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手性吡咯烷作为阿尔茨海默病和神经退行性疾病的多效治疗剂。

Chiral pyrrolidines as multipotent agents in Alzheimer and neurodegenerative diseases.

机构信息

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari, Via Orabona, 4, 70125 Bari, Italy.

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari, Via Orabona, 4, 70125 Bari, Italy.

出版信息

Bioorg Med Chem. 2024 Aug 1;110:117829. doi: 10.1016/j.bmc.2024.117829. Epub 2024 Jul 3.

Abstract

In pharmaceutical science and drug design the versatility of the pyrrolidine scaffold relating to spatial arrangement, synthetic accessibility and pharmacological profile is a largely explored and most likely interesting one. Nonetheless, few evidences suggest the pivotal role of pyrrolidine as scaffold for multipotent agents in neurodegenerative diseases. We then challenged the enrolling in the field of Alzheimer disease of so far not ravelled targets of this chemical cliché with a structure based and computer-aided design strategy focusing on multi-target action, versatile synthesis as well as pharmacological safeness. To achieve these hits, ten enantiomeric pairs of compounds were obtained and tested, and the biological data will be here presented and discussed. Among the novel compounds, coumarin and sesamol scaffolds containing analogues resulted promising perspectives.

摘要

在药物科学和药物设计中,吡咯烷骨架在空间排列、合成可及性和药理学特性方面的多功能性是一个被广泛探索且极有可能有趣的方面。尽管如此,仍有一些证据表明吡咯烷作为神经退行性疾病中多效性药物支架的关键作用。然后,我们使用基于结构和计算机辅助设计的策略,将这一化学模式的靶点应用于阿尔茨海默病领域,该策略侧重于多靶点作用、多功能合成以及药理安全性,以此来挑战这一领域。为了实现这些目标,我们获得并测试了十个对映体化合物对,这里将呈现和讨论生物数据。在新型化合物中,香豆素和芝麻酚支架的类似物显示出了很有前景的研究方向。

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