Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1986-04-25
1989-06-27
Lee, Mary C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514188, 544179, 544181, 544225, 546 4, 548103, A61K 3140, A61K 31435, C07F 400
Patent
active
048430692
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The invention relates to medicament formulations containing ruthenium compounds with an antitumoral action, and methods for the treatment of cancers.
PRIOR ART
Of the compounds of the platinum metals, the complex compound cis-diamminedichloroplatinum (II) has proved to be a potent antitumoral agent. An inhibition of tumor growth has also been observed with compounds of the other platinum metals in studies with animal experiments (for example T. Giraldi et al., Cancer Res. 37 [1977] 2662-6). An antitumoral action of ruthenium red is reported by L. J. Anghileri (Z. Krebsforsch. 83 [1975] 213-7). The potential suitability of ruthenium complexes for cancer therapy is discussed by M. J. Clarke, ACS Symp. Ser. 140 [1980] 157-180. The synthesis of complex compounds of trivalent ruthenium with pyrazole and imidazole is described by F. Kralik et al, Collection Czechoslov. Chem. Commun. 26 [1961] 1298.
DESCRIPTION OF THE INVENTION
It has been found that the complex compounds of the general formula I ].sub.1+p+q I radical containing one or more ring nitrogen atoms, They are therefore suitable as chemotherapeutics for the treatment of cancers. As chemotherapeutic agents with few side effects, they are suitable for the treatment of tumors, for example ovarian tumors, mammary tumors, stomach tumors, prostate tumors, lung tumors, bladder tumors and, in particular, colorectal tumors, and other malignant neoplasms. The compounds are accordingly useful for alleviating pain and suffering associated with cancer therapy, for inhibition and regression of tumors and for alleviating symptoms and increasing life expectancy.
The invention therefore relates to medicament formulations containing these ruthenium complex compounds, and use of the complex compounds for preparation of medicament formulations, in particular those useful for treating cancers, and methods for the treatment of organisms suffering from cancer.
Particularly preferred medicament formulations are those containing complex compounds of the general formula I' ].sub.1+p+q I' substituted by hydroxyl, amino, halogen, C.sub.2 -C.sub.4 -alkyl, C.sub.2 -C.sub.4 -alkenyl, C.sub.1 -C.sub.4 -alkylmercapto, formyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, C.sub.1 -C.sub.4 -alkoxycarbonyl-C.sub.1 -C.sub.4 -alkylene, di-C.sub.1 -C.sub.4 -alkylamino, di-C.sub.1 -C.sub.4 -alkylamine-C.sub.1 -C.sub.4 -alkylene, di-C.sub.1 -C.sub.4 -alkylaminocarbonyl, di-C.sub.1 -C.sub.4 -alkylaminocarbonyl-C.sub.1 -C.sub.4 -alkylene, hydroxyiminomethine, phenyl, benzyl, benzoyl, pyrrolidino, piperidino, pyrrol-1-yl or pyrrol-1-yl-C.sub.1 -C.sub.4 -alkylene, or denotes a ring ##STR1## wherein R1' denotes hydrogen, sodium, C.sub.1 -C.sub.4 -alkyl or phenyl and R2' together denote a group --(CH.sub.2).sub.s --, wherein s represents an integer from 4 to 8, -alkyl, amino or phenyl, preferably hydrogen or methyl, -alkyl, amino or phenyl, preferably hydrogen or methyl, and -alkyl, amino or phenyl, preferably hydrogen or methyl, but at least one of the radicals R3', R4' or R5' denotes hydrogen,
Particularly preferred medicament formulations are those containing complex compounds of the general formula I" ].sub.1+p+q I" 4-position, by hydroxyl, amino, chlorine, diethylamino, dimethylamino, hydroxyiminomethine, phenyl, pyrrolidino, piperidino or pyrrol-1-ylmethyl, or denotes pyrrole, imidazole, 1-methylimidazole, 4-methylimidazole, pyrazole, 4-methylpyrazole, triazole, 1-sodium pyrazole, 1-phenyltetrazole, 5-phenyltetrazole, adenine, guanine, purine or cytosine and
Especially preferred medicament formulations are those containing imidazolium diimidazoletetrachlororuthenate(III), bisimidazolium imidazolepentachlororuthenate(III), bispyrazolium pyrazolehydroxotetrachlororuthenate(III), and/or bis(4-methylpyrazolium) (4-methylpyrazole)hydroxotetrachlororuthenate(III).
The compounds of the general formula Ia ].sub.1+p+q Ia contains one or more nitrogen atoms, with the exception of pyrazole and imidazole, and
Preferred compounds are those of the general formula Ia' ].sub.1+p+q Ia' substituted b
REFERENCES:
patent: 4549018 (1985-10-01), Siedle
Keller Heimo
Keppler Bernhard
Asta Pharma AG
Lee Mary C.
Richter J
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