JPH0251427B2 - - Google Patents
Info
- Publication number
- JPH0251427B2 JPH0251427B2 JP58075868A JP7586883A JPH0251427B2 JP H0251427 B2 JPH0251427 B2 JP H0251427B2 JP 58075868 A JP58075868 A JP 58075868A JP 7586883 A JP7586883 A JP 7586883A JP H0251427 B2 JPH0251427 B2 JP H0251427B2
- Authority
- JP
- Japan
- Prior art keywords
- residue
- group
- substituted
- lower alkyl
- partially saturated
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 2
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical group C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000005577 anthracene group Chemical group 0.000 claims description 2
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical group N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
- LJJQENSFXLXPIV-UHFFFAOYSA-N fluorenylidene Chemical group C1=CC=C2[C]C3=CC=CC=C3C2=C1 LJJQENSFXLXPIV-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 claims description 2
- VUNXBQRNMNVUMV-UHFFFAOYSA-N phenyl(piperazin-1-yl)methanone Chemical class C=1C=CC=CC=1C(=O)N1CCNCC1 VUNXBQRNMNVUMV-UHFFFAOYSA-N 0.000 claims description 2
- 125000005543 phthalimide group Chemical group 0.000 claims description 2
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ILKHFVMVAPOCMU-UHFFFAOYSA-N (4-hydroxyphenyl)-(4-propan-2-ylpiperazin-1-yl)methanone Chemical compound C1CN(C(C)C)CCN1C(=O)C1=CC=C(O)C=C1 ILKHFVMVAPOCMU-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- TWADEBCIPVNACR-ZDUSSCGKSA-N (2s)-2-(n-(4-methylphenyl)sulfonylanilino)propanoic acid Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N([C@@H](C)C(O)=O)C1=CC=CC=C1 TWADEBCIPVNACR-ZDUSSCGKSA-N 0.000 description 1
- SKAWDTAMLOJQNK-UHFFFAOYSA-N 2-acetamido-3-(4-hydroxyphenyl)propanoic acid ethyl ester Chemical compound CCOC(=O)C(NC(C)=O)CC1=CC=C(O)C=C1 SKAWDTAMLOJQNK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- TUWTVRGEVPWFIX-UHFFFAOYSA-N 2-fluoren-9-ylideneacetic acid Chemical compound C1=CC=C2C(=CC(=O)O)C3=CC=CC=C3C2=C1 TUWTVRGEVPWFIX-UHFFFAOYSA-N 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 229940122644 Chymotrypsin inhibitor Drugs 0.000 description 1
- 101710137926 Chymotrypsin inhibitor Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- YMCVHPPZDKEUHF-UHFFFAOYSA-N [4-(4-propan-2-ylpiperazine-1-carbonyl)phenyl] 2-fluoren-9-ylideneacetate Chemical compound C1CN(C(C)C)CCN1C(=O)C(C=C1)=CC=C1OC(=O)C=C1C2=CC=CC=C2C2=CC=CC=C21 YMCVHPPZDKEUHF-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、新規なベンゾイルピペラジンエステ
