JPS60197663A - Sulfamoylamidine derivative and its preparation - Google Patents
Sulfamoylamidine derivative and its preparationInfo
- Publication number
- JPS60197663A JPS60197663A JP59053891A JP5389184A JPS60197663A JP S60197663 A JPS60197663 A JP S60197663A JP 59053891 A JP59053891 A JP 59053891A JP 5389184 A JP5389184 A JP 5389184A JP S60197663 A JPS60197663 A JP S60197663A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- derivative
- lower alkyl
- sulfamoylamidine
- 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
Links
Abstract
Description
【発明の詳細な説明】
本発明は胃酸分泌抑制剤として有用な下記一般式（Ｉ）
で示される新規スルファモイルアミジン誘導体及びその
酸付加塩並びにそれらの製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention provides the following general formula (I) useful as a gastric acid secretion inhibitor:
The present invention relates to novel sulfamoylamidine derivatives and acid addition salts thereof, and methods for producing them.
は２乃至４の整数を意味する。以下同様）上記一般式（
Ｉ）のＲや後記一般式のぼが意味する低級アルキル基は
炭素数が１乃至５の直鎖又は分枝状のアルキル基であっ
て、具体的にはメチル基、エチル基、プロピル基、イソ
プロピル基、ブチル基、イソブチル基、ペンチル（アミ
ル）基、インペンチル基等が挙げられる。means an integer from 2 to 4. The same applies hereafter) The above general formula (
The lower alkyl group meant by R in I) and the general formula No. 1 below is a linear or branched alkyl group having 1 to 5 carbon atoms, and specifically includes a methyl group, an ethyl group, a propyl group, Examples include isopropyl group, butyl group, isobutyl group, pentyl (amyl) group, impentyl group, and the like.
前記一般式（Ｉ）の本発明化合物は塩を形成する。本発
明には化合物（Ｉ）の酸付加塩も包含され、かかる塩と
しては種々の鉱酸２例えば塩化水素酸、臭化水素酸、ヨ
ウ化水素酸、硫酸、硝酸、リン酸などや種々の有機酸２
例えばフマール酸、マレイン酸、ピクリン酸などとの酸
付加塩が挙げられる。The compound of the present invention of general formula (I) forms a salt. The present invention also includes acid addition salts of compound (I), and such salts include various mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, etc. organic acid 2
Examples include acid addition salts with fumaric acid, maleic acid, picric acid, and the like.
本発明化合物（Ｉ）やその酸付加塩は以下に例示する方
法によって合成される。The compound (I) of the present invention and its acid addition salts are synthesized by the methods exemplified below.
（ｒＶ）
（反応式中ｄは低級アルキル基を意味する）本発明化合
物（Ｉ）は一般式（ｎ）で示されるイミデート誘導体と
一般式（ＩＩＩ）で示されるスルファミド誘導体とを反
応させることによって製造される。(rV) (d in the reaction formula means a lower alkyl group) The compound (I) of the present invention can be obtained by reacting an imidate derivative represented by the general formula (n) with a sulfamide derivative represented by the general formula (III). Manufactured.
反応は通常溶媒中で行なわれ、溶媒としては例えばメタ
ノール、エタノール、インプロパノール等のアルコール
、クロロホルム、エーテル。The reaction is usually carried out in a solvent, such as alcohols such as methanol, ethanol, and impropanol, chloroform, and ether.
テトラヒドロンラン、ベンゼン等が適当である。Tetrahydrone, benzene, etc. are suitable.
これらの溶媒は水を含まないものが好ましい。These solvents preferably do not contain water.
反応温度は特に制限はないが、室温乃至加温下に行うの
が有利である。また９反応液の液性は中性乃至塩基性が
好ましい。There is no particular restriction on the reaction temperature, but it is advantageous to carry out the reaction at room temperature or with heating. Further, the liquid properties of the reaction solution 9 are preferably neutral to basic.
