Synthesis and Biological Activities of Novel 2,4-Diaminopyrimidine Derivatives Bearing Indole Moiety

doi:10.6023/cjoc201611006

Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (4): 967-974.DOI: 10.6023/cjoc201611006 Previous Articles Next Articles

ARTICLE

含吲哚环2,4-二氨基嘧啶类化合物的合成及抗肿瘤活性

黎秋, 汪雨, 胡孟金, 陈鹏, 游文玮, 赵培亮

南方医科大学药学院广东省新药筛选重点实验室广州 510515

收稿日期:2016-11-03 修回日期:2016-12-19 发布日期:2016-12-29
通讯作者: 赵培亮 E-mail:plzhao@smu.edu.cn
基金资助:
国家自然科学基金（Nos.21102069、21372113）、广州市珠江科技新星专项（No.2012J2200051）资助项目.

Synthesis and Biological Activities of Novel 2,4-Diaminopyrimidine Derivatives Bearing Indole Moiety

Li Qiu, Wang Yu, Hu Mengjin, Chen Peng, You Wenwei, Zhao Peiliang

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutica Science, Southern Medical University, Guangzhou 510515

Received:2016-11-03 Revised:2016-12-19 Published:2016-12-29
Contact: 10.6023/cjoc201611006 E-mail:plzhao@smu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21102069, 21372113), and the Project of Science and Technology New Star in Zhujiang Guangzhou City (No. 2012J2200051).

1. Synthesis and Biological Activities of Novel 2,4-Diaminopyrimidine Derivatives Bearing Indole Moiety.PDF(825KB)

Abstract

Based on our previous work, twenty-three novel 2,4-diaminopyrimidine derivatives bearing indole moiety were designed and synthesized. Structures of all compounds were elucidated by ¹H NMR, ¹³C NMR and HRMS. Antiproliferative activities for all these compounds were evaluated by the method of methyl thiazolyl tetrazolium (MTT) assay against four cancer cell lines (HeLa, MD-MBA-231, PC-3 and HCT116), and the results demonstrated that some compounds possessed significant antitumor activities in vitro. Particularly, the most promising ethyl (2-((2-benzoyl-5-chloro-1H-indol-3-yl)amino)- 5-nitropyrimidin-4-yl)glycinate (8j) displayed 2.0- and 0.5-fold improvement compared to fluorouracil in inhibiting HCT116, and MD-MBA-231 cell proliferation with IC₅₀ values of 23.15 and 36.88 mmol/L, respectively. These findings suggest that compound 8j may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.

Key words: indole, pyrimidine, synthesis, antiproliferative activity

Cite this article

Li Qiu, Wang Yu, Hu Mengjin, Chen Peng, You Wenwei, Zhao Peiliang. Synthesis and Biological Activities of Novel 2,4-Diaminopyrimidine Derivatives Bearing Indole Moiety[J]. Chin. J. Org. Chem., 2017, 37(4): 967-974.

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含吲哚环2,4-二氨基嘧啶类化合物的合成及抗肿瘤活性

Synthesis and Biological Activities of Novel 2,4-Diaminopyrimidine Derivatives Bearing Indole Moiety

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