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

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Chao B,Tong XK,Tang W,Li DW,He PL,Garcia JM,Zeng LM,Gao AH,Yang L,Li J,Nan FJ,Jacobs M,Altmeyer R,Zuo JP,Hu YH

doi

10.1021/jm2015952

subject

Has Abstract

pub_date

2012-04-12 00:00:00

pages

3135-43

issue

7

eissn

0022-2623

issn

1520-4804

journal_volume

55

pub_type

杂志文章

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