Lipophilicity is one of the principal QSAR parameters which influences among others the pharmacodynamics and pharmacokinetic properties of a drug candidates. In this paper, the lipophilicity of 14 amide derivatives of 1,3-dimethyl-2,6-dioxopurin-7-yl-alkylcarboxylic acids as multifunctional TRPA1 channel antagonists and phosphodiesterase 4/7 inhibitors with analgesic activity were investigated, using reversed-phase thin-layer chromatography method. It was observed that the retention behavior of the analyzed compounds was dependent on their structural features i.e. an aliphatic linker length, a kind of substituent at 8 position of purine-2,6-dione scaffold as well as on a substitution in a phenyl group. The experimental parameters (R_M0) were compared with computationally calculated partition coefficient values by Principal Component Analysis (PCA). To verify the influence of lipophilic parameter of the investigated compounds on their biological activity the Kruskal-Wallis test was performed. The lowest lipophilicity was observed for the compounds with weak PDE4/7 inhibitory potency. The differences between the lipophilicity of potent inhibitors and inactive compounds were statistically significant. It was found that the presence of more lipophilic propoxy- or butoxy- substituents as well as the elongation of the aliphatic chain to propylene one between the purine-2,6-dione core and amide group were preferable for desired multifunctional activity.

亲脂性是影响候选药物的药效学和药代动力学特性的主要 QSAR 参数之一。在本文中，使用反相研究了 1,3-二甲基-2,6-二氧嘌呤-7-基-烷基羧酸的 14 种酰胺衍生物作为多功能 TRPA1 通道拮抗剂和具有镇痛活性的磷酸二酯酶 4/7 抑制剂的亲脂性。薄层色谱法。据观察，所分析化合物的保留行为取决于它们的结构特征，即脂肪族接头长度、嘌呤-2,6-二酮支架的 8 位取代基以及苯基中的取代基。实验参数（R _M0) 通过主成分分析 (PCA) 与计算计算的分配系数值进行比较。为了验证所研究化合物的亲脂性参数对其生物活性的影响，进行了 Kruskal-Wallis 测试。对于具有弱 PDE4/7 抑制效力的化合物，观察到最低的亲脂性。有效抑制剂和非活性化合物的亲脂性之间的差异具有统计学意义。发现更多亲脂性丙氧基或丁氧基取代基的存在以及在嘌呤-2,6-二酮核和酰胺基团之间的脂族链向丙烯链的延伸对于所需的多功能活性是优选的。