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Journal articles
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 (Shanghai - China)
- CAS - Chinese Academy of Sciences [Beijing] (52 Sanlihe Rd., Beijing, 100864 - China)
- Shanghai Institute of Materia Medica (France)
2
Centre de recherche Université de Hong-Kong-Pasteur (Hong Kong University Pasteur Research Centre - 1/F Dexter HC Man Building 8, Sassoon Road Pokfulam - Hong Kong SAR China)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
4
University College Medical School (London, - United Kingdom)
- University College Medical School (France)
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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https://hal-riip.archives-ouvertes.fr/pasteur-00698608
Contributor : Francois Kien <>
Submitted on : Thursday, May 17, 2012 - 4:25:37 AM
Last modification on : Monday, October 8, 2018 - 5:44:06 PM
Contributor : Francois Kien <>
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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- HAL Id : pasteur-00698608, version 1
- DOI : 10.1021/jm2015952
- PUBMED : 22448770
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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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