Title: Synthesis and biological evaluation of 6-substituted 5-alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs
Authors: Yu, Mingyan ×
Liu, Shuai
Fan, Erkang
Pannecouque, Christophe
De Clercq, Erik
Liu, Xinyong #
Issue Date: May-2011
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
Series Title: ChemMedChem vol:6 issue:5 pages:826-833
Article number: 10.1002/cmdc.201000555
Abstract: A series of new 5-alkyl-2-phenylaminocarbonylmethylthiopyrimidin-4(3H)-ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti-HIV activity in MT-4 cells. Most of these new congeners exhibited moderate to good activities against the wild-type virus, with EC(50) values in the range of 1.40-0.19 μM. Among them, 2-[(4-cyanophenylamino)carbonylmethylthio]-6-(2-chloro-6-fluorobenzyl)-5-ethylpyrimidin-4(3H)-one 4 b6 is one of the compounds endowed with the highest broad-spectrum HIV-1 inhibitory activity, with EC(50) values of 0.19±0.005 μM against the wild-type virus, 1.05±0.24 μM (twofold resistance) against the E138K strain, and 2.38±0.13 μM (4.5-fold resistance) against the Y181C strain. Furthermore, reverse transcriptase (RT) inhibition assays against wild-type HIV-1 RT were performed with selected derivatives, confirming that the main target of these compounds is HIV-1 RT and that these new S-DABO analogues act as non-nucleoside RT inhibitors (NNRTIs). Structure-activity relationship and molecular modeling analyses of these new congeners 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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