JPS6154018B2 - - Google Patents
Info
- Publication number
- JPS6154018B2 JPS6154018B2 JP14920078A JP14920078A JPS6154018B2 JP S6154018 B2 JPS6154018 B2 JP S6154018B2 JP 14920078 A JP14920078 A JP 14920078A JP 14920078 A JP14920078 A JP 14920078A JP S6154018 B2 JPS6154018 B2 JP S6154018B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- general formula
- reaction
- compound
- tetrahydrofuran
- 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
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000003266 anti-allergic effect Effects 0.000 description 3
- 239000000043 antiallergic agent Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 150000005130 benzoxazines Chemical class 0.000 description 2
- -1 cinnamoyl group Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 231100000430 skin reaction Toxicity 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NZHGWWWHIYHZNX-UHFFFAOYSA-N 2-((3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl)amino)benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-UHFFFAOYSA-N 0.000 description 1
- JYYLQSCZISREGY-UHFFFAOYSA-N 2-amino-4-chlorobenzoic acid Chemical compound NC1=CC(Cl)=CC=C1C(O)=O JYYLQSCZISREGY-UHFFFAOYSA-N 0.000 description 1
- LGPVTNAJFDUWLF-UHFFFAOYSA-N 2-amino-4-fluorobenzoic acid Chemical compound NC1=CC(F)=CC=C1C(O)=O LGPVTNAJFDUWLF-UHFFFAOYSA-N 0.000 description 1
- BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 1
- HGDZRSNJGRIAKS-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)prop-2-enoyl chloride Chemical compound COC1=CC=C(C=CC(Cl)=O)C=C1OC HGDZRSNJGRIAKS-UHFFFAOYSA-N 0.000 description 1
- XPMYQNSUVAGTKP-UHFFFAOYSA-N 4-chloro-2-[3-(3,4-dimethoxyphenyl)prop-2-enoylamino]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)NC1=CC(Cl)=CC=C1C(O)=O XPMYQNSUVAGTKP-UHFFFAOYSA-N 0.000 description 1
- COTNHQMQRACFGM-UHFFFAOYSA-N 4-fluoro-2-[(3,4,5-trimethoxybenzoyl)amino]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NC=2C(=CC=C(F)C=2)C(O)=O)=C1 COTNHQMQRACFGM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000244188 Ascaris suum Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
本発明は一般式（）
（式中、Ｘはハロゲン原子を、ｎは０〜１の整数
を、Ｒは任意の位置に１〜３個置換したメトキシ
基を意味する）で表わされる新規なアントラニル
酸誘導体に関するものである。
尚、前記説明のＸのハロゲン原子は弗素、塩
素、臭素及び沃素等の各ハロゲン原子を意味する
ものである。
近年、Ｎ―（３，４―ジメトキシシンナモイ
ル）アントラニル酸に優れた抗アレルギー作用が
存在することが確認された。（J.pharmacol.58，
483―488，1976）この化合物は従来の抗アレルギ
ー剤とは異なり、抗原抗体反応により惹起される
ケミカルメデイエーター遊離を抑制する抗アレル
ギー剤である。
本発明者等は更に優れた抗アレルギー剤の開発
を目的に一連の新規なアントラニル酸誘導体を合
成し、その薬理作用を種々検討したところ、特に
アントラニル酸の４位にハロゲン原子を、又メト
キシ基が１〜３個置換したところのベンゾイル基
及びシンナモイル基を２位に導入すると薬理活性
が増強され且つ副作用も少ないことを見出し本発
明を完成した。
以下に本発明のもつ抗アレルギー作用を薬理実
験によつて示す。
実験法
A.ラツトでのホモロガス受身皮膚反応
Tada，Ｔ et al（Tada T.＆ Okumura，
Ｋ：J.Immunol，106，1002，1971）の方法に準
拠してホモロガス受身皮膚反応（Homolog.
