新型吡唑基-噻吩、噻吩并[3,2-b]吡啶、吡唑并[3,4-d]噻吩并[3,2-b]吡啶和吡并[2,3-d]噻吩并[3]的便捷合成和抗癌评价,2-b]吡啶衍生物,Journal of Heterocyclic Chemistry

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新型吡唑基-噻吩、噻吩并[3,2-b]吡啶、吡唑并[3,4-d]噻吩并[3,2-b]吡啶和吡并[2,3-d]噻吩并[3]的便捷合成和抗癌评价,2-b]吡啶衍生物
Journal of Heterocyclic Chemistry ( IF 2.0 ) Pub Date : 2021-03-15 , DOI: 10.1002/jhet.4262
Ghada S. Masaret ₁

Affiliation

新合成的 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate 被用作合成吡唑基-噻吩衍生物的前体，该衍生物在处理后发生环化与苯甲醛衍生物合成吡唑并[3,4- d ]噻吩并[3,2- b ]吡啶。用异硫氰酸苯酯对吡唑基-噻吩衍生物进行碱性处理，随后加入氯丙酮和/或溴乙酸乙酯，得到噻唑基-吡唑基噻吩。此外，结构单元 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate 被转化为相应的 thieno[3,2- b]吡啶化合物通过与（DMF-DMA）反应和/或在乙醇钠中加热。此外，7-羟基-5-氧代-N-苯基-2-(苯基氨基)-4,5-二氢噻吩并[3,2 - b ]吡啶-3-甲酰胺与2-亚芳基丙二腈反应生成了新的环状吡喃并[ 3,2 - b ]吡啶-3-甲酰胺。 2,3- d ]噻吩并[3,2- b ]吡啶。针对 HepG2、PC3 和 MCF-7 癌细胞以及正常成纤维细胞 (WI38) 评估了制备的基于噻吩的化合物。吡唑并[3,4- d ]噻吩并[3,2- b ]吡啶和吡喃并[2,3- d ]噻吩并[3,2- b] 被氯苯基取代的吡啶化合物表现出对 HepG2 癌细胞系的有希望的细胞毒活性，而没有任何人类毒性。对合成的噻吩化合物的对接研究提供了关于 NS5B 酶与 PDB ID (4TLR) 的晶体结构的结合相互作用的宝贵见解。

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Convenient synthesis and anticancer evaluation of novel pyrazolyl-thiophene, thieno[3,2-b]pyridine, pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine derivatives

The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo[3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b]pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).

更新日期：2021-03-15

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