JPS59134720A - Antitumor agent - Google Patents
Antitumor agentInfo
- Publication number
- JPS59134720A JPS59134720A JP813483A JP813483A JPS59134720A JP S59134720 A JPS59134720 A JP S59134720A JP 813483 A JP813483 A JP 813483A JP 813483 A JP813483 A JP 813483A JP S59134720 A JPS59134720 A JP S59134720A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- reaction
- alkyl
- compound
- tropolone
- 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
Landscapes
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は一般式
％式％
で表わされるトロポロノ系化合物またはその金属錯化合
物をイＪ効成分とする抗腫瘍薬に関するものである。な
１９１式中の各記号は次の意味を有する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an antitumor drug containing a tropolono compound represented by the general formula % or a metal complex thereof as an active ingredient. Each symbol in formula 191 has the following meaning.
ＲｌｏＨまたはアルキル基
Ｒコニアルキルまたは複素環基
本発明の化合物は新規のものであり，次の反応式で示さ
れる方法により製造される。RloH or alkyl group R conialkyl or heterocycle The compounds of the invention are novel and can be prepared by the method shown in the following reaction scheme.
すなわら、トロボロノ系化合物，例えば１１−イノプロ
に゛ルトロボロノヒノキチオール）とヘノノフルテヒ］
・レエチルアセクールとの混合物をノリ力ゲルカラムク
ロマＩ・で分離精製すると３−（αー工トキノベルル
（１−Ａ））Ａひα．αービス（６−イノプロビルー２
−）１イドロキノ−３−トロボリル）トルエノ（■）が
得られる。また、１・口ポ四ノと１−工）・キノイノク
ロマンを同様に加臥して反応させると３（＋−イノクロ
マニル）１−ロホロノ（＋−Ｂ）か得うれる。これらの
トロボロノ系化合物は常法によりすトリウム塩。In other words, troborono-based compounds, such as 11-inopro, ``altroboronohinokitiol'' and henonofrutech.
- When the mixture with rhethylacecool was separated and purified using Nori Riki Gel Column Chroma I, 3-(α-processed tokinoberul(1-A))A-α. α-bis(6-inoprovir-2
-) 1-hydroquino-3-troboryl)tolueno (■) is obtained. In addition, if 1.kinochroman and 1.kinochroman are reacted in the same manner, 3(+-inochromanyl)1-roholono(+-B) can be obtained. These troborono compounds are prepared as thorium salts using conventional methods.
または銅錯塩に導くことができる。Or it can lead to copper complex salts.
上記の方法で得られた化合物には強い抗腫瘍作用をもつ
ものがあり、医薬品としての用途が期待される。Some of the compounds obtained by the above method have strong antitumor effects and are expected to be used as pharmaceuticals.
実施例１
３−（１−イノクロマニル）−６−イソプロピルトロポ
ロノ（１−Ｂ−Ｉ Ｈ式中Ｒ’＝イノプロピル基）の製
造１−エトキノイノクロマノ８１５２と４−イソプロピ
ルトロポロ７５ｇをアルゴン気流中−（’ １５０−１
６０℃に８時間加熱溶融する。Example 1 Production of 3-(1-inochromanyl)-6-isopropyltropolono (1-B-IH formula, R' = inopropyl group) 1-ethoquinoinochromano 8152 and 75 g of 4-isopropyltropolono were heated with argon. In airflow - (' 150-1
Heat and melt at 60°C for 8 hours.
反応混合物をノリノＪケルカラトクロマ１−で分離精製
する。ヘノセノ溶出部からり＋１３５−１３８℃の結晶
（１−Ｂ−１）４１３ｇ（４６％）を得る。The reaction mixture was separated and purified using Norino J Kelkarato Chroma 1-. From the henoceno-eluted portion, 413 g (46%) of crystals (1-B-1) were obtained at +135-138°C.
実施例２
３−（ｌ−イノクロマニル）トロボロノ（１−Ｂ−２）
（式１式％）
ｌ−エトキノイソクロマノ２．９ｇとトロボロン１３ｇ
の混合物をアルゴン気流中で１５０ １６０℃に１５時
間加熱溶融する。反応混合物をシリカゲルカラムクロマ
トで分離精製する。石油エーテル−酢酸エチルのＵ合溶
媒俗出部から明＋ Ｉ ７５−１７８℃の結晶（ｌ
Ｂ−２） １．２５ｇ（’ＩＬｉ％）を得る。Example 2 3-(l-inochromanyl)troborono (1-B-2)
(Formula 1 Formula %) 2.9 g of l-ethoquinoisochromano and 13 g of trobolone
The mixture was heated and melted at 150-160°C for 15 hours in an argon stream. The reaction mixture is separated and purified using silica gel column chromatography. Crystals (l
B-2) Obtain 1.25 g ('ILi%).
