JPS63227570A - Isoquinoline derivative - Google Patents

Isoquinoline derivative

Info

Publication number
JPS63227570A
JPS63227570A JP5866387A JP5866387A JPS63227570A JP S63227570 A JPS63227570 A JP S63227570A JP 5866387 A JP5866387 A JP 5866387A JP 5866387 A JP5866387 A JP 5866387A JP S63227570 A JPS63227570 A JP S63227570A
Authority
JP
Japan
Prior art keywords
formula
group
lower alkyl
isoquinoline
isoquinoline derivative
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.)
Pending
Application number
JP5866387A
Other languages
Japanese (ja)
Inventor
Haruyoshi Honda
本田 晴義
Susumu Sato
進 佐藤
Hideaki Matsuda
松田 秀明
Kazuo Isomae
磯前 和男
Tatsuhiko Katori
香取 達彦
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SSP Co Ltd
Original Assignee
SSP Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by SSP Co Ltd filed Critical SSP Co Ltd
Priority to JP5866387A priority Critical patent/JPS63227570A/en
Publication of JPS63227570A publication Critical patent/JPS63227570A/en
Pending legal-status Critical Current

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  • Other In-Based Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

NEW MATERIAL:An isoquinoline derivative shown by formula I [R is acyl; R' is lower alkoxy or NR1R2 (R1 is H or lower alkyl; R2 is lower alkyl which may contain substituent group or R1 and R2 together with neighboring N are bonded to form ring which may contain other different atom and/or substituent group)]. EXAMPLE:1-Dimethylamino-3-acetamino-isoquinoline. USE:An anti-inflammatory drug drug and analgesic effective for diseases such as arthritis, lumbago, toothache and heat disease and an antiarrhythmic agent. PREPARATION:A 1-halogeno-isoquniline shown by formula II (X is halogen) is reacted with a nucleophilic compound shown by formula III to give a compound shown by formula I.

Description

【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、新規なイソキノリン誘導体に関し、更に詳細
には医薬品として有用なインキノリン誘導体に関する。
DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to novel isoquinoline derivatives, and more particularly to inquinoline derivatives useful as pharmaceuticals.

〔従来の技術及びその問題点〕[Conventional technology and its problems]

従来、種々の薬理作用を有するインキノリン誘導体が知
られているが、このうち3−アシルアミノ−イソキノリ
ン誘導体については、殺虫作用を有する誘導体(米国特
許第3,247,212号明細書)が知られているにす
ぎず、それ以外の薬理作用を有する3−アクルアミノ−
イソキノリン誘導体については未だ報告をみない。
Hitherto, inquinoline derivatives having various pharmacological actions have been known, but among these, 3-acylamino-isoquinoline derivatives have an insecticidal action (U.S. Pat. No. 3,247,212). 3-Acruamino-
There have been no reports regarding isoquinoline derivatives yet.

本発明は、従゛来公知の殺虫作用に限らず、種々の薬理
作用を有する新規な3−アシルアミノ−イソキノリン誘
導体を提供することを目的とする。
An object of the present invention is to provide a novel 3-acylamino-isoquinoline derivative having various pharmacological actions in addition to the conventionally known insecticidal action.

〔問題点を解決するための手段〕[Means for solving problems]

本発明者は、種々の3−アシルアミノ−イソキノリン誘
導体を合成し、その薬理作用を探索したところ、(I)
式で表わされる新規化合物が強い抗炎症作用、鎮痛作用
、及び抗不整脈作用等を有し、関節炎、腰痛、歯痛ある
いは心疾患等の諸疾患に対し有用なものであることを見
い出し、本発明を完成した。
The present inventor synthesized various 3-acylamino-isoquinoline derivatives and investigated their pharmacological effects, and found that (I)
We have discovered that the novel compound represented by the formula has strong anti-inflammatory effects, analgesic effects, anti-arrhythmic effects, etc., and is useful for various diseases such as arthritis, lower back pain, tooth pain, and heart disease, and have developed the present invention. completed.

