Abstract In this study, lipophilicity of 21 cycloalkylspiro-5-hidantoins was assessed. The overall goal of lipophilicity evaluation is preliminary investigation which should result in a decrease of the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity assessment was done by reversed-phase thin-layer chromatography and in silico methods. Chromatographic analyses were performed on C-18 modified thin-layer of silica gel with a two-component mobile phase consisting of water and organic solvent (acetonitrile, acetone, dioxane, or tetrahydrofuran) in different ratios. The chromatographic lipophilicities (R M 0) were discussed and compared with computational log Ps calculated with various algorithms as well as in silico ADMET descriptors using linear regression and multivariate approach (hierarchical cluster analysis and principal component analysis). A high correlation was obtained between R M 0 values and calculated log P indicating a strong relationship between the variables. Multivariate data analysis enabled the comparison of the chemical structures, lipophilicity, pharmacokinetic predictors and toxicity of the investigated compounds. Graphical Abstract

中文翻译：

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选定螺乙内酰脲的色谱亲脂性和生物活性参数的比较研究

摘要 本研究评估了 21 种环烷基螺-5-hidantoins 的亲脂性。亲脂性评估的总体目标是初步调查，这将导致进入临床试验的化合物传统上的高损耗率降低。亲脂性评估通过反相薄层色谱法和计算机方法进行。色谱分析是在 C-18 改性硅胶薄层上进行的，流动相由不同比例的水和有机溶剂（乙腈、丙酮、二恶烷或四氢呋喃）组成。讨论了色谱亲脂性 (RM 0) 并与使用各种算法计算的计算 log Ps 以及使用线性回归和多元方法（分层聚类分析和主成分分析）的计算机 ADMET 描述符进行了比较。在 RM 0 值和计算的 log P 之间获得了高度相关性，表明变量之间存在很强的相关性。多变量数据分析能够比较所研究化合物的化学结构、亲脂性、药代动力学预测因子和毒性。图形概要 研究化合物的药代动力学预测因子和毒性。图形概要 研究化合物的药代动力学预测因子和毒性。图形概要