention can be produced as follows.
即ち、本発明に係わる前記一般式（１）で示される化合
物は、次の一般式（１１）
（式中、Ｒ１及びＲ２は前述と同意義を表わし、Ｘはハ
ロゲン原子を表わす。）
で示すれるハロゲノアセトアミド誘導体と、次の一般式
（ｔｌ＋ ）
Ｒ３−Ｈ（ＩＩＩ）
（式中、Ｒ３は前述と同意義を表わす。）で示される化
合物とを、溶媒の存在下で反応きせることにより製造す
ることができる。That is, the compound represented by the general formula (1) according to the present invention is represented by the following general formula (11) (wherein R1 and R2 represent the same meanings as above, and X represents a halogen atom). A compound represented by the following general formula (tl+) R3-H (III) (wherein R3 represents the same meaning as above) in the presence of a solvent. can do.
本発明の方法において使用される溶媒としては、たとえ
ば、ベンゼン、トルエン、ピリジン、ルチジン、ジメチ
ルホルムアミド、クロロホルム等が挙げられる。Examples of the solvent used in the method of the present invention include benzene, toluene, pyridine, lutidine, dimethylformamide, and chloroform.
又、反応は−１００から溶媒の加熱還流温度下において
行なわれる。Further, the reaction is carried out at a temperature ranging from -100 to reflux temperature of the solvent.
尚、本発明の方法において出発原料となった前記式（１
１）で示されるハロゲノアセトアミド誘導体は一部を除
き公知の物質であり１新規な物質については参考例にそ
の製造方法を記載した。In addition, in the method of the present invention, the above formula (1
The halogenoacetamide derivatives shown in 1) are known substances except for some, and the production method of 1 new substances is described in Reference Examples.
発明の効果
この様にして製造きれる前記一般式（１）で示される新
規なアントラニルアミド誘導体、及びその薬理学的に許
容しつる酸付加塩は、擾れた抗不整脈作用１局所麻酔作
用及び抗潰瘍作用を有し、以下、本発明を実施例によっ
て説明する。Effects of the Invention The novel anthranilamide derivative represented by the general formula (1) and its pharmacologically acceptable oxalic acid addition salt produced in this manner have an antiarrhythmic effect, a local anesthetic effect, and an antiarrhythmia effect. It has an ulcer effect, and the present invention will be explained below with reference to Examples.
参考例１
２−クロロ−Ｎ−［：２−（２，６−シメチルフエニル
アミノカルボニル）フェニル〕アセトアミド
２−アミノ−Ｎ−（２，６−キシリル）安息香酸アミド
４．８０．９及びトリエチルアミン４．０１９のクロロ
ホルム５０ゴ溶液に、氷冷儂拌下、クロロアセチルクロ
リ、ド８．２ ｔｕｔを加え、室温にて３０分間攪拌す
る。反応混合物に炭酸カリウム水溶液を加え、析出結晶
をｐ取する０結晶を水洗し、無色結晶５．１２ 、！９
を得る０エタノールより再結晶して、融点２１８〜２１
９°の無色針状晶を得る。Reference Example 1 2-chloro-N-[:2-(2,6-dimethylphenylaminocarbonyl)phenyl]acetamide 2-amino-N-(2,6-xylyl)benzoic acid amide 4.80.9 and To a solution of 4.019 grams of triethylamine in 50 grams of chloroform, add 8.2 grams of chloroacetyl chloride while stirring on ice, and stir at room temperature for 30 minutes. An aqueous potassium carbonate solution was added to the reaction mixture, and the precipitated crystals were washed with water to give 5.12 colorless crystals! 9
Recrystallize from 0 ethanol to obtain a melting point of 218-21
Colorless needles of 9° are obtained.
