摘要
目的 :寻找活性强、毒性低的新抗肿瘤化合物。方法 :以哌嗪为起始原料 ,通过与 [二 (4 氟苯 ) ]甲基氯反应得到 1 [二 (4 氟苯 )甲基 ]哌嗪Ⅰ ,Ⅰ分别通过烷基化、烷基二硫代甲酰化、酰基化和Mannich反应在哌嗪的 4 位引入具有抗肿瘤活性的基团 ,得到 9个未见文献报道的 1 [二 (4 氟苯 )甲基 ] 4 取代哌嗪衍生物Ⅱa i。通过SRB法和MTT法测试了它们对 8种瘤株生长的抑制率。结果 :改进了关键中间体Ⅰ的制备方法 ,使收率由文献的5 4%提高到 74%。初步生物活性实验结果表明 ,该类化合物对瘤株Skov3(人体卵巢癌 )较对其它瘤株有较强的抑制率 ;比较化合物Ⅱc和Ⅱg的结构和活性 ,可以发现二硫代酯基的存在与否对不同瘤株生长的抑制率有明显影响 ;4 位引入苄基可使活性有所提高。结论 :1 [二 (4 氟苯 )甲基 ] 4
To look for a new kind of anti tumor compounds with high activity and low toxicity. Methods: Piperazine was reacted with [bi (4 fluorophenyl)]methyl chloride in the presence of phase transfer catalyst to form the key intermediate Ⅰ. The different kinds of antitumor groups were introduced into 4 position of Ⅰ via different reactions, including alkylation, alkyldithioformylation, Mannich reaction, and acylation, to give the corresponding 1 [bi (4 fluorophenyl)methyl] 4 substituted piperazines Ⅱa i. The tumor inhibition of compounds Ⅱa iwas tested against the growth of eight kinds of cells by SRB or MTT method. Results: The synthetic method of key intermediate Ⅰwas improved and the yield was increased from 54% to 74%. Preliminary result of biological activity showed that this kind of compounds exhibited higher tumor inhibition against skov3 than against other kinds of tested cells. In comparison with the structures and activities of compounds Ⅱc and Ⅱg, the presence of dithioester group in the molecules affected the biological activity obviously. The introduction of benzyl in the 4 position of piperazine could enhance the biological activity. Conclusion: 1 [Bi (4 fluorophenyl)methyl] 4 substituted benzyl piperazine is a potential anti tumor compounds.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2001年第3期213-216,共4页
Journal of Peking University:Health Sciences
关键词
哌嗪类
化学合成
1-[二-(4氟苯)甲基]-4-取代哌嗪
抗肿瘤药
药理学
Piperazines/chem syn
1 [bi (4 fluorophenyl)methyl] 4 substituted piperazines
Antineoplastic agents/chem syn
Antineoplastic agents/pharmacol
