JPS6337094B2 - - Google Patents
Info
- Publication number
- JPS6337094B2 JPS6337094B2 JP54081096A JP8109679A JPS6337094B2 JP S6337094 B2 JPS6337094 B2 JP S6337094B2 JP 54081096 A JP54081096 A JP 54081096A JP 8109679 A JP8109679 A JP 8109679A JP S6337094 B2 JPS6337094 B2 JP S6337094B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- compound
- solution
- amidinophenyl
- acetate
- 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
Links
- -1 α-naphthyl group Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 239000007853 buffer solution Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- IYELGEUXPAPULN-UHFFFAOYSA-N 2-hydroxybenzenecarboximidamide Chemical class NC(=N)C1=CC=CC=C1O IYELGEUXPAPULN-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 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
- 230000000052 comparative effect Effects 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 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 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FKMJXALNHKIDOD-LBPRGKRZSA-N TAMe Chemical compound NC(=N)NCCC[C@@H](C(=O)OC)NS(=O)(=O)C1=CC=C(C)C=C1 FKMJXALNHKIDOD-LBPRGKRZSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229960004072 thrombin Drugs 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
- 239000012588 trypsin Substances 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
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-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
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229940122644 Chymotrypsin inhibitor Drugs 0.000 description 1
- 101710137926 Chymotrypsin inhibitor Proteins 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
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 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
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000007788 liquid 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
- 238000000691 measurement method Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- VGKONPUVOVVNSU-UHFFFAOYSA-N naphthalen-1-yl acetate Chemical compound C1=CC=C2C(OC(=O)C)=CC=CC2=C1 VGKONPUVOVVNSU-UHFFFAOYSA-N 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は新規なアシルアミジノフエノール誘導
体、更に詳細には次の一般式（）
（式中、Ｒはα―ナフチル基又は５，６，７，
８―テトラヒドロ―β―ナフチル基を示す）で表
わされるアシルアミジノフエノール誘導体及びそ
の酸付加塩に関する。
本発明者は種々のアミジノフエノール誘導体を
合成し、その薬理作用を検索していたところ、上
記一般式（）で表わされるアシルアミジノフエ
ノール誘導体が種々の蛋白分解酵素、例えばキモ
トリプシン、トリプシン、スロンビン等に対し阻
害作用を有することを見出し、本発明を完成し
た。
従つて、本発明は新規なアシルアミジノフエノ
ール誘導体を提供するものである。
本発明化合物（）は、例えば次の反応に従つ
て、芳香族カルボン酸（）にアミジノフエノー
ル（）を作用させることにより製造される。
（式中、Ｒは前記と同じものを示す）
芳香族カルボン酸（）とアミジノフエノール
（）との反応は、通常のエステル化反応、例え
ば芳香族カルボン酸またはその誘導体を直接ある
いは縮合剤の存在下アミジノフエノールまたはそ
の反応性誘導体と反応させることにより実施され
る。
このようにして得られた化合物（）は、更
に、常法に従つて、例えば塩酸、硫酸、リン酸お
よび臭化水素酸塩等の無機酸塩；あるいは酢酸、
プロピオン酸、マレイン酸、フマル酸、酒石酸、
クエン酸、メタンスルホン酸、ベンゼンスルホン
酸およびトルエンスルホン酸等の有機酸塩に導く
ことができる。
斯くして得られた本発明化合物（）の酵素阻
害作用を試験した結果は次の通りである。
(1) キモトリプシン阻害作用
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4′―アミジノフエニル シクロヘキサ
ンカルボキシレート（比較化合物１）及びキモト
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２）を
用いた。
結果は第１表の通りである。
(2) トリプシン阻害作用
村松らの方法〔ザ・ジヤーナル・オブ・ビオケ
ミストリー58，214（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、緩衝液
（0.1Mトリス―塩酸緩衝液：PH8.0に塩化カルシ
ウム10mMを溶解した溶液）0.1mlおよびトリプ
シン2.5μｇ／mlの緩衝液溶液0.1mlを混合した溶
液を10分間インキユベートし、これにトシルアル
ギニンメチルエステル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。
結果は第１表の通りである。
(3) スロンビン阻害作用測定法
田村らの方法〔バイオキミカ・エト・バイオフ
イズイカ・アクタ484，417（1977）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、
緩衝液（0.1Mリン酸ナトリウム緩衝液；PH7.4）
0.1mlおよびスロンビン37.5unit／mlの緩衝液溶液
0.1mlを混合した溶液を10分間インキユベートし、
これにトシルアルギニンメチルエステル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。
結果は第１表の通りである。