元素分析値 Ｃ１７Ｈ１７ＣＩＮ２０２理論値 Ｃ，６
４，４６；Ｈ，５，４１１Ｎ、 ８．８４実験値 Ｃ，
６４，４８ｉＨ，５，４８ｉＮ、 ８．８１実施例Ｉ
Ｎ Ｃ２−（２，６−シメチルフエニルアミ７カルボ
ニル）フェニル〕−４−メチル−１−ビペラジンアセト
アミド
参考例１で得た２−クロロ−Ｎ−（２−（２゜６−シメ
チルフエニルアミノカルボニル）フェニルジアセトアミ
ド３．１１１１．１−メチルピペラジン２．１１Ｆ及び
ジメチルホルムアミドＴｍｌの混合物を、室温にて３０
分間攪拌する。度忘混合物に水を加え水酸化ナトリウム
水溶液にてアルカリ性となし、酢酸エチル抽出する。酢
酸エチル層は水洗。Elemental analysis value C17H17CIN202 theoretical value C,6
4,46; H, 5,411N, 8.84 experimental value C,
64,48iH, 5,48iN, 8.81 Example I N C2-(2,6-dimethylphenylamino7carbonyl)phenyl]-4-methyl-1-biperazineacetamide 2 obtained in Reference Example 1 -Chloro-N-(2-(2゜6-dimethylphenylaminocarbonyl)phenyldiacetamide 3.11 A mixture of 2.11 F and dimethylformamide (Tml) was added at room temperature for 30 minutes.
Stir for a minute. Add water to the mixture, make it alkaline with an aqueous sodium hydroxide solution, and extract with ethyl acetate. Wash the ethyl acetate layer with water.
脱水後、溶媒を留去し、淡黄色納品３．５’ｌを得る。After dehydration, the solvent is distilled off to obtain 3.5'l of a pale yellow product.
ベンゼンより再結晶して、融点１８３〜１８４°の淡黄
色プリズム晶を得る。Recrystallization from benzene gives pale yellow prismatic crystals with a melting point of 183-184°.
元素分析値 Ｃ２２Ｈ２８Ｎ４０．２
理論値 Ｃ，６９，４５ｉＨ，７，４２；Ｎ、 １４．
７２実験値 Ｃ，６９，５１；Ｈ，７，４９１，１４，
４７参考例２
２−クロロ−Ｎ−〔２−（３−メトキシ７二二ルアミ７
カルボニル）フェニル〕アセトアミド２−アミ／−Ｎ−
（３−メトキシフェニル）安息香酸アミド２Ｂ、２０＆
、トリエチルアミン１４゜６０．９． クロロホルム
１００ゴ及びクロロアセチルクロリド１６１０ｇを泪い
て、参考例１と同様に処理し、無色結晶２’４．０！ｌ
を得る。エタノ一ルより再結晶して、融点１６２〜１６
３°の無色針状晶を得る。Elemental analysis value C22H28N40.2 Theoretical value C,69,45iH,7,42;N, 14.
72 experimental value C, 69,51; H, 7,491,14,
47 Reference Example 2 2-Chloro-N-[2-(3-methoxy72-dylami7
carbonyl)phenyl]acetamido 2-amino/-N-
(3-Methoxyphenyl)benzoic acid amide 2B, 20&
, triethylamine 14°60.9. 100 grams of chloroform and 1,610 grams of chloroacetyl chloride were mixed and treated in the same manner as in Reference Example 1 to obtain colorless crystals of 2'4.0! l
get. Recrystallized from ethanol, melting point 162-16
Colorless needles of 3° are obtained.
