吡唑并[1,5-a]嘧啶酮类M通道开放剂脂水分配系数的测定及计算

Detection and Calculation for Lipohilicity (Log P) of PPOs compound M Channel Openers

目的计算并测定吡唑并[1,5-a]嘧啶酮类(PPOs)化合物QO-58,QO-58-L及QO-58-Cl的脂水分配系数,并比较两者的相符程度。方法摇瓶法(正辛醇/水)处理样品,水相用C18固相萃取小柱浓缩,高效液相色谱外标法测定QO-58,QO-58-L和QO-58-Cl水相和油相中的浓度,并分别计算其脂水分配系数(log P)。结果 QO-58的logP=2.43,QO-58-L的logP=1.07,QO-58-Cl的logP=5.50。结论 PPOs结构修饰后的脂水分配系数发生了较大改变,与计算结果趋势相符。

Objective To calculate and detect the lipohilicity(Log P)of PPOs compound,including QO-58,QO-58-L,QO-58-Cl as M channel openers,and to compare the conformity of two results.Methods Determined by high performance liquid chromatography,the peak area of QO-58,QO-58-L and QO-58-Cl can infer their lipid-water partition coef icient(octanol/water).The fixed phase is Spherisorb C18(34/118)10L 4.6í250 mm reverse column,and the mobile phases are acetonitrile-0.2mol/L ammonium acetate(57:43,QO-58),acetonitrile-0.2mol/L ammonium acetate(57:43,QO-58-L),methanol-0.2mol/L ammonium acetate(85:15,QO-58-Cl).Results QO-58 log P=2.43,QO-58-L log P=1.07,QO-58-Cl log P=5.50.Conclusion After structural modification,the lipid-water partition coef icient of PPOs wil change.Software verifies its trend correct.