Famiglini, Valeria Regina, Giuseppe La Coluccia, Antonio Masci, Domiziana Brancale, Andrea Badia, Roger Riveira-Muñoz, Eva Esté, José A. Crespan, Emmanuele Brambilla, Alessandro Maga, Giovanni Catalano, Myriam Limatola, Cristina Formica, Francesca Romana Cirilli, Roberto Novellino, Ettore Silvestri, Romano Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV‑1 Agents We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs <b>8</b>–<b>37</b> showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N–Y181C HIV-1 strains. Six racemic mixtures, <b>8</b>, <b>23</b>–<b>25</b>, <b>31</b>, and <b>33</b>, were separated at semipreparative level into their pure enantiomers. The (<i>R</i>)-<b>8</b> enantiomer bearing the chiral (α-methylbenzyl) was superior to the (<i>S</i>)-counterpart. IAS derivatives bearing the (<i>S</i>) alanine unit, (<i>S</i>)-<b>23</b>, (<i>S</i>,<i>R</i>)-<b>25</b>, (<i>S</i>)-<b>31</b>, and (<i>S</i>)-<b>33</b>, were remarkably more potent than the corresponding (<i>R</i>)-enantiomers. Compound <b>23</b> protected hippocampal neuronal cells from the excitotoxic insult, while efavirenz (EFV) did not contrast the neurotoxic effect of glutamate. The present results highlight the chiral IASs as new NNRTIs with improved resistance profile against the mutant HIV-1 strains and reduced neurotoxic effects. racemic mixtures;chiral indolyarylsulfones;NNRTI;semipreparative level;EFV;alanine unit;excitotoxic insult;K 103N HIV;Chiral Indolylarylsulfone Non-Nucleoside;WT NL 4-3 strain;Transcriptase Inhibitors;enantiomer;resistance profile;chiral IASs;Compound 23;IAS derivatives;New Potent;K 103N Y 181C Y 188L 2017-06-19
    https://acs.figshare.com/articles/journal_contribution/Chiral_Indolylarylsulfone_Non-Nucleoside_Reverse_Transcriptase_Inhibitors_as_New_Potent_and_Broad_Spectrum_Anti-HIV_1_Agents/5173390
10.1021/acs.jmedchem.6b01906.s001