Sosnovsky G, Li S W
Life Sci. 1985 Apr 15;36(15):1479-83. doi: 10.1016/0024-3205(85)90056-6.
The spin labeled nitrosourea 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6- tetramethyl-piperidinyl)-1-nitrosourea (SLCNU, 4) and its analogues 5-7 were synthesized either by a regio-selective method or by a conventional route via the nitrosation of the spin labeled intermediates (11a-e). Nitrosation of the ureas 11a-e with dinitrogen tetraoxide resulted in better yields than those obtained with sodium nitrite. The nitrosoureas 4-8 were tested for their anticancer activity against the lymphocytic leukemia P388 in mice. Thus, either at the equal molar dose or at the dose of equal toxicity level, the SLCNU (4) was found to be more active than the clinically used CCNU (1). Unlike CCNU (1) whose LD50 is 56 mg/kg, the SLCNU (4) possesses a low toxicity (LD50 123 mg/kg). Therefore, SLCNU (4) is a promising new entry into the nitrosourea class of anticancer drugs.
自旋标记亚硝基脲1-(2-氯乙基)-3-(1-氧基-2,2,6,6-四甲基哌啶基)-1-亚硝基脲（SLCNU，4）及其类似物5-7通过区域选择性方法或经由自旋标记中间体（11a-e）的亚硝化反应，采用常规路线合成。用四氧化二氮对脲11a-e进行亚硝化反应，其产率高于用亚硝酸钠时的产率。对亚硝基脲4-8针对小鼠淋巴细胞白血病P388的抗癌活性进行了测试。因此，无论是在等摩尔剂量还是在等毒性水平剂量下，发现SLCNU（4）比临床使用的CCNU（1）活性更高。与LD50为56 mg/kg的CCNU（1）不同，SLCNU（4）具有低毒性（LD50 123 mg/kg）。因此，SLCNU（4）是亚硝基脲类抗癌药物中有前景的新成员。
