JPH0366698A - Benzo[a]phenazine derivative - Google Patents
Benzo[a]phenazine derivativeInfo
- Publication number
- JPH0366698A JPH0366698A JP1204211A JP20421189A JPH0366698A JP H0366698 A JPH0366698 A JP H0366698A JP 1204211 A JP1204211 A JP 1204211A JP 20421189 A JP20421189 A JP 20421189A JP H0366698 A JPH0366698 A JP H0366698A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- benzo
- formulas
- phenazine 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
Links
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
産業上の利用分野
本発明は抗腫瘍活性を有するベンゾ［ａ］フェナジン誘
導体に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to benzo[a]phenazine derivatives having antitumor activity.
従来の技術
ベンゾ［ａコフエナジン誘導体としては、特開昭６２−
７２号公報に記載の化合物がある。Conventional technology As a benzo[a-coffenazine derivative,
There is a compound described in Publication No. 72.
発明が解決しようとする課題
しかしながら、前記公報記載の化合物は水に溶けにくい
ため、水溶性の向上が望まれていた。Problems to be Solved by the Invention However, since the compounds described in the above publications are difficult to dissolve in water, it has been desired to improve their water solubility.
課題を解決するための手段
本発明者らは、前記課題を解決すべく鋭意努力した結果
、特開昭６２−７２号公報に記載の式で表される化合物
に中性糖を付加した化合物が水溶性に優れていることを
見いだし、本発明を完成した。Means for Solving the Problems As a result of our earnest efforts to solve the above problems, the present inventors have discovered a compound obtained by adding a neutral sugar to the compound represented by the formula described in JP-A-62-72. They discovered that it has excellent water solubility and completed the present invention.
すなわち、本発明は式
で表される基を示す、）で表されるベンゾ［ａ］フェナ
ジン誘導体である。That is, the present invention is a benzo[a]phenazine derivative represented by ), which represents a group represented by the formula.
本発明の化合物は下記反応式により製造することができ
る。The compound of the present invention can be produced by the following reaction formula.
すなわち、式（１）の化合物と式（■）（式中、Ｘはハ
ロゲン原子を示す、）で表される化合物を有機溶媒中、
塩基存在下反応させることにより式（Ｉ［）の化合物に
おいてＲが
Ｈ２
である化合物（Ｎ）を得る。That is, the compound of formula (1) and the compound represented by formula (■) (in the formula, X represents a halogen atom) are mixed in an organic solvent,
By reacting in the presence of a base, a compound (N) of formula (I[) in which R is H2 is obtained.
ここで、有機溶媒としてはＮ、Ｎ−ジメチルホルムアミ
ド、ジメチルスルホキシドなどを用いることができる。Here, N,N-dimethylformamide, dimethyl sulfoxide, etc. can be used as the organic solvent.
また、塩基としては炭酸ナトリウム、炭酸カリウム、ト
リメチルアミン、トリエチルアミン、ピリジン、４−ジ
メチルアミノピリジンなどを用いることができる。ハロ
ゲン原子とは、塩素、臭素、ヨウ素である。Further, as the base, sodium carbonate, potassium carbonate, trimethylamine, triethylamine, pyridine, 4-dimethylaminopyridine, etc. can be used. Halogen atoms are chlorine, bromine, and iodine.
なお、式（Ｉ［［）の化合物はハネシアン（Ｓ 、 Ｈ
ａｎａｓ−ｓｉａｎ）らの方法［カルボヒトレート・リ
サーチ（Ｃａｒｂｏｈｙｄ、 Ｒｅｓ、 ） 、第２４
巻、第４５ページ（１９７２年〉］によって得ることが
できる。In addition, the compound of formula (I [[) is honeysian (S , H
[Carbohydrate Research (Carbohyd, Res.), No. 24]
Vol., p. 45 (1972)].
このようにして得た式（ＩＶ）の化合物は有機溶媒中、
希塩酸などの酸と室温で反応させることにより式（Ｖ）
で表される化合物［式（Ｉ［）の化合物においてＲが
ＣＨ
である化合物］を、希塩酸などの酸と加熱して反応させ
ることにより式（Ｖｌ）で表される化合物［式（ＩＦ）
の化合物においてＲが
である化合物コを得ることができる。The compound of formula (IV) thus obtained was prepared in an organic solvent.
Formula (V) by reacting with an acid such as dilute hydrochloric acid at room temperature.
[In the compound of formula (I[), R is
A compound represented by formula (Vl) [formula (IF)] is reacted with an acid such as dilute hydrochloric acid by heating.
A compound in which R is can be obtained.
ここで、有機溶媒としてはメタノール、エタノールなど
を用いることができる。Here, methanol, ethanol, etc. can be used as the organic solvent.
