Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars.
Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars.
复制标题
高活性新型抗肿瘤亚硝基脲糖的合成和初步生物学评价的基本原理。
DOI：
10.1021/jm00121a005
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发表时间：
1989
影响因子：
7.3
通讯作者：
A. Gouyette
中科院分区：
文献类型：
--
作者：
P. Roger;C. Monneret;J. Fournier;P. Choay;R. Gagnet;C. Gosse;Y. Letourneux;G. Atassi;A. Gouyette
合成了各种新的二脱氧糖或三脱氧糖的亚硝基脲衍生物。研究了一系列二脱氧糖和三脱氧糖的亚硝基脲衍生物的羟基取代模式、异头中心的构型和糖部分的绝对构型对抗肿瘤活性的影响。所有化合物在体内对L1210白血病、B16黑色素瘤和刘易斯肺癌均显示出非常显著的活性。发现甲基3-[3-（2-氯乙基）-3-亚硝基脲基]-2，3-二脱氧-α-D-阿拉伯-吡喃己糖苷24（NSC 609224）是活性最高的化合物。当在第1天用20 mg/kg的24（NSC 609224）处理时，至少90%的携带L1210白血病和B16黑色素癌的小鼠显示出超过60天的存活，对于该化合物的LD 50值为42 mg/kg。
Various new nitrosoureido derivatives of di- or trideoxy sugars were synthesized. The influence of the hydroxyl substitution pattern, the configuration at the anomeric center, and the absolute configuration of the sugar moiety on the antitumor activity of a series of nitrosoureido derivatives of di- and trideoxy sugars was studied. All compounds showed a very significant activity in vivo against L1210 leukemia, B16 melanocarcinoma, and Lewis lung carcinoma. Methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-2,3-dideoxy-alpha-D-arabino- hexopyranoside, 24 (NSC 609224), was found to be the most active compound. When treated with 24 (NSC 609224) at 20 mg/kg on day 1, at least 90% of the L1210 leukemia and B16 melanocarcinoma bearing mice showed a survival of over 60 days for a LD50 value for this compound of 42 mg/kg.