元素分析値 Ｃ１６Ｈ１５ＣＩＮ２０３理論値 Ｃ，６
０，２９：Ｈ，４，７４；Ｎ、 ８．７９実験値 Ｃ，
６０，１７；Ｈ，４，８８；Ｎ、 ８．７２実施例２
４−ベンジル−Ｎ−（２−（３−メトキシフェニルアミ
７カルボニル）フェニル）−１−ピペラジンア七ドアミ
ド
参考例２で得た２−クロロ−Ｍ−Ｃ２−（３−メトキシ
フェニルアミ７カルボニル）フェニル〕アセトアミド２
．００ｇ、１−ベンジルビペラノン２、２０９及びジメ
チルホルムアミドＬ５ｍｌの混合物を５０〜６０°にて
３０分間加熱攪拌する。Elemental analysis value C16H15CIN203 theoretical value C,6
0,29:H, 4,74;N, 8.79 experimental value C,
60,17; H, 4,88; N, 8.72 Example 2 4-benzyl-N-(2-(3-methoxyphenylami7carbonyl)phenyl)-1-piperazinamide obtained in Reference Example 2 2-chloro-M-C2-(3-methoxyphenylami7carbonyl)phenyl]acetamide 2
．． A mixture of 00 g, 1-benzylbiperanone 2,209, and 5 ml of dimethylformamide was heated and stirred at 50 to 60° for 30 minutes.
以下、実施例１と同様に処理し、無色結晶２．５０ｇを
得る。メタノールより再結晶して融点１８４〜１８５°
の無色プリズム晶を得る。Thereafter, the same treatment as in Example 1 is carried out to obtain 2.50 g of colorless crystals. Recrystallized from methanol, melting point 184-185°
Obtain colorless prismatic crystals.
元素分析値 Ｃ２７Ｈ３ＯＮ４０３
理論値 Ｃ９７０，７２１，６，５９ｉＮ、 １２．２
２実験値 Ｃ，７０，４３ｉＨ，６，６８；Ｎ、 １２
．２２実施例３
４−メチル−Ｎ−〔２−（４−メチルフェニルアミ７カ
ルボニル）フェニルシー１−ピペラジンアセトアミド
２−クロロ−Ｎ−Ｃ２−（４−メチルフェニルアミノカ
ルボニル）フェニルジアセトアミド４．００ｇ、１−メ
チルビペラジン３．３１ｇ及びベンゼン２００ ｍｌの
混合物を、５時間加熱還流する。以下、実施例１と同様
に処理し、無色結晶２．１５Ｅを得る。ジメチルホルム
アミド及び水の混液より再結晶して、融点２０６〜２０
７°の無色プリズム晶を得る。Elemental analysis value C27H3ON403 Theoretical value C970,721,6,59iN, 12.2
2 Experimental value C, 70, 43iH, 6, 68; N, 12
．． 22 Example 3 4-Methyl-N-[2-(4-methylphenylamino7carbonyl)phenylcy 1-piperazineacetamide 2-chloro-N-C2-(4-methylphenylaminocarbonyl)phenyldiacetamide 4.00 g A mixture of 3.31 g of 1-methylbiperazine and 200 ml of benzene is heated under reflux for 5 hours. Thereafter, the same treatment as in Example 1 is carried out to obtain colorless crystal 2.15E. Recrystallized from a mixture of dimethylformamide and water, melting point 206-20
A colorless prism crystal of 7° is obtained.
元素分析値 Ｃ２１Ｈ２６Ｎ４０２
理論値 Ｃ，６８，８３；Ｈ，７，１５；Ｎ、 １５．
２９実験値 Ｃ，６８，６８；Ｈ，７，２８ｉＬ １５
．４０以下、実施例１〜３に記載した方法により、実施
例４〜１４の化合物を得る。Elemental analysis value C21H26N402 Theoretical value C, 68, 83; H, 7, 15; N, 15.
29 Experimental value C, 68, 68; H, 7, 28iL 15
．． 40 Below, the compounds of Examples 4 to 14 are obtained by the methods described in Examples 1 to 3.