PCA）を170〜190ｇのウイスター系雄ラツトで
試験した。即ち、ブタ回虫（Ascaris suum）の
抽出蛋白にジニトロフエノール（DNP）を反応
させDNP―As（Dinitro phenyl coupled
Ascaris suum ectract）を得て、これを抗原と
した。この抗原によつて抗DNP―Asラツト血清
を作製し抗体とした。この充分な力価を有する抗
体をラツトの除毛背部皮内に一側に３ケ所0.1
ml／siteずつ注射し、他側３ケ所には生理食塩液
を0.1ml／site皮内注射して実験過誤のチエツク
をした。48時間後に0.25％エバンス・ブルーを含
む抗原（蛋白量として2.0mg）液1.0ml／ratを静脈
注射した。30分後にラツトを放血致死させ剥皮を
行つて色素漏出面積及びHarada，M.et al
（Harada，M.，Takeuchi，M.，Fukao，T.＆
Katagiri，K.：J.pharm.pharmacol.，23，218，
1971）の方法で漏出色素量を測定した。
薬物は抗原投与の２時間前に200mg/Kgを腹腔内
及び経口投与した。又、対照薬としてＮ―３，４
―ジメトキシシンナモイル）アントラニル酸（Ｎ
―5′）を選んだ。
The present invention is based on the general formula () (wherein, X is a halogen atom, n is an integer of 0 to 1, and R is a methoxy group substituted with 1 to 3 arbitrary positions). In addition, the halogen atom of X in the above description means each halogen atom such as fluorine, chlorine, bromine, and iodine. In recent years, it has been confirmed that N-(3,4-dimethoxycinnamoyl)anthranilic acid has an excellent antiallergic effect. (J.pharmacol. 58 ,
483-488, 1976) Unlike conventional antiallergic agents, this compound is an antiallergic agent that suppresses the release of chemical mediators caused by antigen-antibody reactions. The present inventors synthesized a series of new anthranilic acid derivatives with the aim of developing even better antiallergic agents, and conducted various studies on their pharmacological effects. The present invention was completed by discovering that pharmacological activity is enhanced and side effects are reduced by introducing a benzoyl group or a cinnamoyl group substituted with 1 to 3 groups into the 2-position. The antiallergic effect of the present invention will be shown below through pharmacological experiments. Experimental method A. Homologous passive skin response in rats Tada, T. et al (Tada T. & Okumura,
Homologous passive skin reaction (Homolog.
PCA) was tested in male Wistar rats weighing 170-190 g. That is, DNP-As (Dinitro phenyl coupled
Ascaris suum ecttract) was obtained and used as an antigen. Anti-DNP-As rat serum was prepared using this antigen and used as an antibody. This antibody with sufficient titer was applied at 3 sites on one side at 0.1
ml/site was injected, and 0.1 ml/site of physiological saline was intradermally injected at three locations on the other side to check for experimental errors. After 48 hours, 1.0 ml/rat of an antigen (2.0 mg protein) solution containing 0.25% Evans Blue was intravenously injected. After 30 minutes, the rats were killed by exsanguination, skin was peeled, and the area of pigment leakage was determined by Harada, M. et al.
(Harada, M., Takeuchi, M., Fukao, T. &
Katagiri, K.: J.pharm.pharmacol., 23 , 218,
The amount of leaked dye was measured using the method of (1971). The drug was administered intraperitoneally and orally at 200 mg/Kg 2 hours before antigen administration. In addition, N-3,4 was used as a control drug.
-dimethoxycinnamoyl)anthranilic acid (N
-5′) was selected.
【表】
以上の薬理実験の結果より本発明の化合物は優
れた抗アレルギー作用を有し、しかも経口投与で
有効であることが判明した。
次に本発明の化合物の製造法について説明する
がこれらは一例にすぎず、他の化学的類似方法に
よつても製造されるものである。
製造法 Ａ
一般式（）で表わされる化合物に一般式
（）で表わされる芳香族カルボン酸の反応性誘
導体を反応させる方法。
（式中、Ｘ，ｎ及びＲは前記と同じ意味を有す
る）
製造法 Ｂ
一般式（）で表わされるベンゾオキサジン誘
導体を加水分解する方法。
（式中、Ｘ，ｎ及びＲは前記と同じ意味を有す
る）
更に具体的に説明すると、製造法Ａは一般式
（）で表わされるアントラニル酸誘導体に、一
般式（）で表わされる芳香族カルボン酸の反応
性誘導体（例えば酸ハライド、酸無水物）をテト
ラヒドロフラン、アセトン、クロロホルム、ピリ
ジン、ベンゼン、トルエン等の有機溶媒中反応さ
せればよい。又、酸ハライドを使用する場合は脱
酸剤（例えばトリメチルアミン、トリエチルアミ
ン、ピリジン、ジメチルアニリン、炭酸ナトリウ
ム、炭酸カリウム等）を使用すれば反応は速やか
に進行する。又、当該方法で得られたアントラニ
ル酸誘導体のうちエステル体は要望により更に加