ル類、更に詳細には、次の一般式（）
（式中、Ａは単結合、アルキレン基、ビニレン
基、−Ｏ−アルキレン基又はメチン基を示す。Ｒ
は低級アルキル基、低級アルコキシ基、オキソ
基、ニトロ基又はハロゲン原子で置換されていて
もよく、また部分的に飽和されていてもよい二環
性炭素環残基；オキソ基を有していてもよいフル
オレン残基；フルオレニリデン基；アンスラセン
残基；低級アルキル基で置換されていてもよく、
また部分的に飽和されていてもよいフエナンスレ
ン残基；低級アルキル基、低級アルコキシ基で置
換されていてもよいベンゾフラン残基若しくはチ
アナフテン残基；オキソ基、フエニル基で置換さ
れていてもよく、また部分的に飽和されていても
よいベンゾピラン残基若しくはベンゾアジン残
基；フタルイミド残基；ベンゾジアジン残基；低
級アルキル基、フエニル基で置換されていてもよ
いイソオキサゾール残基；アルキレンジオキシベ
ンゼン残基又はキサンテン残基を示す。但し、Ａ
が単結合、Ｒが
The present invention relates to novel benzoylpiperazine esters, more specifically, the following general formula () (In the formula, A represents a single bond, an alkylene group, a vinylene group, an -O-alkylene group, or a methine group.R
is a bicyclic carbocyclic residue which may be substituted with a lower alkyl group, a lower alkoxy group, an oxo group, a nitro group or a halogen atom, and may also be partially saturated; fluorene residue; fluorenylidene group; anthracene residue; optionally substituted with a lower alkyl group;
Also, a phenanthrene residue that may be partially saturated; a benzofuran residue or a thianaphthene residue that may be substituted with a lower alkyl group or a lower alkoxy group; an oxo group or a phenyl group may be substituted; benzopyran residue or benzazine residue which may be partially saturated; phthalimide residue; benzodiazine residue; isoxazole residue which may be substituted with a lower alkyl group or phenyl group; alkylenedioxybenzene residue or Shows xanthene residues. However, A
is a single bond, R is
村松らの方法〔ザ・ジヤーナル・オブ・ビオケ
ミストリー62，408（1967）参照〕により、被検化
合物のジメチルスルホキシド溶液0.1ml、水0.1ml
及びキモトリプシン10μｇ／mlの緩衝液溶液
（0.1M・トリス−塩酸緩衝液；PH8.0）0.1mlを混
合した溶液を10分間インキユベートし、これにア
セチル−Ｌ−チロシンエチルエステル25mMの緩
衝液溶液0.2mlを混合し、37℃で30分間反応させ、
残存する基質の量をヘステリン法により発色さ
せ、530nmの吸光度を測定し求めた。なお比較化
合物としては、キモトリプシンの阻害剤として知
られるトシルフエニルアラニンクロロメチルケト
ン（比較化合物）を用いた。
結果は第１表の通りである。
According to the method of Muramatsu et al. [see The Journal of Biochemistry 62 , 408 (1967)], 0.1 ml of a dimethyl sulfoxide solution of the test compound and 0.1 ml of water were prepared.
A mixed solution of chymotrypsin 10 μg/ml and 0.1 ml of a buffer solution (0.1 M Tris-HCl buffer; PH 8.0) was incubated for 10 minutes, followed by a 0.2 ml of acetyl-L-tyrosine ethyl ester 25 mM buffer solution. ml and reacted at 37 °C for 30 min.
