Based on some common structural features of known compounds interfering with p53 pathways and our previously synthesized benzamides, we synthesized new ethyl 5-(4-substituted benzamido)-1-phenyl-1H-pyrazole-4-carboxylates 26a-c, ethyl 5-(4-substituted benzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylates 27a-c and N-(1H-indazol-6-yl)-4-substituted benzamides 31a,b bearing in the 4 position of the benzamido moiety the 2-phenylpropanamido or 2-phenoxyacetamido or cinnamamido groups. A preliminary test to evaluate the antiproliferative activity against human lung carcinoma H292 cells highlighted how compound 26c showed the best activity. This last was therefore selected for further studies with the aim to find the mechanism of action. Compound 26c induces intrinsic apoptotic pathway by activating p53 and is also able to activate TRAIL-inducing death pathway by promoting increase of DR4 and DR5 death receptors, downregulation of c-FLIPL and caspase-8 activation.

中文翻译：

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带有吡唑或吲唑核的新型4-（3-苯基丙酰胺基），4-（2-苯氧基乙酰胺基）和4-（肉桂酰胺基）取代的苯甲酰胺：合成，生物学评估和作用机理。

基于已知化合物干扰p53途径和我们先前合成的苯甲酰胺的一些共同结构特征，我们合成了新的5-（4-取代的苯甲酰胺）-1-苯基-1H-吡唑-4-羧酸乙酯26a-c，5-乙基（4-取代的苯甲酰胺）-1-（吡啶-2-基）-1H-吡唑-4-羧酸酯27a-c和N-（1H-吲唑-6-基）-4-取代的苯甲酰胺31a，b苯甲酰胺基的4位是2-苯基丙酰胺基或2-苯氧基乙酰胺基或肉桂酰胺基。评估抗人肺癌H292细胞抗增殖活性的初步测试突出了化合物26c如何表现出最佳活性。因此，选择了这最后一个用于进一步研究，目的是寻找作用机理。