A strategy for the design of potential drugs for the treatment of neurodegenerative diseases is considered. This strategy is based on multipharmacophore compounds combining several characteristic structural moieties (scaffolds) of different neuroactive substances within the one molecule. Various synthetic approaches to such compounds are considered and exemplified by the synthesis of conjugates of phenothiazine, tetrahydro-γ-carboline, carbazole, and aminoadamantane moieties linked through a series of spacers. Data on the biological activity of compounds acquired within the framework of complex screening system are presented. In particular, effects of the novel compounds on cholinesterase enzyme systems, glutamate receptors, mitochondrial structures, formation of microtubule systems, as well as their antioxidant properties, were evaluated. For some multipharmacophore structures, the appearance of neurobiological properties that are not characteristic of the parent compounds was observed, thus providing new opportunities for the design of original highly efficient multitarget drugs. The acquired results allowed us to select several leading compounds that have successfully passed preclinical trials.

考虑了一种用于治疗神经退行性疾病的潜在药物的设计策略。该策略基于将不同神经活性物质的几个特征结构部分（支架）结合在一个分子内的多药效团化合物。考虑了此类化合物的各种合成方法，并通过合成吩噻嗪、四氢-γ-咔啉、咔唑和通过一系列间隔物连接的氨基金刚烷部分的缀合物来举例说明。介绍了在复杂筛选系统框架内获得的化合物的生物活性数据。特别是，评估了新化合物对胆碱酯酶系统、谷氨酸受体、线粒体结构、微管系统形成及其抗氧化特性的影响。对于一些多药效团结构，观察到母体化合物不具备的神经生物学特性的出现，从而为设计原创高效多靶点药物提供了新的机会。获得的结果使我们能够选择几种已成功通过临床前试验的领先化合物。