実施例３
３−（α−工）−キノベノカレ） −〇−（）７０ピル
トロ；Ｉ！’ｌ：＋７（Ｉ−Ａ ）（式中Ｒ’−イノプ
ロピル、Ｒ２−）、ニル、Ｒ′＝エチル基）の！！Ｉ造
ベノソアルテヒドレエチルアセクール５９ノと４−イソ
プロピルトロポロノ４．５ｇの混合物をアルゴン気流中
で１６０−１７０’Ｃに６時間加熱溶融する。反応混合
物をシリカゲルカラムクロマトで分離精製Ｔる。石油エ
ーテル−酢酸エチルの混合溶媒溶出部分より粘調な油状
物（ｂ１１＝１４０°／Ｑ、ＱＱ５＋ｎｍ）Ｉｇ ）
（１−Ａ ） １９（１２％）を得る。Example 3 3-(α-tech)-Kinobenokare) -〇-()70 Pirtro;I! 'l:+7(I-A) (in the formula R'-inopropyl, R2-), nyl, R'=ethyl group)! ! A mixture of 59 grams of benosoaltehyde ethyl acecure and 4.5 g of 4-isopropyl troporono was heated and melted at 160-170'C for 6 hours in an argon stream. The reaction mixture is separated and purified using silica gel column chromatography. Oily substance (b11=140°/Q, QQ5+nm) Ig) which is more viscous than the mixed solvent elution part of petroleum ether-ethyl acetate
(1-A) 19 (12%) is obtained.
実施例４
α、α−ビス（６−イツブロビルー２−ハｒドロキノ’
、＋ トロボリル）トルエン（１１） （式中Ｒ
１−イノプロビル。Ｒ２−フェニル基）の製造
実施例３の方法でノリ力ゲルカラムクロマ１−に、１ル
Ｉ ＡＵ）浴出についで第２の溶出部からｌ１ｌｐ
１９！Ｊ−２００℃の結晶（Ｉ＋＋３１（ｄ’（２８％
）を得る。Example 4 α,α-bis(6-itubroby-2-halodoquino'
, + troboryl) toluene (11) (in the formula R
1-Inoprovir. Preparation of R2-phenyl group) Using the method of Example 3, apply 1lIp to Noriyoku Gel Column Chroma 1- from the second elution part after bathing 1lIAU).
19! J-200℃ crystal (I++31(d'(28%
).
実施例５
：１−（１−イノクロマニル）−６−イソプロピルトロ
ポロノｕ、］ｘｉａ、、ｔ （Ｉ Ｂ−−ｌ Ｃｏ
） （式中Ｒ１−イノフロビルイ（）の製造実施例１
の方法て得ｊ、：Ｉ’−Ｂ−１の１９と酢酸銅Ｏδ９を
メタノール５＋、＋ｍｔとり１フＩ：Ｉ ；ｌ−ルｌ−
１−５（Ｉにとかし室温で２時間攪拌する１１反応？昆
合物をクロロホルム・で抽出する。クロロホルム層を分
Ｉｌｌ！ ｌ、 、水洗１１：・２燥移躬媒を濃縮する
とＩｌ中２９０°２上の緑色結晶（ＩＢＭ−Ｃｏ２１ｇ
（８３％）を得る。Example 5: 1-(1-inochromanyl)-6-isopropyltropolonu,]xia,,t (I B--l Co
) (Preparation Example 1 of R1-Inofrovir()
19 of I'-B-1 and copper acetate Oδ9 were obtained by the method of
1-5 (Dissolved in I and stirred at room temperature for 2 hours. 11 reaction? Extract the mixture with chloroform. The chloroform layer was washed with water. Green crystals on °2 (IBM-Co21g
(83%).