The amount of remaining substrate was determined by developing color using the hesterin method and measuring the absorbance at 530 nm. As a comparative compound, tosylphenylalanine chloromethyl ketone (comparative compound), which is known as a chymotrypsin inhibitor, was used. The results are shown in Table 1.
【表】
(注) 被検化合物番号は実施例番号で示した。
次に実施例を挙げて本発明を説明する。
実施例 １
１−イソプロピル−４−〔４−（５，６，７，８
−テトラヒドロナフタレン−１−アセチルオキ
シ）ベンゾイル〕ピペラジン・塩酸塩：
５，６，７，８−テトラヒドロナフタレン−１
−酢酸1.9ｇ（10ミリモル）、１−（４−ヒドロキ
シベンゾイル）−４−イソプロピルピペラジン
2.48ｇ（10ミリモル）及び４−ジメチルアミノピ
リジン122mg（１ミリモル）の酢酸エチル20ml溶
液に、ジシクロヘキシルカルボジイミド2.48ｇ
（12ミリモル）を加え室温にて３時間撹拌する。
次いで不溶物を去し、1N−塩酸20mlにて抽出
する。酢酸エチルで栓浄後、炭酸水素ナトリウム
にて中和し、酢酸エチルにて抽出する。飽和食塩
水にて洗浄後硫酸ナトリウムにて乾燥して減圧濃
縮する。次いでシリカゲルカラムクロマトグラフ
イー（シリカゲル80ｇ、溶出溶媒：クロロホルム
−メタノール30：１）にて精製すると無色油状物
を定量的収率で得る。更にこれをエタノール20ml
に溶解し、氷冷下、等モルの塩化水素を含むエタ
ノール溶液を加えた後エーテルを加えると無色結
晶が得られる。
収量： 2.96ｇ（64.7％）
m.p. 214〜216℃
元素分析： C26H32N2O3・HClとして
Ｃ Ｈ Ｎ
計算値（％） 68.33 7.28 6.13
実測値（％） 68.30 7.24 6.28
実施例 ２
１−イソプロピル−４−〔４−（９−フルオレニ
リデンアセチルオキシ）ベンゾイル〕ピペラジ
ン：
９−フルオレニリデン酢酸2.67ｇ（12ミリモ
ル）、１−（４−ヒドロキシベンゾイル）−４−イ
ソプロピルピペラジン2.48ｇ（10ミリモル）及び
４−ジメチルアミノピリジン122mg（１ミリモル）
のクロロホルム20ml溶液にジシクロヘキシルカル
ボジイミド2.48ｇ（12ミリモル）を加え、室温に
て３時間撹拌する。生じた不溶物を去し、減圧
濃縮する。次いで酢酸エチル20mlにて不溶物を
去し、1N−塩酸60mlにて抽出する。酢酸エチル
で洗浄後、炭酸水素ナトリウムにて中和し、クロ
ロホルム60mlにて抽出する。２回水洗後、硫酸マ
グネシウムにて乾燥し減圧濃縮すると黄色結晶を
得る。次いで酢酸エチル−石油エーテルにて再結
晶すると黄色プリズム晶が得られる。
収率： 56.7％
m.p. 169〜170℃
元素分析： C29H28N2O3として
Ｃ Ｈ Ｎ
計算値（％） 76.97 6.24 6.19
実測値（％） 76.97 6.19 5.97
実施例 ３
１−イソプロピル−４−〔４−（チアナフテン−
２−アセチルオキシ）ベンゾイル〕ピペラジ
ン・メタンスルホン酸塩：
１−イソプロピル−４−（４−ヒドロキシベン
ゾイル）ピペラジン2.2ｇ及びチアナフテン−２
酢酸2.0ｇのクロロホルム40ml溶液に、ジシクロ
ヘキシルカルボジイミド2.2ｇを加え、室温で一
夜撹拌する。次いで不溶物を去し、0.5N−塩
酸24mlにて抽出する。酢酸エチルで洗浄した後、
水層を2N−水酸化ナトリウムで中和し、酢酸エ
チルにて抽出する。水洗、乾燥後、溶媒を留去す
ると粗油状物が得られる。更に常法に従つて、メ
タンスルホン酸塩とすると無色プリズム晶が得ら
れる。
収量： 2.1ｇ（45.7％）
m.p. 175〜177℃
元素分析： C24H26N2O3S・CH3SO3Hとして
Ｃ Ｈ Ｎ
計算値（％） 57.89 5.85 5.40
実測値（％） 57.63 5.93 5.12
実施例 ４〜64
実施例１〜３と同様に処理して第２表の化合物
を得た。[Table] (Note) Test compound numbers are shown as example numbers.
Next, the present invention will be explained with reference to Examples. Example 1 1-isopropyl-4-[4-(5,6,7,8
-Tetrahydronaphthalene-1-acetyloxy)benzoyl]piperazine hydrochloride: 5,6,7,8-tetrahydronaphthalene-1
-1.9 g (10 mmol) of acetic acid, 1-(4-hydroxybenzoyl)-4-isopropylpiperazine
2.48 g of dicyclohexylcarbodiimide was added to a solution of 2.48 g (10 mmol) and 122 mg (1 mmol) of 4-dimethylaminopyridine in 20 ml of ethyl acetate.
(12 mmol) and stirred at room temperature for 3 hours.
