JPS58225092A - Pyrido(1,2,3-de)(1,4)benzoxazine-6-carboxylic acid derivative - Google Patents
Pyrido(1,2,3-de)(1,4)benzoxazine-6-carboxylic acid derivativeInfo
- Publication number
- JPS58225092A JPS58225092A JP10918182A JP10918182A JPS58225092A JP S58225092 A JPS58225092 A JP S58225092A JP 10918182 A JP10918182 A JP 10918182A JP 10918182 A JP10918182 A JP 10918182A JP S58225092 A JPS58225092 A JP S58225092A
- Authority
- JP
- Japan
- Prior art keywords
- pyrido
- benzoxazine
- carboxylic acid
- dihydro
- oxo
- 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
Abstract
Description
【発明の詳細な説明】
本発明は一般式（１）
（式中、Ｒは水素または低級アルキル基を表わし、ルは
１または２である。）で示される１０位に二環性アミ７
基を有する９−フルオロ−７−オキソ−２，８−ジヒド
ロ−７Ｈ−ピリド（１，２，３−ａｅ） （１，４）ペ
ンゾオギサジンー６−カルボン酸誘導体およびその塩に
関するものである。Detailed Description of the Invention The present invention provides a bicyclic amine 7 at the 10th position represented by the general formula (1) (wherein R represents hydrogen or a lower alkyl group, and R is 1 or 2).
9-Fluoro-7-oxo-2,8-dihydro-7H-pyrido(1,2,3-ae) (1,4) penzogisazine-6-carboxylic acid derivative and its salt be.
ここで低級アルキル基としてメチル、エチル。Here, methyl and ethyl are used as lower alkyl groups.
１番−ブロピル、１−プロピル等が挙げられる。Examples include 1-bropyl, 1-propyl, and the like.
また、塩としては、塩酸、硫酸、メタンスルポン酸の如
き無機酸もしくは有機酸との塩、あるいはカルボン酸の
ナトリウム塩やカルシウム塩の如きアルカリ金属塩もし
くはアルカリ土類金属塩があげられる。Examples of the salt include salts with inorganic or organic acids such as hydrochloric acid, sulfuric acid and methanesulfonic acid, and alkali metal salts or alkaline earth metal salts such as sodium salts and calcium salts of carboxylic acids.
次に９本発明の化合物の製造法の例を反応式で示して説
明する。Next, an example of a method for producing the compound of the present invention will be described using a reaction formula.
すなわち、へ１０−ジフルオロ−７−オキソ−２，３−
ジヒドロ−７Ｈ−ピリド（１，２，８−ｄｏ ）（’１
．４）ベンゾオキサジン−６−カルボン酸誘導体（１）
を式（ｌｉｔ）で表わされる二環性アミンと反応させる
ことにより目的とする化合物（Ｉ）を得ることができる
。That is, he10-difluoro-7-oxo-2,3-
Dihydro-7H-pyrido (1,2,8-do) ('1
．． 4) Benzoxazine-6-carboxylic acid derivative (1)
The target compound (I) can be obtained by reacting with a bicyclic amine represented by formula (lit).
本反応を更に詳細に説明すれば化合物（ＩＩ）を。This reaction will be explained in more detail with compound (II).
ジメチルスルホキシド、スルホラン、ジメチルホルムア
ミド、ジメチルアセトアミドもしくは水の如き極性溶媒
中で原料に対し２モル比以上のアミン類（ｌｆｔ）と、
または１〜２モル比のトリエチルアミン、ジメチルア：
す′ンもしくは炭酸カリウムの如き脱酸剤の存在下１〜
１．２モル比のアミンｆＡ（ＩＩＩ）と室温ないし２０
０℃、好ましくは７０〜１５０℃で１時間ないし４８時
間加熱。amines (lft) in a polar solvent such as dimethyl sulfoxide, sulfolane, dimethylformamide, dimethylacetamide or water in a molar ratio of 2 or more to the raw material;
or 1 to 2 molar ratios of triethylamine and dimethylamine:
In the presence of a deoxidizing agent such as water or potassium carbonate,
1.2 molar ratio of amine fA(III) and room temperature to 20
Heating at 0°C, preferably 70-150°C for 1 hour to 48 hours.
