Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors.

Bo Chao 1 Xian-Kun Tong 1 Wei Tang 1 De-Wen Li 1 Pei-Lan He 1 Jean-Michel Garcia 2 Li-Min Zeng 1 An-Hui Gao 1 Li Yang 1 Jia Li 1 Fa-Jun Nan 1 Michael Jacobs 3, 4 Ralf Altmeyer 2 Jian-Ping Zuo 1, * You-Hong Hu 1, *
* Corresponding author
1 State Key Laboratory of Drug Research
2 Centre de recherche Université de Hong-Kong-Pasteur
3 Royal Free
4 University College Medical School
Abstract : 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(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.
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Submitted on : Thursday, May 17, 2012 - 4:25:37 AM
Last modification on : Monday, October 8, 2018 - 5:44:06 PM

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Bo Chao, Xian-Kun Tong, Wei Tang, De-Wen Li, Pei-Lan He, et al.. Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors.. Journal of Medicinal Chemistry, American Chemical Society, 2012, 55 (7), pp.3135-43. ⟨10.1021/jm2015952⟩. ⟨pasteur-00698608⟩

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