JPS63258890A - Platinum urea complex - Google Patents
Platinum urea complexInfo
- Publication number
- JPS63258890A JPS63258890A JP9402487A JP9402487A JPS63258890A JP S63258890 A JPS63258890 A JP S63258890A JP 9402487 A JP9402487 A JP 9402487A JP 9402487 A JP9402487 A JP 9402487A JP S63258890 A JPS63258890 A JP S63258890A
- Authority
- JP
- Japan
- Prior art keywords
- platinum
- diamine
- nitrate
- equivalent
- added
- 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
- AUNXTZJFRGHQSC-UHFFFAOYSA-N platinum;urea Chemical compound [Pt].NC(N)=O AUNXTZJFRGHQSC-UHFFFAOYSA-N 0.000 title 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000003973 alkyl amines Chemical class 0.000 claims abstract description 8
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 8
- 150000004985 diamines Chemical class 0.000 claims abstract description 7
- 150000001450 anions Chemical class 0.000 claims abstract description 6
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000004982 aromatic amines Chemical group 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 12
- 239000007864 aqueous solution Substances 0.000 abstract description 7
- 125000002947 alkylene group Chemical group 0.000 abstract description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 231100000417 nephrotoxicity Toxicity 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 2
- NWAHZABTSDUXMJ-UHFFFAOYSA-N platinum(2+);dinitrate Chemical compound [Pt+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O NWAHZABTSDUXMJ-UHFFFAOYSA-N 0.000 abstract description 2
- 229910001961 silver nitrate Inorganic materials 0.000 abstract description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000013049 sediment Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000013076 target substance Substances 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 239000004202 carbamide Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- -1 diamine platinum (II) derivative Chemical class 0.000 description 3
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- VYIWZEHRTLSWFL-UHFFFAOYSA-N [Pt+2].NCC1NCCC1 Chemical compound [Pt+2].NCC1NCCC1 VYIWZEHRTLSWFL-UHFFFAOYSA-N 0.000 description 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- POQBJIOLWPDPJE-UHFFFAOYSA-N cyclohexane-1,2-diamine;platinum Chemical compound [Pt].NC1CCCCC1N POQBJIOLWPDPJE-UHFFFAOYSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 150000003058 platinum compounds Chemical class 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 1
- 229910000367 silver sulfate Inorganic materials 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔発明の目的〕
本発明は、抗腫瘍作用を有する新規な白金環状ウレア錯
体に関する。DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] The present invention relates to a novel platinum cyclic urea complex having antitumor activity.
従来より、種々の白金化合物が抗腫瘍作用を有すること
が知られており、たとえばシスプラチン（Ｂ、 Ｒｏｓ
ｅｎｂｅｒｇ ａｔ ａｌ、 Ｎａｔｕｒｅ ２２２ｓ
３８５．１９６５）マタハマロナー） （１，２−ジ
アミノシクロヘキサン）白金（■）（特開昭５３−３１
６４８）などが報告されている。しかしこれら白金錯体
の多くは、腎臓毒性が強く、水に対する溶解度が低い為
、製剤が困難である。It has been known that various platinum compounds have antitumor effects, such as cisplatin (B, Ros
enberg at al, Nature 222s
385.1965) Matahamaroner) (1,2-diaminocyclohexane) platinum (■) (JP-A-53-31
648) etc. have been reported. However, many of these platinum complexes have strong renal toxicity and low solubility in water, making it difficult to formulate them.
本発明者等はジアンミン又はジアミン白金（ＩＩ）誘導
体と環状アルキレンウレアとの反応によって生成する白
金錯体が、腎臓毒性、骨髄抑制等の副作用が著しく低く
、水に対する溶解度が非常に高い抗腫瘍剤であることを
見い出し、本発明を完成するに至った・
〔発明の構成〕
本発明は、式
Ｈ
〔式中、人は炭素数２から５の直鎖または分枝鎖アルキ
レンを示し、点線は０〜０間またはＣ〜Ｎ間の一方が二
重結合であることを示し、Ｘｏは陰イオンを示し、ｎは
１又は、２を示し、Ｂ及びＤは同−又は異なるＮＨ，、
−級アルキルアミン、二級アルキルアミン、芳香族アミ
ンを示すか又はＢ、Ｄが一緒になってジアミンを示す。The present inventors have discovered that the platinum complex produced by the reaction of diamine or diamine platinum (II) derivative with cyclic alkylene urea is an antitumor agent with extremely low side effects such as renal toxicity and bone marrow suppression, and with extremely high solubility in water. [Structure of the Invention] The present invention is based on the formula Indicates that one between ~0 or between C and N is a double bond, Xo represents an anion, n represents 1 or 2, B and D are the same or different NH,
It represents a -class alkylamine, a secondary alkylamine, an aromatic amine, or B and D together represent a diamine.
