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Claims for Patent: 4,657,927

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Claims for Patent: 4,657,927

Title: Malonato platinum compounds
Abstract:Malonato platinum coordination compounds and a method of treating malignant tumors sensitive to a planar dsp.sup.2 platinum (II) coordination compound or an octahedral d.sup.2 sp.sup.3 platinum (IV) coordination compound comprising the parenteral administration to an affected animal of a solution of the compound.
Inventor(s): Cleare; Michael J. (East Lansing, MI), Hoeschele; James D. (East Lansing, MI), Rosenberg; Barnett (East Lansing, MI), Van Camp; Loretta (East Lansing, MI)
Assignee: Research Corporation (New York, NY)
Application Number:06/497,806
Patent Claims: 1. A method for treating malignant tumors sensitive to a planar dsp.sup.2 platinum(II) coordination compound or an octahedral d.sup.2 sp.sup.3 platinum(IV) coordination compound in animals which comprises parenterally administering to an animal affected with said malignant tumor a solution containing in an amount sufficient to cause regression of the tumor a platinum coordination compound of the formula:

or

wherein:

x=1 or 2;

y=1 or 2;

z=0, 1 or 2, provided that when y=2, z=0, and when y=1, z is greater than 0;

R and R.sub.1 are selected from the group consisting of H, lower alkyl, aryl, aralkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, OH and combine with the carbon atom to form a cycloalkyl or cycloalkenyl group;

when x=1, A is HR.sub.2 N--CHR.sub.3 --CHR.sub.4 --NR.sub.5 H and when x=2, A is H.sub.2 NR.sub.6 or an amino acid; wherein R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of H, CH.sub.3, C.sub.2 H.sub.5, hydroxy and lower alkoxy, provided that R.sub.2 and R.sub.5 may also be aryl or aralkyl and each R.sub.6 is the same or different and is selected from the group consisting of H, lower alkyl, aryl, aralkyl, hydroxy lower alkyl, hydroxy- and alkoxyl-amines and alkoxyl alkyl amines;

when z=1, L is a bidentate anionic ligand, and

when z=2, L is a monodentate anionic ligand.

2. A method for treating malignant tumors sensitive to a planar dsp.sup.2 platinum(II) coordination compound or an octahedral d.sup.2 sp.sup.3 platinum(IV) coordination compound in animals which comprises orally administering to an animal affected with said malignant tumor a solution containing in an amount sufficient to cause regression of the tumor a platinum coordination compound of the formula:

or

wherein:

x=1 or 2;

y=1 or 2;

z=0, 1 or 2, provided that when y=2, z=0, and when y=1, z is greater than 0;

R and R.sub.1 are selected from the group consisting of H, lower alkyl, aryl, aralkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, OH and combine with the carbon atom to form a cycloalkyl or cycloalkenyl group;

when x=1, A is HR.sub.2 N--CHR.sub.3 --CHR.sub.4 --NR.sub.5 H and when x=2, A is H.sub.2 NR.sub.6 or an amino acid; wherein R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of H, CH.sub.3, C.sub.2 H.sub.5, hydroxy and lower alkoxy, provided that R.sub.2 and R.sub.5 may also be aryl or aralkyl and each R.sub.6 is the same or different and is selected from the group consisting of H, lower alkyl, aryl, aralkyl, hydroxy lower alkyl, hydroxyl- and alkoxyl-amines and alkoxyl alkyl amines;

when z=1, L is a bidentate anionic ligand, and

when z=2, L is a monodentate anionic ligand.

3. A composition suitable for parenteral administration to an animal affected with a malignant tumor sensitive to a planar dsp.sup.2 platinum(II) coordination compound or an octahedral d.sup.2 sp.sup.3 platinum(IV) coordination compound comprising a pharmaceutically acceptable carrier and a platinum coordination compound of the formula:

or

wherein:

x=1 or 2;

y=1 or 2;

z=0, 1 or 2, provided that when y=2, z=0, and when y=1, z is greater than 0;

R and R.sub.1 are selected from the group consisting of H, lower alkyl, aryl, aralkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, OH and combine with the carbon atom to form a cycloalkyl or cycloalkenyl group;

when x=1, A is HR.sub.2 N--CHR.sub.3 --CHR.sub.4 --NR.sub.5 H and when x=2, A is H.sub.2 NR.sub.6 or an amino acid; wherein R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of H, CH.sub.3, C.sub.2 H.sub.5, hydroxy and lower alkoxy, provided that R.sub.2 and R.sub.5 may also be aryl or aralkyl and each R.sub.6 is the same or different and is selected from the group consisting of H, lower alkyl, aryl, aralkyl, hydroxy lower alkyl, hydroxyl- and alkoxyl-amines and alkoxyl alkyl amines;

when z=1, L is a bidentate anionic ligand, and

when z=2, L is a monodentate anionic ligand, said compound being present in an amount sufficient to cause regression of said tumor.

4. A composition suitable for oral administration to an animal affected with a malignant tumor sensitive to a planar dsp.sup.2 platinum(II) coordination compound or an octahedral d.sup.2 sp.sup.3 platinum(IV) coordination compound comprising a pharmaceutically acceptable carrier and a platinum coordination compound of the formula:

or

wherein:

x=1 or 2;

y=1 or 2;

z=0, 1 or 2, provided that when y=2, z=0, and when y=1, z is greater than 0;

R and R.sub.1 are selected from the group consisting of H, lower alkyl, aryl, aralkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, OH and combine with the carbon atom to form a cycloalkyl or cycloalkenyl group;

when x=1, A is HR.sub.2 N--CHR.sub.3 --CHR.sub.4 --NR.sub.5 H and when x=2, A is H.sub.2 NR.sub.6 or an amino acid; wherein R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of H, CH.sub.3, C.sub.2 H.sub.5, hydroxy and lower alkoxy, provided that R.sub.2 and R.sub.5 may also be aryl or aralkyl and each R.sub.6 is the same or different and is selected from the group consisting of H, lower alkyl, aryl, aralkyl, hydroxy lower alkyl, hydroxyl- and alkoxyl-amines and alkoxyl alkyl amines;

when z=1, L is a bidentate anionic ligand, and

when z=2, L is a monodentate anionic ligand, said compound being present in an amount sufficient to cause regression of said tumor.
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