Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib

被引：45

作者：

Li, Yong-Tao ^{[1
,2
,3
]}

Wang, Jing-Han ^{[1
,2
,3
]}

Pan, Cheng-Wen ^{[1
,2
,3
]}

Meng, Fan-Fei ^{[1
,2
,3
]}

Chu, Xiao-Qian ^{[3
]}

Ding, Ya-hui ^{[1
,2
]}

Qua, Wen-Zheng ^{[1
,2
,3
]}

Li, Hui-ying ^{[3
]}

Yang, Cheng ^{[1
,2
,3
]}

Zhang, Quan ^{[1
,2
]}

Bai, Cui-Gai ^{[3
]}

Chen, Yue ^{[1
,2
]}

机构：

[1] Nankai Univ, Coll Pharm, Collaborat Innovat Ctr Chem Sci & Engn Tianjin, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China

[2] Nankai Univ, Tianjin Key Lab Mol Drug Res, Tianjin 300071, Peoples R China

[3] Tianjin Int Joint Acad BioMed, High Throughput Mol Drug Discovery Ctr, Tianjin 300457, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Chronic myelogenous leukemia; K562; KG-1a; Imatinib; Synthesis; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CANCER STEM-CELLS; BCR-ABL; TYROSINE KINASE; PHILADELPHIA-CHROMOSOME; MEDICINAL CHEMISTRY; INHIBITORS; RESISTANCE; BIOISOSTERISM;

D O I：

10.1016/j.bmcl.2016.01.068

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1419 / 1427

页数：9

共 38 条

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N-[2-Methyl-5-(triazol-1-yl)phenyl]pyrimidin-2-amine as a Scaffold for the Synthesis of Inhibitors of Bcr-Abl [J].