Department of Pharmacy and Biotecnology (FaBit), Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Department of Life Science, Università degli Studi di Siena, Via A. Moro 2, 53100, Siena, Italy.
Eur J Med Chem. 2019 May 1;169:89-102. doi: 10.1016/j.ejmech.2019.02.075. Epub 2019 Mar 4.
In the present work we describe the synthesis, characterization and evaluation of neuroprotective effects of a focused library of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines. Furthermore, the new dihydropyridines were subjected to functional in vitro assays in cardiac tissues and vascular smooth muscle to determine their possible selectivity in counteracting the effects of neurodegeneration. In particular the strategy adopted for designing the compounds involves the imidazo[2,1-b]thiazole nucleus. The observed properties show that substituents at C2 and C6 of the bicyclic scaffold are able to influence the cardiovascular parameters and the neuroprotective activity. In comparison to nifedipine, a set of derivatives such as compound 6, showed a neuroprotective profile of particular interest.
在本工作中,我们描述了一系列具有神经保护作用的 4-咪唑并[2,1-b]噻唑-1,4-二氢吡啶的合成、表征和评估。此外,新的二氢吡啶还进行了心脏组织和血管平滑肌的体外功能测定,以确定它们在对抗神经退行性变的影响方面可能具有的选择性。特别是设计化合物所采用的策略涉及咪唑并[2,1-b]噻唑核。观察到的性质表明,双环支架的 C2 和 C6 上的取代基能够影响心血管参数和神经保护活性。与硝苯地平相比,一组衍生物,如化合物 6,显示出特别有趣的神经保护作用。