Novel water soluble Pt (II) anti-cancer ligand and its preparing method

Abstract

The present invention relates to a new kind of water soluble anticancer Pt (II) compound, cis-[2-substitutent- (4Rú¼5R)-4ú¼5-bis(aminoethyl)-lú¼3-dioxycyclopentaneíñ3-hydroxy-1ú¼1-cyclobutane dicarboxylic radical- Pt (II)], with the substitutent being methyl, ethyl or isopropyl radical. One of the preparation process includes the reaction of material cis-[PtA2I2], with A2 being 2-substitutent- (4Rú¼5R)-4ú¼5-bis(aminoethyl)-lú¼3-dioxycyclopentane, and 3-hydroxy-1ú¼1- cyclobutane dicarboxyl-Ag, filtering to separate AgI, concentrating the mother liquid and freeze drying to obtain the coarse product. The other preparation process includes the first reaction of cis-[PtA2I2] and Ag2SO4, filtering to separate AgI, the reaction of the mother liquid and 3-hydroxyl-1ú¼1-cyclobutane dicarboxylic Ba, filtering to separate BaSO4, concentrating mother liquid, and freeze drying to obtain the coarse product. The coarse product is re-crystallized in water / alcohol system to obtain refined product. The compound of the present invention has anticancer activity and less toxic side effect, and may be clinical use for treating cancers.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to a class of water-soluble platinum (II) anticancer complexes and a preparation method thereof. Background technique [0002] Carboplatin is the second-generation platinum anticancer drug after cisplatin, and its chemical name is cis-1,1-cyclobutane dicarboxylate · diammine platinum (II). The structure of carboplatin retains the anticancer active part (NH 3 ) 2 Pt 2+ , and introduce hydrophilic 1,1-cyclobutane dicarboxylate as leaving group, the solubility is greatly improved, the water solubility reaches 17mg / ml, which is 17 times higher than the solubility of cisplatin (1mg / ml), so card The toxicity of platinum, especially nephrotoxicity and gastrointestinal side effects, is significantly lower than that of cisplatin, making carboplatin one of the most effective anticancer drugs recognized in the world. In the pharmacopoeias of most countries in the world, it is widely used ...

AI Technical Summary

Problems solved by technology

Although some new platinum-based anticancer drugs have been introduced in recent years, such as Nadaplatin, Oxaliplatin, Eptaplatin, and Loplatin, their water solubility is low. Compared with carboplatin, its comprehensive curative effect is not as good as carboplatin and its toxic and side effects are greater than carboplatin [You Qidong, Gou Shaohua, Research Progress of Anti-tumor Platinum Complexes, Progress in Medicinal Chemistry, 2003, 2: 161-187], so the development of water-soluble Platinum-based antitumor complexes with good activity, high activity and low toxicity are one of the development directions of platinum-based anticancer drugs [Ernest Wong, Christen M G, Current Status of Platinum-based AntitumorDrugs, Chem.Rev., 1999, 99: 2451-2466]

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