Then, insoluble materials were removed and the mixture was extracted with 20 ml of 1N hydrochloric acid. After washing with ethyl acetate, neutralize with sodium hydrogen carbonate and extract with ethyl acetate. Wash with saturated brine, dry over sodium sulfate, and concentrate under reduced pressure. The product was then purified by silica gel column chromatography (80 g of silica gel, elution solvent: chloroform-methanol 30:1) to obtain a colorless oil in quantitative yield. Add this to 20ml of ethanol
Colorless crystals are obtained by dissolving the mixture in 100% water, adding an ethanol solution containing an equimolar amount of hydrogen chloride under ice cooling, and then adding ether. Yield: 2.96g (64.7%) mp 214-216℃ Elemental analysis: C 26 H 32 N 2 O 3・HCl as C H N Calculated value (%) 68.33 7.28 6.13 Actual value (%) 68.30 7.24 6.28 Example 2 1 -isopropyl-4-[4-(9-fluorenylideneacetyloxy)benzoyl]piperazine: 2.67 g (12 mmol) 9-fluorenylideneacetic acid, 2.48 g (10 mmol) 1-(4-hydroxybenzoyl)-4-isopropylpiperazine ) and 4-dimethylaminopyridine 122 mg (1 mmol)
Add 2.48 g (12 mmol) of dicyclohexylcarbodiimide to a 20 ml solution of chloroform and stir at room temperature for 3 hours. The resulting insoluble material is removed and concentrated under reduced pressure. Next, insoluble matter was removed with 20 ml of ethyl acetate, and the mixture was extracted with 60 ml of 1N hydrochloric acid. After washing with ethyl acetate, neutralize with sodium hydrogen carbonate and extract with 60 ml of chloroform. After washing twice with water, it is dried over magnesium sulfate and concentrated under reduced pressure to obtain yellow crystals. Then, recrystallization from ethyl acetate-petroleum ether yields yellow prism crystals. Yield: 56.7% mp 169-170°C Elemental analysis: as C 29 H 28 N 2 O 3 C H N Calculated value (%) 76.97 6.24 6.19 Actual value (%) 76.97 6.19 5.97 Example 3 1-isopropyl-4- [4-(Thianaphthene-
2-acetyloxy)benzoyl]piperazine methanesulfonate: 2.2 g of 1-isopropyl-4-(4-hydroxybenzoyl)piperazine and 2-thianaphthene
Add 2.2 g of dicyclohexylcarbodiimide to a solution of 2.0 g of acetic acid in 40 ml of chloroform, and stir overnight at room temperature. Then, insoluble materials were removed and the mixture was extracted with 24 ml of 0.5N hydrochloric acid. After washing with ethyl acetate,
The aqueous layer is neutralized with 2N sodium hydroxide and extracted with ethyl acetate. After washing with water and drying, the solvent is distilled off to obtain a crude oil. Furthermore, when it is converted into methanesulfonate according to a conventional method, colorless prism crystals are obtained. Yield: 2.1g (45.7%) mp 175-177℃ Elemental analysis: C 24 H 26 N 2 O 3 S・CH 3 SO 3 H Calculated value (%) 57.89 5.85 5.40 Actual value (%) 57.63 5.93 5.12 Examples 4 to 64 The compounds shown in Table 2 were obtained in the same manner as in Examples 1 to 3.
【表】【table】
【表】【table】
【表】【table】
【表】【table】
【表】【table】
【表】【table】
【表】【table】
Claims (1)
基、−Ｏ−アルキレン基又はメチン基を示す。Ｒ
は低級アルキル基、低級アルコキシ基、オキソ
基、ニトロ基又はハロゲン原子で置換されていて
もよく、また部分的に飽和されていてもよい二環
性炭素環残基；オキソ基を有していてもよいフル
オレン残基；フルオレニリデン基；アンスラセン
残基；低級アルキル基で置換されていてもよく、
また部分的に飽和されていてもよいフエナンスレ
ン残基；低級アルキル基、低級アルコキシ基で置
換されていてもよいベンゾフラン残基若しくはチ
アナフテン残基；オキソ基、フエニル基で置換さ
れていてもよく、また部分的に飽和されていても
よいベンゾピラン残基若しくはベンゾアジン残
基；フタルイミド残基；ベンゾジアジン残基；低
級アルキル基、フエニル基で置換されていてもよ
いイソオキサゾール残基；アルキレンジオキシベ
ンゼン残基又はキサンテン残基を示す。但し、Ａ
が単結合、Ｒが【式】で、R1がＨ 又はアルコキシ基の場合を除く。） で表わされるベンゾイルピペラジンエステル類。[Claims] 1. General formula (In the formula, A represents a single bond, an alkylene group, a vinylene group, an -O-alkylene group, or a methine group.R
is a bicyclic carbocyclic residue which may be substituted with a lower alkyl group, a lower alkoxy group, an oxo group, a nitro group or a halogen atom, and which may be partially saturated; fluorene residue; fluorenylidene group; anthracene residue; optionally substituted with a lower alkyl group;
