高活性新型抗肿瘤亚硝基脲糖的合成原理及初步生物学评价

Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars.

作者信息

Roger P, Monneret C, Fournier J P, Choay P, Gagnet R, Gosse C, Letourneux Y, Atassi G, Gouyette A

机构信息

Département de Chimie Thérapeutique, Institut Choay, Montrouge, France.

出版信息

J Med Chem. 1989 Jan;32(1):16-23. doi: 10.1021/jm00121a005.

DOI:10.1021/jm00121a005

PMID:2909727

Abstract

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.

摘要

合成了各种二脱氧糖或三脱氧糖的新型亚硝基脲衍生物。研究了羟基取代模式、异头中心的构型以及糖部分的绝对构型对一系列二脱氧糖和三脱氧糖亚硝基脲衍生物抗肿瘤活性的影响。所有化合物在体内对L1210白血病、B16黑色素瘤和Lewis肺癌均表现出非常显著的活性。发现3-[3-(2-氯乙基)-3-亚硝基脲基]-2,3-二脱氧-α-D-阿拉伯-己吡喃糖苷（24，NSC 609224）是活性最高的化合物。当在第1天以20mg/kg的剂量用24（NSC 609224）处理时，至少90%携带L1210白血病和B16黑色素瘤的小鼠存活超过60天，该化合物的LD50值为42mg/kg。