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目的 为寻找高效低毒的雌激素受体拮抗剂 ,设计合成了新结构骨架的三苯乙烯类化合物。方法 通过McMurry反应得到三苯乙烯中间体 ,再经醚化反应得到目的物。通过抗小鼠子宫增重实验测定化合物的拮抗活性 ,竞争性结合雌激素受体实验测定化合物对受体的亲和力。结果 本文共合成了 35个新化学实体 ,并利用X 射线晶体衍射和氢谱确定了化合物的构型。结论 所有化合物均能与受体结合 (IC50 <10 -6mol·L-1) ,其中化合物35与受体的亲和力最大。某些化合物抑制子宫的增长 ,表现为拮抗作用 ;有的则促进子宫的增长 ,表现为激动作用。其中化合物 14和 2 7对子宫的抑制作用强于或相当于他莫昔芬 ,有待进一步研究
OBJECTIVE To find a highly effective and low toxicity estrogen receptor antagonist, a new trinophthalide compound was designed and synthesized. Methods The tristyrene intermediate was obtained by McMurry reaction, and the target product was obtained by etherification. Compounds were tested for antagonistic activity by anti-mouse uterine weight gain and competitive binding for estrogen receptor assays to determine compound affinity for the receptor. Results A total of 35 new chemical entities were synthesized and their structures were confirmed by X-ray crystallography and 1H-NMR. Conclusion All compounds can bind to the receptor (IC50 <10 -6 mol·L-1), of which compound 35 has the highest affinity with the receptor. Some compounds inhibit the growth of the uterus, showing antagonism; while others promote the growth of the uterus, showing the role of excitement. Among them, compounds 14 and 27 inhibited uterus more or less than tamoxifen for further study