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Title: Synthesis and anti-HIV Activity of aryl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazones as potent non-nucleoside reverse transcriptase inhibitors
Authors: Ma, Xiao-Dong ×
Yang, Shi-Qiong
Gu, Shuang-Xi
Chen, Fen-Er
De Clercq, Erik
Balzarini, Jan
Pannecouque, Christophe #
Issue Date: Dec-2011
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
Series Title: ChemMedChem vol:6 issue:12 pages:2225-2232
Abstract: A series of novel diarylpyrimidines (DAPYs) with a ketone hydrazone substituent on the methylene linker between the pyrimidine nucleus and the aryl moiety at the C-4 position were synthesized, and their antiviral activity against human immunodeficiency virus (HIV)-1 in MT-4 cells was evaluated. Most compounds of this class exhibited excellent activity against wild-type HIV-1, with EC50 values in the range of 1.7-13.2 nm. Of these compounds, 2-bromophenyl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazone (9k) displayed the most potent anti-HIV-1 activity (EC50=1.7 +/- 0.6 nm), with excellent selectivity for infected over uninfected cells (SI=5762). In addition, the 4-methyl phenyl analogue 9d (EC50=2.4 +/- 0.2 nm, SI=18461) showed broad spectrum HIV inhibitory activity, with EC50 values of 2.4 +/- 0.2 nm against wild-type HIV-1, 5.3 +/- 0.4 mu m against HIV-1 double-mutated strain RES056 (K103N+Y181C), and 5.5 mu m against HIV-2 ROD strain. Furthermore, structure-activity relationship (SAR) data and molecular modeling results for these compounds are also discussed.
ISSN: 1860-7179
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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