The present invention provides novel acylamidinophenol derivatives, more specifically, the following general formula () (In the formula, R is an α-naphthyl group or 5,6,7,
8-tetrahydro-β-naphthyl group) and its acid addition salt. The present inventor synthesized various amidinophenol derivatives and searched for their pharmacological actions, and found that the acylamidinophenol derivative represented by the above general formula ( The present invention was completed based on the discovery that it has an inhibitory effect on Therefore, the present invention provides novel acylamidinophenol derivatives. The compound () of the present invention is produced by reacting an aromatic carboxylic acid () with an amidinophenol (), for example, according to the following reaction. (In the formula, R represents the same thing as above.) The reaction between the aromatic carboxylic acid () and the amidinophenol () can be carried out by a normal esterification reaction, for example, by directly reacting the aromatic carboxylic acid or its derivative or in the presence of a condensing agent. This is carried out by reacting with a lower amidinophenol or a reactive derivative thereof. The compound () obtained in this way can be further treated with inorganic acid salts such as hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromide; or acetic acid,
propionic acid, maleic acid, fumaric acid, tartaric acid,
It can lead to organic acid salts such as citric acid, methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid. The results of testing the enzyme inhibitory effect of the thus obtained compound of the present invention () are as follows. (1) Chymotrypsin inhibitory effect 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 used.
A mixed solution of 10 μg/ml of chymotrypsin and 0.1 ml of a buffer solution (0.1 M Tris-HCl buffer; PH 8.0) was incubated for 10 minutes, followed by 0.2 ml of a buffer solution of 25 mM acetyl-L-tyrosine ethyl ester. Mix and react at 37℃ for 30 minutes.
The amount of remaining substrate was determined by developing color using the hesterin method and measuring the absorbance at 530 nm. As comparative compounds, 4'-amidinophenyl cyclohexanecarboxylate (comparative compound 1) and tosylphenylalanine chloromethyl ketone (comparative compound 2), which is known as a chymotrypsin inhibitor, were used. The results are shown in Table 1. (2) Trypsin inhibitory effect According to the method of Muramatsu et al. [see The Journal of Biochemistry 58 , 214 (1967)], 0.1 ml of a dimethyl sulfoxide solution of the test compound and a buffer solution (0.1 M Tris-HCl buffer: A mixture of 0.1 ml of a solution of 10 mM calcium chloride dissolved in pH 8.0 and 0.1 ml of a buffer solution of 2.5 μg/ml trypsin was incubated for 10 minutes, and then 0.2 ml of a buffer solution of 25 mM tosylarginine methyl ester was mixed.
The mixture was mixed and reacted at 37°C for 30 minutes, and the amount of remaining substrate was determined by developing color using the hesterin method and measuring the absorbance at 530 nm. The results are shown in Table 1. (3) Thrombin inhibitory effect measurement method According to the method of Tamura et al.
0.1ml of dimethyl sulfoxide solution of test compound,
Buffer (0.1M sodium phosphate buffer; PH7.4)
0.1ml and thrombin 37.5unit/ml buffer solution
Incubate the mixed solution of 0.1ml for 10 minutes,
This was mixed with 0.2 ml of a 25 mM buffer solution of tosyl arginine methyl ester, reacted at 37°C for 30 minutes, and the amount of remaining substrate was determined by developing color using the hesterin method and measuring the absorbance at 530 nm. The results are shown in Table 1.
