JPS62106080A - Ethanolamine derivative and antihyperlipemia containing same - Google Patents
Ethanolamine derivative and antihyperlipemia containing sameInfo
- Publication number
- JPS62106080A JPS62106080A JP24579385A JP24579385A JPS62106080A JP S62106080 A JPS62106080 A JP S62106080A JP 24579385 A JP24579385 A JP 24579385A JP 24579385 A JP24579385 A JP 24579385A JP S62106080 A JPS62106080 A JP S62106080A
- Authority
- JP
- Japan
- Prior art keywords
- ethanolamine
- antihyperlipemia
- ethanolamine derivative
- derivative
- present
- 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.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
１０発明の背景
技術分野
本発明は新規なエタノールアミン誘導体お工びこれｔ含
有する抗高脂血症剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION 10. Background Technical Field of the Invention The present invention relates to an antihyperlipidemic agent containing a novel ethanolamine derivative.
先行技術
抗高脂血症作用？有する物質はニコチン酸ぜはじめ、種
々知られているが、必ずしも／４足すべき楽効全示すと
は云い難い。また、高脂血症は心筋梗塞、脳使購あるい
は動脈硬化症等の危険因子であり、これｔ有効に予防す
る抗高脂血症剤の出現が強く望まれている。Prior art antihyperlipidemic effect? Various substances are known, including nicotinic acid, but it cannot be said that they necessarily exhibit all the beneficial effects that should be added. Furthermore, hyperlipidemia is a risk factor for myocardial infarction, cerebral palsy, arteriosclerosis, etc., and there is a strong desire for the development of antihyperlipidemic agents that can effectively prevent these.
■０発明の目的
本発明者等はエタノールアミン誘導体？咄々合成し、そ
れらの薬理作用を鋭意研究しｔ結果、本発明において使
用されるエタノールアミン誘導体が優れた抗高脂血症剤
用に有することｒ見い出し本発明？完成させるに至った
。■0 Purpose of the Invention Are the inventors producing ethanolamine derivatives? As a result of rapid synthesis and intensive research into their pharmacological effects, we have discovered that the ethanolamine derivatives used in the present invention are excellent antihyperlipidemic agents. I ended up completing it.
従って本発明は前記式ｆｉ＋で示されたエタノールアミ
ン誘導体お工びこれ？占有すり強力な抗菌Ｊ猶皿症Ｍｌ
１缶提供することｔ目的とする。本発明で使用するエタ
ノールアミン誘導体は２明な血？′５脂質低下作用？有
し、篩面？ｌｖ涌質に起因する動脈硬化症の予防剤とし
て有用である。Therefore, the present invention uses the ethanolamine derivative represented by the formula fi+. Possessed strong antibacterial J
The purpose is to provide 1 can. Is the ethanolamine derivative used in the present invention two types of blood? '5 Lipid lowering effect? Has phloem surface? It is useful as a preventive agent for arteriosclerosis caused by lvl.
かかる目的？達成する本発明は、 ｈ式山で表わされる
エタノールアミン誘導体である。The purpose? The invention achieved is an ethanolamine derivative represented by the formula h.
ざらに、本発明は一般式（１）
で衣わされろエタノールアミン誘導体を含有する抗高脂
血症剤である。In summary, the present invention is an antihyperlipidemic agent containing an ethanolamine derivative represented by the general formula (1).
■０発明の詳細な説明
本発明のエタノールアミン誘導体は、リノール酸あるい
はこの反応性誘導体とエタノールアミンと？縮合させる
ことにＬつ得られる。縮合させるとき用いられる縮合剤
としては、例えばクロル蜂峡エチルが好４ｖｃ用いられ
る。前記反応性誘導体としてはカルゼン酸りロリドヤカ
ルボン酸のチアゾリノンチオンアミド誘導体盆挙げるこ
とができる。■0 Detailed Description of the Invention The ethanolamine derivative of the present invention combines linoleic acid or its reactive derivative with ethanolamine? L is obtained by condensation. As the condensing agent used in the condensation, for example, chloroethyl chloride is preferably used. Examples of the reactive derivatives include thiazolinonethionamide derivatives of carboxylic acid and loridoyacarboxylic acid.
