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Updated: Jun 11, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents
Sheng-Jiao Yan1, Han Zheng, Chao Huang
1Key Laboratory of Medicinal Chemistry for Natural Resources (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
Abstract:
Novel polyhalo 2,4-diaminoquinazolines 3a-3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74-95%). A series of highly functionalized 2,4-diaminoquinazolines 4-5 were then synthesized based on 3a-3c. The anticancer activities of compounds 3-5 were evaluated in vitro against human cell lines such as Skov-3, HL-60, A431, A549, and HepG-2. Some of the compounds showed excellent cytotoxic activity and 5a was found to be the most potent derivative, with an IC(50) value lower than 2.5 microg/mL against the five tumor cell lines, making it more active than cisplatin. Representative compounds were also preliminarily evaluated as HIV-1 inhibitors in vitro, and 3c showed the most potent anti-HIV-1 activity with EC(50) values of 0.6 and 1.6 microg/mL, and TI values of >59.6 and 66.6, respectively.
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