【摘要】 应用比较分子场分析法(CoMFA)、比较分子相似性指数法(CoMSIA)和全息定量构效关系法(HQSAR)对21种四氢异喹啉类选择性雌激素受体调节剂进行了定量构效关系研究.分别考察了不同的叠合方法对场分析方法(CoMFA和CoMSIA)、不同场的组合方式对CoMSIA、不同的碎片参数对HQSAR模型构建的影响.根据CoMFA和CoMSIA模型的等值线图、HQSAR模型的原子贡献图,提出了改进四氢异喹啉类选择性雌激素受体调节剂选择性的方法,为合成新型药物分子提供理论支持.更多还原

【Abstract】 Two- and three-dimensional quantitative structure-activity relationships were studied on a series of tetrahydroisoquinoline derivatives by using comparative molecular field analysis(CoMFA).comparative molecular similarity indices analysis(CoMSIA) and hologram quantitative structure-activity relationship (HQSAR).Different alignments were used in order to investigate the effects on the CoMFA and CoMSIA models.Different combinations of fields and different fragment parameters were also applied to exploring the effects on the CoMSIA and HQSAR models.According to the contour maps of CoMFA and CoMSIA model and the atom contribution map of HQSAR model,the rational drug design methods were introduced to improve the selectivity of selective estrogen receptor modulators.This can provide a theoretical basis for drug synthesis.更多还原