Phosphatase CDC25B Inhibitors Produced by Basic Alumina-Supported One-Pot Gram-Scale Synthesis of Fluorinated 2‑Alkylthio-4-aminoquinazolines Using Microwave Irradiation
journal contributionposted on 2018-04-25, 11:52 authored by Jin Liu, Yu-Ling Wang, Ji-Hong Zhang, Jian-Shan Yang, Han-Chuan Mou, Jun Lin, Sheng-Jiao Yan
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 μM 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.
Phosphatase CDC 25B Inhibitors Producedantitumor activitiesphosphatase CDC 25B inhibitorsmicrowave irradiationisothiourea substrate scopeHTMicrowave Irradiationtumor cell linesIC 50 valuesHCT 116colon adenocarcinomaprotocol featuresDDPhepatocyte carcinomatarget compoundscompound 3 elung adenocarcinoma2- alkylthio-substituted 4- aminoquinazolines9.44 μ MBasic Alumina-Supported One-Pot Gram-Scale Synthesisenergy efficiency2- alkylthio -4-aminoquinazolinesatom efficiencycytotoxic effectSGCgram-scale synthesissolid-support agent