新型CDK抑制剂的设计和合成

论文编号:ZY063    论文字数:5699,页数:18

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

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

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