对胺基马尿酸盐类似物的构效关系研究

QSAR STUDIES OF p-AMIDOHIPPURAT ANALOGS AND EXPERIMENTAL PROVEMENT OF DESPOPOULOS' THEORY

采用分子动力学的模拟退火技术和MonteCarlo方法寻找了 2 0个胺基马尿酸盐类似物的优势构象 ,用分子力学方法进行了结构优化 ,再用半经验量子化学方法中的PM3对之进行了进一步优化 ,并做了电子结构计算 .根据计算结果对该类配合物的肾小管分泌机制进行了讨论 :此类化合物具有良好肾小管分泌能力 ,结果显示分子中羰基氧电荷、羧基双键氧和羧基单键氧电荷之和∑Q均处在一个很小的区间内 .据此推论羰基氧、羧基双键氧和羧基单键氧均参予了与肾小管受体的相互作用 ,而且它们是以协同作用与肾小管受体分子作用 .这与Despopoulos理论一致 .

Optimized geometries of a series of p -amidohippurat analogs are obtained by using simulated annealing method and Monte Carlo method of molecular dynamics method. These complexes are optimized by molecular mechanics and then by semi-empirical quantum mechanics method—PM3 while the electronic structures are calculated. Several chemical descriptors are obtained. Uptake mechanism of tubular excretion is developed which is in accordance with Despopoulos' theory.