本発明において有効成分若しくは有効成分の１つとして
使用されるエタノールアミン誘導体は２明な血清脂質低
下作用ケ有し、高血清脂質に起因する疾恵であれば有効
に作用するが、特に血清コレステロールや血清トリグリ
セリドが高値となる高脂血症、動脈硬化症、心筋梗塞ま
たは脳梗塞の予防剤として使用嘔れ、投与量は一般に成
人１日延３００〜２０００ηで［Ｆ］す、心受に工り１
〜３回に分けて投与するのが工い。投与方法は投与に適
した任宮の形態ケとることができ、特に蛇口投与が望ま
しいが、静注も可能である。The ethanolamine derivative used as an active ingredient or one of the active ingredients in the present invention has two distinct serum lipid-lowering effects, and is effective in treating diseases caused by high serum lipids, especially serum cholesterol. It is used as a prophylactic agent for hyperlipidemia, arteriosclerosis, myocardial infarction, or cerebral infarction, where serum triglycerides are high.The dose is generally 300 to 2000 η per day for adults. Ri1
It is best to administer the drug in three doses. The method of administration can be in any form suitable for administration, with faucet administration being particularly preferred, but intravenous injection is also possible.
本発明で使用する前記化合物は単独または通常の方法で
製剤担体あるいは賦形剤と混合され、錠剤、散剤、カプ
セル剤、顆粒剤に製剤化される。担体あるいは賦形剤の
例として炭酸カルシウム、リン酸カルシウム、でんぷん
、しょ糖、乳糖、メルク、ステアリン酸マグネシウム蝮
があげられる。本発明は、上記の固形剤の他に油性懸濁
剤、シロツプのような液剤とすることもできる。The compound used in the present invention may be formulated into tablets, powders, capsules, or granules either alone or mixed with pharmaceutical carriers or excipients in a conventional manner. Examples of carriers or excipients include calcium carbonate, calcium phosphate, starch, sucrose, lactose, Merck, and magnesium stearate. In addition to the above-mentioned solid formulations, the present invention can also be formulated into liquid formulations such as oily suspensions and syrups.
本発明で使用する前記化合物？サイクロデキストリンで
包接し安定化することもできる。The above-mentioned compound used in the present invention? It can also be stabilized by inclusion with cyclodextrin.
仄：Ｃ笑施例Ｊ・・よ、び試峡例ケ示して本発明ケさら
にＡ本釣にａ明する。B: Example J... and an example of a test gorge to further explain the present invention.
実施例−／
アルゴン’Ｘｙ−１’Ｈ気下、（Ｊ 、 １２−オクタ
デカツエン酸１．０００ ｒτ乾燥クロロホルム２０成
に俗解し１こＡｊｆ？Ｊ、に室温にて塩化オキザリル０
．５０ｄ’ｒ添加し２時間反応させた。反応混′ｅ、Ｌ
リクロロホルムと残余の塩化オキプリル全減圧下に留去
し、得られ之９，１２−オクタデカツエン酸塩化」勿τ
再び乾（呆クロロホルム２彪にｊＪ ７軒した。Example-/Under argon 'Xy-1'H, (J, 12-octadecatsuenoic acid 1.000 rτ dry chloroform 20 min.) Oxalyl chloride 0.
．． 50 d'r was added and reacted for 2 hours. Reaction mix'e, L
Lichloroform and the remaining occipryl chloride were distilled off under reduced pressure to obtain 9,12-octadecatenate acid salt.
Dry again (laughing chloroform 2 Biao) JJ 7 houses.
一方アル」ゞン雰囲気下、エタノールアミン１、（＋
９ ｉｔ ｙ ７．乾燥クロロホルム２０ｍ／：に層群
した俗撤に魚水炭岐カリウム９９ Ｏｒ、ｙ ３−朋］
えた。該混成に至温にて先に得たり、１２−オクタアカ
ツエン〔戊塩ｆヒ′１勿のクロロホルム（Ｇ孜を添〕用
し３０ガ反応δせｌと。反応混放工９不ｆ＆物τ０．＆
云し、母液に水？加えクロロホルムで３回抽出した。On the other hand, under an alkaline atmosphere, ethanolamine 1, (+
9 it y 7. Dry chloroform 20m/: 99 Or, y 3-tomo]
I got it. The mixture was first obtained at very low temperature, and then 12-octaacatsuene (chloride salt and chloroform (G) was added) was reacted for 30 hours. &
So, water in the mother liquor? In addition, the mixture was extracted with chloroform three times.
抽出有機層全水洗し、無水硫酸ナトＩＪウムで乾燥後、
溶媒で減圧留去し抽出残渣１．２ Ｏｒ ’に得た。該
残渣？シリカゲルカラムクロマトグラフィーに付し、ク
ロロホルム・メタノール９８対２浴出画分よりＮ−（９
，１２−オクタデカジェノイル）−２−アミンエタノー
ル１．０５５５”（ｒ得た。After washing the entire extracted organic layer with water and drying with anhydrous sodium sulfate,
The solvent was distilled off under reduced pressure to obtain an extraction residue with a concentration of 1.2 Or'. The residue? The N-(9
, 12-octadecajenoyl)-2-amine ethanol 1.0555" (r) was obtained.
