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US 5,665,343 AGranted
Polymeric platinum complex, preparation thereof, and anticancer agent comprising thereof
AssigneesIl-Yang Pharm. Co., Ltd, Korea Institute of Science and Technology
InventorsYoun Soo Sohn, Hyounggee Baek, Yang Ha Cho, Ok-Sang Jung
Life of this patent
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Abstract
A novel polymeric platinum complex represented by the following formula (I): ##STR1## wherein, S, A, x, m and n are defined as above, a process for preparation thereof, and the use thereof as an anticancer agent.
Claims16
A polymeric platinum complex represented by following formula (I):
- ##STR6## wherein, polymeric backbone is a polyphosphazene having P=N repeating unit;
- S represents hydroxy group, alkoxy group such as methoxy, ethoxy or (2-methoxy)ethoxy group, or alkylamine group such as methylamine or dimethylamine group as solubilizing group and S is attached to the phosphorus on the polymeric backbone through an oxygen or nitrogen atom:
- A represents ammonia, or C.sub.1 -C.sub.3 alkylamine such as methylamine, ethylamine or cyclopropylamine as monodentate neutral ligand, or -type bidentate chelate amine selected from the group consisting of ethylenediamine, propylenediamine, 2-hydroxy-1,3-diaminopropane, 2,2-dimethyl-1,3-diaminopropane, 1,1-diaminomethylcyclobutane, tetrahydro-4H-pyrane-4,4-dimethanamine, 2,2-bisaminomethyl-1,3-propandio and trans(.+-.)-1,2-diaminocyclohexane;
- x designating the type of dicarboxylic amino acid as ion group represents 0, 1 or 2, M designates two sodium or potassium ions or alkaline metal ions or one calcium or barium ion or one alkaline earth metal ion;
- m is 0.2 to 1;
- and n is 10 to 100.
3 more elements
A process for the preparation of a polymeric platinum complex of the formula ##STR7## comprising:
- (a) mixing poly(dichlorophosphazene) in a solvent selected from the group consisting of benzene, toluene, tetrahydrofuran and dioxane with sufficient amounts of a dicarboxylic amino acid selected from the group consisting of derivatives of aminomalonic acid, aspartic acid and glutamic acid and a solubilizing agent having the formula SH to form a polymeric precipitate;
- (b) hydrolyzing the product of (a) with alkaline metal hydroxide or alkaline earth metal hydroxide and mixing the resulting mixture at room temperature for sufficient time to produce an alkaline metal salt of formula (II) or alkaline earth metal salt of formula (III) ##STR8## respectively;
- (c) reacting the product of (b) with a diamine platinum (II) salt of formula (IV) ##STR9## in a molar ratio of 1:0.2 to 1:1, in an aqueous solution at room temperature to obtain the polymeric complex of Formula I:
- wherein the polymeric backbone is a polyphosphazene having P=N repeating unit;
- S is hydroxy, alkoxy or alkylamine, and S is attached to the phosphorous on the polymeric backbone through an oxygen or nitrogen atom;
- A is ammonia or C.sub.1 -C.sub.3 alkylamine or A when taken together with the other A forms a AA type bidendate chelate amine selected from the group consisting of ethlyenediamine, propylenediamine, 2-hydroxy-1,3-diaminopropane, 2,2-dimethyl-1,3-diaminopropane, 1,1-diaminomethylcyclobutane, tetrahydro-4H-pyrane-4,4-dimethanamine, 2,2-bis-aminomethyl-1,3-propandiol and trans(.+-.)-1,2-diaminocyclohexane;
- x is 0, 1 or 2;
- M is two alkaline metal ions or two ammonium or one alkaline earth ion;
- m is 0.2 to 1;
- n is 10-100;
- M (I) is alkaline earth metal or ammonium;
- M (II) is an alkaline earth metal ion;
- and
- X.sub.2 is an anion.
11 more elements
Dependencies are inferred from the claim text.