Fluorine-containing anthracycline derivatives having hydroxyl group(s) mono- or di-o-aminoalkanoylated in the sugar moiety thereof
申请人:ZAIDAN HOJIN BISEIBUTSU KAGAKU KENKYU KAI
公开号:EP0761678A1
公开(公告)日:1997-03-12
To provide novel fluorine-containing anthracycline derivatives having high antitumor activities and a solubility in water, there have now been synthesized a 7-O-(2,6-dideoxy-2-fluoro-3-O- or -4-O- or -3,4-di-O-aminoalkanoyl-α-L-talopyranosyl)daunomycinone or -adriamycinone of general formula (I) shown below, as well as a 7-O-(3-O- or -4-O-or -3,4-di-O-aminoalkanoyl-2,6-dideoxy-2,6,6,6-tetrafluoro-α-L-talopyranosyl- or -2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranosyl)adriamycinone of general formula (II) shown below:-
wherein either one or both of A1 and A2 is or are an α-amino acid residue or an ω-amino acid residue and T denotes a fluorine or hydrogen atom. The novel fluorine-containing anthracycline derivatives of general formulae (I) and (II) are highly active against tumors and soluble in water, and they are useful as antitumor agents administrable in the form of injectable solution.
为了提供具有高抗肿瘤活性和水溶性的新型含氟蒽环类衍生物,现已合成了通式(I)如下的7-O-(2,6-二脱氧-2-氟-3-O-或-4-O-或-3,4-二-O-氨基烷酰基-α-L-吡喃甘露糖基)daunomycinone或-adriamycinone、以及下表所示通式(II)的 7-O-(3-O-或-4-O-或-3,4-二-O-氨基烷酰基-2,6-二脱氧-2,6,6,6-四氟-α-L-吡喃他酰胺基-或-2,6-二脱氧-6,6,6-三氟-α-L-来苏己吡喃糖基)阿霉素酮:-
其中 A1 和 A2 中的一个或两个是 α-氨基酸残基或 ω-氨基酸残基,T 表示氟原子或氢原子。通式(I)和(II)的新型含氟蒽环类衍生物具有很强的抗肿瘤活性,可溶于水,可作为抗肿瘤药物以注射液的形式给药。