Also, a phenanthrene residue that may be partially saturated; a benzofuran residue or a thianaphthene residue that may be substituted with a lower alkyl group or a lower alkoxy group; an oxo group or a phenyl group may be substituted; benzopyran residue or benzazine residue which may be partially saturated; phthalimide residue; benzodiazine residue; isoxazole residue which may be substituted with a lower alkyl group or phenyl group; alkylenedioxybenzene residue or Shows xanthene residues. However, A
Except when is a single bond, R is [Formula], and R 1 is H or an alkoxy group. ) Benzoylpiperazine esters represented by
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58075868A JPS59204173A (en) | 1983-04-28 | 1983-04-28 | Benzoylpiperazine esters |
| AU15931/83A AU545463B2 (en) | 1982-06-25 | 1983-06-20 | Benzoyl piperacine esters |
| AT83303583T ATE28868T1 (en) | 1982-06-25 | 1983-06-22 | BENZOYLPIPERAZINE ESTERS AND PROCESS FOR THEIR PREPARATION. |
| DE8383303583T DE3372966D1 (en) | 1982-06-25 | 1983-06-22 | Benzoylpiperazine esters and a process for their production |
| EP83303583A EP0098713B1 (en) | 1982-06-25 | 1983-06-22 | Benzoylpiperazine esters and a process for their production |
| ES523561A ES523561A0 (en) | 1982-06-25 | 1983-06-23 | PROCESS TO PRODUCE A BENZOILPIPERAZINE ESTER. |
| CA000431034A CA1210005A (en) | 1982-06-25 | 1983-06-23 | Benzoylpiperazine esters and a process for their production |
| DK290583A DK158983C (en) | 1982-06-25 | 1983-06-23 | METHOD OF ANALOGUE FOR THE PREPARATION OF BENZOYL PIPERAZINE ESTERS OR ACID ADDITION SALTS. |
| KR1019830002868A KR900003278B1 (en) | 1982-06-25 | 1983-06-25 | Process for preparing benzoyl-piperazine esters |
| US06/796,525 US4898876A (en) | 1982-06-25 | 1985-11-12 | Benzoylpiperazine esters and a process for their production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58075868A JPS59204173A (en) | 1983-04-28 | 1983-04-28 | Benzoylpiperazine esters |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59204173A JPS59204173A (en) | 1984-11-19 |
| JPH0251427B2 true JPH0251427B2 (en) | 1990-11-07 |
Family
ID=13588659
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58075868A Granted JPS59204173A (en) | 1982-06-25 | 1983-04-28 | Benzoylpiperazine esters |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59204173A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2763944B1 (en) * | 1997-06-03 | 2000-12-15 | Centre Nat Rech Scient | NOVEL COUMARIN DERIVATIVES, PROCESSES FOR THEIR PREPARATION AND THEIR USE AS DRUGS AS PROTEASE INHIBITORS |
-
1983
- 1983-04-28 JP JP58075868A patent/JPS59204173A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59204173A (en) | 1984-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1309594B1 (en) | Benzimidazole derivatives, preparation and therapeutic use thereof | |
| KR900003278B1 (en) | Process for preparing benzoyl-piperazine esters | |
| EP0540400A1 (en) | Quinoline derivatives, useful as angiotensin II antagonists | |
| JPS59222484A (en) | Tetrahydronaphthylcarboxylic acid phenyl ester derivative | |
| EP1248785B1 (en) | Novel tetrahydropyridines, preparation method and pharmaceutical compositions containing same | |
| JPH08269062A (en) | Pyripyropene derivative | |
| JPH0251427B2 (en) | ||
| BE1008216A4 (en) | HETEROCYCLIC CHEMOLUMINESCENT DERIVATIVES. | |
| JP3207017B2 (en) | Method for producing benzylsuccinic acid derivative and intermediate for producing the same | |
| JPS631940B2 (en) | ||
| CA1152103A (en) | Purification process and preparation of itanoxone suitable for therapeutic use | |
| JPS6136748B2 (en) | ||
| JP3725587B2 (en) | Amino group-containing benzoate derivatives | |
| JPS6412269B2 (en) | ||
| RU2034842C1 (en) | Quinoline derivative and a method of its synthesis | |
| JPS58118566A (en) | Novel heterocyclic acetic acid derivative and manufacture | |
| JP3097273B2 (en) | Host functional material | |
| JPH0427977B2 (en) | ||
| JPS58225079A (en) | Benzoylpiperazine compound | |
| JPS6140669B2 (en) | ||
| US4841071A (en) | 6-substituted-4-hydroxy-tetrahydropyran-2-ones | |
| JPH0761979A (en) | Bisphenol derivative and its production | |
| JPS6340183B2 (en) | ||
| JPS6337094B2 (en) | ||
| JPS6121469B2 (en) |