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Title: Structure-based bioisosterism design, synthesis and biological evaluation of novel 1,2,4-triazin-6-ylthioacetamides as potent HIV-1 NNRTIs
Authors: Zhan, Peng ×
Li, Xiao
Li, Zhenyu
Chen, Xuwang
Tian, Ye
Chen, Wenmin
Liu, Xinyong
Pannecouque, Christophe
De Clercq, Erik #
Issue Date: Dec-2012
Publisher: Pergamon Press
Series Title: Bioorganic & Medicinal Chemistry Letters vol:22 issue:23 pages:7155-7162
Article number: 10.1016/j.bmcl.2012.09.062
Abstract: The development of new HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating novel chemical entities of increased potency. Previous investigations in our laboratory resulted in the discovery of several novel series of arylazolylthioacetanilides as potent NNRTIs. In this study, based on the structure-based bioisosterism strategy, novel 1,2,4-triazin-6-yl thioacetamide derivatives were designed, synthesized and evaluated for their anti-HIV activity in MT-4 cells. Among them, the most promising compound was 8b15 with double-digit nanomolar activity against wild-type HIV-1 (EC(50)=0.018±0.007μM) and moderate activity against the double mutant strain RES056 (EC(50)=3.3±0.1μM), which indicated that 1,2,4-triazin-6-yl thioacetamide can be used as a novel scaffold to develop a new class of potent NNRTIs active against both wild-type and drug-resistant HIV-1 strains. In addition, preliminary structure-activity relationship (SAR) and molecular modeling results are also briefly discussed, which provide some useful information for the further design of novel NNRTIs.
URI: 
ISSN: 0960-894X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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