1. Academic Validation
  2. Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents

Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents

  • Bioorg Med Chem Lett. 2010 Aug 1;20(15):4432-5. doi: 10.1016/j.bmcl.2010.06.056.
Sheng-Jiao Yan 1 Han Zheng Chao Huang Yu-Yun Yan Jun Lin
Affiliations

Affiliation

  • 1 Key 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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