【表】
本発明化合物１：4′―アミジノフエニルナフチル
―１―アセテート
本発明化合物２：4′―アミジノフエニル５，６，
７，８―テトラヒドロナフチル―２―
アセテート
第１表より明らかな如く、本発明化合物（）
は優れた蛋白分解酵素阻害作用を有し、〓臓疾患
治療剤等の医薬品として有用なものである。
以下更に実施例を挙げ説明する。
実施例 １
4′―アミジノフエニル５，６，７，８―テトラ
ヒドロナフチル―２―アセテート：
ｐ―アミジノフエノール・メタンスルホン酸塩
2.44ｇのピリジン20ml溶液に５，６，７，８―テ
トラヒドロナフチル―２―アセチルクロリド3.34
ｇを氷冷下撹拌しながら滴下した。室温にて一夜
撹拌し、不溶物を去後、液にエーテルを加え
ればアメ状の沈澱を得た。この沈澱をクロロホル
ムに溶かし、シリカゲルクロマトグラフ〔溶出溶
媒；クロムホルム―メタノール（10：１）〕に付
して、得られた溶出液を濃縮乾固した。これをエ
タノールに溶かし、３当量のメタンスルホン酸を
加えた後、更にエーテルを加えれば結晶が得られ
た。エタノール―エーテルより再結晶すれば融点
173〜175℃の4′―アミジノフエニル5.6，７，８
―テトラヒドロナフチル―２―アセテート・一メ
タンスルホン酸塩0.8ｇ（収率18.8％）を得た。
元素分析値：C19H20N2O2・CH3SO3Hとして
Ｃ Ｈ Ｎ
計算値(%)59.39 5.98 6.93
実験値(%)59.29 6.10 6.84
実施例 ２
4′―アミジノフエニル ナフチル―１―アセテ
ート：
ｐ―アミジノフエノール・メタンスルホン酸塩
4.65ｇをジメチルホルムアミド10mlおよびピリジ
ン40mlの混合溶液に溶解し、これに氷冷下、１―
ナフチル酢酸クロリド8.2ｇを滴下した。更に室
温にて２時間撹拌し、不溶物を去し、母液にエ
ーテルを加えるとアメ状沈澱が得られた。これを
メタノールに溶解しエーテルを加えると、融点
197.5〜198.5℃の結晶として、4′―アミジノフエ
ニル ナフチル―１―アセテート・一メタンスル
ホンン酸塩2.05ｇ（収率25.6％）が得られた。
元素分析値：C19H16N2O2・CH3SO3Hとして
Ｃ Ｈ Ｎ
計算値(%)59.99 5.03 7.00
実験値(%)59.98 4.95 7.05[Table] Inventive compound 1: 4'-amidinophenyl naphthyl-1-acetate Inventive compound 2: 4'-amidinophenyl 5,6,
7,8-tetrahydronaphthyl-2-
Acetate As is clear from Table 1, the compound of the present invention ()
has an excellent proteolytic enzyme inhibitory effect and is useful as a pharmaceutical agent for treating heart diseases. Examples will be further described below. Example 1 4'-amidinophenyl 5,6,7,8-tetrahydronaphthyl-2-acetate: p-amidinophenol methanesulfonate
3.34 g of 5,6,7,8-tetrahydronaphthyl-2-acetyl chloride in 20 ml of pyridine solution
g was added dropwise while stirring under ice-cooling. After stirring at room temperature overnight and removing insoluble matter, ether was added to the liquid to obtain a candy-like precipitate. This precipitate was dissolved in chloroform and subjected to silica gel chromatography [elution solvent: chromiumform-methanol (10:1)], and the resulting eluate was concentrated to dryness. This was dissolved in ethanol, 3 equivalents of methanesulfonic acid was added, and then ether was added to obtain crystals. If recrystallized from ethanol-ether, the melting point
4'-amidinophenyl 5.6,7,8 at 173-175℃
-Tetrahydronaphthyl-2-acetate monomethanesulfonate 0.8g (yield 18.8%) was obtained. Elemental analysis value: C 19 H 20 N 2 O 2・CH 3 SO 3 H Calculated value (%) 59.39 5.98 6.93 Experimental value (%) 59.29 6.10 6.84 Example 2 4′-amidinophenyl naphthyl-1-acetate : p-amidinophenol methanesulfonate
Dissolve 4.65 g in a mixed solution of 10 ml of dimethylformamide and 40 ml of pyridine, and add 1-
8.2 g of naphthyl acetate chloride was added dropwise. The mixture was further stirred at room temperature for 2 hours to remove insoluble matter, and ether was added to the mother liquor to obtain a candy-like precipitate. When this is dissolved in methanol and ether is added, the melting point is
2.05 g (yield 25.6%) of 4'-amidinophenyl naphthyl-1-acetate monomethanesulfonate was obtained as crystals at 197.5-198.5°C. Elemental analysis value: C 19 H 16 N 2 O 2・CH 3 SO 3 H Calculated value (%) 59.99 5.03 7.00 Experimental value (%) 59.98 4.95 7.05
