JPS6056130B2 - Novel salicylic acid derivatives - Google Patents
Novel salicylic acid derivativesInfo
- Publication number
- JPS6056130B2 JPS6056130B2 JP3188378A JP3188378A JPS6056130B2 JP S6056130 B2 JPS6056130 B2 JP S6056130B2 JP 3188378 A JP3188378 A JP 3188378A JP 3188378 A JP3188378 A JP 3188378A JP S6056130 B2 JPS6056130 B2 JP S6056130B2
- Authority
- JP
- Japan
- Prior art keywords
- salicylic acid
- acid derivatives
- acid
- integer
- formula
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は一般式（Ｉ）
（Ｘ）ｍ
σ（ＣＨＥＨ）ｎＣ０ＮＨ −Ｒ
（Ｉ）
〔式中、Ｒは水素原子又は低級アルキル基を、Ｘは低級
アルコキシ基を、ｎは０又は１の整数を、ｍは１〜３の
整数（但し、ｎが０の場合、ｍはの整数のみを示す）を
意味する〕で表わされる新規なサルチル酸誘導体に関す
るものである。Detailed Description of the Invention The present invention is based on the general formula (I) (X)m σ(CHEH)nC0NH -R (I) [wherein, R is a hydrogen atom or a lower alkyl group, X is a lower alkoxy group, n is an integer of 0 or 1, and m is an integer of 1 to 3 (however, when n is 0, m is an integer only)].
前記一般式（Ｉ）におけるＲ及びＸに就いて更に具体的
に説明するとＲの低級アルキル基としては、例えばメチ
ル、エチル、ｎ−プロピル、イソプロピル、ｎ−ブチル
及びイソブチル基等があげられる。又、Ｘの低級アルコ
キシ基としては、例えばメトキシャエトキシ、ｎ−プロ
ポキシ、イソプロポキシ９ ｎ−ブトキシ及びイソブト
キシ基等があげられる。本発明の前記一般式（Ｉ）のサ
リチル酸誘導体は文献未載の新規化合物であり、顕著な
抗アルルギー作用及び解熱、鎮痛、抗炎症作用等を有し
、医薬品として産業上有用な化合物である。To explain R and X in the general formula (I) more specifically, examples of the lower alkyl group of R include methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl groups. Examples of the lower alkoxy group for X include methoxyethoxy, n-propoxy, isopropoxy, n-butoxy, and isobutoxy groups. The salicylic acid derivative of the general formula (I) of the present invention is a new compound that has not been described in any literature, and has remarkable anti-allergic, antipyretic, analgesic, and anti-inflammatory effects, and is an industrially useful compound as a pharmaceutical.
本発明の化合物は下記の反応式で示す方法によつて収率
よく得ることが出来るが、これらの製法は−例にすぎず
勿論他の化学添類似方法によつても製造することが出来
るものである。The compound of the present invention can be obtained in good yield by the method shown in the reaction formula below, but these production methods are merely examples, and of course, it can also be produced by other similar chemical addition methods. It is.
製造法
一般式（■）で表わされる化合物に一般式（■）で表わ
されるカルボン酸の反応性誘導体を反応させる方法。Production method A method in which a compound represented by the general formula (■) is reacted with a reactive derivative of a carboxylic acid represented by the general formula (■).
（式中、Ｍ，ｎ，Ｘ及びＲは前記と同じ意味を有する）
前記製造法を更に具体的に説明すると、当該方法は一般
式（■）で表わされるサルチル酸誘導体に、一般式（■
）で表わされる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。(In the formula, M, n, X and R have the same meanings as above)
To explain the above production method more specifically, the method involves adding a salicylic acid derivative represented by the general formula (■) to a salicylic acid derivative represented by the general formula (■).
) Reactive derivatives of carboxylic acids (eg, acid halides, acid anhydrides) may be reacted in an organic solvent such as tetrahydrofuran, acetone, chloroform, pyridine, benzene, or toluene.
又、酸ハライドを使用する場合は５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，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
に進行しサリチル酸誘導体（■）を得ることが出来る。
以下に本発明のもつ抗アレルギー作用を薬理実ｌ験によ
つて示す。Furthermore, when using an acid halide, the reaction can proceed quickly and salicylic acid derivatives (■) can be obtained by using a deoxidizing agent (for example, trimethylamine, triethylamine, pyridine, sodium carbonate, potassium carbonate, etc.).
The antiallergic effect of the present invention will be shown below through pharmacological experiments.
尚、比較対照薬として本発明の化合物と類似するＮ−（
２，４ージヒドロキシベンゾイル）−４−アミノサリチ
ル酸を用いた。実験方法同種受身皮膚反応抑制試験
ＪＴａｄａらの方法（Ｔａｄａ，Ｔ．ａｎ
ｄＯｋｕｎｌｕｒｍ，Ｋ．；Ｊ．ＩｍｍｕｒｌＯｌ．ｌ
Ｏ６，ｌＯＯ２，ｌ９７ｌ）に準じて作製した払ＰＮＰ
−Ａｓｃａｒｉｓラット血清を用いて、同種受身皮膚反
応を行なつた。In addition, as a comparative drug, N-(
2,4-dihydroxybenzoyl)-4-aminosalicylic acid was used. Experimental method Allogeneic passive skin reaction inhibition test
The method of JTada et al.
dOkunlurm, K. ;J. ImmurlOl. l
06, lOO2, l97l)
- Allogeneic passive skin reactions were performed using Ascaris rat serum.
