Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Patent
1990-12-04
1992-03-31
Prescott, Arthur C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
556 40, C07F 1500
Patent
active
051010542
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel fluorine-containing platinum complex and a pharmaceutical composition containing the same. The fluorine-containing platinum complex of the present invention has growth inhibitory activity of towards cancer cells, and is expected to be useful as an anti-tumor agent.
PRIOR ART
It is known that cisplatin [chemical name: cis-dichlorodiamine platinum (II), hereinafter referred to as CDDP] has potent anti-tumor activity, particularly against various kinds of solid cancers. However, CDDP has some side effects such as toxicity to the kidneys, and vomiting. Especially when it is employed clinically, the dose thereof must be limited owing to the toxicity to the kidneys. Hence, the anti-tumor effect thereof cannot be fully obtained. Further, there have been many problems, such as that CDDP does not exhibit sufficient anti-tumor activity against tumor cells which have already become cisplatin resistant (drug resistance), and the like.
Although there have been many attempts to prepare various new derivatives, none has succeeded in satisfying the need for strong anti-tumor activity, effectiveness against tumor cells having drug-resistance, and low toxicity.
There have been prepared many platinum complexes as derivatives having the above-mentioned anti-tumor activity, and some of them have been reported to have anti-tumor activity. The present inventors have intensively studied to obtain a platinum complex having more improved anti-tumor activity, have prepared various platinum complexes wherein a specific fluorine-containing 1,3-propanediamine is used as a ligand, and have found that those complexes have stronger anti-tumor activity than conventional derivatives, and are effective against tumor cells which have already become drug resistant, and further have fewer side effects. The present invention has been accomplished based on the above findings.
An object of the present invention is to provide a novel fluorine-containing platinum complex which has excellent anti-tumor activity. Another object of the present invention is to provide an anti-tumor composition comprising as an active ingredient the said fluorine-containing platinum complex.
DISCLOSURE OF THE INVENTION
The fluorine-containing platinum complex of the present invention is a compound of the formula: ##STR3## wherein R.sub.1 is a fluorine atom or a trifluoromethyl group, to form a group of the formulae: ##STR4## Y is a hydroxyl group or a halogen atom, and n is 0 or 1.
In the compounds of the above formula (1), the lower alkyl group for R.sub.2 is a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, and the like. The halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
Representatives of the compound of the above formula (1) are as follows: (II) (II) (II) (II) (II) Cis-(2-methyl-2-trifluoromethyl-1,3-propanediamine)-1,1-cyclobutanedicarbo xylato platinum (II) (IV) Cis-dichloro-trans-dihydroxy-(2-methyl-2-trifluoromethyl-1,3-propanediamin e) platinum (IV) (II) platinum (II)
The novel fluorine-containing platinum complex of the present invention can be prepared by various methods.
For instance, the fluorine-containing platinum complex of the present invention is prepared by reacting a ligand of the formula: ##STR5## wherein R.sub.1 and R.sub.2 are the same as defined above, with a platinum compound.
The said ligand (2) is prepared by using a fluoroalkylmalonate as a starting compound by the following processes. ##STR6## wherein R.sub.1 and R.sub.2 are the same as defined above, R is a lower alkyl group such as a methyl group, an ethyl group, and the like.
That is, the desired ligand, the fluorine-containing 1,3-propanediamine (2), is prepared by treating a fluoroalkylmalonate (3) with ammonia in a conventional method to give an acid amide (4), reducing the acid amide (4) with a conventional reducing agent for re
REFERENCES:
patent: 4921984 (1990-05-01), Nowatari et al.
patent: 4937358 (1990-06-01), Bitha et al.
patent: 5028727 (1991-07-01), Verbeek et al.
patent: 5034553 (1991-07-01), Verbeek et al.
Iwai Hiroyuki
Shimokawa Kazuhiro
Yamashita Tsuneo
Daikin Industries Ltd.
Prescott Arthur C.
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