水分解することができる。加水分解は、水、酢
酸、メタノール、エタノール及び水とアルコール
類、水と酢酸等の混合溶媒中、酸（例えば塩酸、
硫酸等）又はアルカリ、（例えば水酸化カリウ
ム、水酸化ナトリウム等）の存在下に、室温又は
加熱下に反応させればよい。反応条件は使用する
溶媒、酸又はアルカリの量及び温度によつて適宜
選択される。
製造法Ｂは一般式（）で表わされるベンゾオ
キサジン誘導体を水酸化ナトリウム、水酸化カリ
ウム等のアルカリ又は塩酸、硫酸等の鉱酸は加水
分解することによつて行われる。
以下に実施例を示し、本発明を更に具体的に説
明する。
実施例 １
４―クロルアントラニル酸3.4ｇをテトラヒド
ロフラン50mlとトリエチルアミン３mlとの混液に
溶解した。これに３，４―ジメトキシケイ皮酸ク
ロリド4.5ｇのテトラヒドロフラン溶液を室温下
にゆつくり滴下した。その後、室温で３時間撹拌
した。反応終了後、減圧下に溶媒を留去し残渣に
水及び希塩酸を加えて弱酸性とし、折出する結晶
を濾取してジメチルホルムアミド―水より再結晶
すると無色プリズム晶のＮ―（３，４―ジメトキ
シシンナモイル）―４―クロルアントラニル酸
5.9ｇを得た。
この物質の融点及び元素分析値は次の通りであ
つた。
融 点 225〜257℃
元素分析値 C18H16ClNO5
理 論 値 Ｃ：59.76 Ｈ：4.46 Ｎ：3.87
実 測 値 Ｃ：59.73 Ｈ：4.51 Ｎ：3.81
実施例 ２
４―フルオロアントラニル酸1.6ｇをテトラヒ
ドロフラン20mlとジメチルアニリン1.6ｇとの混
液に溶解した。これに３，４，５―トリメトキシ
ベンゾイルクロリド2.3ｇのテトラヒドロフラン
溶液を室温下にゆつくり滴下した。その後、室温
で５時間撹拌した。反応終了後、減圧下に溶媒を
留去し残渣に水及び希塩酸を加えて弱酸性とし、
析出する結晶を濾取してメタノールより再結晶す
ると無色針状晶のＮ―（３，４，５―トリメトキ
シベンゾイル）―４―フルオロアントラニル酸
2.1ｇを得た。
この物質の融点及び元素分析値は次の通りであ
つた。
融 点 232〜233℃
元素分析値 C17H16FNO6
理 論 値 Ｃ：58.45 Ｈ：4.62 Ｎ：4.01
実 測 値 Ｃ：58.41 Ｈ：4.56 Ｎ：4.08
実施例 ３〜５
以下、実施例１〜２の方法に準じて下記の化合
物を合成した。[Table] The results of the above pharmacological experiments revealed that the compound of the present invention has an excellent antiallergic effect and is effective when administered orally. Next, the method for producing the compound of the present invention will be explained, but these are only examples, and the compound can also be produced by other chemically similar methods. Production method A: A method in which a compound represented by the general formula () is reacted with a reactive derivative of an aromatic carboxylic acid represented by the general formula (). (In the formula, X, n and R have the same meanings as above.) Production method B A method of hydrolyzing a benzoxazine derivative represented by the general formula (). (wherein, Reactive derivatives of acids (eg, acid halides, acid anhydrides) may be reacted in an organic solvent such as tetrahydrofuran, acetone, chloroform, pyridine, benzene, toluene, or the like. Furthermore, when using an acid halide, the reaction will proceed quickly if a deoxidizing agent (for example, trimethylamine, triethylamine, pyridine, dimethylaniline, sodium carbonate, potassium carbonate, etc.) is used. Furthermore, among the anthranilic acid derivatives obtained by this method, the ester form can be further hydrolyzed if desired. Hydrolysis is carried out using an acid (e.g. hydrochloric acid,
The reaction may be carried out in the presence of a sulfuric acid, etc.) or an alkali (for example, potassium hydroxide, sodium hydroxide, etc.) at room temperature or under heating. The reaction conditions are appropriately selected depending on the solvent used, the amount of acid or alkali, and the temperature. Production method B is carried out by hydrolyzing the benzoxazine derivative represented by the general formula () with an alkali such as sodium hydroxide or potassium hydroxide or a mineral acid such as hydrochloric acid or sulfuric acid. EXAMPLES The present invention will be explained in more detail with reference to Examples below. Example 1 3.4 g of 4-chloroanthranilic acid was dissolved in a mixture of 50 ml of tetrahydrofuran and 3 ml of triethylamine. A solution of 4.5 g of 3,4-dimethoxycinnamic acid chloride in tetrahydrofuran was slowly added dropwise to this at room temperature. Thereafter, the mixture was stirred at room temperature for 3 hours. After the reaction, the solvent is distilled off under reduced pressure, water and dilute hydrochloric acid are added to the residue to make it weakly acidic, and the precipitated crystals are filtered and recrystallized from dimethylformamide-water to give colorless prism crystals of N-(3, 4-Dimethoxycinnamoyl)-4-chloroanthranilic acid