すなわち、本発明は次の一般式(I) 〔式中、Rはアクル基を示し、R′は低級アル低級アル
キル基、R2は置換基を有することのある低級アルキル
基を示すか、あるいはR1とR2が一緒になって隣接す
る窒素原子と共に他の異種原子を含んでもよく、また置
換基を有していてもよい環を形成する)を示す〕で表わ
されるイソキノリン誘導体を提供するものである。
That is, the present invention relates to the following general formula (I) [wherein R represents an acyl group, R' represents a lower alkyl group, R2 represents a lower alkyl group which may have a substituent, or R1 and R2 together with the adjacent nitrogen atom form a ring which may contain other heteroatoms and which may have a substituent. .

上記(I)式において、R1とR2が一緒になって形成
する基としては、例えば次の基 (式中、鳥は水素原子、低級アルキル基、ヒドロキシ置
換低級アルキル基、ハロゲン原子が置換することのある
アリール基、アラルキル基またはホルミル基を示す)。
In the above formula (I), the group formed by R1 and R2 together is, for example, the following group (in the formula, bird is substituted with a hydrogen atom, a lower alkyl group, a hydroxy-substituted lower alkyl group, or a halogen atom). aryl, aralkyl or formyl group).

が挙げられる。can be mentioned.

本発明の一般式(I)で表わされる化合物は、例えば次
の反応式に従って、公知の方法により容易に得られる1
−ハロゲノ−イソキノリン類(2)に求核化合物に)を
反応させることによシ製造される。
The compound represented by the general formula (I) of the present invention can be easily obtained by a known method according to the following reaction formula, for example.
-halogeno-isoquinolines (2) with a nucleophilic compound).

@     に)      (I) (式中、Xはハロダン原子を示し、R,R’は前記し九
意味を有する) 本反応は、室温ないし使用する溶媒の還流温度にて数時
間〜数日間攪拌するか、または封管中敷時間〜数日間加
温することによって実施される。また必要に応じ、金属
ナトリウム、水素化ナトリウム、水酸化ナトリウムまた
は水酸化カリウムなどの塩基の存在下で反応を行なうこ
ともできる。溶媒としてはメタノール、エタノール、含
水アルコール、アセトン、ジメチルホルムアミド、ジオ
キサンまたはエトキシエタノール等が挙げられる。
(I) (In the formula, X represents a halodane atom, and R and R' have the nine meanings described above) This reaction is stirred at room temperature or the reflux temperature of the solvent used for several hours to several days. Alternatively, it can be carried out by heating for several days up to the time required for sealing the insole. Further, if necessary, the reaction can also be carried out in the presence of a base such as metallic sodium, sodium hydride, sodium hydroxide or potassium hydroxide. Examples of the solvent include methanol, ethanol, hydrous alcohol, acetone, dimethylformamide, dioxane, and ethoxyethanol.

かくして得られた本発明のイソキノリン誘導体(I)は
、更に必要に応じて常法によシ、塩酸塩、臭化水素酸塩
、硫酸塩などの無機酸塩、またはマレイン酸塩、フマー
ル酸塩、クエン酸塩、メタンスルホン酸塩などの有機酸
塩とすることができる。
The isoquinoline derivative (I) of the present invention thus obtained can be further treated with an inorganic acid salt such as a hydrochloride, a hydrobromide, a sulfate, or a maleate or a fumarate by a conventional method, if necessary. , citrate, methanesulfonate, and other organic acid salts.

〔作用及び発明の効果〕[Action and effect of the invention]

斯くの如くして得られた本発明の化合物の抗炎症作用に
ついて試験した結果を以下に示す。
The results of testing the anti-inflammatory effect of the compound of the present invention thus obtained are shown below.

6週令のウィスター系ラット金一群5匹とし、18時間
絶食した後、被検化合物を0.5係カルボキンメチルセ
ルロースナトリウム(CMC−Na )溶液に溶解又は
懸濁し、経口投与した。被検化合物投与60分後に1%
カラゲニン生理食塩水溶液0.1 ff17!を右足踏
皮下に注入し、3時間後に定容積(5)を測定し、カラ
を算出した。
After fasting for 18 hours, a test compound was dissolved or suspended in a 0.5 sodium carboxyl methylcellulose (CMC-Na) solution and orally administered to 5 6-week old Wistar rats in one group. 1% 60 minutes after administration of test compound
Carrageenin saline solution 0.1 ff17! was injected subcutaneously into the right foot, and 3 hours later, the fixed volume (5) was measured and the empty volume was calculated.

