对氨基苯甲酸酯同系物透皮速率的分子轨道法研究

用半经验分子轨道法计算得到了13个对氨基苯申酸酯类化合物的电子结构参数,并用逐步多元回归分析法导出了它们通过大鼠腹部皮肤的透皮稳态流率和渗透系数与电子结构参数之间的相关方程式。结果表明,透皮稳态流率和渗透系数均与亲电超离域度之和(∑SE)或净原子电荷绝对值之和(∑Q)具有较好的抛物线型相关性。∑SE和∑Q与正辛醇/水分配系数或分子体积之间也存在很好的线性相关性。

STUDY ON PERCUTANEOUS RATE OF P-AMINOBENZOATES USING MOLECULAR ORBUTAL METHOD

The semiempirical self-consistent field molecular orbital calculation MNDO- PM3method was utilized to obtain the electronic structural parameters of 13 p-aminobenzoates.Stepwisemultiple regression analyses were then utilized to generate quantitative structure-activity relationshipsbetween the percutaneous fluxes or permeability coefficients and the electronic structural parameters.The results showed that both the percutaneous fluxes and permeability coefficients were well correlatedparabolically with the electrophilic superdelocalizabilities summed over all atoms(∑SE) or the sum ofthe absolute values of the net atomic charges(∑Q).Significant correlations were observed between∑SE or ∑Q and the octanol/water partition coefficients or the molecular volumes。