摘要：现如今癌症已成为危害人类生命健康的最大顽症之一，癌症在医学上的专门术语称为恶性肿瘤，肿瘤是人体内正常细胞在不同的因素刺激下出现过度增值或异常分化而形成的新生物，表现为失控性生长。目前治疗癌症的药物中化学合成的多半对人体正细胞产生毒副作用，而特定癌细胞的靶向治疗可以消灭特定的癌症细胞，所以对癌症细胞的靶标研究成为20世纪的热门。计算机辅助药物设计方法越来越受到药物研发部门的重视，通过多种学科和多种计算机软件的交叉综合应用，可以用于实现本课题中细胞周期检查点激酶1（ChK1）作为抗癌药物重要靶点的分子设计。

本论文是将文献查找的具有确定生物活性的（IC50）40个1,7-二氮杂咔唑类似物，进行构效关系研究，讨论其三维立体空间结构与抑制活性关系，建立QSAR模型，利用其对此类抑制剂生物活性进行稳定性统计和能力预测，开发的模型能够详细检测影响生物活性的分子结构因子，此外，这些模型可以预测新类似物的生物活性。最后所得三维等值图为合成高活性的化合物能提供理论指导作用。69809

在本文的最后我们针对1,7-二氮咔唑类的化合物中的一种3-芳基-6-甲腈-1，7-二氮咔唑进行了合成方法的分析研究，设计出了一条可行的合成路线。然后在此基础上，我们又进行了合成工艺的放大，包括物料衡算以及设备选型。希望所做的研究能够对今后的继续研究起到一定的作用与意义。

毕业论文关键词： 癌症；计算机辅助药物设计；3D-QSAR；细胞周期检查点激酶1抑制剂

Molecular Design and Synthesis of Kinase ChK1 Inhibitor for Cell Cycle Checkpoint

Abstract:Now cancer has become one of the greatest chronic disease endangering human life and health, called malignant tumor in medical terminology. The tumor is a kind of new organism that normal human cells’ emerging excessive value-added or abnormal differentiation stimulated in different factors form with the performance of runaway growth.Currently, most of the chemical synthesis of cancer drugs in the treatment of human positive cells produce toxic side effects, and specific cancer cells targeted therapy can eliminate specific cancer cells. So the target cells of cancer research becomes a popular research in the 20th century. Computer-aided drug design methods are becoming more and more important in drug research and development. Through the cross-synthesis of many disciplines and computer software, it can be used to realize the important role of Chk1 as a target spot in anticancer drugs.

In this paper, 40 GNE-783 analogues with definite bioactivity were found and the relationship between the three-dimensional spatial structure and inhibitory activity was discussed. The QSAR model was established. The results show that the three-dimensional isotope diagrams can provide theoretical guidance for the synthesis of highly active compounds.The developed models were able to examine in detail the molecular structural factors that affect biological activity, and that these models can predict the biological activity of novel analogs.The resulting three-dimensional equivalence map provides a theoretical guidance for the synthesis of highly active compounds.

We have studied the synthesis of 3-aryl-6-carbonitrile-1,7-diazocarbazole in the compound of 1,7-diazocarbazole and designed a feasible synthetic route at the end of this paper,. Then we have carried out the synthesis process of amplification on this basis, including material accounting and equipment selection. It is hoped that the research can play a certain role and significance to the future research.

Keywords: Cancer ; Computer aided drug design; 3D-QSAR; Chk1 inhibitors 

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