Ｒが水素原子であるスルファミドを原料化合物（ＩＩＩ
）として使用するときは一般式（ＴＶ）で示されるダイ
マーが同時に副生ずる。Sulfamide in which R is a hydrogen atom is used as a raw material compound (III
), a dimer represented by the general formula (TV) is simultaneously produced as a by-product.
これらの化合物の単離は同化合物の理化学的性質の相違
な利用して容易に分離することができる。These compounds can be easily isolated by utilizing the different physical and chemical properties of the same compounds.
る。Ru.
単離、精製は、各種クロマトグラフィー、再結晶等通常
用いられる化学操作な適用して行うことができる。Isolation and purification can be carried out by applying commonly used chemical operations such as various chromatography and recrystallization.
本発明によって提供される本発明化合物（Ｉ）やその酸
付加塩はヒスタミンＨ２受容体拮抗作用を有し、その作
用に基づいて胃酸分泌を抑制する。しかも２本発明化合
物は抗コリン作用によらない胃酸分泌抑制作用を示す点
にも特徴があり、抗コリン作用による副作用が指摘され
ているところであり、新しいタイプの胃酸分泌抑制 □
剤として有用である。The present compound (I) and its acid addition salt provided by the present invention have a histamine H2 receptor antagonistic effect, and suppress gastric acid secretion based on this effect. Furthermore, the two compounds of the present invention are also characterized in that they exhibit gastric acid secretion suppressing effects that are not due to anticholinergic effects, and side effects due to anticholinergic effects have been pointed out, making them a new type of gastric acid secretion suppressing □
It is useful as a drug.
本発明化合物（Ｉ）やその酸付加塩は５ｈａｙ ｒａｔ
４１１ｒ法（５ｈａｙら、ガストロエンテロロジー、第
５巻、第４３〜６１頁、１９４５年）により、３０ｍｇ
／ｋｇ以下の投与量で胃酸分泌を有効に抑制することが
確認されている。The compound (I) of the present invention or its acid addition salt has a 5 hay rat
30 mg by the 411r method (5hay et al., Gastroenterology, Vol. 5, pp. 43-61, 1945).
It has been confirmed that gastric acid secretion can be effectively suppressed at a dose of less than /kg.
また１本発明化合物（Ｉ）を製造する過程で副生ずる前
記ダイマー（ＩＶ）も前記薬理活性と同様の活性を示す
ことが認められている。Furthermore, it has been recognized that the dimer (IV) produced as a by-product in the process of producing the compound (I) of the present invention also exhibits the same pharmacological activity as the above-mentioned pharmacological activity.
一般式（Ｉ）で示される化合物やその酸付加塩を主成分
として含有する薬剤は任意慣用の製薬用担体や賦形剤を
用いて任意慣用の方法で調製される。投与は経口、非経
口のいずれの形態であってもよい。投与量は症状や投与
対象の年令、性別等を考慮して個々の場合に応じて適宜
決定されるが２通常成人１日当り５０〜６００ｒｌ１ｇ
であり、これを１回であるいは２〜４回に分けて投与す
るのが適当である。A drug containing the compound represented by formula (I) or its acid addition salt as a main component can be prepared by any conventional method using any conventional pharmaceutical carrier or excipient. Administration may be either oral or parenteral. The dosage is determined depending on the individual case, taking into consideration the symptoms, the age and gender of the recipient, etc. 2 The usual dose is 50 to 600 rl/g per day for adults.
Therefore, it is appropriate to administer this once or in 2 to 4 divided doses.
以下に実施例を掲記し２本発明をさらに詳細に説明する
。EXAMPLES The present invention will be described in further detail with reference to Examples below.
実施例１
エチル４−（（３−ピペリジノメチル）フェノキシコブ
チルイミデート４８ｇをメタノール１００ｍｔに溶解し
、スルファミド３３．８ ｇをメタノール２００ｍ１に
溶かした溶液を加え室温で２日間攪拌する。Example 1 48 g of ethyl 4-((3-piperidinomethyl)phenoxycobutylimidate is dissolved in 100 ml of methanol, and a solution of 33.8 g of sulfamide dissolved in 200 ml of methanol is added thereto and stirred at room temperature for 2 days.