反応させることにより化合物（Ｉ）を得ることができる
。Compound (I) can be obtained by the reaction.
反応終了後、冷却することによって化合物（１）が析出
する場合は、これを濾取し、また析出物を生じない場合
は減圧下に反応液を乾固し残渣を適当な溶媒例えばクロ
ロホルムと水で振とうし、クロロホルム層から化合物（
１）を得る。After completion of the reaction, if compound (1) precipitates by cooling, it is collected by filtration. If no precipitate is formed, the reaction solution is dried under reduced pressure and the residue is mixed with a suitable solvent such as chloroform and water. Shake with water to remove the compound (
1) is obtained.
本発明の一般式（１）で表わされる化合物およびその塩
は緑膿菌を含むグラム陰性−およびダラム陽性菌に対し
て広域な抗菌スペクトルを示し。The compound represented by the general formula (1) of the present invention and its salt exhibits a broad antibacterial spectrum against Gram-negative and Durham-positive bacteria including Pseudomonas aeruginosa.
医薬品としての使用が期待できる。医薬品として使用さ
れているピペミド酸を対照として試験管内抗菌試験にお
ける最小発育阻止濃度を測定した結果を次表に示す。な
お９試験方法は日本化学療法学会指定の方法に準じた。It is expected to be used as a medicine. The following table shows the results of measuring the minimum inhibitory concentration in an in vitro antibacterial test using pipemidic acid, which is used as a pharmaceutical, as a control. The 9 test methods were in accordance with the method specified by the Japanese Society of Chemotherapy.
１（
表 最小発育阻止濃度 ＭＩＯ（μ２へ）次に本発明の
実施例を記載する。1 (Table Minimum Inhibitory Concentration MIO (to μ2)) Examples of the present invention will now be described.
実施例Ｉ
Ｂｔｏ−ジフルオロ−３−メチル−７−オキソ−２，８
−ジヒドロ−’Ｉ Ｈ−ピリド（１，２，３−に加えて
、浴温１２１）〜１８儂）℃で６詩間１１’４拌する。Example I Bto-difluoro-3-methyl-7-oxo-2,8
-dihydro-'I H-pyrido (1,2,3-) and stir at bath temperature 121°C to 18°C for 11'4 hours for 6 hours.
反応液を減圧乾固し、残渣をシリカゲルカラムクロマト
グラフィーで槓製し、メタノール−クロロホルム（５：
１１５）で溶出−４る部分から得られる粗品をエタノー
ルで再結晶すると２．８−ジヒドロ−７Ｈ−ピリド（１
，２，ａ −ｄｏ ）（１，４）ベンゾオキサジン−６
−カルボン酸１３５ ｍすを得る。The reaction solution was dried under reduced pressure, and the residue was filtered by silica gel column chromatography and mixed with methanol-chloroform (5:
The crude product obtained from the fraction eluted with 115) was recrystallized from ethanol to yield 2,8-dihydro-7H-pyrido (1
,2,a-do)(1,4)benzoxazine-6
-135 ml of carboxylic acid are obtained.
