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AssigneeEngelhard Minerals & Chemicals Corporation
InventorsJames D. Hoeschel, Alan R. Amundsen
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Ethylenediamine platinum (II) and 1,2-diaminocyclohexane platinum (II) pyrophosphate complexes are prepared by reaction of the appropriate diaquo platinum (II) salt with a pyrophosphate salt. These complexes possess pronounced anti-tumor activity and low toxicity and thus have high therapeutic indices.
A method for treating malignant sarcoma 180 ascites, lymphoid leukemia L1210, lymphocytic leukemia P388 or B16 melanoma tumors in a mammal afflicted therewith which comprises administering to said mammal an effective amount of an amine platinum(II) pyrophosphate complex useful for treating said tumors, said complex having a structure of the formula:
Dependencies are inferred from the claim text.
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From the US filing history. Foreign family members aren’t listed.
Platinum compounds: without a metal-carbon linkage
Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen
Term ended 7 Mar 1999 (estimated)
USPTO file history isn’t available for this patent, so only indexed dates are shown.
This invention is concerned with certain complexes of platinum(II) containing a pyrophosphate moiety and a bidentate amine moiety. More particularly, this invention is concerned with amine platinum(II) pyrophosphate complexes where the amine moiety is an ethylenediamine or a 1,2-diaminocyclohexane moiety. These compounds have the general formula [{Pt(A)}.sub.2 P.sub.2 O.sub.7 ], where A is either an ethylenediamine or a 1,2-diaminocyclohexane moiety. These complexes are characterized by pronounced activity against in mice combined with low animal toxicity.
FIG. 1 shows the infrared spectrum of the ethylenediamine platinum(II) pyrophosphate complex of Example 1.
FIG. 2 shows the infrared spectrum of the 1,2-diaminocyclohexane platinum(II) pyrophosphate complex of Example 2.
Rosenberg et al reported the discovery that certain platinum coordination compounds are of interest as potential antitumor agents. (Rosenberg et al, "Platinum Compounds: A new Class of Potent Anti-Tumor Agents," Nature, Vol. 222 (Apr. 26. 1969), pp. 385-86). Since then, considerable effort has been expended to evaluate various classes of coordination complexes for similar activity. See, e.g., M. J. Cleare, "Transition Metal Complexes in Cancer Chemotherapy," Coordination Chemistry Reviews, 12 (1974), pp. 349-405. Cis-diammineplatinum pyrophosphate complexes of the empirical formula {Pt(NH.sub.3).sub.2 }.sub.2 P.sub.2 O.sub.7 have been reported; however, they have only marginal activity. (Cleare et al, "Studies of the Antitumor Activity of Group VIII Transition Metal Complexes, Part I, Platinum(II) Complexes, Bioinorganic Chemistry, 2, 187-210 (1973) at p. 199.)
A blue, water soluble, orthophosphate complex of 1,2-diaminocyclohexaneplatinum(II) containing 45.85% platinum (Pt) has been reported to show anti-tumor activity (G. R. Gale et al, "Preparation and Anti-tumor Evaluation of Water-Soluble Derivatives of Dichloro-1,2-diaminocyclohexane platinum," Cancer Treatment Reports 61, pp. 1519-1525 (1977).
In accordance with the present invention, there are provided novel ethylenediamine platinum(II) and 1,2-diaminocyclohexane platinum(II) pyrophosphate complexes which, unlike the known pyrophosphate complex, have exhibited pronounced anti-tumor activity in mice. In addition, they have low mammalian toxicity. As a consequence, in addition to their marked activity, the complexes of this invention have a favorable therapeutic index.