溶媒を減圧留去したのち、残渣を酢酸エチル−メタノー
ルの混合溶媒を展開溶媒としてカラムクロマトグラフィ
ーにて分離する。目的とするフラクションを集め、塩酸
で処理しメタノールにて再結晶すると、融点１８４−１
８７℃を示す４−（ｍ＝（ピペリジノメチル）フェノキ
シ） Ｎ２−スルファモイルブチルアミジン２塩酸塩［
化合物Ｉコ２７．７ｇが得られる。また、他のフラクシ
ョンより副生物として、酢酸エチルより再結晶して融点
１０３−１０４℃を示す３．５− ビス［３−〔ｍ−（
ピペリジノメチル）フェノキシ〕プロピル］ −４Ｈ−
１，２，４，６，−チアトリアジン１，１−ジオキサイ
ド［化合物ｎ ］ ６．９ｇが得られた。After the solvent is distilled off under reduced pressure, the residue is separated by column chromatography using a mixed solvent of ethyl acetate and methanol as a developing solvent. The desired fractions were collected, treated with hydrochloric acid, and recrystallized from methanol, resulting in a melting point of 184-1.
4-(m=(piperidinomethyl)phenoxy) N2-sulfamoylbutyramidine dihydrochloride [
27.7 g of Compound I is obtained. In addition, as a by-product from other fractions, 3.5-bis[3-[m-(
piperidinomethyl)phenoxy]propyl] -4H-
6.9 g of 1,2,4,6,-thiatriazine 1,1-dioxide [compound n] was obtained.
［化合物■コ
元素分析値（Ｃ１６Ｈ２６Ｎ４０３ Ｓ・２ＨＣ１とし
て）ＣＨＮ Ｓ Ｃ１
計算値（％） ４４．９７６．６０１３．１１７．５０
１６．５９実測値（％） ４４．８７６．８４１２．９
０７．６４１６．４０［化合物■］
元素分析値（Ｃ，、Ｈ４，Ｎ、０４Ｓとして）ＨＮＳ[Compound ■ Elemental analysis value (as C16H26N403 S・2HC1) CHN S C1 Calculated value (%) 44.976.6013.117.50
16.59 Actual value (%) 44.876.8412.9
07.6416.40 [Compound ■] Elemental analysis value (as C,, H4, N, 04S) HNS
Claims (2)
加塩(1) A sulfamoylamidine derivative or an acid addition salt thereof represented by the general formula (wherein R is a hydrogen atom or a lower alkyl group, and n means an integer from 2 to 4)
意味する）で示されるイミデート誘導体と一般式 ％式％ （式中Ｒは水素原子又は低級アルキル基を意味する。以
下同様）で示されるスルファミド誘導体とを反応させる
ことを特徴とする一般式で示されるスルファモイルアミ
ジン誘導体の製法(2) Imidate derivatives represented by the general formula (wherein R' represents a lower alkyl group and n means an integer from 2 to 4) and the general formula %formula% (wherein R represents a hydrogen atom or a lower alkyl group) A method for producing a sulfamoylamidine derivative represented by the general formula, characterized by reacting the sulfamide derivative represented by the following formula.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59053891A JPS60197663A (en) | 1984-03-21 | 1984-03-21 | Sulfamoylamidine derivative and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59053891A JPS60197663A (en) | 1984-03-21 | 1984-03-21 | Sulfamoylamidine derivative and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS60197663A true JPS60197663A (en) | 1985-10-07 |
Family
ID=12955343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59053891A Pending JPS60197663A (en) | 1984-03-21 | 1984-03-21 | Sulfamoylamidine derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60197663A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022034121A1 (en) | 2020-08-11 | 2022-02-17 | Université De Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
-
1984
- 1984-03-21 JP JP59053891A patent/JPS60197663A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022034121A1 (en) | 2020-08-11 | 2022-02-17 | Université De Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
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