実施例４
Ｎ−［： ２−（２−メトキシフェニルアミ７カルボニ
ル）フェニルシー４−メチル−１−ヒ°ペラジンアセト
アミド
無色針状晶
融点 １５４〜１５５° （ベンゼン）元素分析値 Ｃ
２１Ｈ２６Ｎ４０３
理論値 Ｃ，６５，９５；Ｈ，６，８５；Ｊ １４．６
５実験値 Ｃ１６５，７４；Ｈ，６，７５；Ｎ、 １４
．４３実施例５
Ｎ−（２−（３−メトキシフェニルアミノカルボニル
ンアセトアミド
無色プリズム晶
融点 ２０５〜２０６° （メタノール）元素分析値
Ｃ２１Ｈ２６Ｎ４０３
理論値 Ｃ１６５，９５；Ｈ，６，８５ｉＮ、 １４．
６５実験値 Ｃ，６５，８５；Ｈ，６，９０；Ｎ、 １
４．６９実施例６
４−（２−ヒドロキシエチル）−Ｎ−（２−（３−メト
キシ７ヱニルアミノカルボニル）フェニルツー１−ピペ
ラジンアセトアミド
無色プリズム晶
融点 １８０〜１３１° （酢酸エチル）元素分析値
Ｃ２１Ｈ２５Ｎ３０４
理論値 Ｃ，６４，０６ｉＨ，６゜８４ ｉＮ、 １３
．５８実験値 Ｃ，６３，８７ｉＨ，６，９１ｉＮ、
１３．５１実施例７
Ｎ−１：２−（３−メトキシフェニルアミ７カルボニル
ンフエニル）−２−（オクタヒドロ−２Ｈ−ビリド（１
，２−ａ）ピラジン−２−イル）アセトアミド
無色針状晶
融点 １９２〜１９３°（エタノール）元素分析値 Ｃ
２４Ｈ３ＯＮ４０３
理論値 Ｃ，６８，２２ｉｌ（、７，１６ｉＮ、 １３
．２６実験値 Ｃ，６７，９３；Ｈ，７，３６ｉＮ、
１１１６実施例８
Ｎ−（２−（４−メトキシフェニルアミ７カルボニル）
フェニルツー４−メチル−１−ピペラジンアセトアミド
無色プリズム晶
融点 １６０〜１６１° （ベンゼン）元素分析値 Ｃ
２１Ｈ２６Ｎ４０３
理論値 Ｃ，６５，９５；Ｈ，６，８５；Ｎ、 １４．
６５実験値 Ｃ，６５，９６；ｌ（、６，９１ｉＮ、
１４．５４実施例９
！’ｒ−（２−（２−クロロフェニルアミ７７ルガニル
アセトアミド
淡褐色針状晶
融点 １４４〜１４５° （エタノール−インプロピル
エーテル）
元素分析値 Ｃ２０１（２３ｃＩＮ４０２ ・１／２Ｈ
２。Example 4 N-[: 2-(2-methoxyphenylami7carbonyl)phenylcy 4-methyl-1-hyperazineacetamide Colorless needle crystals Melting point 154-155° (Benzene) Elemental analysis value C
21H26N403 Theoretical value C, 65,95; H, 6,85; J 14.6
5 Experimental values C165,74; H,6,75; N, 14
．． 43 Example 5 N-(2-(3-methoxyphenylaminocarbonylonacetamide) Colorless prism crystal Melting point 205-206° (methanol) Elemental analysis value
C21H26N403 Theoretical value C165,95; H, 6,85iN, 14.
65 experimental value C, 65, 85; H, 6, 90; N, 1
4.69 Example 6 4-(2-hydroxyethyl)-N-(2-(3-methoxy7enylaminocarbonyl)phenyl-1-piperazineacetamide Colorless prism crystal Melting point 180-131° (Ethyl acetate) Elemental analysis value
C21H25N304 Theoretical value C, 64, 06iH, 6° 84 iN, 13
．． 58 experimental values C, 63,87iH, 6,91iN,
13.51 Example 7 N-1: 2-(3-methoxyphenylami7carbonylumphenyl)-2-(octahydro-2H-pyrido(1
, 2-a) Pyrazin-2-yl)acetamide colorless needle crystals Melting point 192-193° (ethanol) Elemental analysis value C
24H3ON403 Theoretical value C, 68, 22il (, 7, 16iN, 13
．． 26 experimental value C, 67,93; H, 7,36iN,
1116 Example 8 N-(2-(4-methoxyphenylami7carbonyl)
Phenyl-4-methyl-1-piperazine acetamide colorless prismatic crystal Melting point 160-161° (Benzene) Elemental analysis value C
21H26N403 Theoretical value C, 65,95; H, 6,85; N, 14.
