抗埃博拉病毒药物法匹拉韦及其衍生物pK_b值预测

pK_b Prediction of Favipiravir as Drug for Ebola Virus and Its Derivatives

运用密度泛函理论(DFT B3LYP)和6-31+G(d,p)基组,优化了20种法匹拉韦衍生物的分子结构,分别得到羰基氧的Mulliken、NBO和ESP电荷值,发现其Mulliken电荷值与用ACD Lab6.0预测出来的p Kb值相关性最好,相关系数达0.976;计算了法匹拉韦及其11种衍生物的Mulliken电荷值,带入相关线性方程,发现所得结果与ACD Lab6.0预测结果十分接近,最大误差绝对值仅为0.08,由此也得知法匹拉韦发挥其药理毒理作用可能的部位在羰基氧上。

By density functional theory DFT B3LYP/6-31＋G（d,p） basis set, the molecular structures of 20 kinds of derivatives of favipiravir were optimized, respectively. Mulliken charge, NBO charge and ESP charge of their carbonyloxy were obtained. It＇s found that the Mulliken charge value of the carbonyloxy has good linear relativity with its pKb predicted by ACD Lab 6.0 software, the correlation value is 0.976. Mulliken parameters of the favipiravir and 11 kinds of its derivative with unknown pKb value were calculated, they were substituted into the fitted linear parametric equation, and it＇s found that the computed results is very close to the pKb value predicted by ACD Lab 6.0 software. The results also show that, the possible part of pharmacological and toxicological effects of favipiravir is O atom on the carbonyl.