元素分析値 ０２８Ｈ２２ＦＮ、０４として計算値 ０
６２．０１． １１５７３． Ｎ １１１．８５分析
値 ０６２．２１． Ｈ５，６４，Ｎ ｌＯ，８ｔｌ
実施例２
９、ＩＯ−ジフルλロー８−メチル−７一オキソ＝２＋
３−ジヒドロ−７Ｈ−ピリド（１，２，８−ｄｅ）（１
，４）ベンゾオキサジン−６−カルボン酸および１．４
−ジアザビシクロ（４，４，０）デカンを用い、実施例
１と同様の操作で融点２５０℃（分解）の１０− （１
，４−ジアザビシクロ（４，４，０）デカン−４−・ｆ
ル） −９−’フルオロー８−メチル−７−オキソ−４
３−ジヒドロ−７Ｈ−ピリド（１，２，８−ａｅ ）（
１，４）ベンゾオキサジン−６−カルボン酸を得る。Elemental analysis value 028H22FN, calculated value as 04 0
62.01. 11573. N 111.85 Analysis value 062.21. H5,64,NIO,8tl
Example 2 9, IO-difur λ rho 8-methyl-7-oxo=2+
3-dihydro-7H-pyrido(1,2,8-de)(1
, 4) benzoxazine-6-carboxylic acid and 1.4
- Using diazabicyclo(4,4,0)decane, 10-(1
,4-diazabicyclo(4,4,0)decane-4-/f
-9-'fluoro8-methyl-7-oxo-4
3-dihydro-7H-pyrido (1,2,8-ae) (
1,4) Benzoxazine-6-carboxylic acid is obtained.
Claims (1)
は１または２である。）で示される９−フルオロ−７−
オキソ−２，８−ジヒド０−７ Ｈ−ピリド（ｉ、２．
ａ −ａｅ）（１，４）ベンゾオキサジン−６−カルボ
ン酸誘導体およびその塩。[Claims] General formula (wherein R represents hydrogen or a lower alkyl group), n
is 1 or 2. ) 9-fluoro-7-
Oxo-2,8-dihydro 0-7 H-pyrido (i, 2.
a-ae) (1,4)benzoxazine-6-carboxylic acid derivatives and salts thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10918182A JPS58225092A (en) | 1982-06-25 | 1982-06-25 | Pyrido(1,2,3-de)(1,4)benzoxazine-6-carboxylic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10918182A JPS58225092A (en) | 1982-06-25 | 1982-06-25 | Pyrido(1,2,3-de)(1,4)benzoxazine-6-carboxylic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58225092A true JPS58225092A (en) | 1983-12-27 |
| JPH0355477B2 JPH0355477B2 (en) | 1991-08-23 |
Family
ID=14503700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10918182A Granted JPS58225092A (en) | 1982-06-25 | 1982-06-25 | Pyrido(1,2,3-de)(1,4)benzoxazine-6-carboxylic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58225092A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0159174A2 (en) * | 1984-04-16 | 1985-10-23 | Warner-Lambert Company | Substituted naphthyridine-, quinoline- and benzoxazine- carboxylic acids as antibacterial agents and processes for their production |
| WO2009131973A1 (en) * | 2008-04-23 | 2009-10-29 | Janssen Pharmaceutica Nv | Quinolone derivatives useful as antibacterial agents |
| CN109251211A (en) * | 2016-12-21 | 2019-01-22 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | A kind of quinolonecarboxylic acid compound and its intermediate, preparation method and application |
-
1982
- 1982-06-25 JP JP10918182A patent/JPS58225092A/en active Granted
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0159174A2 (en) * | 1984-04-16 | 1985-10-23 | Warner-Lambert Company | Substituted naphthyridine-, quinoline- and benzoxazine- carboxylic acids as antibacterial agents and processes for their production |
| EP0159174B1 (en) * | 1984-04-16 | 1991-10-23 | Warner-Lambert Company | Substituted naphthyridine-, quinoline- and benzoxazine- carboxylic acids as antibacterial agents and processes for their production |
| WO2009131973A1 (en) * | 2008-04-23 | 2009-10-29 | Janssen Pharmaceutica Nv | Quinolone derivatives useful as antibacterial agents |
| CN109251211A (en) * | 2016-12-21 | 2019-01-22 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | A kind of quinolonecarboxylic acid compound and its intermediate, preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0355477B2 (en) | 1991-08-23 |
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