Abstract
New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. © 2014 Elsevier Masson SAS. All rights reserved.
Original language | English |
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Pages (from-to) | 101-111 |
Journal | European Journal of Medicinal Chemistry |
Volume | 80 |
DOIs | |
Publication status | Published - 10 Jun 2014 |
Keywords
- AIDS
- HIV-1
- Indolylarylsulfone
- Nonnucleoside inhibitor
- Reverse transcriptase