Phosphatase CDC25B Inhibitors Produced by Basic Alumina-Supported One-Pot Gram-Scale Synthesis of Fluorinated 2-Alkylthio-4-aminoquinazolines Using Microwave Irradiation

被引：12

作者：

Liu, Jin ^{[1
]}

Wang, Yu-Ling ^{[2
]}

Zhang, Ji-Hong ^{[2
]}

Yang, Jian-Shan ^{[1
]}

Mou, Han-Chuan ^{[2
]}

Lin, Jun ^{[1
]}

Yan, Sheng-Jiao ^{[1
]}

机构：

[1] Yunnan Univ, Sch Chem Sci & Technol, Minist Educ & Yunnan Prov, Key Lab Med Chem Nat Resource, Kunming 650091, Yunnan, Peoples R China

[2] Kunming Univ Sci & Technol, Fac Life Sci & Technol, Kunming 650504, Yunnan, Peoples R China

来源：

ACS OMEGA | 2018年 / 3卷 / 04期

基金：

中国国家自然科学基金;

关键词：

HETEROCYCLIC KETENE AMINALS; ENVIRONMENTALLY BENIGN; BIOLOGICAL EVALUATION; HYDROXYL-GROUPS; SOLVENT-FREE; IN-VIVO; DERIVATIVES; DISCOVERY; QUINAZOLINE; ANTICANCER;

D O I：

10.1021/acsomega.8b00640

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

An efficient, environmentally benign, and inexpensive procedure has been developed for the synthesis of fluorinated 2-alkylthio-4-aminoquinazolines by microwave irradiation using basic alumina as a solid-support agent as well as a solid base. Notably, this protocol features improved energy efficiency, broad isothiourea substrate scope, easily available starting materials, and high atom efficiency and applicability toward gram-scale synthesis. Additionally, the target compounds were evaluated for the cytotoxic effect against human colon adenocarcinoma (HCT116 and HT29), human gastric cancer (SGC-7901), human lung adenocarcinoma (A549), and human hepatocyte carcinoma (HepG2) cells, and it was found that these compounds have excellent antitumor activities. Among them, compound 3e was found to be one of the most potent derivatives with IC50 values lower than 9.44 mu M against five human tumor cell lines, making it more active than cisplatin (DDP). Furthermore, for the first time, the fluorinated 2-alkylthio-substituted 4-aminoquinazolines were identified as phosphatase CDC25B inhibitors.

引用

页码：4534 / 4544

页数：11