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对32个雌甾衍生物和9个雄甾和孕甾衍生物进行了结构和雌活性相互关系的定量分析(QSAR)。其结果表明雌甾化合物的雌活性作用可用Fujita-Ban的数学模型来表示。即每个衍生物的雌活性作用是甾核1,3,5(10)雌甾三烯的雌活性作用和各碳原子上各种取代基对雌活性的贡献之和。借助于多元回归和电子计算机计算出了甾核结构和各取代基对活性贡献的数值。计算值与实测值非常相近,相关系数R等于0.98。这些数值对于预测由这些位置的取代基所组成的,在化学上可能合成的药物的生物活性有一定参考价值。QSAR分析表明甾体母体、甾核的立体结构及取代基的位置对生物活性均有重要的影响;C-3环戊氧基增强灌服条件下的雌活性,可能与改变药物的吸收分布过程有关。作者认为对整体动物药理活性的QSAR分析要与药物物化性质研究、体外药物受体结合试验及药物代谢研究等多方面结合才能得到正确的认识。
Quantitative analysis (QSAR) of the relationship between structure and estrogen activity was performed on 32 estrogens and 9 androstane and progesterone derivatives. The result shows that the female activity of the estrogen can be expressed by the mathematical model of Fujita-Ban. That is, the feminine activity of each derivative is the sum of the feminine activity of the steroidal 1,3,5 (10) estrostne and the contribution of the various substituents on each carbon atom to the feminine activity. By means of multivariate regression and computerized calculation of the steroid structure and the contribution of each substituent to the activity. Calculated and measured values are very similar, the correlation coefficient R is equal to 0.98. These values are of some value in predicting the bioactivity of chemically synthesized drugs that consist of the substituents at these positions. QSAR analysis showed that steroid precursor, the steroid structure and the position of the substituent have important effects on the biological activity; C-3 cyclopentyloxy enhances the feeding activity under the condition of feeding, which may be related to changing the process of drug absorption and distribution related. The authors believe that the QSAR analysis of pharmacological activity of whole animals should be combined with many aspects such as the study of the physicochemical properties of drugs, the in vitro drug receptor binding assay and the study of drug metabolism to get a correct understanding.