Abstract

Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs₂CO₃ in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160 µM concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure–activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF₃ group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable.

Graphic abstract

中文翻译：

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吡唑并[1,5-a]吡嗪-4(5H)-one衍生物的新合成方法及其对肺腺癌细胞系的抗增殖作用

摘要

从 3,5-二甲基吡唑环和苯乙酮衍生物开始，得到了五种不同的 N-炔丙基化 C-3 取代吡唑。_{这些衍生物在甲醇中使用Cs 2} CO ₃与不同的胺衍生物反应，得到了11种不同的吡唑并[1,5-a]吡嗪-4(5 H )-one衍生物，这些衍生物在文献中没有发现。研究了这些衍生物在 A549 细胞系中的细胞毒性作用。发现两种衍生物的 160 µM 浓度可将细胞死亡率提高至 50%，而两种衍生物可将细胞死亡率提高高达 40%。构效关系 (SAR) 研究揭示了具有长烷基链的酰胺基团和具有p -CF ₃的苯环组对于效率可能很重要。通过对吡唑并吡嗪衍生物的理论 ADMET 研究，预计药代动力学阶段是合适的。

图形摘要