〕を有する４配位２価の白金環状ウレア錯体である。] is a four-coordinated divalent platinum cyclic urea complex.
上記式中、Ａの炭素数２から５の直鎖または分枝鎖アル
キレンは、たとえば−（ＣＨ２）２− ＋−ＣＨ（ＣＨ
，）ＣＨ２−、−ＣＨ（ＣＨ３）ＣＨ（ＣＨ３）−、−
（ＣＨ２）３− 。In the above formula, the linear or branched alkylene having 2 to 5 carbon atoms in A is, for example, -(CH2)2- +-CH(CH
,)CH2-,-CH(CH3)CH(CH3)-,-
(CH2)3-.
−ＣＨ（ＣＨ３）ＣＨ２ＣＨ２−、−ＣＨ２ＣＨ（Ｃ）
（３）ＣＨ２−。-CH(CH3)CH2CH2-, -CH2CH(C)
(3) CH2-.
−ＣＨ（ＣＨ３）ＣＨ（ＣＨ，）ＣＨ２−、−ｃａ（Ｃ
Ｈ３）ｃａ２ｃａ（ｃａ３）−。-CH(CH3)CH(CH,)CH2-, -ca(C
H3) ca2ca(ca3)-.
−（ＣＨ２）４−１または−ＣＨ（ＣＨ３）ＣＨ２ＣＨ
２ＣＨ２−があげられる。好適には−（ＣＨ２）２−ま
たは−（ＣＨ２）３−である。-(CH2)4-1 or -CH(CH3)CH2CH
2CH2- is mentioned. Preferably it is -(CH2)2- or -(CH2)3-.
上記式中、Ｘの陰イオンとしては、たとえば硝酸イオン
、過塩素酸イオン、硫酸イオンまたは炭酸イオンであシ
、好適には硝酸または硫酸イオンである。In the above formula, the anion of X is, for example, nitrate ion, perchlorate ion, sulfate ion or carbonate ion, preferably nitric acid or sulfate ion.
Ｘが一価の陰イオンである場合はｎは２でありＸが二価
の陰イオンの場合はｎは１である。When X is a monovalent anion, n is 2, and when X is a divalent anion, n is 1.
上記式中、Ｂ及びＤの一級アルキルアミンは、たとえば
ＣＨ３ＮＨ２，Ｃ２Ｈ３ＮＨ２，Ｃ３Ｈ，ＮＨ２，ｉｓ
ｏ −Ｃ３Ｈ，ＮＨ７，Ｃ４Ｈ７ＮＨ２，ｓｅｅ−ＣＨ
２ＣＨ２またＶｉｔｅｒｔ−Ｃ４Ｈ２ＮＨ２があげられ
る。In the above formula, the primary alkylamines of B and D are, for example, CH3NH2, C2H3NH2, C3H, NH2, is
o -C3H,NH7,C4H7NH2,see-CH
2CH2 and Vitert-C4H2NH2 are mentioned.
Ｂ及びＤの二級アルキルアミンは、たとえば（ＣＨ３）
２ＮＨ、（０２Ｈ５）２ＮＨ、（Ｃ３Ｈ，）２ＮＨまた
は（１ｓｏ−好適なりおよびＤは、Ｃ２Ｈ３ＮＨ２＋
１ｓｏ−Ｃ３Ｈ，ＮＨ２＊になってジアミンである。The secondary alkylamines of B and D are, for example, (CH3)
2NH, (02H5)2NH, (C3H,)2NH or (1so-preferred and D is C2H3NH2+
It becomes 1so-C3H, NH2* and is a diamine.
本発明の錯体は次式に従って合成される。The complex of the present invention is synthesized according to the following formula.
式（２）において、ＹおよびＹ′は同一または異なって
、Ｈ２Ｏ、硝酸イオン、水酸イオン、過塩素酸イオンま
たはＹとＹ′が一緒になって硫酸イオンもしくは炭酸イ
オンであり、好適にはＨ２Ｏ、硝酸イオン、水酸イオン
またＦｉＹとＹ′が一緒になって硫酸イオンである。In formula (2), Y and Y' are the same or different and are H2O, nitrate ion, hydroxide ion, perchlorate ion, or Y and Y' together are sulfate ion or carbonate ion, preferably H2O, nitrate ion, hydroxide ion, and FiY and Y' together form sulfate ion.