別に1係力2ゲニン生理食塩水溶液0.1−を右足踏皮
下に注°大した対照群の浮腫率も同様に求め、それぞれ
の検体の浮腫抑制率を次式によシ算出した。
Separately, the edema rate of the control group, in which 0.1 - of the 1-force 2-genin physiological saline solution was injected under the skin of the right foot, was similarly determined, and the edema suppression rate of each specimen was calculated using the following formula.

以下余白 第1表 以上の結果から明らかな如く、本発明の化合物(I)は
強い抗炎症作用を有し、抗炎症薬として有用なものであ
る。
As is clear from the results shown in Table 1 below, the compound (I) of the present invention has a strong anti-inflammatory effect and is useful as an anti-inflammatory drug.

〔実施例〕〔Example〕

次に実施例を挙げて説明するが、本発明はこれらに限定
されるものではない。
Next, the present invention will be described with reference to Examples, but the present invention is not limited thereto.

実施例1 1−プロモー3−アセタミイーイソキノリン0.7fに
ジメチルアミン飽和メタノール溶液157!を加え、封
管中80℃で3時間加熱攪拌した。その後、反応液を留
去し、残金にクロロホルムを加え、水洗後、無水硫酸ナ
トリウムにて乾燥した。クロロホルムを留去し、残金を
7リカダルカラムクロマトグラフイーにて精製し、クロ
ロホルム−エーテル混液よシ再結晶して微黄色結晶の1
−ジメチルアミノ−3−アセタミノーイソキノリン(化
合物番号3)0.4F(収率66.1 % >を得た。
Example 1 0.7f of 1-promo-3-acetamyisoquinoline and 157 g of dimethylamine saturated methanol solution! was added, and the mixture was heated and stirred at 80° C. for 3 hours in a sealed tube. Thereafter, the reaction solution was distilled off, chloroform was added to the residue, washed with water, and dried over anhydrous sodium sulfate. Chloroform was distilled off, and the residue was purified by 7 ricadal column chromatography and recrystallized from a chloroform-ether mixture to give pale yellow crystals.
-Dimethylamino-3-acetaminoisoquinoline (compound number 3) 0.4F (yield: 66.1%) was obtained.

実施例2 1−プロモー3−アセタミノーイソキノリン1.Ofに
無水ビベラゾン3.26 t、エトキシエタノール40
mを加え、2時間還流攪拌した。その後、反応液を留去
し、残金にクロロホルムを加え、水洗後、無水硫酸ナト
リウムにて乾燥した。クロロホルムを留去し、残金をシ
リカダルカラムクロマトグラフィーにて精製し、クロロ
ホルム−エーテル混液より再結晶して無色結晶の1−(
1−ピベラゾニル)−3−アセタミノーイソキノリン(
化合物番号4)0.85f(収率83.4%)を得た。
Example 2 1-promo 3-acetaminoisoquinoline 1. Of anhydrous viverazone 3.26 t, ethoxyethanol 40
m was added thereto, and the mixture was stirred under reflux for 2 hours. Thereafter, the reaction solution was distilled off, chloroform was added to the residue, washed with water, and dried over anhydrous sodium sulfate. Chloroform was distilled off, the residue was purified by silica dull column chromatography, and recrystallized from a chloroform-ether mixture to give colorless crystals of 1-(
1-piverazonyl)-3-acetaminoisoquinoline (
Compound No. 4) 0.85f (yield 83.4%) was obtained.

実施例3 実施例1またu2と同様にして第2表に示す化合物を得
た。なお、表中には実施例1及び2で得た化合物も併せ
て示した。
Example 3 The compounds shown in Table 2 were obtained in the same manner as in Example 1 and u2. In addition, the compounds obtained in Examples 1 and 2 are also shown in the table.

