JPS6251693A - 2-octyl-1,3-diaminopropane platinum (ii) dichloride - Google Patents
2-octyl-1,3-diaminopropane platinum (ii) dichlorideInfo
- Publication number
- JPS6251693A JPS6251693A JP60192286A JP19228685A JPS6251693A JP S6251693 A JPS6251693 A JP S6251693A JP 60192286 A JP60192286 A JP 60192286A JP 19228685 A JP19228685 A JP 19228685A JP S6251693 A JPS6251693 A JP S6251693A
- Authority
- JP
- Japan
- Prior art keywords
- octyl
- diaminopropane
- dichloride
- present
- platinum
- 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
- BNLHAYMIQIHBAV-UHFFFAOYSA-L [Pt](Cl)Cl.C(CCCCCCC)C(CN)CN Chemical compound [Pt](Cl)Cl.C(CCCCCCC)C(CN)CN BNLHAYMIQIHBAV-UHFFFAOYSA-L 0.000 title 1
- -1 Dichloro 2-octyl-1,3-diaminopropane platinum(II) Chemical compound 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 7
- VLRSCPPUDNIINJ-UHFFFAOYSA-N 2-octylpropane-1,3-diamine;hydrochloride Chemical compound Cl.CCCCCCCCC(CN)CN VLRSCPPUDNIINJ-UHFFFAOYSA-N 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 229910020427 K2PtCl4 Inorganic materials 0.000 abstract 1
- 230000003327 cancerostatic effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- CLSUSRZJUQMOHH-UHFFFAOYSA-L platinum dichloride Chemical compound Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 10
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 5
- 229960004316 cisplatin Drugs 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 231100000956 nontoxicity Toxicity 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、ジクロロ ２−オクチル−１，３−ジアミノ
プロパン白金印）に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to dichloro 2-octyl-1,3-diaminopropane (platinum stamp).
これまで金属錯体について多くの研究がなされ、その制
癌作用や抗腫瘍作用についての報告があるが、これらの
金属錯体は制癌作用や抗腫瘍性を有していても毒性が高
いという欠点があった。A lot of research has been done on metal complexes, and there are reports on their anticancer and antitumor effects, but even though these metal complexes have anticancer and antitumor effects, they have the drawback of being highly toxic. there were.
本発明者らは、金属錯体で制癌作用を有し、毒性が少な
い化合物を開発するために鋭意研究を重ねた結果、１，
３−ジアミノプロパンの２位にオクチル基を持つ配位子
と錯形成した白金錯体がその目的に適合し得ることを見
いだし、この知見に基づいて本発明を完成した。The present inventors have conducted intensive research to develop a metal complex with anticancer effect and low toxicity, and have found 1.
It has been discovered that a platinum complex formed with a ligand having an octyl group at the 2-position of 3-diaminopropane is suitable for this purpose, and based on this knowledge, the present invention has been completed.
すなわち、本発明は、下記の化学構造式で表わされるジ
クロロ ２−オクチル−１，３−ジアミノプロパン白金
（ＩＩ）を提供するものである。That is, the present invention provides dichloro 2-octyl-1,3-diaminopropane platinum (II) represented by the following chemical structural formula.
本発明の化合物は、公知の手法によシたとえば次に示す
方法によって合成することができる。The compound of the present invention can be synthesized by a known method, for example, by the method shown below.
すなわち、２−オクチル−１，３−ジアミノプロパン塩
酸塩を少量の水に溶かし、−を１０〜１１に調整し、こ
れにに２ｐｔｃｚ４を少量の水に溶かしたものを加え、
室温で２〜４時間攪拌して反応させることによシ本発明
の化合物を容易に得ることができる。That is, 2-octyl-1,3-diaminopropane hydrochloride is dissolved in a small amount of water, - is adjusted to 10 to 11, and 2ptcz4 dissolved in a small amount of water is added to this.
The compound of the present invention can be easily obtained by stirring and reacting at room temperature for 2 to 4 hours.
本発明の化合物は癌細胞を移植したマウスに投与した場
合、制癌活性を有し、しかも毒性がほとんどない制癌剤
として使用することができる。When the compound of the present invention is administered to mice transplanted with cancer cells, it has anticancer activity and can be used as an anticancer agent with almost no toxicity.
以下、実施例および試験例を挙げて本発明を具体的に説
明する。The present invention will be specifically described below with reference to Examples and Test Examples.
実施例
０．１２の２−オクチル−１，３−ジアミノプロパン塩
酸塩を少量の水に溶かし、これに１ＮのＫＯＨを加えて
声を１０〜１１に調整した。この溶液に、少量の水に溶
かした０、１ｆのに２ＰｔＣ１４を加え、室温で３時間
攪拌させ、生成した沈殿を吸引濾過し、水、メタノール
で順次よく洗った後減圧乾燥し、メタノールにより再結
晶を行ない、０．０７７２のジクロロ ２−オクチル−
１，３−ジアミノプロパン白金（ｎ）を得た。この化合
物は黄色の光沢を持った結晶であるが、融点測定のため
加熱すると分解して黒変した。2-octyl-1,3-diaminopropane hydrochloride of Example 0.12 was dissolved in a small amount of water, and 1N KOH was added thereto to adjust the voice to 10-11. 2PtC14 dissolved in a small amount of water was added to this solution, stirred at room temperature for 3 hours, and the resulting precipitate was suction filtered, washed thoroughly with water and methanol, dried under reduced pressure, and reconstituted with methanol. Perform crystallization to obtain 0.0772 dichloro 2-octyl-
1,3-diaminopropane platinum (n) was obtained. This compound was a shiny yellow crystal, but when heated to measure its melting point, it decomposed and turned black.