式（２）においてＢ、Ｄ、Ｘ およびｎは前述したも
のと同意義である。In formula (2), B, D, X and n have the same meanings as described above.
式（３）においてＡは前述したものと同意義を示す。In formula (3), A has the same meaning as described above.
本発明の化合物は、たとえば次のような方法で合成され
る。The compound of the present invention is synthesized, for example, by the following method.
（４）法
ａｉｍ−ジクロロ−ジアミン白金（ＩＩ）と２当量の硝
酸銀または１当量の硫酸銀を反応させ、生成したｅｌｇ
−ジアコージアミン白金（Ｉｌｌの硝酸塩または硫酸塩
（２）の水溶液に環状アルキレンウレアを１当量ないし
％当量加え、必要に応じて１規定カセイソーダを加えｐ
）１７に調節する。この溶液を０°〜１００℃で１時間
〜４０日間、好適には室温〜６０℃で１０時間〜４０日
間攪拌する。反応液を必要に応じて濃縮した後、有機溶
媒、たとえばメタノール、エタノール、イソプロノ母ノ
ールまたはエーテルを加え析出した沈殿をＦ取すること
により目的化合物（１）が得られる。ここに得られ次沈
殿は必要に応じてダイヤイオンＣＨＰ−２０Ｐ 、セフ
ァデックスまたはイオン交換樹脂などを用いて精製する
ことができる。(4) elg produced by reacting aim-dichloro-diamine platinum (II) with 2 equivalents of silver nitrate or 1 equivalent of silver sulfate
- Add 1 equivalent to % equivalent of cyclic alkylene urea to an aqueous solution of diacodiamine platinum (II) nitrate or sulfate (2), add 1N caustic soda if necessary, and p
) Adjust to 17. The solution is stirred at 0° to 100°C for 1 hour to 40 days, preferably at room temperature to 60°C for 10 hours to 40 days. After concentrating the reaction solution as necessary, an organic solvent such as methanol, ethanol, isopronopronol, or ether is added, and the precipitate is collected by F to obtain the target compound (1). The precipitate obtained here can be purified using Diaion CHP-20P, Sephadex, ion exchange resin, etc., if necessary.
（Ｂｌ法
（Ａｌ法により得られたｃｉｓ−ジアコージアミン白金
（Ｉ［）の硝酸塩又は硫酸塩（２）の水溶液より減圧下
水を留去するとｃｉｍ−シナイトレート（ジアミン）白
金（ＩＩ）又はｅｉｓ−サルフェート（ジアミン）白金
（ＩＩ）が得られる。このものの水懸濁液に環状アルキ
レンウレア０．５肖量ないし１当量及びカセイソーダ１
当竜を加え、（Ｎ法と同様に反応処理すると目的化合物
が得られる。(By distilling water under reduced pressure from an aqueous solution of nitrate or sulfate (2) of cis-diacordiamine platinum (I[) obtained by the Bl method (Al method), cim-cinitrate (diamine) platinum (II) or Eis-sulfate (diamine) platinum(II) is obtained, which is suspended in water with 0.5 parts to 1 equivalent of cyclic alkylene urea and 1 part of caustic soda.
The target compound is obtained by adding the compound and carrying out the reaction in the same manner as in the N method.
（Ｃ）法
（Ａｌ法により得られたｃｉｇ−ジアコージアミン白金
（ＩＩ）の硝酸塩又は硫酸塩（２）の水溶液に１当量の
カセイソーダを加え、室温で１時間ないし１４時間攪拌
したのち、減圧下水を留去するとビス（ハイドロキソー
ａｉｍ −（ジアミン）白金（■））の硝酸塩捷たは硫
酸塩が得られる。このものの水溶液に環状アルキレンウ
レア０．５乃至１当量を加え、室温〜５０℃で１日〜４
０日間攪拌反応ののち（Ａ）法と同様に処理し、目的化
合物を得ることが出来る。1 equivalent of caustic soda was added to an aqueous solution of the nitrate or sulfate (2) of cig-diacordiamine platinum (II) obtained by method (C) (Al method), and after stirring at room temperature for 1 to 14 hours, the pressure was reduced. When the sewage is distilled off, the nitrate or sulfate of bis(hydroxo aim -(diamine)platinum (■)) is obtained.To an aqueous solution of this, 0.5 to 1 equivalent of cyclic alkylene urea is added, and the mixture is heated from room temperature to 50°C. 1 to 4 days
After stirring the reaction for 0 days, the desired compound can be obtained by treatment in the same manner as in method (A).
