4-X-N-Y-6-氮杂雄-4-烯-3-酮衍生物对3BHSD的抑制活性与结构关系研究

应用分子力学方法MM 和半经验量子化学AM1法得到了17种4-X-N-Y-6-氮杂雄-4-烯-3-酮衍生物的优势构象，再利用量子化学算法和分子图形学技术获得电子结构参数和几何结构参数，采用多元线性回归分析和人工神经网络误差反传算法(BP)，将这些参数和4-X-N-Y-6-氮杂雄-4-烯-3-酮衍生物对3β-羟类固醇脱氢酶(3BHSD)的抑制活性相关联。结果表明，4-X-N-Y-6-氮杂雄-4-烯-3-酮衍生物对3BHSD的抑制活性大小和分子范德华体积(V)、分子最高占用轨道能(EHOMO)及9号碳原子的净电荷(Q)的相关性较好，成功地建立了17种4-X-N-Y-6-氮杂雄-4-烯-3-酮衍生物的构效关系式。HOMO轨道组成分析表明，A环上的4号、5号碳原子和羰基氧原子(O18)及B环上的7号、8号碳原子和6号氮原子可能是与受体作用时的活性位点。

Study on the relationships between the structure and inhibition activity of 4-X-N-Y-6 azaandrost-4 -en-3-ones toward 3 BHSD

To analyze the QSAR of 17 4-X-N-Y-6 Azaandrost-4-en-3-ones,MM_+ molecular mechanics method and semi-empiricalAM1 method had been performed.Using multivariate regression analysis(MLR)and standard back-propagation algorithm of artificialneural network(BP),we obtained a significant QSAR.It could be concluded as bellows:the inhibition activity of4-X-N-Y-6 Azaan-drost-4-en-3-ones toward 3BHSD were highly correlated with van der Waals volume,the highest occupied orbital energy and net chargeof C_9.Successful QSAR with correlation for 17 4-X-N-Y-6 Azaandrost-4-en-3-ones was developed.The analysis of HOMO of 4-X-N-Y-6 Azaandrost-4-en-3-ones indicated that the C_4,the C_5 and the O_(18) of carbonyl of ring A together with the C_7,the C_8 and the N_6 of ringB might be active centers that influenced acceptors.