Platinum Compounds Of Malonic Acid Derivative Having Leaving Group Containing Amino Or Alkylamino

摘要

Disclosed are a class of platinum compounds of malonic acid derivatives having a leaving group containing an amino or alkylamino, and pharmaceutically acceptable salt thereof, preparation method thereof and pharmaceutical composition containing the compounds. Also disclosed are uses of the compounds for treating cell proliferative diseases especially cancers. The platinum compounds of the present invention have high solubility in water, low toxicity and strong anti-tumor effect.

主权项

1. Compounds of formula A,or pharmaceutically acceptable salts, solvates, stereoisomers, or prodrugs thereof, wherein:
R0 may or may not exist. When R0 exists, it is selected from alkyl, naphthenic base, alkoxy alkyl, alkyl amino alkyl, heterocycle, alkenyl and chain alkynyl, which are unsubstituted; or optionally substituted by halogen, hydroxyl, alkoxy, alkyl, alkoxy alkyl, naphthenic base, heterocycle, aryl, provided that R0 do not contain unsaturated bond, or R0 contains unsaturated bond, while the atom of the unsaturated bond cannot be directly connected with nitrogen atom; and then formula A is quaternary ammonium, while when R0 does not exist, formula A is tertiary amine; R1 and R2 may be the same or different, and selected from hydrogen, alkyl, naphthenic base, alkoxy alkyl, alkyl amino alkyl, heterocycle, alkenyl, and alkynyl, which are unsubstituted; or optionally substituted by halogen, hydroxyl, alkoxy, alkyl, alkoxy alkyl, naphthenic base, heterocycle, and aryl, provided that R1 and R2 do not contain unsaturated bond, or R1 and/or R2 contains unsaturated bond, while the atom of the unsaturated bond cannot be directly connected with nitrogen atom; R1, R2 and the atoms connected with them may form a closed saturated or unsaturated heterocycle. For example, it can be ternary, quaternary, pentabasic, hexahydric, heptabasic or octatomic ring; the above may be optionally condensed with other rings and may be optionally substituted by halogen, hydroxyl, alkoxy, alkyl, alkoxy alkyl, naphthenic base, heterocycle, and aryl, provided that the atom connected with nitrogen atom is saturated carbon atom; R3 is the alkyl or naphthenic base of C4, it can be substituted by one or more alkoxy, hydroxyl, alkyl, halogen, halogenated alkyl, alkoxy alkyl, and heterocycle. R4 and R5 may be the same or different, and selected from: hydrogen, hydroxyl, alkyl, naphthenic base, alkoxy, alkoxy alkyl, heterocycle, alkenyl, chain alkynyl; wherein alkyl, alkenyl, chain alkynyl, naphthenic base, alkoxy alkyl, alkyl amino alkyl and heterocycle can be unsubstituted or optionally substituted, preferably substituted by halogen, hydroxyl, alkoxy, straight chain or branched-chain alkyl, alkoxy alkyl, naphthenic base and heterocycle; R4, R5 and the atoms connected with them may form a closed ring, which may be quaternary, pentabasic, hexahydric, heptabasic or octatomic ring; the above rings may be optionally condensed with other rings and may be optionally substituted.