Sosnovsky G, Li S W, Rao N U
Department of Chemistry, University of Wisconsin-Milwaukee 53201.
Z Naturforsch C J Biosci. 1987 Jul-Aug;42(7-8):921-31. doi: 10.1515/znc-1987-7-832.
The spin labeled nitrosoureas 7a-e and 12 were synthesized and evaluated in vivo for their anticancer activities against the murine lymphocytic leukemia P388. Compounds 7a-c, 7e and 12 possessed activities ranging from 31 to 542 percent increase in life span (%ILS), whereas compound 7d was marginal (%ILS = 21). All CD2F1 male mice treated with the most active compounds (7a and 12) at 35 mg/kg for 9 days were alive after 30 days, whereas all mice treated with the clinical drug CCNU (1c) succumbed. Compounds 7a-e and 12 were further evaluated for their antineoplastic activity against lymphoid leukemia L 1210. Compounds 7a and 12 exhibited, on day 60, a %ILS of 713 and 620, respectively. The lipophilicities of compounds 7a-e and 12 were determined using the EPR and UV methods. Compounds 7a and 12 which differ from CCNU and MeCCNU by the replacement of the cyclohexyl and methylcyclohexyl groups with six and five membered nitroxyl radical moieties were more hydrophilic than the clinical drugs.
合成了自旋标记的亚硝基脲7a - e和12，并在体内评估了它们对小鼠淋巴细胞白血病P388的抗癌活性。化合物7a - c、7e和12的活性使寿命延长了31%至542%（寿命延长百分比，%ILS），而化合物7d的活性较弱（%ILS = 21）。所有以35 mg/kg的最具活性化合物（7a和12）处理9天的CD2F1雄性小鼠在30天后均存活，而所有用临床药物CCNU（1c）处理的小鼠均死亡。进一步评估了化合物7a - e和12对淋巴白血病L 1210的抗肿瘤活性。在第60天时，化合物7a和12的寿命延长百分比分别为713和620。使用电子顺磁共振（EPR）和紫外（UV）方法测定了化合物7a - e和12的亲脂性。与CCNU和MeCCNU不同，化合物7a和12用六元及五元硝酰基部分取代了环己基和甲基环己基，它们比临床药物更具亲水性。