抗腫瘍試験
ＫＢ−細胞増りｌ′１抑制試験
Ｋ Ｒ細胞をＥａｇ１６＋ｔ ｍｉｎｉｍ、１１ ｅｓ
ｓｅｎｔｉａｌ ｒｎｅｔｌｉｕｍ （ＭＥＭ）−１（
）％（：ａｌｆ 式１１培地に入れ、５％炭酸カス培養
器中３７°Ｃ’（”；’Ｓ （ｊしたものを用いて実施
した。初日にはＫＢ細胞を２×］０“７ｍ１個を含むよ
うに花ＩＮシ、その３ＩＩＩＬを６０咽の時３１皿に植
える。Antitumor test KB-cell increase l'1 suppression test K R cells Eag16+t minimum, 11 es
sential rnetium (MEM)-1 (
)% (:alf) Placed in Formula 11 medium at 37°C in a 5% carbon dioxide incubator. Plant the 3IIIL in 31 plates at the age of 60 so that it contains flowers.
第２１−Ｊ目に試験薬物をそれぞれ１００．３０．１０
． ：３． ］ ｔｔｇ／ｌＩｌになるように加えて同
様をこ１ご浴する。第１１日日に生存した細胞を時Ｓ（
皿面、Ｌリドリフ、）を用いてはずし、細胞数を計測す
る。このとき、 １′１１１＋血敬か薬物を加えなかっ
た方のコノトロールに比して実ｆ７ｊｆｉ（１’、。の
増列°１抑制をｌＪ＜すのに必要とした薬物の霞度（Ｅ
Ｄｓｏ）を求め、その薬物の癌細胞増殖抑制効果として
表現した。その結果を表１に示した。。100.30.10 respectively on the 21st-J day of the test drug.
．． :3. ] Add so that the ratio is ttg/lIl and bathe in the same manner. Cells that survived on the 11th day were collected at S (
Remove using a plate (L-lidrif) and count the number of cells. At this time, the degree of drug haze (E
Dso) was determined and expressed as the cancer cell proliferation inhibitory effect of the drug. The results are shown in Table 1. .
担がんマウスの延命効果試験
ＣＤＦマウスの６匹を１グループとしてＰ：３８８腫瘍
の細胞１０６個を各マウスに移植したのち、第１日、第
５日日に試験薬物をマウスの腹腔内に投与する。延命効
果の判定は無処理ＩＩＴの生存日数に対する投与ＢＹの
生存日数の比（７７６％）で表示した。Life extension effect test on tumor-bearing mice After 106 cells of P:388 tumor were transplanted into each group of 6 CDF mice, the test drug was intraperitoneally administered to the mice on the 1st and 5th day. Administer. The survival effect was evaluated as the ratio (776%) of the survival days of administered BY to the survival days of untreated IIT.
その結果を表Ｉに示した。The results are shown in Table I.
Claims (1)
ール（旧３＝ｌ）、 アルアルキル（ ａｒａｌｋ．
１＋ｌ ） 、 ｇたはｍＶＬ：環ノ，（を、Ｒ１は
アルキルまたは複素環基で表わされる１−ロボロノ系化
合物．またはその金属錯化合物を（−＋効成分とする抗
ＩＩΦ瘍薬。）[Claims] General formula % formula % (wherein R' is H or an alkyl group, R2 is alkylyl (formerly 3=l), aralkyl (aralk.
1+l), g or mVL: a 1-loborono compound in which R1 is an alkyl or a heterocyclic group, or a metal complex thereof (-+ an anti-IIΦ tumor drug as an active ingredient).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP813483A JPS59134720A (en) | 1983-01-20 | 1983-01-20 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP813483A JPS59134720A (en) | 1983-01-20 | 1983-01-20 | Antitumor agent |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18108783A Division JPS59134744A (en) | 1983-09-28 | 1983-09-28 | Tropolone derivative having antitumor action |
| JP58181088A Division JPS59134745A (en) | 1983-09-28 | 1983-09-28 | Tropolone derivative having antitumor action |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59134720A true JPS59134720A (en) | 1984-08-02 |
| JPH0414089B2 JPH0414089B2 (en) | 1992-03-11 |
Family
ID=11684813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP813483A Granted JPS59134720A (en) | 1983-01-20 | 1983-01-20 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59134720A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015526396A (en) * | 2012-06-22 | 2015-09-10 | ユニバーシティ オブ コネチカット | Substituted tropolone derivatives and methods of use thereof |
-
1983
- 1983-01-20 JP JP813483A patent/JPS59134720A/en active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015526396A (en) * | 2012-06-22 | 2015-09-10 | ユニバーシティ オブ コネチカット | Substituted tropolone derivatives and methods of use thereof |
| US9790158B2 (en) | 2012-06-22 | 2017-10-17 | University Of Connecticut | Substituted tropolone derivatives and methods of use |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0414089B2 (en) | 1992-03-11 |
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