つづいて該化合′吻１．０００ｆｋアルゴン雰囲気下乾
燥クロロホルム４Ｑｍに俗解した浴液に室温にてニコチ
ン酸塩化物塩酸塩７１６ｎりつついて無水炭酸カリウム
１．７０８ｒｋ加え一夜反尾、させた。反応混液：つ不
溶′吻ｒ濾去し、母液に水ゲ加えた後、１規定水酸化リ
チウム水ｆ８Ｋにて中和した。これよりクロロホルムで
３回抽出、水洗した。抽出有機層全無水硫酸ナトリウム
で乾燥後溶媒を減圧留去し抽出残渣１．４１６１Ｆ七得
た。Subsequently, 716 n of nicotinic acid chloride hydrochloride was added to a bath solution of 4 Qm of dry chloroform under 1.000 fk of argon atmosphere at room temperature, and 1.708 k of anhydrous potassium carbonate was added thereto and allowed to simmer overnight. Reaction mixture: The insoluble mixture was filtered off, water was added to the mother liquor, and the mixture was neutralized with 1N lithium hydroxide (f8K). This was extracted three times with chloroform and washed with water. The entire extracted organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain an extracted residue of 1.4161F.
核残直？シリカゲルカラムクロマトグラフィーに付しク
ロロホルム乃至クロロホルム・メタノール９８対２浴出
画分エリ Ｎ−（９，１２−オクタデカジェノイル）−
２−アミンエチルニコチネー）１．（１８６ｒ”、（得
た。このものの物理化学的データは下記式（Ｉ）の構造
ケ支持する。Nuclear remnants? The chloroform to chloroform/methanol 98/2 bath fraction was subjected to silica gel column chromatography.
2-Amineethylnicotine) 1. (186r'', (obtained). The physicochemical data of this product support the structure of the following formula (I).
工Ｒν０Ｈ０Ｌ５（Ｈ−”）： ３４６（１，１７２５
，１６７０゜ａｘ
１５９５．１５１５
１ Ｈ−ＮＭＲ（ＣＤＣｌ２）δ（ｐｐｍ） ： ２．
７５ （２Ｈ、ｂｔ、 Ｊ＝５Ｈｚ）、３．６５ （２
Ｈ、ｑ 、 Ｊ ＝５．５Ｈｚ ）、４．４７（２Ｈ、
ｔ 、 Ｊ＝５．５Ｈｚ ）、７．３５（ＩＨ，ｄｄ。Engineering Rν0H0L5 (H-”): 346 (1,1725
, 1670°ax 1595.1515 1 H-NMR (CDCl2) δ (ppm): 2.
75 (2H, bt, J=5Hz), 3.65 (2
H, q, J = 5.5Hz), 4.47 (2H,
t, J=5.5Hz), 7.35 (IH, dd.
Ｊ＝８Ｈｚ、５Ｈｚ）、８．２３（ＩＨ，ｄｔ、Ｊ＝８
Ｈｚ。J=8Hz, 5Hz), 8.23(IH, dt, J=8
Hz.
２Ｈｚ）、８．７３（ＩＨ，ｄｄ、Ｊ＝５Ｈｚ、２Ｈｚ
）、９．１６（ＩＨ，ｄ、Ｊ＝２Ｈｚ）
ｒｎａｓｓ（ｍ／ｅ） ： ４２８ （分子イオンビー
ク）、３（１５゜〔試琺例〕
Ｗｉｓｔａｒ−Ｋｉｎｇラット（雄性１体ｚ１７ｏｆ？
）に前記化合物の５％アラビアゴム懸濁液ｒ経口投与す
る。その３０分後に１０チコレステロール、１％コール
酸及びコーン油の混合物７１ （ＩｒＩＬｌ／ｋ１７経
ロ投与する。2Hz), 8.73 (IH, dd, J=5Hz, 2Hz
), 9.16 (IH, d, J = 2Hz) rnass (m/e): 428 (molecular ion beak), 3 (15° [Example] Wistar-King rat (1 male z17of?
) A 5% suspension of gum arabic of the above compound is administered orally. Thirty minutes later, a mixture of 10 ticholesterol, 1% cholic acid and corn oil 71 (IrILl/k17) was administered orally.
