艾普列特与乙基纤维素溶混性的计算机模拟(英文)

A Computer Simulation of Miscibility of Epristeride with Ethyl Cellulose

使用计算机辅助分子建模（ＣＡＭＭ）、分子力学和蒙特卡罗方法，模拟了一种有效的人类５α－还原酶（ＥＣ１．３．１．３０）抑制物艾普列特与乙基纤维素（ＥＣ）的溶混性。模拟结果显示，在２７３Ｋ至３１６Ｋ的温度范围内，艾普列特与乙基纤维素能以任何比例混溶。得出Ｅｍｉｘ（Ｔ）＝Ａ＋ＢＴ＋Ｃ／Ｔ模型，Ａ＝０．３０１０Ｅ＋０４，ｂ＝－２．１１８Ｅ－０１，ｃ＝－０．１６４９Ｅ＋４，以及Ｅｍｉｘ（Ｔ）模型标准方差，ｓ＝０．３９４７Ｅ０３ｋｃａｌ／ｍｏｌ。对乙基纤维素及艾普列特与乙基纤维素混溶过程的能量和构象分析表明，混溶过程中有分子内和分子间氢键形成。对两相混溶体系进行了热力学分析。

The miscibility of epristeride (SK&F105657, 17thyl)amino]carbonyl]androsta3,5diene3carboxylic acid), a potent human 5(reductase (EC 1.3.1.30) inhibitor,and Ethocel (ethyl cellulose, EC) was simulated based on the methods of computeraided molecular modeling(CAMM), molecular mechanics, and MonteCarlo method. The simulation result showed that epristeride and ethyl cellulose could be mixed with any ratio in the range between 273K and 316K. Based upon the concerned calculations, Emix(T)=A+BT+C/T model were gotten to match to the energy of mixing, for this simulation, A=0.3010E+04, B=-0.2118E-01, and C=-0.1649E+04, with Emix(T) model standard deviation, S=0.3947E-03 kcal/mol. Energetic and conformational studies of EC and miscibility of epristeride with EC also indicated some conformational changes recorded in the process, especially the forming of intramolecular and intermolecular hydrogen bond, which contributed to the miscibility of EC and epristeride. Thermodynamic analyses of the mixing binary sysethyl cellulose(EC), miscibility, computeraided molecular modeling(CAMM), molecular mechanics, MonteCarlo methodtem were also conducted.