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Updated: Aug 10, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: synthesis, resolution, and
Krzysztof Krajewski1, Yijun Zhang, Damon Parrish
1Laboratory of Medicinal Chemistry, CCR, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Abstract:
We synthesized, separated into enantiomers, and tested for the HIV-1 reverse transcriptase inhibitory activity a group of analogs of dimethyl-1-(1-piperidynyl)cyclobuta[b][1]benzothiophene-2,2a(7bH)-dicarboxylate (NSC-380292). Absolute configurations of the enantiomers were determined based on absolute X-ray structures and analysis of CD spectra. Within pairs of enantiomers the (R,R)-enantiomer was always much more potent HIV-1 reverse transcriptase inhibitor.
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