Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives as a New Class of Potent Dengue Virus Inhibitors
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- 作者：Bo Chao ; Xian-Kun Tong ; Wei Tang ; De-Wen Li ; Pei-Lan He ; Jean-Michel Garcia ; Li-Min Zeng ; An-Hui Gao ; Li Yang ; Jia Li ; Fa-Jun Nan ; Michael Jacobs ; Ralf Altmeyer ; Jian-Ping Zuo ; You-Hong Hu
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：April 12, 2012
- 年：2012
- 卷：55
- 期：7
- 页码：3135-3143
- 全文大小：383K
- 年卷期：v.55,no.7(April 12, 2012)
- ISSN：1520-4804
文摘
The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC<sub>50sub> = 0.15 渭M). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure鈥揳ntidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC<sub>50sub> = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.