In view of the anticancer effect of nitrosoureas a set of four new N-(2-chloroethyl)-N-nitrosourea (CENU) derivatives was synthesized. An in silico absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) prediction study revealed that the CENU derivatives satisfied all the required criteria for oral administration and introduced them as remarkable anticancer candidates in the central nervous system (CNS). A comparative solvatochromic study including the Kamlet-Taft, Catalán and Laurence models indicated that the solvatochromic behavior of the CENUs depended on both, unspecific and specific solvent–solute interactions. In detail, the solvatochromic effect of the solvent polarity on the absorption and emission maxima was significant for all CENUs, whereas the solvatochromic effect of the solvent’s ability to donate or accept hydrogen bonds on the absorption and emission maxima was critically dependent on the electron density of the N’-aryl group. From the solvatochromic comparison method, excellent correlations (r ≥ 0.890) were obtained between the ADME parameters and the solvatochromic regression coefficients obtained by the Catalán model. As potential stabilizers, inclusion complexes of the investigated CENU derivatives with β-cyclodextrin (β-CD) were also explored. The spectrofluorimetric host–guest experiments included double-reciprocal Benesi-Hildebrand plots as well as the molar ratio and continuous variation plots (Job’s plots), which established a 1:1 β-CD to CENU binding stoichiometry and relatively high affinities of β-CD for CENU derivatives.

考虑到亚硝基脲的抗癌作用，合成了一组四个新的N-（2-氯乙基）-N-亚硝基脲（CENU）衍生物。一个在硅片吸收，分布，代谢，排泄和毒性（ADME / Tox）的预测研究表明，CENU衍生物满足口服所需的所有标准，并将其作为中枢神经系统（CNS）的重要抗癌候选物引入。包括Kamlet-Taft，Catalán和Laurence模型的比较溶剂化变色研究表明，CENU的溶剂变色行为取决于非特异性和特定的溶剂-溶质相互作用。详细地，对于所有CENU，溶剂极性对吸收和发射最大值的溶剂化变色效应都是显着的，而溶剂在吸收和发射最大值上的给定或接受氢键的能力的溶剂化效应关键取决于电子的密度。在ñ-芳基。从溶剂化变色比较方法，优良的相关性（ř 进行的ADME参数和被加泰罗尼亚模型获得的溶剂化回归系数之间获得≥0.890）。作为潜在的稳定剂，还研究了所研究的CENU衍生物与β-环糊精（β -CD）的包合物。荧光光谱主客体实验包括双倒数Benesi-Hildebrand图以及摩尔比和连续变化图（乔布斯图），建立了1：1β -CD与CENU结合化学计量关系和相对较高的β -CD亲和力用于CENU衍生物。