JPS607634B2 - Thienodiazepine derivatives - Google Patents
Thienodiazepine derivativesInfo
- Publication number
- JPS607634B2 JPS607634B2 JP51009753A JP975376A JPS607634B2 JP S607634 B2 JPS607634 B2 JP S607634B2 JP 51009753 A JP51009753 A JP 51009753A JP 975376 A JP975376 A JP 975376A JP S607634 B2 JPS607634 B2 JP S607634B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- acid
- dihydro
- diazepine
- thieno
- 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
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は、一般式 で表わされる新規なチェノジアゼピン誘導体に関する。[Detailed description of the invention] The present invention is based on the general formula This invention relates to a novel chenodiazepine derivative represented by:
上記式中、Ｒは水素、低級アルキル（メチル、エチル、
プロピル、イソプロピル、プチルなど）を、・Ｘはハロ
ゲン（ＣＩ、Ｂｒ、Ｆなど）を示す。本発明の一般式（
１）の化合物は、たとえば、一般式（式中、Ｒ，Ｘは前
記と同義である。In the above formula, R is hydrogen, lower alkyl (methyl, ethyl,
・X represents halogen (CI, Br, F, etc.). General formula of the present invention (
The compound of 1) is, for example, a compound of the general formula (wherein R and X are as defined above).
）で表わされる化合物を鍔金属水素化物で還元する事に
より製造される。) is produced by reducing the compound represented by tsuba metal hydride.
還元剤である錆金属水素化物としては、たとえば、水素
化ホウ素ナトリウム、水素化ホウ素リチウム、水素化ア
ルミニウムリチウム、水素化アルミニウムナトリウム、
水素化モノ（又はジ又はトリ）アルコキシアルミニウム
リチウム（又はナトリウム）、或いはソジウムジヒドロ
ビス−（２ーメトキシェトキシ）ーアルミネート等が挙
げられる。Examples of rust metal hydrides that are reducing agents include sodium borohydride, lithium borohydride, lithium aluminum hydride, sodium aluminum hydride,
Examples include lithium (or sodium) mono(or di- or tri)alkoxyaluminum hydride, or sodium dihydrobis-(2-methoxyshethoxy)-aluminate.
反応は通常、溶媒中で室温ないいま溶媒の沸点下で数分
ないいま数時間行われる。The reaction is usually carried out in a solvent at room temperature or below the boiling point of the solvent for several minutes to several hours.
又、必要に応じて冷却下反応させる事も出来る。溶媒と
しては、還元剤の種類により異なるが、たとえば水、ア
ルコール類（メタノール、エタノール、プロパノール、
イソプ。Moreover, the reaction can be carried out under cooling if necessary. The solvent varies depending on the type of reducing agent, but examples include water, alcohols (methanol, ethanol, propanol,
Aesop.
パノールなど）、エーテル類（ジェチルェーテル、ジブ
チルェーナル、テトラヒドロフラン、ジオキサン、モノ
グラィム、ジグラィムなど）、芳香族炭化水素類（ベン
ゼン、トルエン、キシレンなど）、ピリジンなど、或い
はこれらの混合溶媒などの中から反応を阻害しない溶媒
を適宜選択して用いられる。なお、水素化ホウ素ナトリ
ウムなどの様な緩和な還元剤を使用すればＣ−７位のア
セチル基のみ選択的に還元されるが、水素化アルミニウ
ムリチウムなどの様な強い還元剤を使用する場合、Ｃ−
７位のアセチル基のほかにアミド基も還元されるで、た
とえば、低温で反応させるなど反応条件を弱くする必要
がある。一般式（１）の化合物は分子内に不整炭素原子
を１個有するので光学異性体を有し、通常ラセミ体とし
て得られるが、必要に応じてそれぞれの光学異性体に分
割する事も出来る。(panol, etc.), ethers (diethyl ether, dibutylenal, tetrahydrofuran, dioxane, monoglyme, diglyme, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), pyridine, etc., or a mixed solvent of these to inhibit the reaction. A suitable solvent can be selected and used. Note that if a mild reducing agent such as sodium borohydride is used, only the acetyl group at the C-7 position is selectively reduced, but if a strong reducing agent such as lithium aluminum hydride is used, C-
In addition to the acetyl group at position 7, the amide group is also reduced, so it is necessary to weaken the reaction conditions, for example by conducting the reaction at a low temperature. Since the compound of general formula (1) has one asymmetric carbon atom in its molecule, it has optical isomers and is usually obtained as a racemate, but it can also be separated into each optical isomer if necessary.
