分化诱导剂的合成及晶体结构

合成出四个分化诱导剂，N,N,N',N'-四乙酰已二胺(Ⅰ),1,6-二烟酰已二胺(Ⅱ),1,6-二(3,5-二氧哌嗪)已烷(Ⅲ)和1,6-二[3,3'-(5,5-二甲乙内酰脲)]已烷(Ⅳ)，对合成方法和路线进行了优化，通过元素分析、质谱、核磁和红外进行了表征，测定了化合物Ⅲ对人白血病细胞的分化诱导活性，利用单晶X射线四圆衍射测定了化合物Ⅳ的晶体结构，并与化合物Ⅰ,Ⅱ,Ⅲ的晶体结构进行了比较。

Synthesis and crystal structures of cancer cell differentiation inducers

Four effective differentiation inducers, the derivatives of HMBA, N, N, N', N'-tetracetylhexamethylenediamine, N, N'-hexamethylenebis (3- pyridinecarboxamide), 4,4'-(hexane-1, 6-diyl)bis(piperazine-2,6-dione) and 3,3'-(hexane-1,6-diyl) bis (5,5-dimethylhydantoin), have been synthesized and identified by MS, NMR, IR and elemental analysis. The synthetic methods and routes have been optimized. The anticancer activity of 4,4'-(hexane-1,6-diyl)bis(piperazine-2,6-dione) against human erythroleukemia K562 cells was tested and its potency is ten times greater than ICRF-154[4,4'-(ethane-1,2-diyl)bis (piperazine- 2, 6-dione)].The structure of compound Ⅳ was determined by single crystal X-ray diffraction and compared with compoundsⅠ,Ⅱ, Ⅲ. In the structures of these compounds, the hexamethylene chain is fully extended, which can increase the flexibility of the molecule. There are hydrogen bonds in compounds Ⅱ,Ⅲ,Ⅳ. It is found that the hydrogen bonds and the ring structure of the functional groups can influence the activity of the compounds.