本発明によりて得られる化合物は、マウス白血病Ｌ１２
１０に対し、シスプラチンと同等以上の抗腫瘍作用を有
し、しかもシスプラチン耐性のマウス白血病Ｌ１２１０
に対しても十分有効である。箇た腎臓電性、骨髄抑制な
どの副作用は弱く、極めて水溶性が高い念め、投与が容
易である。The compound obtained according to the present invention can be used for murine leukemia L12.
Mouse leukemia L1210, which has an antitumor effect equal to or higher than that of cisplatin against 10, and is resistant to cisplatin.
It is also sufficiently effective for It has weak side effects such as increased renal electrification and bone marrow suppression, and is easy to administer because it is extremely water-soluble.
本発明に係る白金錯体を制癌剤として投与するに当って
は、通常非経口的に例えば注射剤として適用させる。そ
の投与量は年令・病状等によっても異なるが、通常成人
１日８１０ダ乃至数Ｉを数回に分けて投与する。When administering the platinum complex according to the present invention as an anticancer agent, it is usually administered parenterally, for example, as an injection. The dosage varies depending on age, medical condition, etc., but is usually 810 Da to several I a day for adults, divided into several doses.
次に実施例をあげて本発明を更に具体的に説明するが、
本発明はこれによって限定されるものではない。Next, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited thereby.
実施例１
エチレンジアミン白金（ＩＩ）シナイトレート（３７９
■）の水懸濁液にＩＮ−水酸化ナトリウム水溶液１ｄを
加え１時間室温で攪拌する。Example 1 Ethylenediamineplatinum(II) cinitrate (379
Add 1 d of IN-sodium hydroxide aqueous solution to the aqueous suspension of (2) and stir at room temperature for 1 hour.
エチレンウレア（６０＃）を加え１０日間２８℃で攪拌
する。反応液の不溶物を戸去し、減圧下水を留去する。Add ethylene urea (60#) and stir at 28°C for 10 days. Insoluble matter in the reaction solution was removed, and water was distilled off under reduced pressure.
残留物を少量の水にとかし、ダイヤイオンＣＨＰ ２０
−Ｐ （約Ｚｏｏ扉／）カラムにかけ水で溶出、目的物
質を含む画分を凍結乾燥すると無色粉末の目的物１２０
■が得られた。Dissolve the residue in a small amount of water and add Diaion CHP 20.
-P (approximately Zoo door/) column, elute with water, freeze-dry the fraction containing the target substance, and the target substance 120 becomes a colorless powder.
■ was obtained.
ＮＭＲスペクトル（２７０ＭＨｚ −Ｄ２０ ）δｐｐ
ｌ：２．２−２．７（８Ｈ，ｍ）、３．２０（２Ｈ，ｔ
、Ｊ＝７．７Ｈｚ）、３．７７（２Ｈ、ｔ 、 Ｊ＝７
．７Ｈｚ ） 。NMR spectrum (270MHz-D20) δpp
l: 2.2-2.7 (8H, m), 3.20 (2H, t
, J=7.7Hz), 3.77(2H,t, J=7
．． 7Hz).
実施例２
２−アミノメチルピロリジン白金（ＩＩ）ジナイトレで
４日間攪拌する。反応液中の不溶物を戸去し、Ｆ液にエ
チレンウレア（１００■）を加え１力月間２８℃に放置
する。反応液中の不溶物を戸去しＦ液を減圧下濃縮する
。残留物をダイヤイオンＣＨＰ−２０Ｐカラムにかけ、
水で溶出し、目的物質を含む画分を凍結乾燥すると無色
粉末の目的物９１■が得られた。Example 2 Stir with 2-aminomethylpyrrolidine platinum(II) dinitre for 4 days. Insoluble materials in the reaction solution were removed, and ethylene urea (100 μl) was added to solution F, which was then left at 28° C. for one month. Insoluble matter in the reaction solution was removed, and Solution F was concentrated under reduced pressure. The residue was applied to a Diaion CHP-20P column,
Elution with water and lyophilization of the fraction containing the target substance yielded the target substance 91■ as a colorless powder.
ＮＭＲ（２７０ＭＨｚ −Ｄ２０ ）δ工：１．３〜２
．２ （８Ｈ，ｍ） 、 ２．２〜３．５（ＩＯＨ，ｍ
） 、 ３．７〜３．８５’（２Ｈ，ｍ）、３．９〜４
．１５（２Ｈ，ｍ）。NMR (270MHz-D20) delta: 1.3-2
．． 2 (8H, m), 2.2-3.5 (IOH, m
), 3.7-3.85' (2H, m), 3.9-4
．． 15 (2H, m).