一般式（１）の化合物は無機酸（たとえば、塩酸、硫酸
、臭化水素酸など）或いは有機酸（たとえば「メタンス
ルホン酸、パラトルェンスルホン酸、酢酸、しゆう酸、
マレイン酸、フマール酸、クエン酸など）と処理する事
により酸付加塩とする事も出来る。The compound of general formula (1) is an inorganic acid (for example, hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) or an organic acid (for example, methanesulfonic acid, paratoluenesulfonic acid, acetic acid, oxalic acid,
It can also be converted into acid addition salts by treatment with maleic acid, fumaric acid, citric acid, etc.).
本発明の化合物は筋弛緩、抗ケィレン、鎮静、抗不安作
用等、或いは又鎮痛作用を有し、たとえば筋弛緩剤、抗
ケィレン剤、鎮静剤、抗不安薬、マイナートランキラィ
ザーとして、或いは又鎮痛剤として有用である。The compounds of the present invention have muscle relaxant, anti-inflammatory, sedative, anxiolytic, etc., or analgesic effects, such as as muscle relaxants, anti-inflammatory agents, sedatives, anxiolytics, minor tranquilizers, or Useful as an analgesic.
次に〜本発明による化合物と既知の類似化合物との抗け
いれん作用に関する薬理比較試験を示す。Next, pharmacological comparative tests regarding the anticonvulsant effects of the compound according to the present invention and known similar compounds will be shown.
本発明よる化合物は後述の実施例で得られた化合物を用
い、比較対象としては特関昭４７−３４３９１号公報〜
侍開昭４７−４２７９４号公報および西独国特許出願公
開第１９６１７２７号明細書に開示されている化合物の
うち、それぞれの代表的化合物を用いた。Compounds according to the present invention are those obtained in the Examples described below, and for comparison, Tokusekki No. 47-34391~
Among the compounds disclosed in Samurai Publication No. 47-42794 and West German Patent Application No. 1961727, representative compounds thereof were used.
方法
一群６匹からなるマウスに試験化合物を腹腔内投与し「
１５分後にベンチレンテトラゾール１５０の９／ｋ９
を皮下投与した。Method A test compound was administered intraperitoneally to a group of 6 mice.
After 15 minutes, Bentilenetetrazol 150 9/k9
was administered subcutaneously.
ベンチレンテトラゾール投与３時間後、死亡したマウス
数を教え、致死率を５０％抑制するに必要な試験化合物
の投与量（ＥＤ５。値）を求めて、抗けいれん作用の指
標とした。この結果を第１表に示す。結果第１表
試験化合物Ａ〜Ｆは、次の通りである。Three hours after administration of ventrenetetrazole, the number of mice that died was reported, and the dose of the test compound required to suppress the mortality rate by 50% (ED5 value) was determined, which was used as an index of anticonvulsant action. The results are shown in Table 1. Results Table 1 Test compounds A to F are as follows.
Ａ：５一（ｏークロロフエニル）−７一（１ーハイドロ
キシヱチル）一１・３ージヒドロー２Ｈ−チエノ−〔２
・３一ｅ〕一１・４−ジアゼピンー２−オン（本発明の
実施例１の化合物）
Ｂ：１−メチル一５−（ｏークロロフエニル）−７一（
１ーハイド。A: 5-(o-chlorophenyl)-7-(1-hydroxyethyl)-1,3-dihydro-2H-thieno-[2
・31e]-1,4-diazepin-2-one (compound of Example 1 of the present invention) B: 1-methyl-5-(o-chlorophenyl)-7-(
1-Hyde.
キシエチル）一１・３ージヒドロー２Ｈ−チヱノー〔２
・３一ｅ〕−１・４ージアゼピンー２ーオン（本発明の
実施例２の化合物）
Ｃ：５一ｏ−クロロフエニル−７ーエチルー２・３−ジ
ヒドロ−ＩＨーチヱノ−〔２・３一ｃ〕〔１・４〕ジア
ゼピン（特関昭４７−３４３９１号公報の化合物）Ｄ：
′１ーメチルカルノゞモイルー５一ｏークロロフエニル
ー７−エチル一２・３ージヒドロ−ＩＨーチエノ−〔２
・３−ｅ〕〔１・４〕ジアゼピン（特開昭４７−４２７
９４号公報の化合物）Ｅ：７−クロロー１・３ージヒド
ロ−５ーフエニル−２日ーチエノ〔２・３一ｅ〕一１・
４ージアゼピンー２ーオン（西独国特許出願公開第１９
６１７２７号明細書の化合物）Ｆ−７ークロロー１・３
ージヒドロ−１ーメチル−５−フエニルー２日ーチエノ
〔２・３−ｅ〕−１・４−ジアゼピンー２ーオン（西独
国特許出願公開第１９６１７２７号明細書の化合物）本
発明の化合物をこれらの医薬として用いる場合「それ自
体あるいは適宜の薬理的に許容される担体、賦形剤、希
釈剤と混合し、粉末、額粒、錠剤、カプセル剤、注射剤
等の形態で経口的又は非経口的に投与することも出来る
。xyethyl)-1,3-dihydro 2H-thieno[2
・31e]-1,4-diazepine-2-one (compound of Example 2 of the present invention) C:51o-chlorophenyl-7-ethyl-2,3-dihydro-IH-thieno-[2,31c][1・4] Diazepine (compound disclosed in Tokusekki Publication No. 47-34391) D:
'1-Methylcarnomoyl-5-o-chlorophenyl-7-ethyl-2,3-dihydro-IH-thieno-[2
・3-e] [1.4] Diazepine (JP-A-47-427
Compound of Publication No. 94) E: 7-chloro1.3-dihydro-5-phenyl-2day-thieno[2.31e]11.
