摘要
设计合成了以籍次乙基为桥将雌激素通过 3 OH醚化与 4种不同哌嗪环相连的衍生物 ,包括中间体共合成了 12个化合物 ,其中 8个目标物及 3个中间体未见文献报道 .结构经质谱、核磁共振谱、红外光谱及元素分析确定 .同时测定了目标物对体外培养小鼠胚胎长骨生长的影响 ,结果显示由雌酚酮和雌二醇与不同的哌嗪环相连所得到的衍生物抑制骨吸收、促进骨形成的作用均不低于相应的母体雌激素 .表明哌嗪环的引入不影响雌激素对骨的药理作用 ,所合成的 4种化合物可以作为骨靶向雌激素的弹头 ,进一步与骨靶向载体连接 .
Eight of the derivatives of estrogen in which estrone or estradiol was linked respectively to 1,4 piperazine 2 carboxylic acid methyl ester,2 ketopiperazine,3 oxo 2 acetic acid ethyl ester and 2,5 piperazinedione through ethyl were designed and synthesized.All of the target compounds and three of the inter mediates were new compounds.The structures of these new compounds were confirmed by MS, 1H NMR, 13 C NMR,IR and elemental analysis.The effects of the target compounds on bone growth were determined.The results showed that the activities of enhancing bone information and inhibiting bone resorption of all the target compounds synthesized were not lower than that of their original estrogen.The results indicated that the effects of estrogen on bones were not changed by importing piperazine rings and suggested that the target compounds synthesized could be used for synthesis of bone targeted estrogen.
出处
《中国药物化学杂志》
CAS
CSCD
2000年第1期38-41,共4页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金!No .39430 12 0
关键词
雌激素
哌嗪类衍生物
合成
骨吸收
骨形成
estrogen
piperazines
synthesis
bone information
bone resorption
