哌啶酮类法尼基转移酶抑制剂的设计、合成及初步抗肿瘤活性研究  

Design, Synthesis and Antitumor Activity of Piperidone Inhibitors of Farnesyltransferase

作　　者：葛燕丽[1] 姜凤超[1] 

机构地区：[1]华中科技大学同济医学院药学院,武汉430030

出　　处：《化学学报》2005年第17期1613-1620,F0007,共9页Acta Chimica Sinica

摘　　要：利用计算机辅助药物设计软件Catalyst构建了哌啶酮类法尼基转移酶抑制剂的药效团模型,结合所构建的药效团模型,设计并合成出17个哌啶酮类化合物,其中16个目标化合物未见文献报道,其结构均经IR,MS及1HNMR等确证.利用MTT法得到其对于肿瘤细胞抑制的IC50值.初步生物活性测试表明,目标化合物均具有抑瘤活性,其中11个化合物的IC50值低于阳性对照5-Fu,并且实测值与所构建的药效团模型的预测值相关性较好.The hypothesis of piperidone inhibitors of farnesyltransferase was built with the computer-aided drug design software--Catalyst. According to the hypothesis and structure-activity relationship of piperidone inhibitors, 17 novel piperidone inhibitors of farnesyltransferase were designed and synthesized. All compounds were characterized by IR, MS and 1H NMR. The IC50 value of the target compounds against human Hela cells was evaluated and the result showed that all compounds exhibited antitumor activity, furthermore, the IC50 value of eleven compounds was smaller than that of 5-Fu. The tested activities of the target compounds were fit to those estimated using the hypothesis that was built by Catalyst, and the excellent correlation was got.

关 键 词：哌啶酮类法尼基转移酶抑制剂 计算机辅助药物设计 药效团 构效关系 抗肿瘤活性 酮类化合物 设计软件 酶抑制剂 哌啶 活性研究 

分 类 号：TQ464[化学工程—制药化工]