65 experimental value C,65,96;l(,6,91iN,
14.54 Example 9! 'r-(2-(2-Chlorophenylamide 77 Luganylacetamide pale brown needle crystals Melting point 144-145° (ethanol-inpropyl ether) Elemental analysis value C201 (23cIN402 ・1/2H
2.
理論値 Ｃ， ６０．６８；Ｈ． ６．１１ ；Ｎ，
１４．１５実験値 Ｃ， ６０．９９ ；Ｈ， ６．０
４ ；Ｎ， １４．１８実施例１Ｏ
Ｎ−（２−（３−クロロフェニルアミノカルボニル）フ
ェニルツー４−メチル−１−ピペラジンアセトアミド
無色針状晶
融点 １６７〜１６８°（ベンゼン）
元素分析値 Ｃ２０Ｈ２３ＣＩＮ４０２理論値 Ｃ，
６２．０９ ｉＨ， ５．９９ ｉＮ， １４．４８実
験値 Ｃ， ６２．００ ｉＨ， ５．８１ ；Ｎ，
１４．２９実施例１１
Ｎ−（２−（４−クロロフェニルアミ７カルボニル）フ
ェニルツー４−メチル−１−ピペラジンアセトアミド
淡橙色プリズム品
融点 ２２７〜２２８° （エタノール）元素分析値
Ｃ２０Ｈ２３ＣＩＮ４０２理論値 Ｃ， ６２．０９
ｉＨ． ５．９９ ；Ｎ， １４．４８実験値 Ｃ，
６２．０６ ；Ｈ． ６．１３ ；Ｎ． １４．４２実
施例１２
４−メチル−Ｎ−（２−（２−メチルフェニルアミ７カ
ルボニル）フェニルツー１−ヒ°ペラジンアセトアミド
無色プリズム晶
融点 １４３〜１４４° （ベンゼン）元素分析値 Ｃ
２１Ｈ２６Ｎ４０２
理論値 Ｃ， ６８．Ｈ ｉｆ（、 ？．１５；犯１５
．２９実験値 Ｃ， ６８．６９ ；Ｈ， ７．２８
；Ｎ， １５．３５実施例１３
４−メチル７Ｎ−（２−（３−メチルフェニルアミ７カ
ルボニル）フェニルツー１−ピペラジンアセトアミド
無色プリズム晶
融点 １９０〜１９１°（エタノール）元素分析値 Ｃ
２１Ｈ２６Ｎ４０２
理論値 Ｃ，６８，８３；Ｈ，？、１５ ｉＮ、 １５
．２９実験値 Ｃ，６９，０２；Ｈ，７，３７ｉＮ、
１５．２６実施例１４
Ｎ−（２−（４−メチルフェニルアミ７カルボニル）フ
ェニル）−２−（１，２，３，４−テトラヒドロイソキ
ノリン−２−イル）アセトアミド無色針状晶Theoretical value C, 60.68; H. 6.11 ;N,
14.15 Experimental value C, 60.99; H, 6.0
4;N, 14.18 Example 1O N-(2-(3-chlorophenylaminocarbonyl)phenyl-4-methyl-1-piperazineacetamide colorless needle crystals Melting point 167-168° (benzene) Elemental analysis value C20H23CIN402 theoretical value C,
62.09 iH, 5.99 iN, 14.48 experimental value C, 62.00 iH, 5.81;N,
14.29 Example 11 N-(2-(4-chlorophenylami7carbonyl)phenyl-4-methyl-1-piperazineacetamide Pale orange prism product Melting point 227-228° (ethanol) Elemental analysis value
C20H23CIN402 theoretical value C, 62.09
iH. 5.99 ; N, 14.48 experimental value C,
62.06 ;H. 6.13;N. 14.42 Example 12 4-Methyl-N-(2-(2-methylphenylami7carbonyl)phenyl-1-hyperazineacetamide Colorless prism crystal Melting point 143-144° (Benzene) Elemental analysis value C
21H26N402 Theoretical value C, 68. H if(, ?.15; crime 15
．． 29 Experimental value C, 68.69; H, 7.28
;N, 15.35 Example 13 4-Methyl 7N-(2-(3-methylphenylami7carbonyl)phenyl-1-piperazineacetamide Colorless prism crystal Melting point 190-191° (ethanol) Elemental analysis value C
21H26N402 Theoretical value C, 68, 83; H,? , 15 iN, 15
．． 29 experimental value C, 69,02; H, 7,37iN,
15.26 Example 14 N-(2-(4-methylphenylami7carbonyl)phenyl)-2-(1,2,3,4-tetrahydroisoquinolin-2-yl)acetamide colorless needles
Claims (1)
原子、ハロゲン原子、低級アルキル基あるいは低級アル
コキシ基を表わし、Ｒ＿３は４位置換ピペラジニル基、
オクタヒドロ−２Ｈ−ピリド〔１，２−ａ〕ピラジン−
２−イル基あるいはテトラヒドロイソキノリン−２−イ
ル基を表わす。） で示されるアントラニルアミド誘導体、及びその薬理学
