PDF(Pubmed)
Abstract：
The biological activity of compounds directly depends on the three-dimensional arrangement of affinity fragments since a high degree of pharmacophore compliance with the binding site is required. 3-Benzylidene oxindoles are privileged structures due to their wide spectrum of biological activity, synthetic availability, and ease of modification. In particular, both kinase inhibitors and kinase activators can be found among 3-benzylidene oxindoles. In this work, we studied model compounds obtained via oxindole condensation with aldehydes and alkylphenones. These condensation products can exist in the form of E- and Z-isomers and also undergo isomerization in solutions. The factors causing isomeric transformation of these compounds were established. Comparative kinetic studies to obtain quantitative characteristics of UV-driven isomerization were first performed. The results obtained indicate dramatic differences in two subclasses, which should be considered when developing biologically active molecules.
摘要：
化合物的生物活性直接取决于亲和片段的三维排列,因为需要与结合位点高度的药效团顺应性。3-苄烯羟吲哚是由于其广泛的生物活性的特权结构，合成可用性，易于修改。特别是,激酶抑制剂和激酶激活剂都可以在3-亚苄基氧吲哚中找到。在这项工作中,我们研究了通过羟吲哚与醛和烷基苯酮缩合获得的模型化合物。这些缩合产物可以以E-和Z-异构体的形式存在,并且还在溶液中经历异构化。建立了导致这些化合物异构转化的因素。首先进行比较动力学研究以获得UV驱动异构化的定量特征。获得的结果表明两个子类存在巨大差异，在开发生物活性分子时应该考虑这一点。
