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Title: Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographic overlays
Authors: Chen, Wenmin ×
Zhan, Peng
Rai, Diwakar
De Clercq, Erik
Pannecouque, Christophe
Balzarini, Jan
Zhou, Zhongxia
Liu, Huiqing
Liu, Xinyong #
Issue Date: Mar-2014
Publisher: Pergamon
Series Title: Bioorganic & Medicinal Chemistry vol:22 issue:6 pages:1863-1872
Article number: S0968-0896(14)00091-1
Abstract: Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino)pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50=0.15-0.84μM), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives.
URI: 
ISSN: 0968-0896
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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