Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. The indole nucleus, frequently encountered as a molecular fragment in natural products and pharmaceutically active compounds, was employed as the initial building block for the synthesis of a series of pyrazino[1,2-a]indoles 1a-k, variably substituted at the 6, 7, 8 and 9-positions. Compound 1e, bearing the methoxy group at the 8-position of the pyrazino[1,2-a]indole nucleus was identified as a novel potent antiproliferative agent against the human chronic myelogenous leukemia K562 cell line, but it was much less active against several other cancer cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 8- to the 7- or 6-position, to furnish compounds 1f and 1g, respectively, yielded inactive compounds. The analysis of structure-activity relationships observed in the series of investigated compounds may represent the basis for the design of more active molecules.

中文翻译：

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发现 8-甲氧基吡嗪并 [1,2-a] 吲哚作为一种新的抗人白血病 K562 细胞的强效抗增殖剂。结构-活性关系研究

鉴定新型和选择性抗癌剂仍然是药理学研究中一个重要且具有挑战性的目标。吲哚核经常作为天然产物和药物活性化合物中的分子片段出现，被用作合成一系列吡嗪并[1,2-a]吲哚 1a-k 的初始构件，在 6 、7、8 和 9 位。在吡嗪并[1,2-a]吲哚核的8位带有甲氧基的化合物1e被鉴定为一种新型有效的抗人慢性粒细胞白血病K562细胞系增殖剂，但它对几种细胞系的活性要低得多。其他癌细胞系。位置异构体的比较表明，将甲氧基从 8- 位移动到 7- 或 6- 位，分别提供化合物 1f 和 1g，产生无活性的化合物。在一系列研究的化合物中观察到的结构-活性关系的分析可能代表设计更多活性分子的基础。