以下余白Margin below

Claims (1)

【特許請求の範囲】 1、次の一般式( I ) ▲数式、化学式、表等があります▼( I ) 〔式中、Rはアシル基を示し、R′は低級アルコキシ基
または基▲数式、化学式、表等があります▼(R_1は
水素原子または低級アルキル基、R_2は置換基を有す
ることのある低級アルキル基を示すか、あるいはR_1
とR_2が一緒になつて隣接する窒素原子と共に他の異
種原子を含んでもよく、また置換基を有していてもよい
環を形成する)を示す〕 で表わされるイソキノリン誘導体。 2、( I )式中、R′が次の基 ▲数式、化学式、表等があります▼ (式中、R_3は水素原子、低級アルキル基、ヒドロキ
シ置換低級アルキル基、ハロゲン原子が置換することの
あるアリール基、アラルキル基またはホルミル基を示す
) で表わされるものである特許請求の範囲第1項記載のイ
ソキノリン誘導体。
[Claims] 1. The following general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R represents an acyl group, and R' is a lower alkoxy group or group ▲Mathical formula, There are chemical formulas, tables, etc. ▼ (R_1 is a hydrogen atom or a lower alkyl group, R_2 is a lower alkyl group that may have a substituent, or R_1
and R_2 together form a ring which, together with the adjacent nitrogen atom, may contain other heteroatoms and may have a substituent.] An isoquinoline derivative represented by: 2. In formula (I), R' is the following group ▲ There are mathematical formulas, chemical formulas, tables, etc. The isoquinoline derivative according to claim 1, which is represented by the following formula (representing a certain aryl group, aralkyl group or formyl group)
JP5866387A 1987-03-13 1987-03-13 Isoquinoline derivative Pending JPS63227570A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP5866387A JPS63227570A (en) 1987-03-13 1987-03-13 Isoquinoline derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP5866387A JPS63227570A (en) 1987-03-13 1987-03-13 Isoquinoline derivative

Publications (1)

Publication Number Publication Date
JPS63227570A true JPS63227570A (en) 1988-09-21

Family

ID=13090825

Family Applications (1)

Application Number Title Priority Date Filing Date
JP5866387A Pending JPS63227570A (en) 1987-03-13 1987-03-13 Isoquinoline derivative

Country Status (1)

Country Link
JP (1) JPS63227570A (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039301A1 (en) * 1997-03-04 1998-09-11 Neurogen Corporation 1-(isoquinolin-1-yl)-4-(1-phenylmethyl)piperazines; dopamine receptor subtype specific ligands
US5972945A (en) * 1997-06-13 1999-10-26 Neurogen Corporation 2-aminoalkylaminoquinolines; dopamine receptor subtype specific ligands
US6313141B1 (en) 1997-06-13 2001-11-06 Neurogen Corporation 2-aminoalkylaminoquinolines as dopamine D4 ligands
US6613901B2 (en) 2000-03-08 2003-09-02 Neurogen Corporation 2-aminoalkylaminoquinolines as dopamine D4 ligands
WO2008115593A1 (en) 2007-03-21 2008-09-25 The University Of Montana 1-[(2'-substituted)-piperazin-1'-yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039301A1 (en) * 1997-03-04 1998-09-11 Neurogen Corporation 1-(isoquinolin-1-yl)-4-(1-phenylmethyl)piperazines; dopamine receptor subtype specific ligands
US5972945A (en) * 1997-06-13 1999-10-26 Neurogen Corporation 2-aminoalkylaminoquinolines; dopamine receptor subtype specific ligands
US6313141B1 (en) 1997-06-13 2001-11-06 Neurogen Corporation 2-aminoalkylaminoquinolines as dopamine D4 ligands
US6613901B2 (en) 2000-03-08 2003-09-02 Neurogen Corporation 2-aminoalkylaminoquinolines as dopamine D4 ligands
WO2008115593A1 (en) 2007-03-21 2008-09-25 The University Of Montana 1-[(2'-substituted)-piperazin-1'-yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents
US7887784B2 (en) 2007-03-21 2011-02-15 University Of Montana 1-[(2′-substituted)-piperazin-1′ -yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents

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