Neocarzinostatin derivatives, having anticancer activity. have the formula (A)
wherein (NCS) represents a divalent neocarzinostatin residue in which a hydrogen atom is removed from each of the primary amino groups of the alanine residue at the N-terminal of neocarzinostatin and of the primary amino group of the lysine residue at the 20th position from the N-terminal of neocarzinostatin and (SMA) represents a monovalent partially half-esterified styrene-maleic acid copolymer residue having a weight-average molecular weight of 800 to 2,500 and consisting of structural units of
(a) the styrene residue
(b) the half-esterified maleic acid residue
wherein R is an alcohol residue wherein the hydroxyl group has been removed from an alkanol having 1 to 4 carbon atoms, ethylene glycol monoalkyl ether in which the alkyl group has 1 or 2 carbon atoms or glycerine dialkyl ether wherein the alkyl group has 1 or 2 carbon atoms;
(c) the maleic acid residue
and
(d) a residue having the following formula in which a hydroxyl group of one carboxyl group of a maleic acid residue has been removed to provide the link bonding the monovalent partially half-esterified styrene-maleic acid copolymer residue to the neocarzinostatin residue
具有抗癌活性的新卡西诺司他汀衍
生物具有式(A)
其中(
NCS)代表二价新卡西诺司他汀残基,其中新卡西诺司他汀 N 端丙
氨酸残基的伯
氨基和新卡西诺司他汀 N 端第 20 位赖
氨酸残基的伯
氨基中各去掉了一个氢原子;(SMA)代表一价部分半酯化
苯乙烯-
马来酸共聚物残基,其重量-平均分子量为 800 至 2 500,由以下结构单元组成
(a)
苯乙烯残基
(b) 半酯化
马来酸残余物
其中 R 是醇残余物,其中羟基已从具有 1 至 4 个碳原子的烷醇、
乙二醇单烷基醚(其中烷基具有 1 或 2 个碳原子)或
甘油二烷基醚(其中烷基具有 1 或 2 个碳原子)中除去;
(c)
马来酸残余物
及
(d) 具有下式的残余物,其中
马来酸残余物的一个羧基的羟基已被去除,以 提供连接单价部分半酯化
苯乙烯-
马来酸共聚物残余物和新卡西诺他汀残余物 的键合连接