Title: Design and synthesis of a new series of modified CH-diarylpyrimidines as drug-resistant HIV non-nucleoside reverse transcriptase inhibitors
Authors: Meng, Ge ×
Liu, Yang
Zheng, Aqun
Chen, Fener
Chen, Wenxue
De Clercq, Erik
Pannecouque, Christophe
Balzarini, Jan #
Issue Date: Jun-2014
Series Title: European Journal of Medicinal Chemistry vol:82 pages:600-611
Article number: S0223-5234(14)00483-8
Abstract: This article reports the design, synthesis and antiviral evaluation of a new series of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The basic skeleton of these target 18 molecules is diarylpyrimidine featuring a substituted amino group between the pyrimidine scaffold and the aryl wing. All of the new compounds have been characterized by spectra analysis. The entire target molecules were evaluated for their in vitro anti-HIV activity with controlling group of FDA approved drugs. Most of them showed good to potent activities against wild-type (WT) HIV-1 with IC50 values in the range of 0.0175-69.21 μM. 2-(4-Cyanophenylamino)-4-(2-cyanovinylphenylhydrazonomethyl)pyrimidine (1d) displayed potent anti-HIV-1 activity against WT HIV-1 with a selectivity index (SI) of 106367 and an IC50 value of 1.75 nM, which was 47 fold lower than that of AZT. Compound 1d also showed a broad-spectrum inhibitory activity, with an IC50 value of 5.33 μM and 5.05 μM against both HIV-1 double-mutated (K103N/Y181C) strain and HIV-2 strain, respectively. The preliminary structure-activity relationship (SAR) was also investigated. The binding modes with HIV-1 RT for both the wild type and mutant type have also been discussed.
ISSN: 0223-5234
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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