以上の投与？１日１回連銃７日間行い、最終投与の４時
間後にエーテル麻酔下、腹部大動脈より採血し、４℃で
１６：ＨＩＸｒ、１０分間遠心し血ｒｆｔ ｋ得る。血
清中の総コレステロール量及びトリダリセライド址？血
清脂質測定試薬（化コレステロールは■−コレスターゼ
；ニッスイ、トリグリセライドはＶ−トリグラーゼ；ニ
ッスイ）全円いて測定し友。結果を社１に示す。More doses? The injection is repeated once a day for 7 days, and 4 hours after the final administration, blood is collected from the abdominal aorta under ether anesthesia and centrifuged at 4° C. and 16:HIXr for 10 minutes to obtain blood rft k. Total cholesterol amount and tridarycerides in serum? Serum lipid measuring reagents (for cholesterol, use ■-cholestase; Nissui; for triglyceride, use V-trigase; Nissui) for complete measurements. The results are shown in Company 1.
（６匹／群の平均値）
（＞４千工自）
急性毒性
ＩＣＪ系雄性マウス（５週令）を用いて、経口投与によ
る急性毒性試験全行った。本発明で使用する化合物のＬ
Ｄ５ｏ値はいずれも４ｆ／に９以上であり、旨い安全性
が確認された。(Average value of 6 mice/group) (>4,000 man-hours) Acute toxicity All acute toxicity tests were conducted by oral administration using male ICJ mice (5 weeks old). L of the compound used in the present invention
The D5o values were all 4f/9 or higher, confirming good safety.
■９発明の作用効果
本発明によれば新規なエタノールアミン誘導体お工びこ
れ金含有する抗高脂血症剤が提供される。(9) Effects of the Invention According to the present invention, an antihyperlipidemic agent containing a novel ethanolamine derivative and gold is provided.
本発明において使用されるエタノールアミン誘導体は血
清コレステロールや血清トリグリセリドｒ低下させろ作
用ｒ有するので、７１ｈ脂血症に起因する疾患、特に動
脈硬化症、心筋梗塞、まｆｃ、は脳梗塞等の予防剤とし
て有効に使用することができめ。Since the ethanolamine derivative used in the present invention has the effect of lowering serum cholesterol and serum triglyceride, it is a preventive agent for diseases caused by 71h lipidemia, especially arteriosclerosis, myocardial infarction, cerebral infarction, etc. It can be effectively used as a.
、・曾＼,・So＼
Claims (2)
血症剤。(2) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼An antihyperlipidemic agent containing an ethanolamine derivative represented by (I).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24579385A JPS62106080A (en) | 1985-11-01 | 1985-11-01 | Ethanolamine derivative and antihyperlipemia containing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24579385A JPS62106080A (en) | 1985-11-01 | 1985-11-01 | Ethanolamine derivative and antihyperlipemia containing same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62106080A true JPS62106080A (en) | 1987-05-16 |
| JPH0156066B2 JPH0156066B2 (en) | 1989-11-28 |
Family
ID=17138911
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24579385A Granted JPS62106080A (en) | 1985-11-01 | 1985-11-01 | Ethanolamine derivative and antihyperlipemia containing same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62106080A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0228314A2 (en) * | 1985-11-01 | 1987-07-08 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Use of ethanol/amine derivatives in treating or preventing hyperlipemia |
| US8765964B2 (en) | 2009-09-01 | 2014-07-01 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE46608E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
-
1985
- 1985-11-01 JP JP24579385A patent/JPS62106080A/en active Granted
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0228314A2 (en) * | 1985-11-01 | 1987-07-08 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Use of ethanol/amine derivatives in treating or preventing hyperlipemia |
| US8765964B2 (en) | 2009-09-01 | 2014-07-01 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US8765963B2 (en) | 2009-09-01 | 2014-07-01 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE45261E1 (en) | 2009-09-01 | 2014-11-25 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE45275E1 (en) | 2009-09-01 | 2014-12-02 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US8940903B2 (en) | 2009-09-01 | 2015-01-27 | Catabasis Pharmaceuticals, Inc. | Niacin conjugated fatty acid mixtures and their uses |
| US9238077B2 (en) | 2009-09-01 | 2016-01-19 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US9278136B2 (en) | 2009-09-01 | 2016-03-08 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US9486534B2 (en) | 2009-09-01 | 2016-11-08 | Catabasis Pharmaceuticals, Inc. | Niacin conjugated fatty acid mixtures and their uses |
| USRE46608E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE46605E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0156066B2 (en) | 1989-11-28 |
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