即ち、体重１７０〜１９０ｇのＷｉｓｔａｒ系ラットの
剪毛背部の２ケ所に抗体（１１０３倍希釈溶液）を０．
１ｍ１／Ｓｉｔｅ皮膚感作した。４８時間後に０．２５
％エバンスブルー添加抗体液（蛋白量２．０Ｔｎ９）１
．０ｒｒ１１／Ｒａｔを尾静脈内に注射し、皮膚反応を
誘発させた。That is, the antibody (1103 times diluted solution) was applied at 0.00 to 2 points on the shaved back of a Wistar rat weighing 170 to 190 g.
1 ml/site skin sensitization was performed. 0.25 after 48 hours
% Evans blue added antibody solution (protein amount 2.0Tn9) 1
．． Orr11/Rat was injected into the tail vein to induce a skin reaction.
抗原投与後３紛にラットを放血致死させ、背部皮膚を剥
離後、滲出色素量を４）１ａｒａｄａらの方法（Ｈａｒ
ａｄａ，Ｍ．，Ｔａｋｅｕｃｈｉ，Ｍ．，ＦｕｋｕＯ，
Ｔ．＆Ｋａｔａｇｉｒｉ，Ｋ．；Ｊ．Ｐｈａｒｍ．Ｐｈ
ａｒｍａｃＯｌ．，２３，２ｌ８，ｌ９７ｌ）で測定し
、下式により対照群に対する滲出色素抑制立を求めた。
被検薬及び比較対照薬のＮ−（２，４ージヒドロキシベ
ンゾイル）−４−アミノサリチル酸は０．５％トラガン
ト漿生理食塩水に懸濁し、腹腔内及び経口投与は各々抗
原投与の１時間及び２時間前に行なつた。又、対照群に
は溶媒のみを投与した。水水；対照群に対しＰ＜０．０
１で有意差があること を示す。Three days after administering the antigen, the rats were killed by exsanguination, and the back skin was peeled off, and the amount of exuded pigment was measured using the method of Arada et al.
ada, M. , Takeuchi, M. ,FukuO,
T. & Katagiri, K. ;J. Pharm. Ph
armacOl. , 23, 2l8, 197l), and the suppression of exuded pigment relative to the control group was determined using the following formula.
The test drug and the comparative drug, N-(2,4-dihydroxybenzoyl)-4-aminosalicylic acid, were suspended in 0.5% tragacanth serum physiological saline, and intraperitoneal and oral administration was performed at 1 hour and 1 hour after antigen administration, respectively. I did it two hours ago. In addition, only the solvent was administered to the control group. Water water; P<0.0 vs. control group
A value of 1 indicates a significant difference.
Ｐ．Ｏ： （経口投与）１．Ｐ： （腹腔内投与）以上
の薬理実験の結果より本発明の化合物は比較対照薬と比
し、顕著な抗アレルギー作用を有し、気管支喘息，じん
ま疹，アトピー性皮膚炎，アレルギー性鼻炎治療薬など
の抗アレルギー剤として極めて有用であると考えられる
。P. O: (oral administration) 1. P: (Intraperitoneal administration) The results of the above pharmacological experiments show that the compound of the present invention has a significant antiallergic effect compared to the comparative drug, and is effective against bronchial asthma, hives, atopic dermatitis, and allergic rhinitis. It is considered to be extremely useful as an antiallergic agent such as a therapeutic drug.
以下に実施例を示し、本発明を更に具体的に説明する。EXAMPLES The present invention will be explained in more detail with reference to Examples below.
実施例１５−アミノサリチル酸３．１Ｖをテトラヒドロ
フラン３０ｍ１とトリエチルアミン３ｍ１との混液に溶
解した。Example 15-3.1 V of aminosalicylic acid was dissolved in a mixture of 30 ml of tetrahydrofuran and 3 ml of triethylamine.
これに３，４，５−トリメトキシ安息香酸クロリド４．
６ｙのテトラヒドロフラン溶液を冷却下に滴下した。そ
の後、室温で５時間攪拌した。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ｐ取してジメチルホルムアミドより再結晶
すると無色プリズム晶のＮ−（３，４，５−トリメトキ
シベンゾイル）−５−アミノサリチル酸４．７′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。To this, 3,4,5-trimethoxybenzoic acid chloride 4.
