发布时间：2015-04-01 来源：人大经济论坛

制药工程论文范文 目 录 中文摘要 英文摘要 目录 1 绪论1 1.1 论文背景介绍1 1.2 目标化合物概述1 2 目标分子的设计和合成路线2 2.1 目标化合物的设计思路2 2.2 目标化合物的逆合成分析4 2.3 合成路线5 3 实验部分6 3.1实验仪器：6 3.2实验方法：6 4 讨论与结果12 感 谢13 参考文献14 摘 要：目前为止文献报道的CDK7抑制剂主要有两种：一、细胞周期依赖性激酶抑制因子（CKI）；二、小分子抑制剂[6]。小分子化合物又有三种，其中以3-（1氢-吲哚-2-取代）-1氢-吲唑类化合物具有较高的体内外活性,且研究得较为深入。当吲唑6－位取代基为氰基，吲哚环上取代基为吗啉甲基时活性最好，其IC50值仅为11nM。本课题以3-（1氢-吲哚-2-取代）-1氢-吲唑类化合物类化合物为先导化合物，根据生物电子等排、环类似物等设计原理，将吲哚环的4位碳用氮取代，以及对侧链进行系统结构改造，设计相应合成路线，完成8个目标化合物合成，进行计算机虚拟活性测试。 关键词：CDK7抑制剂; 抗肿瘤; 计算机模拟; 吲唑-4氮杂吲哚 Abstract:So far,as reported in literature,there are two kinds of CDK7 inhibitors,one is cyclin-dependent protein kinase inhibition factor(CKI),and the other is small molecular compounds.During small molecular compounds, 3-(1H-indol-2-yl)- 1H -indazole has the most activation both in vivo and vitro and is deep researched.when it is nitrile group substituted in the indazole 6- position,it has the best activation,the IC50 is only 11nM.In our project, 3-(1H-indol-2-yl)-1H-indazole was kept as primary backbone,replaced 4-C in the indole ring with N,and the substituted side chains were systematically revised according to the drug design principle as:bioisosterism,ring analogs and the others.In this way,several kinds of target compounds were designed and synthesized as the CDK7 inhibitor. Keywords：CDK7 inhibitor;antitumor;computer simulation;indazole-4azaindole