実施例３
２−アミノメチルピリジン白金（ＩＩ）ジナイトレー）
（３００ダ）の水懸濁液にＩＮ−水酸化す） ＩＪウム
水溶液０．７ｄを加え２８℃で一夜攪拌する。Example 3 2-aminomethylpyridine platinum(II) dinitrate)
Add 0.7 d of an aqueous solution of IN-hydroxide (IN-hydroxide) to an aqueous suspension of (300 da) and stir at 28°C overnight.
反応液にエチレンウレア（４２η）を加え２８℃に１力
月放置する。反応液中の不溶物を戸去し、Ｆ液を減圧下
濃縮する。残留物をダイヤイオンＣＨＰ−２０Ｐカラム
にかけ、水で溶出し、目的物質を含む両分を凍結乾燥す
ると無色粉末の目的物３３■が得られた。Ethylene urea (42η) was added to the reaction solution and left at 28°C for 1 month. Insoluble matter in the reaction solution was removed, and Solution F was concentrated under reduced pressure. The residue was applied to a Diaion CHP-20P column, eluted with water, and both fractions containing the target substance were lyophilized to obtain the target substance 33.1 as a colorless powder.
ＮＭＲ（２７０■（ｚ 、Ｄ ２０ ）δｐｐＩ：３．
２７（２Ｈ，Ｌ 、 Ｊ＝７．２Ｈｚ） 、 ３．８９
（２Ｈ，ｔ 、 Ｊ ＝７．２Ｈｚ） 。NMR (270■(z,D20)δppI:3.
27 (2H, L, J=7.2Hz), 3.89
(2H, t, J = 7.2Hz).
４．００（２Ｈ，ｄ、Ｊ＝１８Ｈｚ）、４．１０（２Ｈ
，ｄ、Ｊ ＝１８ｆ（ｚ）。4.00 (2H, d, J=18Hz), 4.10 (2H
, d, J = 18f(z).
７．３３（２Ｈ，ｔ、Ｊ ＝６Ｈｚ）、７．４３（２Ｈ
，ｄ、Ｊ ＝７．２Ｈｚ）。7.33 (2H, t, J = 6Hz), 7.43 (2H
, d, J = 7.2Hz).
７．９２（２Ｈ，ｄ、ｔ Ｊ＝６．７．２Ｈｚ）、８．
０１（２Ｈ，ｄ、Ｊ＝６Ｈｚ）。7.92 (2H, d, t J = 6.7.2Hz), 8.
01 (2H, d, J=6Hz).
実施例４
ジアンミン白金（ｎ）シナイトレートより実施例１と同
様に反応、処理すると目的化合物が得られた。Example 4 Diammineplatinum (n) cinitrate was reacted and treated in the same manner as in Example 1 to obtain the target compound.
Claims (1)
レンを示し、点線はＣ〜Ｏ間またはＣ〜Ｎ間の一方が二
重結合であることを示し、Ｘ＾■は陰イオンを示し、ｎ
は１又は２を示し、Ｂ及びＤは同一又は異なって、ＮＨ
＿３、一級アルキルアミン、二級アルキルアミン、芳香
族アミンを示すか又はＢ、Ｃが一緒になってジアミンを
示す。〕を有する４配位２価の白金環状ウレア錯体。[Claims] Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. indicates that one of them is a double bond, X^■ indicates an anion, and n
represents 1 or 2, B and D are the same or different, and NH
_3 represents a primary alkylamine, a secondary alkylamine, an aromatic amine, or B and C together represent a diamine. ] A four-coordinate divalent platinum cyclic urea complex.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62094024A JPH0739431B2 (en) | 1987-04-16 | 1987-04-16 | Platinum urea complex |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62094024A JPH0739431B2 (en) | 1987-04-16 | 1987-04-16 | Platinum urea complex |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63258890A true JPS63258890A (en) | 1988-10-26 |
| JPH0739431B2 JPH0739431B2 (en) | 1995-05-01 |
Family
ID=14098991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62094024A Expired - Lifetime JPH0739431B2 (en) | 1987-04-16 | 1987-04-16 | Platinum urea complex |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0739431B2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0655752A (en) * | 1992-06-09 | 1994-03-01 | Eastman Kodak Co | Defective donor detection method |
-
1987
- 1987-04-16 JP JP62094024A patent/JPH0739431B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0655752A (en) * | 1992-06-09 | 1994-03-01 | Eastman Kodak Co | Defective donor detection method |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0739431B2 (en) | 1995-05-01 |
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