Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2
机构：[1]Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, P. R. China.[2]Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 852, P. R. China.[3]Department of Pharmacy, Huizhou First Maternal and Child Health Care Hospital, Huizhou 516000, P. R. China.
Preclinical and clinical studies have demonstrated the synergistic effect of microtubule-targeting agents in combination with Janus kinase 2 (JAK2) inhibitors, prompting the development of single agents with enhanced therapeutic efficacy by dually inhibiting tubulin polymerization and JAK2. Herein, we designed and synthesized a series of substituted 2-amino[1,2,4]triazolopyrimidines and related heterocycles as dual inhibitors for tubulin polymerization and JAK2. Most of these compounds exhibited potent antiproliferative activity against the selected cancer cells, with compound 7g being the most active. This compound effectively inhibits both tubulin assembly and JAK2 activity. Furthermore, phosphorylated compound 7g (i.e., compound 7g-P) could efficiently convert to compound 7g in vivo. Compound 7g, whether it was administered directly or in the form of a phosphorylated prodrug (i.e., compound 7g-P), significantly inhibited the growth of A549 xenografts in nude mice. The present findings strongly suggest that compound 7g represents a promising chemotherapeutic agent with high antitumor efficacy.
基金：
This work was financially supported by the Department ofEducation of Guangdong Province (Grant 2021ZDJS092), theScience and Technology Planning Project of GuangdongProvince (2021B1212040016), and National College StudentsInnovation and Entrepreneurship Training Program (Grant3221001932).
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外文
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出版当年[2022]版：
大类|1 区医学
小类|1 区药物化学
最新[2025]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, P. R. China.
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推荐引用方式(GB/T 7714)：
Chen Li,Hu Yunfei,Lu Zhonghui,et al.Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2[J].Journal of medicinal chemistry.2023,doi:10.1021/acs.jmedchem.3c01690.
APA：
Chen Li,Hu Yunfei,Lu Zhonghui,Lin Zeyin,Li Lanqing...&Hu Jinhui.(2023).Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2.Journal of medicinal chemistry,,
MLA：
Chen Li,et al."Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2".Journal of medicinal chemistry .(2023)
医学