元素分析値（（！ｕＨｚｓＮ２ｃ４ Ｐｔとして）計算
値（％） Ｃ：２９２１ Ｈ：５．７９ Ｎ：６
Ａ９実測値（％） Ｃ：２９．５０ Ｈ：５．６６
Ｎ：６．０７ＩＲ（ＫＢｒ） ： ３２４９．３２０
６．３［４（νＮＨ）；１５８８（δＮＨ）。Elemental analysis value ((! uHzsN2c4 Pt) Calculated value (%) C: 2921 H: 5.79 N: 6
A9 actual value (%) C: 29.50 H: 5.66
N: 6.07IR (KBr): 3249.320
6.3[4(νNH); 1588(δNH).
５７９、５２５（νＮＭ） ；１０８ｃＦｎ’（ｖＭｃ
ｌ）試験例
ＣＤＦ Ｉ系雄マウス（６週齢９体重１６〜２０１）の
腹腔内にＰ６８８白血病細胞を移植したもの８匹を一群
とし、試験に供した。579, 525 (νNM); 108cFn' (vMc
l) Test Example A group of 8 CDF I male mice (6 weeks old, 9 weight, 16-201 kg) with P688 leukemia cells transplanted intraperitoneally was subjected to the test.
本発明の化合物、対照薬シスプラチン各３．１５■／Ｋ
ｇをそれぞれ１日１回、５日間別個の群の被験動物に腹
腔内投与し、その生存日数を被験薬を投与しない他群の
被験動物のそれと比較した結果、Ｔ／Ｃ％は、本発明の
化合物が１３０、対照薬シスプラチンが２９７であった
。Compound of the present invention, control drug cisplatin, each 3.15■/K
g was intraperitoneally administered to test animals in separate groups once a day for 5 days, and the survival days were compared with those of test animals in other groups to which the test drug was not administered. The number was 130 for this compound, and 297 for the control drug cisplatin.
また、毒性の指標として体重の変化を、被験薬投与群と
コントロール群（被験薬不投与群）について測定した。In addition, changes in body weight were measured as an indicator of toxicity in the test drug administration group and the control group (test drug non-administration group).
その結果を第１図に示す。The results are shown in FIG.
図においてＡは本発明の化合物投与群のカーブを、Ｂは
対照薬シスプラチン投与群のカーブを、Ｃはコントロー
ル群のカーブを示す。In the figure, A shows the curve of the compound administration group of the present invention, B shows the curve of the control drug cisplatin administration group, and C shows the curve of the control group.
これらのカーブを比較検討すると、シスプラチンは活性
が高いが毒性も著しく強いのに対し、本発明の化合物は
活性を有していてしかも毒性がほとんどないことがわか
る。A comparative study of these curves shows that cisplatin has high activity but is also extremely toxic, whereas the compound of the present invention has activity but almost no toxicity.
第１図は、本発明の化合物、対照薬シスプラチンをそれ
ぞれ別個の群の被験動物に投与した際の被験動物の体重
の変化を示す図面である。
図においてＡは本発明の化合物投与群のカーブを、Ｂは
対照薬ンスプラテン投与群のカーブを、Ｃはコントロー
ル群（被験薬不投与群）のカーブを表わす。
特許出願人 白 井 江 芳
特許出願人 大正製薬株式会社
代理人 弁理士 北 川 富 造笛１図
（日）FIG. 1 is a diagram showing changes in the body weight of test animals when the compound of the present invention and the control drug cisplatin were administered to separate groups of test animals. In the figure, A represents the curve of the group administered with the compound of the present invention, B represents the curve of the group administered with the control drug Nplaten, and C represents the curve of the control group (group not administered the test drug). Patent applicant Eho Shirai Patent applicant Taisho Pharmaceutical Co., Ltd. Agent Patent attorney Tomi Kitagawa Fue making diagram 1 (Japanese)
Claims (1)
ン白金（II）1) Dichloro 2-octyl-1,3-diaminopropane platinum(II)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60192286A JPS6251693A (en) | 1985-08-30 | 1985-08-30 | 2-octyl-1,3-diaminopropane platinum (ii) dichloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60192286A JPS6251693A (en) | 1985-08-30 | 1985-08-30 | 2-octyl-1,3-diaminopropane platinum (ii) dichloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6251693A true JPS6251693A (en) | 1987-03-06 |
Family
ID=16288750
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60192286A Pending JPS6251693A (en) | 1985-08-30 | 1985-08-30 | 2-octyl-1,3-diaminopropane platinum (ii) dichloride |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6251693A (en) |
-
1985
- 1985-08-30 JP JP60192286A patent/JPS6251693A/en active Pending
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