5.9g was obtained. The melting point and elemental analysis values of this substance were as follows. Melting point 225-257℃ Elemental analysis value C 18 H 16 ClNO 5 Theoretical value C: 59.76 H: 4.46 N: 3.87 Actual value C: 59.73 H: 4.51 N: 3.81 Example 2 1.6 g of 4-fluoroanthranilic acid It was dissolved in a mixture of 20 ml of tetrahydrofuran and 1.6 g of dimethylaniline. A solution of 2.3 g of 3,4,5-trimethoxybenzoyl chloride in tetrahydrofuran was slowly added dropwise to this at room temperature. Thereafter, the mixture was stirred at room temperature for 5 hours. After the reaction, the solvent was distilled off under reduced pressure and water and diluted hydrochloric acid were added to the residue to make it weakly acidic.
When the precipitated crystals are collected by filtration and recrystallized from methanol, colorless needle-like crystals of N-(3,4,5-trimethoxybenzoyl)-4-fluoroanthranilic acid are obtained.
2.1g was obtained. The melting point and elemental analysis values of this substance were as follows. Melting point 232-233℃ Elemental analysis value C 17 H 16 FNO 6 Theoretical value C: 58.45 H: 4.62 N: 4.01 Actual measurement value C: 58.41 H: 4.56 N: 4.08 Examples 3-5 Below, Examples 1-5 The following compound was synthesized according to method 2.
Claims (1)
を、Ｒは任意の位置に１〜３個置換したメトキシ
基を意味する）で表わされるアントラニル酸誘導
体。[Claims] 1. General formula An anthranilic acid derivative represented by (wherein, X represents a halogen atom, n represents an integer of 0 to 1, and R represents a methoxy group substituted with 1 to 3 arbitrary positions).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14920078A JPS5576852A (en) | 1978-12-01 | 1978-12-01 | Novel derivative of anthranilic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14920078A JPS5576852A (en) | 1978-12-01 | 1978-12-01 | Novel derivative of anthranilic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5576852A JPS5576852A (en) | 1980-06-10 |
| JPS6154018B2 true JPS6154018B2 (en) | 1986-11-20 |
Family
ID=15470003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14920078A Granted JPS5576852A (en) | 1978-12-01 | 1978-12-01 | Novel derivative of anthranilic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5576852A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0634780U (en) * | 1992-10-13 | 1994-05-10 | 古河機械金属株式会社 | Construction vehicle with floor cleaning device |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8820129D0 (en) * | 1988-08-24 | 1988-09-28 | Schering Agrochemicals Ltd | Fungicides |
| MX352516B (en) | 2006-07-05 | 2017-04-06 | Fibrotech Therapeutics Pty Ltd | Therapeutic compounds. |
| CA2709937C (en) | 2007-12-21 | 2016-03-22 | Fibrotech Therapeutics Pty Ltd | Halogenated analogues of anti-fibrotic agents |
| CN102574843B (en) | 2009-10-22 | 2015-06-17 | 法博太科制药有限公司 | Fused ring analogs of antifibrotic agents |
| JP7185631B2 (en) | 2017-02-03 | 2022-12-07 | サータ セラピューティクス プロプライエタリー リミテッド | antifibrotic compound |
-
1978
- 1978-12-01 JP JP14920078A patent/JPS5576852A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0634780U (en) * | 1992-10-13 | 1994-05-10 | 古河機械金属株式会社 | Construction vehicle with floor cleaning device |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5576852A (en) | 1980-06-10 |
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