Ivin B A, Filov V A, Kraĭz B O, Belogorodskiĭ V V, Maliugina L L
Vopr Onkol. 1979;25(7):71-5.
The experiments on rats have shown that there is a linear dependence of the logarithms of reciprocal molar toxic (LD50) and therapeutic (ED50) for sarcoma 45 doses of 6-oxyalkyl-amino-2,4-bis(I-aziridinyl)-sym-triazines and 6-(5-substituted-2,2-dimethyl-1,3-dioxan-5-yl)-amino-2,4-bis(I-aziridinyl)-sym-triazines upon the induction constants of substituents at tertiary carbon, the antitumor activity being more sensitive to the substituent effect compared with the toxicity. The dependence of the logarithms of reciprocal molar therapeutic (ED50 for sarcoma 45 and ED95 for Walker sarcoma) and toxic (LD50 and LD100) doses of the compounds, both synthesized by us and taken from the literature, upon the logarithms of their distribution coefficients in the octanol-water system (IgP) shows a parabolic character with the maximum effect at the extreme point of the parabola. The antitumor activity was more sensitive to a changed IgP than the toxicity.
对大鼠的实验表明，对于肉瘤45，6-氧代烷基氨基-2,4-双（I-氮丙啶基）-对称三嗪和6-（5-取代-2,2-二甲基-1,3-二恶烷-5-基）-氨基-2,4-双（I-氮丙啶基）-对称三嗪的摩尔毒性倒数（LD50）和治疗指数（ED50）的对数与叔碳上取代基的诱导常数呈线性关系，与毒性相比，抗肿瘤活性对取代基效应更为敏感。我们合成的以及取自文献的这些化合物的摩尔治疗指数倒数（肉瘤45的ED50和沃克肉瘤的ED95）和毒性（LD50和LD100）剂量的对数，与其在辛醇-水体系中的分配系数对数（IgP）之间的关系呈抛物线特征，在抛物线的极值点处效应最大。与毒性相比，抗肿瘤活性对IgP的变化更为敏感。
