构效关系__(期刊论文)

4，6，17取代6氮杂4烯3酮甾体类5α还原酶抑制剂构效关系的量子化学研究

http://www.100md.com 《广东药学院学报》 2004年第6期

构效关系,,药物化学；构效关系；AM1量子化学方法；甾体5α还原酶抑制剂,1.1构象优化和电子结构的计算

     摘要目的探寻甾体类5α还原酶抑制剂电子结构与活性的关系。方法应用分子力学MM+法、量子化学AM1法对15个4，6，17取代甾体类5α还原酶抑制剂进行构象优化,计算了化合物的电子结构指数,并应用逐步回归探寻化合物量化指数和活性的关系。结果 ①本组化合物的HOMO、LUMO主要分布在母环A环和B环的C3位到N6位这一区域以及O21位上；②疏水常数logP与药效的关系为非线性关系；③得到较显著的QSAR方程。结论 ①从HOMO的分布角度指出分子的4，6位置可能是与酶作用的活性区域;②解释了疏水常数logP与药效的关系为非线性关系的原因；③研究讨论分子的电子结构与药效的关系。

    关键词药物化学；构效关系；AM1量子化学方法；甾体5α还原酶抑制剂

    Study of structureactivity relationships for 4,6substituted 6azaandrost4en3ones of 5αreductase Inhibitors with quantum chemistry

    GAO Wei，XU Xuan

    (1.Department of Pharmacy，Guangdong College of Pharmacy，Guangzhou 510240，China； 2.Department of Chemistry，South China Normal University, Guangzhou 510631，China)

    Abstract Objective To analyze the structureactivity relationships of 4,6,17substituted 6azaandrost4en3ones of 5αreductase inhibitors. Methods To calculate and study by use of molecular mechanics MM+ and quantum chemistry methods AM1, the methods of stepwise regression had been performed. Results ①The component of HOMO and LUMO mainly distributed from C3 to N6 and O21 on the ring A,B; ②logP affects the activity in a nonlinear way; ③The significant QSAR model was set up. Conclusion ①Sites at 4, 6 are the possible active area where compounds interact with enzyme from distribution of HOMO. ②The reason for logP affected the activity in a nonlinear way was explained. ③We discussed the structureactivity relationships. ......

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