Wiley, Chemical Biology & Drug Design, 2(87), p. 283-289, 2015
DOI: 10.1111/cbdd.12657
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Through a structure-based molecular hybridization and bioisosterism approach, a series of novel 2-(pyridin-3-yloxy)acetamide derivatives were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cell cultures. Biological results showed that three compounds (Ia, Ih and Ij) exhibited moderate inhibitory activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 8.18 μM to 41.52 μM. Among them, Ij was the most active analogue possessing an EC50 value of 8.18 μM. In order to further confirm the binding target, four compounds were selected to implement an HIV-1 RT inhibitory assay. In addition, preliminary structure–activity relationships (SARs) analysis and some predicted physicochemical properties of three active compounds Ia, Ih and Ij were discussed in detail. Molecular docking studies were also carried out to investigate the binding modes of Ij and the lead compound GW678248 in the binding pocket of RT, which provided beneficial information for further rational design of NNRTIs.This article is protected by copyright. All rights reserved.