発明の効果
本発明により強い抗腫瘍活性を有し、しかも水溶性の向
上が計られた化合物を提供することができる。Effects of the Invention According to the present invention, it is possible to provide a compound having strong antitumor activity and improved water solubility.
実施例
実施例１ 式（ＩＶ）の化合物の製造
式（Ｉ）の化合物１．９０ ｇ及び式（Ｉ［［）の化合
物ｌ、７５ｇを１５０−のＮ、Ｎ−ジメチルホルムアミ
ドに溶解し、式（Ｉ）の化合物１．９０ｇ及び粉末炭酸
カリウム１、００ ｇを加え、５０〜６０℃で２４時間
撹拌した。Examples Example 1 Preparation of compound of formula (IV) 1.90 g of compound of formula (I) and 75 g of compound l of formula (I[[) were dissolved in 150-N,N-dimethylformamide, and 1.90 g of compound (I) and 1.00 g of powdered potassium carbonate were added, and the mixture was stirred at 50 to 60°C for 24 hours.
反応液を濾過し、減圧濃縮して得た黒赤色の残渣をシリ
カゲルカラムクロマトグラフィー（溶出液；クロロホル
ム：エタノール−２０： １ ） ニ付し、得られた分
画にｎ−ヘキサンを加えて結晶化、更にクロロホルム−
エタノールより再結晶して黄色の目的物ｌ、１４ｇを得
た。The reaction solution was filtered and concentrated under reduced pressure. The black-red residue obtained was subjected to silica gel column chromatography (eluent: chloroform:ethanol-20:1), and n-hexane was added to the resulting fraction to crystallize it. oxidation, then chloroform-
Recrystallization from ethanol gave 14 g of the yellow target product.
ＩＲ（ＫＢｒ錠） １７４２ｃｍ−’Ｅｌ−ＭＳ
ｍ／ｚ ６７６（Ｍ”）実施例２ 式（Ｖ）の化合
物の製造
実施例１で得た式（ＩＶ）の化合物１．５０ｇに０．３
規定塩酸１５０ｄを加え、室温で９時間撹拌した。次い
でメタノール７５ｍ４！を加えて更に室温で１１時間撹
拌を続けた０反応液を減圧濃縮し、残渣をシリカゲルカ
ラムクロマトグラフィー（溶出液；クロロホルム：メタ
ノール−１：１）に付し、目的物をａｍした。これを更
にエタノールから再結晶し、１．１２ｇを得た。IR (KBr tablet) 1742cm-'El-MS
m/z 676 (M”) Example 2 Production of compound of formula (V) 0.3 to 1.50 g of compound of formula (IV) obtained in Example 1
150 d of normal hydrochloric acid was added, and the mixture was stirred at room temperature for 9 hours. Next, 75m4 of methanol! The reaction mixture was further stirred at room temperature for 11 hours. The reaction solution was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: chloroform:methanol-1:1) to obtain the desired product. This was further recrystallized from ethanol to obtain 1.12 g.
ＩＲ（ＫＢｒ錠） ３４３０ｃ ｍ−’ 、 １７２
０ｃ ｍ−’ＦＡＢ−ＭＳ 、ｍ／ｚ ６３７（
Ｍ”−ａｌ）実施例３ 式（ｌの化合物の製造
実施例１で得た式（ＩＶ）の化合物１．ＱＯｇに０．５
規定塩酸１００ｄを加え、４０°Ｃで１２時間撹拌した
１次いでエタノール４０−を加えて減圧濃縮し、残渣を
シリカゲルカラムクロマトグラフィー（溶出液；クロロ
ホルム：メタノール−
的物を単離した．これを更にメタノールから再結晶し、
０． ６０ ｇを得た。IR (KBr tablet) 3430cm-', 172
0c m-'FAB-MS, m/z 637 (
M”-al) Example 3 Preparation of compound of formula (l) Compound of formula (IV) obtained in Example 1 0.5 to QOg
After adding 100 d of normal hydrochloric acid and stirring at 40°C for 12 hours, 40 ml of ethanol was added and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol). Recrystallized from methanol,
0. 60 g was obtained.
Claims (1)
、表等があります▼ で表される基を示す。）で表されるベンゾ［ａ］フェナ
ジン誘導体。(1) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ Numerical formulas, chemical formulas, tables, etc. A benzo[a]phenazine derivative represented by ▼.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1204211A JPH0366698A (en) | 1989-08-07 | 1989-08-07 | Benzo[a]phenazine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1204211A JPH0366698A (en) | 1989-08-07 | 1989-08-07 | Benzo[a]phenazine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0366698A true JPH0366698A (en) | 1991-03-22 |
Family
ID=16486677
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1204211A Pending JPH0366698A (en) | 1989-08-07 | 1989-08-07 | Benzo[a]phenazine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0366698A (en) |
-
1989
- 1989-08-07 JP JP1204211A patent/JPH0366698A/en active Pending
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