汤仲明, 吴加金, 毛效求, 陈美云, 黎耀明. 某些雌甾衍生物结构和雌活性相互关系的定量分析J. 药学学报, 1980, 15(7): 410-421.
引用本文: 汤仲明, 吴加金, 毛效求, 陈美云, 黎耀明. 某些雌甾衍生物结构和雌活性相互关系的定量分析J. 药学学报, 1980, 15(7): 410-421.
Tang Zhongming, Wu Jiajin, Mao Xiaoqiu, Chen Meiyun , Li Yaoming, . QUANTITATIVE STUDIES ON THE STRUCTURE-ACTIVITY RELATIONSHIPS OF 1, 3, 5 (10) ESTRA-TRIENE DERIVATIVESJ. Acta Pharmaceutica Sinica, 1980, 15(7): 410-421.
Citation: Tang Zhongming, Wu Jiajin, Mao Xiaoqiu, Chen Meiyun , Li Yaoming, . QUANTITATIVE STUDIES ON THE STRUCTURE-ACTIVITY RELATIONSHIPS OF 1, 3, 5 (10) ESTRA-TRIENE DERIVATIVESJ. Acta Pharmaceutica Sinica, 1980, 15(7): 410-421.

某些雌甾衍生物结构和雌活性相互关系的定量分析

QUANTITATIVE STUDIES ON THE STRUCTURE-ACTIVITY RELATIONSHIPS OF 1, 3, 5 (10) ESTRA-TRIENE DERIVATIVES

  • 摘要: 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。

     

    Abstract: Quantitative relationships between the structure and estrogenic activity of 28 derivatives of 1,3,5(10) estratriene series have been examined by multiple variable regression analysis. The results indicate that the estrogenic activity of a derivative may be regarded as the total sum of the activity contributed by the unsubstituented parent structure 1,3,5(10)estra-triene on the one hand and that by the substituents on the other. Since the correlation coefficient is equal to 0.98, the additivity model can be accepted. The effective value of a given substituent is a constant. The contributions elicited by hydroxy, methoxy, cyclopetoxy and other oxygen containing groups at C-3 and C-17β positions are unanimously positive i.e. to enhance the biological activity. On the contrary, contributions elicited by groups at C-2, C-6, C-13, C-16 and C-17α positions, except the 17α ethynyl group, are negative. Since the group contribution of a substituent varies with different positions attached, it seems reasonable to infer that the steric effects may play an important role inestrogenic activity.

     

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