Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania.
"Costin D. Nenitescu" Center of Organic Chemistry, Romanian Academy, 202B Splaiul Independenței, 060023 Bucharest, Romania.
Molecules. 2021 Oct 25;26(21):6435. doi: 10.3390/molecules26216435.
A series of new pyrrole derivatives were designed as chemical analogs of the 1,4-dihydropyridines drugs in order to develop future new calcium channel blockers. The new tri- and tetra-substituted -arylpyrroles were synthesized by the one-pot reaction of 1-methyl-3-cyanomethyl benzimidazolium bromide with substituted alkynes having at least one electron-withdrawing substituent, in 1,2-epoxybutane, acting both as the solvent and reagent to generate the corresponding benzimidazolium N3-ylide. The structural characterization of the new substituted pyrroles was based on IR, NMR spectroscopy as well as on single crystal X-ray analysis. The toxicity of the new compounds was assessed on the plant cell using L. species and on the animal cell using Kellogg and Straus crustaceans. The compounds showed minimal phytotoxicity on rootlets and virtually no acute toxicity on nauplii, while on , it induced moderate to high toxicity, similar to nifedipine. Our research indicates that the newly synthetized pyrrole derivatives are promising molecules with biological activity and low acute toxicity.
为了开发未来的新型钙通道阻滞剂，我们设计了一系列新的吡咯衍生物作为 1,4-二氢吡啶类药物的化学类似物。通过 1-甲基-3-氰甲基苯并咪唑溴化物与至少一个吸电子取代基的取代炔烃在 1,2-环氧丁烷中的一锅反应，生成相应的苯并咪唑 N3-叶立德，合成了新型三取代和四取代芳基吡咯。新取代吡咯的结构表征基于 IR、NMR 光谱以及单晶 X 射线分析。使用 L.物种对植物细胞和 Kellogg 和 Straus 甲壳类动物对动物细胞评估了新化合物的毒性。这些化合物对根毛的植物毒性极小，对无节幼体几乎没有急性毒性，而对 ，则诱导中等至高度毒性，类似于硝苯地平。我们的研究表明，新合成的吡咯衍生物是具有生物活性和低急性毒性的有前途的分子。