的に許容しうる酸付加塩。[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. substituted piperazinyl group,
Octahydro-2H-pyrido[1,2-a]pyrazine-
It represents a 2-yl group or a tetrahydroisoquinolin-2-yl group. ) and pharmacologically acceptable acid addition salts thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59175202A JPS6153268A (en) | 1984-08-24 | 1984-08-24 | Anthranilamide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59175202A JPS6153268A (en) | 1984-08-24 | 1984-08-24 | Anthranilamide derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6153268A true JPS6153268A (en) | 1986-03-17 |
Family
ID=15992076
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59175202A Pending JPS6153268A (en) | 1984-08-24 | 1984-08-24 | Anthranilamide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6153268A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0278478U (en) * | 1988-12-06 | 1990-06-15 | ||
| WO2001068609A1 (en) * | 2000-03-14 | 2001-09-20 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivatives |
| US6298750B1 (en) | 1998-08-25 | 2001-10-09 | Daimlerchysler Ag | Steering wheel for a motor vehicle, and a method for producing a steering wheel rim |
| US7763638B2 (en) | 2004-03-01 | 2010-07-27 | Actelion Pharmaceuticals Ltd. | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
| US8247560B2 (en) | 2007-12-28 | 2012-08-21 | Actelion Pharmaceuticals Ltd. | Trisubstituted 3,4-dihydro-1H-isoquinolin compound, process for its preparation, and its use |
-
1984
- 1984-08-24 JP JP59175202A patent/JPS6153268A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0278478U (en) * | 1988-12-06 | 1990-06-15 | ||
| US6298750B1 (en) | 1998-08-25 | 2001-10-09 | Daimlerchysler Ag | Steering wheel for a motor vehicle, and a method for producing a steering wheel rim |
| WO2001068609A1 (en) * | 2000-03-14 | 2001-09-20 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivatives |
| US6703392B2 (en) | 2000-03-14 | 2004-03-09 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivatives |
| CN100393703C (en) * | 2000-03-14 | 2008-06-11 | 埃科特莱茵药品有限公司 | 1,2,3,4-tetrahydroisoquinoline derivatives |
| US7763638B2 (en) | 2004-03-01 | 2010-07-27 | Actelion Pharmaceuticals Ltd. | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
| US8247560B2 (en) | 2007-12-28 | 2012-08-21 | Actelion Pharmaceuticals Ltd. | Trisubstituted 3,4-dihydro-1H-isoquinolin compound, process for its preparation, and its use |
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