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Updated: May 17, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity
Di-Liang Guo1, Xing-Jie Zhang, Rui-Rui Wang
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, PR China.
Abstract:
A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC(50) values of 0.14 and 0.15 μM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).
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