Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Patent
1990-08-03
1991-08-20
Prescott, Arthur C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
556136, C07F 1500
Patent
active
050415808
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel platinum complex having an antitumor activity, which is valuable as a medicine such as an antitumor agent, and to an antitumor agent comprising this complex as an active ingredient.
BACKGROUND ART
Some platinum complexes represented by cisplatin [namely, cis-diamminedichloro platinum (II)] show a prominent antitumor effect, and are applied as chemotherapeutic agents for malignant tumors to various disease cases.
Cisplatin, however, has a very strong toxicity such as nephrotoxicity, and therefore, the remedial affect of cisplatin is hindered by this strong toxicity.
Second generation platinum complexes represented by platinum (II) cis-diammine-1,1-cyclobutanedicarboxylate, carboplatin, were developed, and although the nephrotoxicity is moderated in these platinum complexes, the antitumor activity is lower than that of cisplatin.
Accordingly, the development of a chemotherapeutic agent having a toxicity lower than those of the conventional platinum complexes, and a higher antitumor effect, is desired.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a molecular depiction of one composition within the scope of the invention; e.g. see Example 1.
DISCLOSURE OF THE INVENTION
The inventors carried out investigations with a view to solving the above-mentioned problem, and have proposed a novel selenious acid-platinum complex and an antitumor agent comprising this complex as an active ingredient (Japanese Patent Application No. 63-176828). After further investigations, the inventors found a novel binuclear platinum complex having a high antitumor effect, and as a result, completed the present invention.
More specifically, in accordance with the present invention, there are provided a novel binuclear platinum complex represented by the following formula I, II or III, di-.mu.-sulfoacetate-bis[(cis-diaminocyclohexane)platinum (II)] and an antitumor agent comprising the platinum complex as an active ingredient: ##STR1##
BEST MODE OF CARRYING OUT THE INVENTION
The novel binuclear platinum complex of the present invention (hereinafter referred to as the compound of the present invention) can be obtained, for example, in the following manner.
Namely, a dinitrato-platinum complex containing 1,2-diaminocyclohexane as the carrier ligand is used as the starting material, and the platinum complex is brought into contact with an OH.sup.- type anion exchange resin, to convert the nitrato group to a hydroxyl group, and then reacted with sulfoacetic acid.
As specific examples of the dinitrato-platinum complex, there can be mentioned dinitrato(1,2-diaminocyclohexane)platinum (II), dinitrato(1,2-diaminoethane)platinum (II), and dinitratodiammineplatinum (II).
As the OH.sup.- anion exchange resin, there can be mentioned Diaion SA10AOH (supplied by Mitsubishi Kasei).
When the platinum complex is brought into contact with the anion exchange resin, any batch method and column method can be adopted, so long as a good contact between the resin and the platinum complex is obtained. From the viewpoint of efficiency, the column method is preferable.
For reacting the obtained reaction mixture with sulfoacetic acid, preferably sulfoacetic acid is incorporated and dissolved in the reaction mixture and the resulting mixture allowed to stand for about 30 minutes to about 2 hours. After the reaction, the solution is concentrated to precipitate a crystal, and the crystal is recovered by filtration and dried to obtain the intended compound.
In the case of the dinitrato-platinum complex valuable as the starting material of the compound of the present invention, for example, dinitrato(diaminocyclohexane)platinum (II), there are considered trans-compounds represented by dinitrato-(1R,2R)-diaminocyclohexaneplatinum (II) and dinitrato-(1S,2S)-diaminocyclohexaneplatinum (II), and cis-compounds represented by dinitrato-cis-diaminocyclohexaneplatinum (II). For the cis-compound, at least three structures including a conformer are considered.
Accordingly, the compound of the present invention in
REFERENCES:
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patent: 4797393 (1989-01-01), Farrell et al.
Stewart et al, "Bis(Monobromoacetato)1,2-Diamino Cyclohexane Platinum(II)", Jrnl of Clinical Hematology and Oncology, vol. 7, No. 4, pp. 867-876, (1977).
Kidani et al, "Antitumor . . . Complexes of 1,2 Cyclohexanediamine Isomers", Gann, vol. 69, No. 2, pp. 263-265, (1978).
Fujii Yuichi
Miyamoto Ken
Prescott Arthur C.
Tsumura & Co.
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