4-Diazepine-2-one (West German Patent Application Publication No. 19)
Compound of specification No. 61727) F-7-chloro 1,3
-dihydro-1-methyl-5-phenyl-2-thieno[2,3-e]-1,4-diazepine-2-one (compound of German Patent Application No. 1961727) The compound of the present invention is used as a pharmaceutical for these. "Administer by itself or mixed with appropriate pharmacologically acceptable carriers, excipients, diluents, orally or parenterally in the form of powder, granules, tablets, capsules, injections, etc. You can also do that.
投与量は対象疾患、症状、化合物によっても異なるが、
経口投与の場合通常成人１日あたり約０．１〜５００雌
程度である。次に若干の実施例を挙げて本発明化合物を
説明する。The dosage varies depending on the target disease, symptoms, and compound, but
Oral administration is usually about 0.1 to 500 females per adult day. Next, the compounds of the present invention will be explained with reference to some examples.
実施例 １
５−（ｏークロロフエニル）一７−アセチルー１・３ー
ジヒドロ−２日ーチエノ〔２・３−ｅ〕−１・４ージア
ゼピンー２ーオン６．３夕をエタノール４０の‘に溶解
し、これに水素化ホウ素ナトリウム０．８夕を加えて室
温で４時間櫨拝する。Example 1 5-(o-chlorophenyl)-7-acetyl-1,3-dihydro-2-thieno[2,3-e]-1,4-diazepine-2-one was dissolved in 40 parts of ethanol and added to it. Add 0.8 g of sodium borohydride and stir at room temperature for 4 hours.
次にこれを氷水に注ぎクロロホルムで抽出する。水洗、
無水硫酸マグネシウムで乾燥後、クロロホルムを減圧留
去する。残査を酢酸エチルで再結晶すると、５一（ｏー
クロロフヱニル）一７一（１−ハイドロキシエチル）一
１・３−ジヒドロー２Ｈ−チエノ〔２・３一ｅ〕一１１
４ージアゼピンー２−オンを白色結晶として得る。融点
２１５ｑｏ実施例 ２水素化ホウ素ナトリウム０．７夕
をエタノール３０の‘及び水１泌に溶解し、これに１ー
メチルー５一（ｏークロロフエニル）一７ーアセチルー
１・３ージヒドロー２Ｈ−チエ／〔２・３一ｅ〕一１・
４ージアゼピンー２ーオン６夕をエタノール２０の‘に
溶解した液を室温で滴下する。Next, pour this into ice water and extract with chloroform. washing with water,
After drying over anhydrous magnesium sulfate, chloroform is distilled off under reduced pressure. When the residue was recrystallized from ethyl acetate, 5-(o-chlorophenyl)-7-1(1-hydroxyethyl)-1,3-dihydro-2H-thieno[2,31e]-11
4-Diazepine-2-one is obtained as white crystals. Melting point: 215 qoExample 0.7 parts of sodium borohydride dihydride was dissolved in 30 parts of ethanol and 1 part of water, and to this was added 1-methyl-5-(o-chlorophenyl)-17-acetyl-1,3-dihydro 2H-thi/[2. 31e]11・
A solution prepared by dissolving 60% of 4-diazepine-2-one in 20% of ethanol is added dropwise at room temperature.
Claims (1)
す。 ）で表わされるチエノジアゼピン誘導体およびその酸付
加塩。[Claims] 1. A thienodiazepine derivative and its acid addition salt represented by the general formula (including mathematical formulas, chemical formulas, tables, etc.) (wherein, R represents hydrogen or lower alkyl, and X represents halogen).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51009753A JPS607634B2 (en) | 1976-01-31 | 1976-01-31 | Thienodiazepine derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51009753A JPS607634B2 (en) | 1976-01-31 | 1976-01-31 | Thienodiazepine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5293784A JPS5293784A (en) | 1977-08-06 |
| JPS607634B2 true JPS607634B2 (en) | 1985-02-26 |
Family
ID=11729043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51009753A Expired JPS607634B2 (en) | 1976-01-31 | 1976-01-31 | Thienodiazepine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS607634B2 (en) |
-
1976
- 1976-01-31 JP JP51009753A patent/JPS607634B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5293784A (en) | 1977-08-06 |
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