New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: Synthesis, resolution, and inhibitory activity

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.

Graphical abstractThe synthesis and HIV-1 reverse transcriptase inhibitory activity of dimethyl-1-(1-piperidynyl)cyclobuta[b][1]-benzothiophene-2,2a(7bH)-dicarboxylate (NSC-380292) enantiomers and its structural analogs are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide