Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV-1 Agents

摘要: We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The IASs 8–37 showed potent inhibition the WT NL4-3 strain mutant K103N, Y181C, Y188L, K103N–Y181C strains. Six racemic mixtures, 8, 23–25, 31, 33, were separated at semipreparative level into their pure enantiomers. (R)-8 enantiomer bearing (α-methylbenzyl) was superior to (S)-counterpart. IAS derivatives (S) alanine unit, (S)-23, (S,R)-25, (S)-31, (S)-33, remarkably more than corresponding (R)-enantiomers. Compound 23 protected hippocampal neuronal cells from excitotoxic insult, while efavirenz (EFV) did not contrast neurotoxic effect glutamate. present results highlight NNRTIs with improved resistance profile against strains reduced effects.