Claims (1)
８―テトラヒドロ―β―ナフチル基基を示す）で
表わされるアシルアミジノフエノール誘導体及び
その酸付加塩。[Claims] First-order general formula () (In the formula, R is an α-naphthyl group or 5,6,7,
8-tetrahydro-β-naphthyl group) and acid addition salts thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8109679A JPS565451A (en) | 1979-06-27 | 1979-06-27 | Acylamidinophenol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8109679A JPS565451A (en) | 1979-06-27 | 1979-06-27 | Acylamidinophenol derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS565451A JPS565451A (en) | 1981-01-20 |
| JPS6337094B2 true JPS6337094B2 (en) | 1988-07-22 |
Family
ID=13736849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8109679A Granted JPS565451A (en) | 1979-06-27 | 1979-06-27 | Acylamidinophenol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS565451A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57179146A (en) * | 1981-04-28 | 1982-11-04 | Torii Yakuhin Kk | Amidine compound |
| JPS5841855A (en) * | 1981-09-07 | 1983-03-11 | Torii Yakuhin Kk | Amidine compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5225740A (en) * | 1975-08-21 | 1977-02-25 | Yuichi Kaneoka | Preparation of o-acyl-amidinophenols or acid addition salts thereof |
-
1979
- 1979-06-27 JP JP8109679A patent/JPS565451A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5225740A (en) * | 1975-08-21 | 1977-02-25 | Yuichi Kaneoka | Preparation of o-acyl-amidinophenols or acid addition salts thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS565451A (en) | 1981-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2760287C2 (en) | ||
| EP0098713B1 (en) | Benzoylpiperazine esters and a process for their production | |
| JPS6241710B2 (en) | ||
| US4620005A (en) | 1-isopropyl-4[(4-tetrahydro-1-naphthoyloxy phenyl)(alkylene)-carbonyl(oxymethlcarbonyl)]piperazines having chymotrypsin-inhibitory activity | |
| JPS6337094B2 (en) | ||
| JPS60166657A (en) | Arginyl-3-carboxy-4-hydroxyanilide | |
| JPS6340183B2 (en) | ||
| US4568690A (en) | 1-Methyl-5-p-methylbenzoylpyrrole-2-acetamidoacetanilides with antiinflammatory, analgesic, antipyretic and anti-platelet aggregant activity | |
| JPS6121469B2 (en) | ||
| RU2103275C1 (en) | 17-halogen-4-azaandrostene derivatives and method of preparation thereof | |
| JPS6215064B2 (en) | ||
| JPS6130559B2 (en) | ||
| JPS6324988B2 (en) | ||
| JPS59212471A (en) | Benzoyl indolecarboxylate | |
| JPS6324994B2 (en) | ||
| JPH0466238B2 (en) | ||
| JPH024588B2 (en) | ||
| JPS58225079A (en) | Benzoylpiperazine compound | |
| JPS6245590A (en) | Novel antibiotic and production thereof | |
| SU702030A1 (en) | Beta-peptidylthioclucosides of n-acetyl-clucosamine as ligands in affine chromatography | |
| JPS6237622B2 (en) | ||
| KR100196461B1 (en) | Benzothiazolin derivatives and process for the preparations thereof | |
| JPS6338023B2 (en) | ||
| JPS59204173A (en) | Benzoylpiperazine esters | |
| JPS588394B2 (en) | Maleimide derivative |