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Updated: May 2, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Discovery of nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors via a
Jun Wang1, Peng Zhan1, Zhenyu Li1
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Jinan, Shandong, PR China.
Abstract:
As a continuation of our efforts to discover and develop back-up analogs of DAPYs, novel substituted nitropyridine derivatives were designed via a structure-based core refining approach, synthesized and evaluated for their in vitro HIV-1 activity in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against wild-type HIV-1 IIIB. Most notably, the compound 7b was identified as the most promising candidate in inhibiting HIV-1 replication with an EC50 value of 0.056 μM and a selective index (SI) of 1251, which were much better than those of NVP (EC₅₀ = 0.23 μM) and DLV (EC₅₀ = 0.51 μM). Some other compounds, 7k, 7c, 7j and 7e, were also endowed with a favorable anti-HIV-1 potency (EC₅₀ = 0.034, 0.11, 0.11 and 0.16 μM, respectively). Some antivirally active compounds also showed moderate inhibitory activity against RT. Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogs provide valuable avenues for future molecular optimization.
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