A solution of 6y in tetrahydrofuran was added dropwise while cooling. Thereafter, the mixture was stirred at room temperature for 5 hours. After the reaction, the solvent was distilled off under reduced pressure, water and dilute hydrochloric acid were added to the residue to make it weakly acidic, and the precipitated crystals were collected and recrystallized from dimethylformamide to form colorless prism crystals of N-(3,4,5 -trimethoxybenzoyl)-5-aminosalicylic acid 4.7' was obtained. The melting point and elemental analysis values of this substance were as follows.
融 点２５０〜２５３′Ｃ
元素分析値Ｃｌ７Ｈｌ７ＮＯ７
理論値Ｃ：５８．７９Ｈ：４．９３Ｎ：４．０３実測値
Ｃ：５８．８３Ｈ：４．８７Ｎ：４．０８実施例２４−
アミノサリチル酸３．１ｆをクロロホルム３０ｍ１とト
リエチルアミン３ｍ１との混液に溶解した。Melting point 250-253'C Elemental analysis value Cl7Hl7NO7 Theoretical value C: 58.79H: 4.93N: 4.03 Actual value C: 58.83H: 4.87N: 4.08 Example 24-
3.1 f of aminosalicylic acid was dissolved in a mixed solution of 30 ml of chloroform and 3 ml of triethylamine.
これに３，４ージメトキシケイ皮酸クロリド４．５ｙの
クロロホルム溶液を冷却下に滴下した。その後、室温で
２時間攪拌し、さらに還流下に１時間反応させた。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
えて弱酸性ととし、析出する結晶を戸取してジメチルホ
ルムアミド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−アミノサリチル
酸２．４ダを得た。この物質の融点及び元素分析値は次
の通りであつた。A chloroform solution of 4.5y of 3,4-dimethoxycinnamic acid chloride was added dropwise to this under cooling. Thereafter, the mixture was stirred at room temperature for 2 hours, and further reacted under reflux for 1 hour. 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 collected and recrystallized from dimethylformamide to form colorless prism crystals of N-(3
, 4-dimethoxycinnamoyl)-4-aminosalicylic acid was obtained. The melting point and elemental analysis values of this substance were as follows.
融 点２５０〜２５１℃
元素分析値Ｃｌ８Ｈｌ７ＮＯ６
理論値Ｃ：６２．９７Ｈ：４．９９Ｎ：４．０８実測値
Ｃ：６２．８９Ｈ：５．０３Ｎ：４．０６以下、実施例
２の方法に準じて下記の化合物を合成した。Melting point 250-251°C Elemental analysis value Cl8Hl7NO6 Theoretical value C: 62.97H: 4.99N: 4.08 Actual value C: 62.89H: 5.03N: 4.06 or less, according to the method of Example 2 The following compounds were synthesized.
Claims (1)
アルコキシきを、ｎは０又は１の整数を、ｍは１〜３の
整数（但し、ｎが０の場合、ｍは３の整数のみを示す）
〕で表わされるサリチル酸誘導体。[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R is a hydrogen atom or a lower alkyl group, X is a lower alkoxy group, n is an integer of 0 or 1, m is an integer from 1 to 3 (however, if n is 0, m only indicates an integer of 3)
] A salicylic acid derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3188378A JPS6056130B2 (en) | 1978-03-20 | 1978-03-20 | Novel salicylic acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3188378A JPS6056130B2 (en) | 1978-03-20 | 1978-03-20 | Novel salicylic acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS54125632A JPS54125632A (en) | 1979-09-29 |
| JPS6056130B2 true JPS6056130B2 (en) | 1985-12-09 |
Family
ID=12343424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3188378A Expired JPS6056130B2 (en) | 1978-03-20 | 1978-03-20 | Novel salicylic acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6056130B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1196348B (en) * | 1984-11-29 | 1988-11-16 | Italfarmaco Spa | COMPOUNDS WITH ANTI-INFLAMMATORY ACTIVITY |
| IL85896A (en) * | 1987-04-06 | 1993-01-14 | Riker Laboratories Inc | Substituted di-tert.- butylphenols and pharmaceutical compositions containing them |
| EP1274675B1 (en) * | 2000-04-19 | 2004-09-01 | Neurotech Co., Ltd. | Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system |
| US6964982B2 (en) | 2000-04-20 | 2005-11-15 | Neurotech Co., Ltd. | Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system |
| JP4113957B2 (en) | 2002-06-19 | 2008-07-09 | アムコア ファーマ， インコーポレイテッド | Tetrafluorobenzyl derivative and pharmaceutical composition for prevention and treatment of acute and degenerative cranial nervous system diseases containing the same |
| KR101333753B1 (en) | 2006-04-13 | 2013-11-28 | 주식회사 아라온테크 | Pharmaceutical composition for treating or preventing degenerative and inflammatory diseases |
| KR100852962B1 (en) | 2007-11-12 | 2008-08-20 | 주식회사 뉴로테크 | Manufacturing method of 2-hydroxy-5-phenylalkylaminobenzoic acid derivatives and their salts |
-
1978
- 1978-03-20 JP JP3188378A patent/JPS6056130B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS54125632A (en) | 1979-09-29 |
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