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新型4,5-二氢噻唑-苯基哌嗪衍生物：作为5-羟色胺能药物的合成、对接研究及药理学评价

Novel 4,5-Dihydrothiazole-Phenylpiperazine Derivatives: Synthesis, Docking Studies and Pharmacological Evaluation as Serotonergic Agents.

作者信息

Andreozzi Giorgia, Karkoszka Natalia, Sparaco Rosa, Corvino Angela, Severino Beatrice, Santagada Vincenzo, Magli Elisa, Gibuła-Tarłowska Ewa, Kotlińska Jolanta H, Gawel Kinga, Capasso Raffaele, Lesniak Anna, Semenko Nataliia, Kaczor Agnieszka A, Bielenica Anna, Biała Grażyna, Caliendo Giuseppe, Kędzierska Ewa, Fiorino Ferdinando

机构信息

Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano, 80131, Napoli, Italy.

Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a Str, 20-093, Lublin, Poland.

出版信息

ChemMedChem. 2025 Aug 2;20(15):e202500288. doi: 10.1002/cmdc.202500288. Epub 2025 Jul 4.

DOI:10.1002/cmdc.202500288
PMID:40458912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12321279/
Abstract

The synthesis of a new series of long-chain arylpiperazine as serotoninergic ligands (FG 1-18) is described. The combination of structural elements including heterocyclic nucleus, propyl chain, and 4,5-dihydrothiazol-2-ylphenylpiperazines leads to the preparation of different derivatives tested for their affinity toward 5-HT, 5-HT, and 5-HT receptors. The compounds with better affinity and selectivity binding profiles toward 5-HT and 5-HT (FG-1, FG-4, FG-5, FG-6, FG-7, FG-8, and FG-18) are selected for further in vivo assays to determine their functional activity. Finally, to rationalize the obtained results, molecular docking studies are performed. The results of pharmacological studies show that compounds FG-1, FG-5, FG-8, and FG-6 exert antidepressant-like effects, and FG-1, FG-18, FG-6, and FG-7 reveal also significant anxiolytic properties. Among the developed derivatives, the most promising compounds seem to be FG-1, which exhibit antidepressant, anxiolytic, and anticonvulsant properties, FG-7 and FG-18 that show features as anxiolytic combine to a pro-cognitive property and notable affinity and selectivity for 5-HT receptor, respectively.

摘要

本文描述了一系列新型长链芳基哌嗪作为5-羟色胺能配体（FG 1-18）的合成。包括杂环核、丙基链和4,5-二氢噻唑-2-基苯基哌嗪在内的结构元素组合，导致制备了不同的衍生物，并测试了它们对5-HT、5-HT和5-HT受体的亲和力。选择对5-HT和5-HT具有更好亲和力和选择性结合谱的化合物（FG-1、FG-4、FG-5、FG-6、FG-7、FG-8和FG-18）进行进一步的体内试验，以确定它们的功能活性。最后，为了合理解释所得结果，进行了分子对接研究。药理学研究结果表明，化合物FG-1、FG-5、FG-8和FG-6具有抗抑郁样作用，FG-1、FG-18、FG-6和FG-7也显示出显著的抗焦虑特性。在已开发的衍生物中，最有前景的化合物似乎是FG-1，它具有抗抑郁、抗焦虑和抗惊厥特性，FG-7和FG-18分别表现出抗焦虑特性，并结合了促认知特性以及对5-HT受体的显著亲和力和选择性。

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